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RATIONALE & OBJECTIVE: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. PREDICTORS: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. OUTCOMES: (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. ANALYTICAL APPROACH: Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. RESULTS: One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). LIMITATIONS: The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. CONCLUSIONS: The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.
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Injúria Renal Aguda , Estado Terminal , Adulto , Humanos , Estudos de Coortes , Estado Terminal/terapia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Unidades de Terapia Intensiva , RimRESUMO
OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care PICU. PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS: Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.
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Lesões Encefálicas/diagnóstico , Lesões Encefálicas/etiologia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Unidades de Terapia Intensiva Pediátrica , Índice de Gravidade de Doença , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/etiologia , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
High-sugar consumption is related to dyslipidemia. How acute exercise affects postprandial lipid and lipoprotein particle responses to a high-sugar meal (HSM) in postmenopausal women is unclear. We examined the effects of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a HSM breakfast the following day in 22 postmenopausal women. Subjects underwent exercise (EX) and no exercise (NE) conditions in the evening 13-16 h before the HSM breakfast consumption, in a random order. During the EX condition, subjects performed supervised aerobic exercise for 60 min at 75% of age-predicted maximum heart rate. The HSM (75.6% carbohydrate and 33% energy needs) was consumed after a 12-h fast. Serum lipids and lipoproteins were assessed at baseline and postprandially (60, 120, 180 min). Repeated measures analysis showed significantly lower area under the curve (geometric means [95% CI]) for triglycerides (TG) (2.96[2.43, 3.61] vs. 3.24[2.70, 3.88] mmol/L*hr; p = 0.049) and very low density lipoprotein particles (VLDLP) (114.6[88.2, 148.9] vs. 134.3[108.1, 166.9] nmol/L*hr; p = 0.02) during the EX versus NE condition. There were no condition effects for other variables. In conclusion, the EX versus NE condition lowered postprandial AUC for TG and VLDLP following HSM consumption in postmenopausal women.Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.
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Desjejum , Açúcares , Glicemia , Estudos Cross-Over , Exercício Físico , Feminino , Humanos , Insulina , Lipoproteínas , Pós-Menopausa , Período Pós-Prandial , TriglicerídeosRESUMO
Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.
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Insuficiência Renal Crônica , Citratos , Creatinina , Estudos Transversais , Humanos , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Estudos RetrospectivosRESUMO
AIMS: The metabolic syndrome (MetS) is a major global problem, and inflammation and insulin resistance appear to be key underpinnings in this cardio-metabolic cluster. MetS predisposes to an increased risk of diabetes and atherosclerotic cardiovascular disease (ASCVD). It has a procoagulant diathesis which included increased platelet activity and impaired fibrinolysis. High density lipoprotein (HDL) appears to be anti-thrombotic. Accordingly, we examined the ratios between platelets to HDL-cholesterol(C) and adiponectin (Adipo) in patients with nascent MetS without the confounding of diabetes, ASCVD and smoking to determine their validity as biomarkers of MetS. METHODS: Patients with nascent MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipids, insulin, and Adipo. Ratios of platelets to HDL-C and Adipo were calculated. RESULTS: Following adjustment for adiposity, only the platelet: HDL ratio was significantly increased in MetS and increased with severity of MetS. Receiver operating characteristic curve analysis showed that the platelet: HDL-C area under the curve (AUC) significantly added to both platelets and platelet lymphocyte ratio AUCs. Also the platelet: HDL-C ratio correlated with all cardio-metabolic features of MetS, high sensitivity C-reactive protein, insulin resistance chemerin, and leptin. CONCLUSIONS: The ratio of platelets: HDL-C is significantly increased in patients with nascent MetS and appear to be a valid biomarker of MetS. It could also emerge as a biomarker for athero-thrombotic risk. However, these preliminary findings need confirmation in large prospective studies.
