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Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes.
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Ácido Araquidônico , Proteína C-Reativa , COVID-19 , Influenza Humana , Interleucina-6 , Infecções por Vírus Respiratório Sincicial , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Araquidônico/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , Estudos Transversais , Vírus da Influenza A , Influenza Humana/sangue , Influenza Humana/diagnóstico , Influenza Humana/virologia , Interleucina-6/sangue , Infecções por Vírus Respiratório Sincicial/sangue , Infecções por Vírus Respiratório Sincicial/diagnóstico , Curva ROCRESUMO
A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
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Ácido Araquidônico , Técnicas Biossensoriais , COVID-19 , SARS-CoV-2 , Humanos , Ácido Araquidônico/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Técnicas Biossensoriais/métodos , SARS-CoV-2/imunologia , Peroxidase do Rábano Silvestre/química , Vírus Sinciciais Respiratórios/imunologia , Imunoensaio/métodos , Estreptavidina/química , Biotina/química , Limite de DetecçãoRESUMO
Background:Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from 1 January 2020 to 31 December 2022 in Hospital Universitari de Sant Joan in Reus. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a notable increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colonoscopies or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitalization included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusions: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of delayed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted interventions in high-risk populations.
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Both infectious and non-infectious diseases can share common molecular mechanisms, including oxidative stress and inflammation. External factors, such as bacterial or viral infections, excessive calorie intake, inadequate nutrients, or environmental factors, can cause metabolic disorders, resulting in an imbalance between free radical production and natural antioxidant systems. These factors may lead to the production of free radicals that can oxidize lipids, proteins, and nucleic acids, causing metabolic alterations that influence the pathogenesis of the disease. The relationship between oxidation and inflammation is crucial, as they both contribute to the development of cellular pathology. Paraoxonase 1 (PON1) is a vital enzyme in regulating these processes. PON1 is an enzyme that is bound to high-density lipoproteins and protects the organism against oxidative stress and toxic substances. It breaks down lipid peroxides in lipoproteins and cells, enhances the protection of high-density lipoproteins against different infectious agents, and is a critical component of the innate immune system. Impaired PON1 function can affect cellular homeostasis pathways and cause metabolically driven chronic inflammatory states. Therefore, understanding these relationships can help to improve treatments and identify new therapeutic targets. This review also examines the advantages and disadvantages of measuring serum PON1 levels in clinical settings, providing insight into the potential clinical use of this enzyme.
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Arildialquilfosfatase , Neoplasias , Humanos , Arildialquilfosfatase/metabolismo , Xenobióticos , Estresse Oxidativo , Lipoproteínas HDL/metabolismo , InflamaçãoRESUMO
SARS-CoV-2 infection in already-vaccinated individuals is still possible and may require hospitalization. The aim of the present study was to evaluate the clinical evolution of patients with COVID-19 admitted to a public hospital. The outcomes were assessed in relation to the predominant viral variant and the vaccination status. This retrospective study was performed on 1295 COVID-19-positive patients who attended a 352-bed university hospital between 2021 and 2022. Clinical variables and vaccination status were recorded. Of the patients, 799 had not been vaccinated (NV, 61.7%), 449 were partially vaccinated (PV, 34.7%), and 47 were completely vaccinated (CV, 3.6%). The mean age of the CV patients was significantly higher than that of PV and NV. Additionally, they had higher percentages of chronic diseases. The outcomes depended on age but not on vaccination status. There were 209 patients admitted during the Omicron-infection period, of whom 70 (33.5%) were NV, 135 (64.6%) were PV, and 4 (1.9%) were CV. In conclusion, correct vaccination greatly reduces the risk of acquiring severe COVID-19. Partial vaccination does not guarantee protection of the population. This highlights the need for continuous vaccination promotion with all recommended doses, while also investigating alternative treatments for those patients who do not respond to the vaccines.
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COVID-19 , Humanos , Espanha/epidemiologia , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2/genética , VacinaçãoRESUMO
Background and aims: HDL particles may act to buffer host cells from excessive inflammatory mediators. The aim of this study is to investigate if the lipid profile provides a prognostic biomarker for COVID-19 outcomes. Methods: This was a prospective study of the characteristics of 125 adult COVID-19 patients with a lipid profile performed on the day of admission analyzed with regard to clinical outcomes. Results: Seventy-seven patients (61.2%) were men, with a mean age of 66.3 (15.6) years. 54.1% had bilateral pneumonia. The all-cause mortality rate during hospitalization was 20.8%. We found a direct association between more severe disease assessed by the WHO classification, admission to the ICU and death with more pronounced lymphopenia, higher levels of CRP, ferritin (p < 0.001), D-dímer and lactate dehydrogenase (LDH) all statistically significant. Lower leves of HDL-c and LDL-c were also associated with a worse WHO classification, ICU admission, and death,. HDL-c levels were inversely correlated with inflammatory markers CRP (r = -0.333; p < 0.001), ferritin (r = -0.354; p < 0.001), D-dímer (r = -0.214; p < 0.001), LDH (r = -0.209; p < 0.001. LDL-c levels were significantly associated with CRP (r = -0.320; p < 0.001) and LDH (r = -0.269; p < 0.001). ROC curves showed that HDL [AUC = 0.737(0.586-0.887), p = 0.005] and lymphocytes [AUC = 0.672(0.497-0.847], p < 0.043] had the best prognostic accuracy to predict death. In a multivariate analysis, HDL-c (ß = -0.146(0.770-0.971), p = 0.014) and urea (ß = 0.029(1.003-1.057), p = 0.027) predicted mortality. Conclusion: Hypolipidemia including HDL levels at admission identifies patients with a higher risk of death and worse clinical manifestations who may require more intensive care.
