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BACKGROUND: An intracardiac foreign body causing recurrent fungemia is a rare clinical situation. Clinicians should be that aware of rare sources of sepsis despite a thorough history and examination. RESULTS: The authors describe a 63 year-old man, with unremarkable past medical history, who presented with a fever for 2 weeks. Blood cultures persistently grew Candida albicans and Streptococcus constellatus. Echocardiogram assessment showed a suspected vegetation over the tricuspid valve. Surgical exploration with median sternotomy and cardiopulmonary bypass revealed a tooth-pick impacted within the right atrium surrounded by vegetation. The authors postulate accidental ingestion of the foreign body and translocation into the right atrium via the esophagus and thoracic cavity. CONCLUSION: Surgical removal of symptomatic intracardiac foreign bodies is highly recommended.
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Candidíase/etiologia , Corpos Estranhos/cirurgia , Migração de Corpo Estranho/cirurgia , Fungemia/etiologia , Candida albicans , Ponte Cardiopulmonar , Corpos Estranhos/complicações , Corpos Estranhos/patologia , Migração de Corpo Estranho/complicações , Migração de Corpo Estranho/patologia , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Raras , Recidiva , Esternotomia/métodos , Resultado do Tratamento , Valva TricúspideRESUMO
A novel pathophysiological model of interest is the association between heart failure (HF) and the gastrointestinal system, the 'gut hypothesis'. The choline and carnitine metabolic by-product, Trimethylamine N-oxide (TMAO) is one of the more prominent molecules associated with the link between HF and the gut. Indeed, TMAO levels are increased in HF populations and higher TMAO levels are associated with poor prognosis, whereas low TMAO levels either at baseline/follow up confer better prognosis. Considering that TMAO levels seem not to be affected by guideline-HF treatment, this model could represent a novel and independent therapeutic target for HF.
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Microbioma Gastrointestinal/fisiologia , Insuficiência Cardíaca/metabolismo , Metilaminas/sangue , Volume Sistólico/fisiologia , Biomarcadores/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , PrognósticoRESUMO
AIMS/HYPOTHESIS: As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. METHODS: We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case-control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was also measured on the CARDS samples. We used the event definition of loss of >20% of baseline eGFR during follow-up from a baseline eGFR of 30-75 ml min-1 [1.73 m]-2. A total of 403 individuals experienced an event during a median follow-up of 7 years. We used discrete-time logistic regression models with tenfold cross-validation to assess association of biomarker panels with loss of kidney function. RESULTS: Twelve biomarkers showed significant association with eGFR decline adjusted for covariates in one or more of the sample sets when evaluated singly. Kidney injury molecule 1 (KIM-1) and ß2-microglobulin (B2M) showed the most consistent effects, with standardised odds ratios for progression of at least 1.4 (p < 0.0003) in all cohorts. A combination of B2M and KIM-1 added to clinical covariates, including baseline eGFR and albuminuria, modestly improved prediction, increasing the area under the curve in the SDR, Go-DARTS and CARDS by 0.079, 0.073 and 0.239, respectively. Neither the inclusion of additional Luminex biomarkers on top of B2M and KIM-1 nor a sparse mass spectrometry panel, nor the larger multiplatform panels previously identified, consistently improved prediction further across all validation sets. CONCLUSIONS/INTERPRETATION: Serum KIM-1 and B2M independently improve prediction of renal decline from an eGFR of 30-75 ml min-1 [1.73 m]-2 in type 2 diabetes beyond clinical factors and prior eGFR and are robust to varying sample storage conditions. Larger panels of biomarkers did not improve prediction beyond these two biomarkers.
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Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Receptor Celular 1 do Vírus da Hepatite A/sangue , Microglobulina beta-2/sangue , Idoso , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/patologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Razão de ChancesRESUMO
Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, ß2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.