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Resistência à Insulina , Síndrome Metabólica , Adiponectina , Biomarcadores , Plaquetas , Quimiocinas , HDL-Colesterol , Humanos , Lipoproteínas HDL , Síndrome Metabólica/diagnóstico , Estudos Prospectivos , TriglicerídeosRESUMO
AIMS: The metabolic syndrome (MetS) is an inflammatory disorder associated with an increased risk for diabetes and atherosclerotic cardiovascular disease (ASCVD). Studies in patients and animal models of obesity and diabetes have shown increased NOD-like receptor family pyrin domain containing 3 (NLPR3) inflammasome activity. However, there is scanty data on the activity of the NLRP3 inflammasome in patients with nascent MetS. The aim of this study was to determine the status of the inflammasome in subcutaneous adipose tissue (SAT) of patients with nascent MetS without concomitant diabetes, ASCVD and smoking. MATERIALS AND METHODS: Patients with nascent MetS and controls were recruited from Sacramento County. Fasting blood samples were collected for biomediators of inflammation and SAT was obtained by biopsy for immunohistochemical (IHC) staining for caspase 1, IL-1ß and IL-18. RESULTS: Caspase1, a marker of inflammasome activity and its downstream mediators IL-1ß and IL-18 were significantly increased in SAT of patients with MetS compared to controls. Significant positive correlations of caspase 1 were obtained with certain cardio-metabolic features, biomediators of inflammation and markers of angiogenesis and fibrosis in SAT. Both mast cell and eosinophil abundance but not macrophage density correlated with caspase1. CONCLUSIONS: We make the novel observation that the SAT of patients with nascent MetS displays increased NLRP3 inflammasome activity manifest by increased caspase 1 in SAT and this may contribute to increased insulin resistance, inflammation and SAT fibrosis in these patients.
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Inflamassomos , Síndrome Metabólica , Gordura Subcutânea , Humanos , Inflamassomos/metabolismo , Síndrome Metabólica/metabolismo , Gordura Subcutânea/metabolismoRESUMO
Understanding the correlates of depression in HIV patients can help identify groups whose members are at increased risk for depression. We conducted a cross-sectional retrospective study among racially diverse, indigent patients living with HIV (PLWH) who were obtaining care in an urban safety-net hospital system and had completed a Patient Health Questionnaire-9 (PHQ-9) in 2014 or 2015. We collected demographics, HIV risk factors, HIV viral loads, CD4 counts, missed visits, and emergency department (ED) visits. Data from the Substance Abuse and Mental Illness Symptoms Screener (SAMISS) were abstracted. Missing data on substance use and CD4 cell counts were imputed to examine the odds of depression (PHQ-9 ≥ 10) by multivariable analysis for a complete case and sensitivity analysis. Stratified analysis by HIV viral suppression (VS) was used to determine the odds of depression among subgroups. Of the 5126 HIV patients (70.8% male,56.3% Black, 44.6% MSM, 6.0% IDU), 1271 (24.8%) experienced depression (PHQ ≥ 10). In a multivariable logistic model female gender, White race, injection drug use (IDU) or men who have sex with men (MSM) as an HIV risk factor, making ≥1 ED visit, having missed any HIV visit, having AIDS, and having a positive drug screen by SAMISS increased the odds for depression. Those who had achieved HIV VS or received efavirenz had lower odds of depression. Even among those with AIDS, those failing to achieve VS were at increased odds for depression, whereas those achieving VS were not. Moderate to severe depression is prevalent among PLWH. Among those with AIDS, HIV VS modifies the odds of depression.
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Infecções por HIV , Minorias Sexuais e de Gênero , Estudos Transversais , Depressão/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Estudos RetrospectivosRESUMO
Aims: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS.Methods: Patients with MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically.Results: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios.Conclusions: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.
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Resistência à Insulina , Síndrome Metabólica , Biomarcadores , Proteína C-Reativa , HDL-Colesterol , Humanos , Síndrome Metabólica/diagnóstico , Estudos Prospectivos , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Moderate intensity exercise is associated with a decreased incidence of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial fibrillation risk. We evaluated the effects of 24 months of high intensity exercise training on left atrial (LA) mechanical and electric remodeling in sedentary, healthy middle-aged adults. METHODS: Sixty-one participants (53±5 years) were randomized to 10 months of exercise training followed by 14 months of maintenance exercise or stretching/balance control. Fourteen Masters athletes were added for comparison. Left ventricular (LV) and LA volumes underwent 3D echocardiographic assessment, and signal-averaged electrocardiographs for filtered P-wave duration and atrial late potentials were completed at 0, 10, and 24 months. Extended ambulatory monitoring was performed at 0 and 24 months. Within and between group differences from baseline were compared using mixed-effects model repeated-measures analysis. RESULTS: Fifty-three participants completed the study (25 control, 28 exercise) with 88±11% adherence to assigned exercise sessions. In the exercise group, both LA and LV end diastolic volumes increased proportionately (19% and 17%, respectively) after 10 months of training (peak training load). However, only LA volumes continued to increase with an additional 14 months of exercise training (LA volumes 55%; LV end diastolic volumes 15% at 24 months versus baseline; P<0.0001 for all). The LA:LV end diastolic volumes ratio did not change from baseline to 10 months, but increased 31% from baseline in the Ex group ( P<0.0001) at 24 months, without a change in controls. There were no between group differences in the LA ejection fraction, filtered P-wave duration, atrial late potentials, and premature atrial contraction burden at 24 months and no atrial fibrillation was detected. Compared with Masters athletes, the exercise group demonstrated lower absolute LA and LV volumes, but had a similar LA:LV ratio after 24 months of training. CONCLUSIONS: Twenty-four months of high intensity exercise training resulted in LA greater than LV mechanical remodeling with no observed electric remodeling. Together, these data suggest different thresholds for electrophysiological and mechanical changes may exist in response to exercise training, and provide evidence supporting a potential mechanism by which high intensity exercise training leads to atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02039154.