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Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alterations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospitalized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19-negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chromatography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites altered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid segregated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with the severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify the potential biomarkers for the diagnosis and prognosis of the disease.
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COVID-19 , Doenças Transmissíveis , Humanos , Estudos Retrospectivos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas , Aprendizado de Máquina , Biomarcadores/metabolismoRESUMO
Since the beginning of the COVID-19 pandemic and until September 2021, Spain suffered five waves of infection, the latter being related to the expansion of the Delta variant and with a high incidence. A vaccination campaign began in December 2020 and by the end of the fifth wave 77.3% of people had been fully vaccinated. Examining the changing dynamics of COVID-19 pandemic and its impact on outcomes among those hospitalized is essential. Our objective was to ascertain any differences in the characteristics and outcomes of hospitalized patients during that period compared to previous waves. We prospectively enrolled 200 consecutively admitted hospital patients from each wave and collected their clinical and demographic data from the medical records, including symptoms, comorbidities, deaths and whether they needed to be admitted to the Intensive Care Unit to receive assisted ventilation. We found that patients in the fifth wave were considerably younger than before, and the mortality rate fell from 22.5 to 2.0%. Admissions to the Intensive Care Unit decreased from 10 to 2%. Patients in the fifth wave had fewer comorbidities, and the age of the patients who died was higher than those who survived. Our results show a marked improvement in patient outcomes in the fifth wave, suggesting success of the vaccination campaign despite the explosion in cases due to the Delta variant.
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COVID-19 , Humanos , COVID-19/epidemiologia , Hospitais , Pandemias , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
Catheter-related infections (CRIs) include catheter-associated urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs), and they are associated with high morbidity, mortality, and healthcare costs. The diagnosis of a CRI is made difficult by its non-specific symptoms. We aimed to investigate the factors influencing the plasma concentration of galectin-3 in catheter-bearing patients and to explore its potential usefulness as an index for CRIs. Circulating the concentrations of galectin-3, we measured the chemokine (C-C) motif ligand 2, procalcitonin, and C-reactive protein in 110 patients with a central catheter, in 165 patients with a urinary catheter, and in 72 control subjects. Catheter-bearing patients had higher concentrations (p < 0.001) of galectin-3 than the control group [central catheter: 19.1 (14.0−23.4) µg/L; urinary catheter: 17.1 (12.7−25.4) µg/L; control group: 6.1 (5.0−8.7) µg/L]. We identified chronic kidney disease as an independent determinant of galectin-3 concentrations in patients with a central catheter, and serum creatinine, cardiovascular disease, and number of days that the catheter was indwelling were identified as determinants in urinary catheter patients. We found that measuring galectin-3 concentrations in urinary catheter patients with a CRI was more accurate for diagnosis than the other parameters. We conclude that the measurement of galectin-3 concentration may be useful for assessing the inflammatory status of catheter-bearing patients and may contribute to the diagnosis of CRIs in those with a urinary catheter.
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The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.
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Arildialquilfosfatase , COVID-19 , Arildialquilfosfatase/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/enzimologia , Hidrolases de Éster Carboxílico , Humanos , SoroRESUMO
BACKGROUND: Lipids are involved in the interaction between viral infection and the host metabolic and immunological responses. Several studies comparing the lipidome of COVID-19-positive hospitalized patients vs. healthy subjects have already been reported. It is largely unknown, however, whether these differences are specific to this disease. The present study compared the lipidomic signature of hospitalized COVID-19-positive patients with that of healthy subjects, as well as with COVID-19-negative patients hospitalized for other infectious/inflammatory diseases. METHODS: We analyzed the lipidomic signature of 126 COVID-19-positive patients, 45 COVID-19-negative patients hospitalized with other infectious/inflammatory diseases and 50 healthy volunteers. A semi-targeted lipidomics analysis was performed using liquid chromatography coupled to mass spectrometry. Two-hundred and eighty-three lipid species were identified and quantified. Results were interpreted by machine learning tools. RESULTS: We identified acylcarnitines, lysophosphatidylethanolamines, arachidonic acid and oxylipins as the most altered species in COVID-19-positive patients compared to healthy volunteers. However, we found similar alterations in COVID-19-negative patients who had other causes of inflammation. Conversely, lysophosphatidylcholine 22:6-sn2, phosphatidylcholine 36:1 and secondary bile acids were the parameters that had the greatest capacity to discriminate between COVID-19-positive and COVID-19-negative patients. CONCLUSION: This study shows that COVID-19 infection shares many lipid alterations with other infectious/inflammatory diseases, and which differentiate them from the healthy population. The most notable alterations were observed in oxylipins, while alterations in bile acids and glycerophospholipis best distinguished between COVID-19-positive and COVID-19-negative patients. Our results highlight the value of integrating lipidomics with machine learning algorithms to explore the pathophysiology of COVID-19 and, consequently, improve clinical decision making.