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Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Rim/metabolismo , Insuficiência Renal Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Modelos Logísticos , Masculino , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Fatores de Risco , Escócia , Fatores de TempoRESUMO
A 60-year-old man intubated for airway protection after smoke inhalation was found to have decompensated hypercapnic respiratory failure. Fiberoptic bronchoscopy revealed obstructive airway slough and pseudomembrane, a manifestation of severe inhalation injury. Veno-venous extracorporeal membrane oxygenation was established for stabilization. The airway casts were removed successfully with periprocedural veno-venous extracorporeal membrane oxygenation support.
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The impacts of high-density microplastics, namely polyamine 6,6 (nylon), polymethyl methacrylate (PMMA) and polyethylene terephthalate (PET), on growth and behaviour of the endangered tri-spine horseshoe crab Tachypleus tridentatus were investigated for 100 days. Negative changes in wet weight and prosomal width of the juveniles were observed in all treatments of microplastics, but significant difference was only detected in prosomal width between control and PMMA. T. tridentatus became significantly less active upon exposure to nylon and PET. The extent of burrowing by T. tridentatus did not significantly differ among the treatments but was overall significantly reduced towards day 100. T. tridentatus exposed to PET significantly showed the lowest survival probability (30 %), compared to the other treatments (70-90 %). In conclusion, high-density microplastics compromised growth and behaviour of juvenile horseshoe crabs. Among the polymers that were tested, PET was considered more harmful and associated with higher mortality.
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Caranguejos Ferradura , Microplásticos , Animais , Plásticos/toxicidade , Nylons , Polimetil MetacrilatoRESUMO
Patients suffering from end-stage heart failure also suffer from multiple cardiovascular comorbidities such as abdominal aortic aneurysm (AAA). Mechanical support with left ventricular assist device with open repair of AAA repair has rarely been reported in literature. The authors describe a 60-year-old male with end-stage heart failure and a symptomatic AAA with sequential left ventricular assist device insertion and open AAA repair with aortic cross-clamping.
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Aneurisma da Aorta Abdominal , Insuficiência Cardíaca , Coração Auxiliar , Procedimentos Cirúrgicos Torácicos , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Procedimentos Cirúrgicos VascularesRESUMO
A novel pathophysiological model of interest is the association between heart failure (HF) and the gastrointestinal system, the 'gut hypothesis'. The choline and carnitine metabolic by-product, Trimethylamine N-oxide (TMAO) is one of the more prominent molecules associated with the link between HF and the gut. Indeed, TMAO levels are increased in HF populations and higher TMAO levels are associated with poor prognosis, whereas low TMAO levels either at baseline/follow up confer better prognosis. Considering that TMAO levels seem not to be affected by guideline-HF treatment, this model could represent a novel and independent therapeutic target for HF.
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Microbioma Gastrointestinal , Insuficiência Cardíaca , Colina/metabolismo , Colina/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Humanos , Metilaminas/metabolismo , Metilaminas/uso terapêuticoRESUMO
OBJECTIVE: To assess the contribution of maternal and placental factors to the development of superimposed preeclampsia in women with chronic hypertension. METHODS: Endothelial and renal function markers were serially assessed in 90 pregnant women with chronic hypertension and controls. RESULTS: Syndecan-1 concentrations were lower at 26-27+6 weeks in women with chronic hypertension who subsequently developed superimposed preeclampsia compared with those who did not. Decreased PlGF and raised urine albumin:creatinine ratio were also associated with development of superimposed preeclampsia. CONCLUSION: Decreased syndecan-1 and PlGF concentrations implicate endothelial glycocalyx disturbance and reduced placental angiogenic capacity, respectively, in the pathophysiology of superimposed preeclampsia.