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Função do Átrio Esquerdo/fisiologia , Remodelamento Atrial , Exercício Físico , Função Ventricular Esquerda/fisiologia , Atletas , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Tridimensional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Fatores de RiscoRESUMO
BACKGROUND: Astronauts returning to earth usually demonstrate reduced orthostatic tolerance when assessed on a tilt table or quiet standing, but no studies have evaluated postflight orthostatic tolerance during activities of daily living, when it is most clinically relevant. Ambulatory blood pressure (BP) variability also is associated with orthostatic intolerance in certain patient populations and can capture clinically significant orthostatic hypotension during activities of daily living, especially when measured on a beat-to-beat basis. We evaluated the impact of prolonged spaceflight on orthostatic tolerance and BP profiles in astronauts. METHODS: Ambulatory beat-to-beat BP was recorded using a portable device for multiple 24-hour time periods before, during, and after 6 months of spaceflight in 12 astronauts (4 women; age 48±5 [mean±SD] years). BP variability in the time domain was calculated as the SD. Systolic BP distribution during activities of daily living was characterized by skewness and kurtosis. RESULTS: In contrast with results from previous studies that used tilt tables or stand tests, no astronaut experienced orthostatic intolerance/hypotension during activities of daily living before or after spaceflight. Also, 24-hour systolic BP decreased in space (120±10 mm Hg before spaceflight versus 106±9 mm Hg during spaceflight; P<0.01), but it returned to normal upon landing (122±13 mm Hg). Diastolic BP was unchanged during and after spaceflight. Systolic and diastolic BP variability remained the same before, during, and after spaceflight (both P>0.05). The skewness of systolic BP increased in space (0.74±0.51 versus 1.43±1.00; P=0.001), indicating that signal fluctuations became asymmetrical; however, it returned to preflight levels after landing (0.51±0.42). The kurtosis increased in space (5.01±7.67 versus 11.10±11.79; P=0.010), suggesting that fluctuations concentrated around the mean with a narrow distribution; however, it also returned to preflight levels (2.21±2.56) after return to earth. CONCLUSIONS: Given current countermeasures including in-flight exercise training and volume resuscitation on return, no astronauts experienced orthostatic hypotension or intolerance during routine (for landing day) activities in the initial 24 hours after landing following 6 months in space. Prolonged exposure to spaceflight had little impact on systolic BP variability and its distribution, although the latter showed a transient change in space (accompanied by mild relative hypotension), all of which returned to preflight values after return to earth.
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Pressão Sanguínea/fisiologia , Voo Espacial , Adulto , Astronautas , Monitorização Ambulatorial da Pressão Arterial/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intolerância Ortostática/diagnósticoRESUMO
OBJECTIVES: To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation. DESIGN: A retrospective cohort study. SETTING: Tertiary PICU. PATIENTS: Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group. CONCLUSIONS: This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.
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Lesões Encefálicas , Oxigenação por Membrana Extracorpórea , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemodinâmica , Homeostase , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVES: An increasing percentage of the US population is obese. Cardiometabolic risk in the population increases with body mass index (BMI), but whether this correlation changes over time is unknown. We analysed the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016 to determine if the prevalence of cardiometabolic disease and cardiovascular events within each BMI category is changing over time as the BMI of the population is increasing. STUDY DESIGN: For each of the nine survey cycles covering this period, we divided the population by BMI category (normal, overweight, class 1 obesity, class ≥2 obesity) and subsequently by the presence of cardiovascular events or cardiometabolic disease. NHANES participants are a group of 5000 individuals/cycle selected to be representative of the US population. We used the weighted data sets to perform trend analyses for each risk/BMI group adjusted for relevant confounders. RESULTS: The distribution of the highest risk category (cardiovascular event) has not changed over time within any BMI category. The distribution of the lowest risk category (cardiometabolically healthy) increased significantly over time in all BMI categories. This was noted in the 18- to 45-year subgroup but not in the group aged >45 years. CONCLUSIONS: The increase in the prevalence of overweight and obese individuals might be associated with a 'healthy obesity' phenotype in those <45 years; however, individuals >45 years showed a proportional increase in associated cardiometabolic risk.
