Advanced research in gastroenterology & hepatology, Mar 27, 2018
Gut microbiota play a critical role in the development of metabolic diseases such as non-alcoholi... more Gut microbiota play a critical role in the development of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD), which is a critical public health issue worldwide. This mini review provides new insights in the association between gut microbiota and liver disease, in order to gain better grasp of microbiota-related metabolic pathways and try to establish the key microbes that are implicated in NAFLD progression. It gives better knowledge to understand a possible cause of this disease and to be closer on the development of new diagnosis and therapies.
BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN... more BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-de...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2006
Background: In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated c... more Background: In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated cardiac troponin T (cTnT) on admission is associated with poorer outcomes despite early reperfusion. Presentation delay is thought to be the most important factor for the elevation of cTnT on admission. We evaluated presentation delay and other potential predictors of elevated cTnT on admission in patients treated with primary percutaneous coronary interventions (PCI) for STEMI. Methods: CTnT was measured upon arrival in the PCI centre in 444 patients with acute STEMI. An elevated cTnT was defined as > 0.05 μg/L. Results: The mean age was 61.7 years and patients were admitted at a median of 155 min after symptom onset. Almost 50% had an elevated cTnT on admission. Patients with a positive cTnT on admission were less likely to have successful primary PCI (87 versus 93%, P=0.048) and had significantly higher rates of one-year mortality (4.9 versus 1.3%, P=0.031). There was a significant ...
Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of... more Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation. Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made. We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (beta = 0.37, p = 0.02) and after surgery (beta = 0.59, p < 0.0001) and negatively with weight loss after surgery (beta = -0.37, p = 0.003). When…
Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after ... more Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered “responders” to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-...
This study investigated the importance of a metabolomic analysis in a complex disease such as non... more This study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis (n = 66) and NASH (n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and ...
Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic develo... more Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, a...
Many patients with clinically severe obesity (CSO) need to undergo bariatric surgery, with possib... more Many patients with clinically severe obesity (CSO) need to undergo bariatric surgery, with possible side effects, so individualized predictive methods are required. Adipocytokines and gut/intestinal microbiota-derived metabolites could be predictive biomarkers of metabolic success post- surgery, but the knowledge in this field is undefined. The objective of this work was to determine whether adipocytokines and microbiota-derived metabolites can be used to predict the metabolic improvement post- surgery in women with CSO. We analyzed circulating levels of some cytokines and some microbiota-derived metabolites at baseline and 12 months post-surgery from 44 women with CSO and 21 women with normal weight. Results showed that glucose, insulin, glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein (LDL-C), and triglycerides levels were decreased post-surgery, while high density lipoprotein increased. Twelve months later, leptin, resistin, lipocalin, PAI-1, TNF-α, and IL-1β levels w...
The delay time from the onset of symptoms to the initiation of intravenous fibrinolytic treatment... more The delay time from the onset of symptoms to the initiation of intravenous fibrinolytic treatment in patients with acute myocardial infarction (AMI) is herein described. A study was carried out of the consecutive AMI diagnosed in the Medical Area of the Emergency Department of the Hospital del Mar in Barcelona, Spain, with a 24-hour follow up from 15 May 1993 to 14 January, 1994. All the patients under the age of 80 years with transmural AMI of any localization and evolution of under 6 hours were considered to receive fibrinolytic treatment. The following delay times were analyzed: total delay time, extrahospitalary delay time and intrahospitalary delay time, which included assistance delay time, delay in fibrinolytic treatment indication and delay time in performance of the same. During the study period 18,316 patients were attended in the Emergency Medical Area, of which 80 corresponded to AMI. Fibrinolytic treatment was initiated with intravenous streptokinase in 33 patients (41....
Advanced research in gastroenterology & hepatology, Mar 27, 2018
Gut microbiota play a critical role in the development of metabolic diseases such as non-alcoholi... more Gut microbiota play a critical role in the development of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD), which is a critical public health issue worldwide. This mini review provides new insights in the association between gut microbiota and liver disease, in order to gain better grasp of microbiota-related metabolic pathways and try to establish the key microbes that are implicated in NAFLD progression. It gives better knowledge to understand a possible cause of this disease and to be closer on the development of new diagnosis and therapies.
BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN... more BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-de...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2006
Background: In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated c... more Background: In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated cardiac troponin T (cTnT) on admission is associated with poorer outcomes despite early reperfusion. Presentation delay is thought to be the most important factor for the elevation of cTnT on admission. We evaluated presentation delay and other potential predictors of elevated cTnT on admission in patients treated with primary percutaneous coronary interventions (PCI) for STEMI. Methods: CTnT was measured upon arrival in the PCI centre in 444 patients with acute STEMI. An elevated cTnT was defined as > 0.05 μg/L. Results: The mean age was 61.7 years and patients were admitted at a median of 155 min after symptom onset. Almost 50% had an elevated cTnT on admission. Patients with a positive cTnT on admission were less likely to have successful primary PCI (87 versus 93%, P=0.048) and had significantly higher rates of one-year mortality (4.9 versus 1.3%, P=0.031). There was a significant ...
Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of... more Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation. Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made. We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (beta = 0.37, p = 0.02) and after surgery (beta = 0.59, p < 0.0001) and negatively with weight loss after surgery (beta = -0.37, p = 0.003). When…
Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after ... more Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered “responders” to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-...
This study investigated the importance of a metabolomic analysis in a complex disease such as non... more This study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis (n = 66) and NASH (n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and ...
Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic develo... more Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, a...
Many patients with clinically severe obesity (CSO) need to undergo bariatric surgery, with possib... more Many patients with clinically severe obesity (CSO) need to undergo bariatric surgery, with possible side effects, so individualized predictive methods are required. Adipocytokines and gut/intestinal microbiota-derived metabolites could be predictive biomarkers of metabolic success post- surgery, but the knowledge in this field is undefined. The objective of this work was to determine whether adipocytokines and microbiota-derived metabolites can be used to predict the metabolic improvement post- surgery in women with CSO. We analyzed circulating levels of some cytokines and some microbiota-derived metabolites at baseline and 12 months post-surgery from 44 women with CSO and 21 women with normal weight. Results showed that glucose, insulin, glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein (LDL-C), and triglycerides levels were decreased post-surgery, while high density lipoprotein increased. Twelve months later, leptin, resistin, lipocalin, PAI-1, TNF-α, and IL-1β levels w...
The delay time from the onset of symptoms to the initiation of intravenous fibrinolytic treatment... more The delay time from the onset of symptoms to the initiation of intravenous fibrinolytic treatment in patients with acute myocardial infarction (AMI) is herein described. A study was carried out of the consecutive AMI diagnosed in the Medical Area of the Emergency Department of the Hospital del Mar in Barcelona, Spain, with a 24-hour follow up from 15 May 1993 to 14 January, 1994. All the patients under the age of 80 years with transmural AMI of any localization and evolution of under 6 hours were considered to receive fibrinolytic treatment. The following delay times were analyzed: total delay time, extrahospitalary delay time and intrahospitalary delay time, which included assistance delay time, delay in fibrinolytic treatment indication and delay time in performance of the same. During the study period 18,316 patients were attended in the Emergency Medical Area, of which 80 corresponded to AMI. Fibrinolytic treatment was initiated with intravenous streptokinase in 33 patients (41....
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Papers by Teresa Auguet