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Hipertensão/complicações , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/etiologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores , Cistatina C/sangue , Feminino , Humanos , Hipertensão/sangue , Lipocalina-2/sangue , Estudos Longitudinais , Placenta , Pré-Eclâmpsia/sangue , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: Elevated serum levels of homocysteine have been shown to be associated with schizophrenia in some studies, but the evidence is still limited and mixed. The aim of the present study was therefore to evaluate the serum homocysteine level in Chinese in schizophrenia patients and assess its association with clinical phenotypes of the disease. METHOD: A total of 250 inpatients and 250 healthy controls were identified at Kowloon Hospital and the Red Cross Blood Donation Centre, respectively. Each subject was evaluated with a structured diagnostic interview. Demographic data were collected and blood was analysed for homocysteine level. The Positive and Negative Syndrome Scale was used to grade clinical symptoms of schizophrenia. Confounding factors affecting homocysteine levels were controlled by strict exclusion criteria or statistical methods. RESULTS: Serum homocysteine level was elevated in Chinese schizophrenia patients. Both male (mean, 12.26 micromol L(-1); control, 11.40 micromol L(-1), p = 0.026) and female (mean, 9.61 micromol L(-1); control, 8.33 micromol L(-1), p < 0.001) patients had a higher serum homocysteine level than the healthy controls, and these differences persisted after controlling for age. There was no significant association between serum homocysteine level and duration of illness, clinical symptoms or age of onset of schizophrenia. CONCLUSION: The serum homocysteine levels were elevated in both male and female Chinese schizophrenia patients. The levels were not apparently related to other clinical parameters.
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Homocisteína/sangue , Esquizofrenia/sangue , Adulto , Idade de Início , Povo Asiático , Estudos de Casos e Controles , Saúde da Família , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
The application of LC-MS for untargeted urinary metabolite profiling in metabonomic research has gained much interest in recent years. However, the effects of varying sample pre-treatments and LC conditions on generic metabolite profiling have not been studied. We aimed to evaluate the effects of varying experimental conditions on data acquisition in untargeted urinary metabolite profiling using UPLC/QToF MS. In-house QC sample clustering was used to monitor the performance of the analytical platform. In terms of sample pre-treatment, results showed that untreated filtered urine yielded the highest number of features but dilution with methanol provided a more homogenous urinary metabolic profile with less variation in number of features and feature intensities. An increased cycle time with a lower flow rate (400 microl/min vs 600 microl/min) also resulted in a higher number of features with less variability. The step elution gradient yielded the highest number of features and the best chromatographic resolution among three different elution gradients tested. The maximum retention time and mass shift were only 0.03 min and 0.0015 Da respectively over 600 injections. The analytical platform also showed excellent robustness as evident by tight QC sample clustering. To conclude, we have investigated LC conditions by studying variability and repeatability of LC-MS data for untargeted urinary metabolite profiling.
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Cromatografia Líquida de Alta Pressão/métodos , Biologia Computacional/métodos , Espectrometria de Massas/métodos , Metabolismo , Urina/química , Adulto , Humanos , Masculino , Análise de Componente Principal , Reprodutibilidade dos Testes , Manejo de EspécimesRESUMO
Thoracic surgery has evolved throughout the decades. The difficulty of accessing the intrathoracic organs through the bony rib-cage has been a challenge for thoracic surgeons. In the past, large incisions stretching across the chest, such as posterolateral thoracotomies with rib spreading was the standard approach to access the lungs. These methods cause large amounts of trauma to the patient, with high rates of mortality and morbidity. However, with the advances in technology and the improvements in surgical technique, thoracic surgery has progressed to minimise trauma to the patient while still maintaining oncological and surgical principles. State-of-the-art technology, combined with wide variety of old and new surgical techniques give the thoracic surgeon a formidable armamentarium. Although there has been a focus on reducing the number and size of surgical wounds, considerations other than surgical approach can reduce the trauma suffered by the patient. Preservation of pulmonary function via organ preservation and anaesthetic techniques to further minimise the systemic inflammation such as non-intubated anaesthesia have also been shown to improve patient outcomes. This article aims to review the recent advances in minimally invasive thoracic surgery.