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Doenças Cardiovasculares , Obesidade , Adulto , Distribuição por Idade , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Obesidade/diagnóstico , Obesidade/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Prevalência , Medição de Risco/métodos , Medição de Risco/tendências , Índice de Gravidade de DoençaRESUMO
AIMS: Metabolic Syndrome (MetS) a global problem, which comprises a cardio-metabolic cluster of risk factors, increases the risk for type-2 diabetes (T2DM) and atherosclerotic cardiovascular diseases (ASCVD). To date, the best laboratory-based biomarker for MetS appears to be high-sensitivity C-reactive protein (hsCRP). Chemerin, a novel adipokine is increased in MetS and appears to contribute to both insulin resistance and inflammation. In this pilot study, we tested if the chemerin:HDL-C or chemerin:adiponectin ratios are better biomarkers for predicting MetS than hsCRP. PATIENTS AND METHODS: We enrolled patients and controls with nascent MetS, uncomplicated by diabetes, ASCVD, macro-inflammation, and smoking using rigorous criteria. Fasting blood samples were obtained in order to calculate insulin resistance in the liver (HOMA-IR) and adipose tissue (ADIPO-IR) and for measurement of chemerin and adiponectin levels. Statistical analyses including receiver operating characteristic (ROC) curves were used to evaluate data. RESULTS: We observed the chemerin:HDL-C ratio is significantly increased in MetS and increases with severity of MetS (p < .001). The chemerin: adiponectin ratio was not significantly increased following adjustment for age and waist circumference. The chemerin:HDL-C ratio correlated with BMI, WC, triglycerides, plasma glucose, HDL-C, and both HOMA-IR and ADIPO-IR. ROC curve analysis showed that the chemerin:HDL-C ratio area under the curve (AUC) was greater than the AUC for hsCRP. CONCLUSION: In this preliminary report, we demonstrate that the ratio of chemerin to HDL-C is a valid biomarker of MetS and appears to be a better predictor than hsCRP. These findings need to be confirmed in larger studies.
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Adiponectina/sangue , Quimiocinas/sangue , HDL-Colesterol/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
BACKGROUND: Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness. METHODS: Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo2max) was measured to quantify changes in fitness. RESULTS: Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo2max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P=0.0018), whereas there was no change in controls (group×time P<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P=0.83). Exercise increased LV end-diastolic volume (group×time P<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P=0.007). CONCLUSIONS: In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02039154.
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Insuficiência Cardíaca/prevenção & controle , Treinamento Intervalado de Alta Intensidade , Contração Miocárdica , Comportamento de Redução do Risco , Comportamento Sedentário , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda , Fatores Etários , Cateterismo Cardíaco , Aptidão Cardiorrespiratória , Ecocardiografia Tridimensional , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Texas , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Remodelação VentricularRESUMO
Metabolic Syndrome (MetS) affects 35% of American adults > 40 yr and portends an increased risk for both atherosclerotic cardiovascular disease (ASCVD) and diabetes. The role of mast cells in the proinflammatory state of MetS is not well elucidated. We propose that mast cells in subcutaneous adipose tissue (SAT) of MetS patients without diabetes or clinical ASCVD contribute to insulin resistance and inflammation. Matched controls ( n = 15) and MetS ( n = 19) subjects were recruited from Sacramento, CA, and selected based on Adult Treatment Panel III criteria. SAT biopsy was performed on all subjects and processed for immunohistochemistry. The SAT sections were stained using Astra Blue stain and tryptase stain for mast cells. Fasting blood was obtained for chemistries and biomarkers. Abundance of mast cells (Astra Blue stain) in SAT of MetS subjects compared with controls was increased 2.5-fold ( P < 0.0001). Mast cells correlated positively and significantly with waist circumference, glucose, triglycerides, homeostatic model of assessment-insulin resistance (HOMA-IR), AT insulin resistance, leptin, interleukin (IL)-1ß, IL-6, chemerin, p38 MAPK activity, and nuclear factor κB activity in circulating monocytes. Mast cells also correlated significantly with markers of fibrosis and angiogenesis. Tryptase staining of mast cells in AT revealed a significant increase ( P = 0.008) with similar correlations. We make the novel observation that there are increased mast cells in SAT of MetS, and these mast cells correlate with insulin resistance (hepatic and adipose tissue), inflammation, and AT fibrosis. Hence, these immune cells appear to occupy a pivotal role in the pathogenesis of MetS.