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We hypothesized that the hepatotoxicity that develops after the induction of oxidative stress (induced by d-galactosamine [GalN]) can be ameliorated by alpha-tocopherol (ATC) and the soy isoflavone daidzein. To test this, we ranked and assigned male Wistar rats into 6 groups, which involved pretreatment (ATC or daidzein) for 1 hour followed by treatment (GalN) for 23 hours. Histopathologic analysis showed that GalN administration induced marked necrosis (P < .001), steatosis (P < .001), both lobular and portal inflammations (P < .001), overall histopathologic score (P < .001), and activation of caspase-3 in the liver (P < .001). Immunohistochemical staining of malondialdehyde-protein adducts, a measure of oxidative stress, was increased in response to GalN (P < .001). Paradoxically, there were increases in total (P < .05) and cytosolic superoxide dismutase (P < .001) activities after GalN administration, indicative of an up-regulation of antioxidant defenses. The concentration of total protein (P < .001), albumin (P < .01), and globulin fractions (P < .001) in the plasma, as well as the activity of aspartate aminotransferase (P < .001), was significantly perturbed after GalN treatment, reflective of overall acute hepatic injury. Administration of daidzein showed a significant amelioration of the Ga1N-induced increase in malondialdehyde-protein adducts (P < .01) and cytosolic superoxide dismutase activities (P < .01) in the liver. However, all other variables were not significantly altered in response to daidzein. In response to ATC pretreatment, the total histopathologic score (P < .05), degree of necrosis (P < .05), and both lobular (P < .05) and portal (P = .05) inflammations were significantly ameliorated. To conclude, both daidzein and ATC protect the liver against oxidative damage possibly via different pathways.
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Citoproteção , Galactosamina/toxicidade , Isoflavonas/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , alfa-Tocoferol/farmacologia , Animais , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Fibres, aponeuroses, and tendons are often considered mechanically "in series" in skeletal muscles. This notion has led to oversimplified calculations of fibre forces from tendon forces, to incorrect derivations of constitutive laws for aponeuroses, and to misinterpretations of the recovery of elastic energy in stretch-shortening cycles of muscles. Here, we demonstrate theoretically, using examples of increasing complexity, that tendon and aponeurosis are not in series in a muscle fibre-aponeurosis-tendon complex. We then demonstrate that assuming the tendon and aponeurosis to be in series can lead to the appearance of mechanical work creation in these passive viscoelastic structures, a result that is mechanically impossible. Finally, we explain the mechanical role of the incompressible muscle matrix in force transmission from fibres to aponeuroses and tendon, and emphasize that incompressibility necessitates the introduction of extra forces necessary to maintain this constraint. Unfortunately, this requirement eliminates, for all but the simplest cases, a theoretical approach of muscle modeling based on intuitive free-body diagrams.
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Modelos Biológicos , Músculos/fisiologia , Tendões/fisiologia , Animais , Fenômenos Biomecânicos , Humanos , Tendões/anatomia & histologiaRESUMO
Ethanol causes extensive damage to the intestinal tract from the oropharynx to the rectum. The jejunum has also been shown to be particularly vulnerable to the deleterious effects of ethanol. We hypothesized that (I) the pathogenesis of acute alcohol-mediated injury in the small intestine involves generation of reactive oxygen species, and consequentially, enhanced lipid peroxidation; (II) the pathogenic changes due to alcohol can be ameliorated with daidzein pretreatment. To test these hypotheses male Wistar rats (n=24) were divided into four groups as follows (pretreatment followed by treatment): [A] carrier+saline (control); [B] daidzein+saline; [C] carrier+ethanol; [D] daidzein+ethanol. Daidzein (100 mg/kg) or carrier (Intralipid) pretreatment was twice administered as a single dose, whereas ethanol (75 mmol/kg) or saline (0.15 mol/l NaCl) treatment was administered once only. At 24 h after ethanol or saline was administered, rats were sacrificed. The analytes 7alpha-and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH), 7alpha-and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH), and 7-ketocholesterol (7-keto) in jejunum were analyzed by HPLC. The data showed that daidzein per se did not affect levels of cholesterol hydroperoxides nor oxysterols. However, there were significant increases in 7alpha- and 7beta-OOHs, 7alpha- and 7beta-OHs, and 7-keto after ethanol dosage compared to controls. Daidzein ameliorated these effects, i.e., values in the daidzein+ethanol group were similar to those in the carrier+saline (control) group. This is the first report showing that (1) cholesterol-derived markers of oxidative stress are increased in the rat jejunum in response to ethanol, indicative of metabolic damage; (2) daidzein pretreatment has protective effects against ethanol-induced injury.