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Mastócitos/imunologia , Síndrome Metabólica/imunologia , Gordura Subcutânea/imunologia , Tecido Adiposo , Adulto , Idoso , Glicemia/metabolismo , Estudos de Casos e Controles , Quimiocinas/metabolismo , Feminino , Fibrose , Humanos , Inflamação , Resistência à Insulina , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Leptina/metabolismo , Masculino , Mastócitos/patologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Monócitos/metabolismo , NF-kappa B/metabolismo , Neovascularização Patológica , Gordura Subcutânea/patologia , Triglicerídeos/metabolismo , Circunferência da Cintura , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Idiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers. Thirty-six adults with idiopathic uric acid nephrolithiasis were randomized to pioglitazone 30 mg/day or matching placebo for 24 weeks. At baseline and study end, participants underwent collection of blood and 24-hour urine in an inpatient research unit while consuming a fixed metabolic diet, followed by assessment of the ammoniagenic response to an acute oral acid load. Twenty-eight participants completed the study. Pioglitazone treatment improved features of the metabolic syndrome. Pioglitazone also reduced net acid excretion and increased urine pH (5.37 to 5.59), the proportion of net acid excreted as ammonium, and ammonium excretion in response to an acute acid load, whereas these parameters were unchanged with placebo. Treatment of patients with idiopathic uric acid nephrolithiasis with pioglitazone for 24 weeks led to a reduction in the acid load presented to the kidney and a more robust ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. Future studies should consider the impact of this targeted therapy on uric acid stone formation.
Assuntos
Cálculos Renais/tratamento farmacológico , Pioglitazona/administração & dosagem , Eliminação Renal/efeitos dos fármacos , Ácido Úrico/urina , Adulto , Idoso , Compostos de Amônio/metabolismo , Compostos de Amônio/urina , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cálculos Renais/urina , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Ácido Úrico/metabolismoRESUMO
To define mild hypoxic-ischemic encephalopathy and distinguish infants at risk of disability in the first 6 hours, this study stratified risk of disability by using early neurologic examination findings of infants enrolled in the Prospective Research for Infants with Mild Encephalopathy cohort. A total Sarnat score of ≥5 when performed at <6 hours of age detected future disability. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01747863.
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Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Hipóxia-Isquemia Encefálica/diagnóstico , Medição de Risco/métodos , Feminino , Seguimentos , Humanos , Hipóxia-Isquemia Encefálica/reabilitação , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
AIM: To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. MATERIALS AND METHODS: The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes. RESULTS: We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of -1.1% (95% CI -2.0% to -0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of -3.7 kg (95% CI -5.8 to -1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)]. CONCLUSIONS: In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Aspart/administração & dosagem , Insulina Detemir/administração & dosagem , Liraglutida/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Pesquisa Comparativa da Efetividade , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Refeições , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the adequacy of the insulin dose prescribed at hospital discharge in a high-risk population and assess patient characteristics that influence insulin dose requirement in the immediate postdischarge period. METHODS: This was a retrospective study conducted at Parkland Health System. We included all patients admitted to a medical floor who received an insulin prescription at discharge and had at least one follow-up visit within 6 months of discharge. All data were extracted by a detailed manual review of each electronic medical record. RESULTS: At the postdischarge follow-up (N = 797, median 33 days from discharge), 60% of patients required an insulin dose adjustment; 47% of the patients required a dose decrease. Significant predictors of a decrease insulin requirement postdischarge included (multiple regression beta coefficient [95% confidence interval]): newly diagnosed diabetes, -12.7 (-17.7, -7.7); ketosis-prone diabetes, -8.4 (-15, -1.8); glycated hemoglobin A1c (HbA1c), <10% (86 mmol/mol) -7.0 (-11.4, -2.6); discharge insulin total daily dose, -5.3 (-9.3, -1.3); and metformin prescription, -4.9 (-8.4, -1.3). CONCLUSION: An insulin dose adjustment (most commonly a decrease) was necessary shortly after discharge in more than half of our patients. A better model to estimate insulin dose at discharge is needed along with short-term follow-up after discharge for insulin titration. A pre-emptive insulin dose reduction at discharge should be considered for patients with newly diagnosed diabetes, ketosis-prone diabetes, metformin prescription, and those with HbA1c <10% at presentation. ABBREVIATIONS: DKA = diabetic ketoacidosis; HbA1c = glycated hemoglobin A1c; KPDM = ketosis-prone diabetes mellitus; TDD = total daily dose.
Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Insulina/uso terapêutico , Glicemia , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes , Alta do Paciente , Estudos RetrospectivosRESUMO
Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods: We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results: Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions: HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.