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Etanol/farmacologia , Isoflavonas/farmacologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fitoestrógenos/farmacologia , Animais , Masculino , Ratos , Ratos WistarRESUMO
PURPOSE: The aim of the study was to investigate the association between serum uric acid (SUA) and cardiovascular risk classes (CRCs) in adolescents using a cluster-based approach. METHODS: A cross-sectional evaluation was carried out in the 2007-2008 school year, including adolescents born in 1990 and enrolled in the schools of Porto, Portugal. The analysis included 1,286 adolescents. To identify CRC, a normal mixture model was performed including several biological cardiovascular risk factors. A multinomial logistic regression model was applied to explore the association between SUA and each CRC. RESULTS: Three classes were extracted using model-based cluster analysis (low, medium, and high CRC). The high CRC accounted for the smallest proportion of participants (5.6%) and represented the adolescents with higher waist circumference, systolic and diastolic blood pressures, total cholesterol, triglycerides, and insulin levels. Adolescents at increased risk of cardiovascular disease had significantly higher mean concentrations of SUA compared with adolescents at low cardiovascular risk (55.0 vs. 51.5 mg/L in males and 41.9 vs. 37.6 mg/L in females). After adjustment and considering low CRC as reference, SUA was positively associated with high CRC in both sexes (odds ratio, 1.04; 95% confidence interval, 1.00-1.07 in males; and odds ratio, 1.04; 95% confidence interval, 1.01-1.07 in females). CONCLUSIONS: Among 17-year-old adolescents, SUA increases were positively associated with higher CRC.
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Doenças Cardiovasculares/etiologia , Ácido Úrico/sangue , Adolescente , Glicemia/análise , Pressão Sanguínea , Doenças Cardiovasculares/sangue , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Modelos Logísticos , Masculino , Portugal/epidemiologia , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
Early life exposures and metabolic programming are associated with later disease risk. In particular lipid metabolism is thought to play a key role in the development of the metabolic syndrome and insulin resistance in later life. Investigative studies of metabolic programming are limited by the ethics and practicalities of sample collection in small infants. Dried blood spots on filter paper, derived from heel pricks are considered as the most suitable option for this age group. We validated a novel lipid profiling method, based on high resolution mass spectrometry to successfully determine the lipid composition of infants using dried blood spots. The spotting and air drying of blood on paper has noticeable effects on many of the lipids, leading to lipid oxidation and hydrolysis, which demand careful interpretation of the obtained data. We compared the lipid profiles from plasma or whole blood samples and the results from dried blood spots to determine if these revealed the same inter-subject differences. The results from dried blood spots were no less reproducible than other lipid profiling methods which required comparatively larger sample volumes. Therefore, lipid profiles obtained from dried blood spots can be successfully used to monitor infancy lipid metabolism and we show significant differences in the lipid metabolism of infants at age 3 versus 12 months.
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BACKGROUND: Quantitative LC-ESI-MS/MS, developed from newborn screening, is increasingly used for targeted metabolite profiling. Dried blood spots (DBS) provide easily obtainable biological samples but long-term stability data are sparse. DBS were stored at ambient temperature (room temperature [RT]; 21°C), -20 and -80°C. Metabolites were analyzed at 12 time points (0-104 weeks) by LC-ESI-MS/MS, using fully quantitative stable isotope dilution. RESULTS: Principal component analysis showed alterations in metabolite stability at different temperatures, with major changes only at RT. Univariate analysis for individual analytes demonstrated increases or reductions in concentration. CONCLUSION: Significant changes are observed in certain DBS metabolites at RT, which are attenuated or not present when frozen. These data will help to inform the design, analysis and interpretation of future DBS studies.