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COVID-19 , Lipidômica , Ácidos e Sais Biliares , Humanos , Aprendizado de Máquina , OxilipinasRESUMO
Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) who maintain undetectable viral loads (VLs) despite not being on antiretroviral therapy (ART). However, this phenotype is heterogeneous, with some of these subjects losing virological control over time. In this longitudinal retrospective study, serum acute-phase glycoprotein profile assessed by proton nuclear magnetic resonance (1H-NMR) was determined in 11 transient controllers (TCs) who spontaneously lost virological control and 11 persistent controllers (PCs) who persistently maintained virological control over time. Both PCs and TCs showed similar acute-phase glycoprotein profiles, even when TCs lost the virological control (GlycB, p = 0.824 and GlycA, p = 0.710), and the serum acute-phase glycoprotein signature in PCs did not differ from that in HIV-negative subjects (GlycB, p = 0.151 and GlycA, p = 0.243). Differences in serum glycoproteins A and B were significant only in ECs compared to HIV-typical progressors (TPs) with < 100 CD4+ T-cells (p < 0.001). 1H-NMR acute-phase glycoprotein profile does not distinguish TCs form PCs before the loss of viral control. ECs maintain a low-grade inflammatory state compared to TPs. PCs revealed a closer serum signature to HIV-negative subjects, reaffirming this phenotype as a closer model of functional control of HIV.
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Proteínas de Fase Aguda/metabolismo , Glicômica , Infecções por HIV/sangue , Paciente HIV Positivo não Progressor , HIV/patogenicidade , Proteoma , Proteômica , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Biomarcadores/sangue , Feminino , Infecções por HIV/diagnóstico , Interações Hospedeiro-Patógeno , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed 'cytokine storm' that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2), and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2, and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation, and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.
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The pandemic caused by the SARS-CoV-2 infection affects many aspects of public health knowledge, science, and practice around the world. Several studies have shown that SARS-CoV-2 RNA in plasma seems to be associated with a worse prognosis of COVID-19. In the present study, we investigated plasma and buffy RNA in patients with COVID-19 to determine its prognostic value. A prospective study was carried out in patients hospitalized for COVID-19, in which RNA was analyzed in plasma and the buffy coat. Morphological and immunohistochemical studies were used to detect the presence of SARS-CoV-2 in the buffy coat. In COVID-19 patients, the obtained RNA concentration in plasma was 448.3 ± 31.30 ng/mL. Of all the patients with positive plasma tests for SARS-CoV-2, 46.15% died from COVID-19. In four cases, tests revealed that SARS-CoV-2 was present in the buffy coat. Abnormal morphology of monocytes, lymphocytes and neutrophils was found. An immunohistochemical study showed positivity in mononuclear cells and platelets. Our results suggest that SARS-CoV-2 is present in the plasma. This facilitates viral dissemination and migration to specific organs, where SARS-CoV-2 infects target cells by binding to their receptors. In our study, the presence of plasma SARS-CoV-2 RNA was correlated with worse prognoses.
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BACKGROUND: Anti-SARS-CoV-2 antibodies have been used in the study of the immune response in infected patients. However, differences in sensitivity and specificity have been reported, depending on the method of analysis. The aim of the present study was to evaluate the diagnostic accuracy of an algorithm in which a high-throughput automated assay for total antibodies was used for screening and two semi-automated IgG-specific methods were used to confirm the results, and also to correlate the analytical results with the clinical data and the time elapsed since infection. METHODS: We studied 306 patients, some hospitalized and some outpatients, belonging to a population with a high prevalence of COVID-19. One-hundred and ten patients were classified as SARS-CoV-2 negative and 196 as positive by polymerase chain reaction. RESULTS: The algorithm and automated assay alone had a specificity and a positive predictive value of 100%, although the sensitivity and negative predictive value of the algorithm was higher. Both methods showed a good sensitivity from day 11 of the onset of symptoms in asymptomatic and symptomatic patients. The absorbance of the total antibodies was significantly higher in severely symptomatic than in asymptomatic or mildly symptomatic patients, which suggests the antibody level was higher. We found 15 patients who did not present seroconversion at 12 days from the onset of symptoms or the first polymerase chain reaction test. CONCLUSION: This study highlights the proper functioning of algorithms in the diagnosis of the immune response to COVID-19, which can help to define testing strategies against this disease.
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Algoritmos , Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Adulto , Idoso , Anticorpos Anti-Idiotípicos/sangue , COVID-19/epidemiologia , Feminino , Humanos , Imunoensaio/métodos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , SARS-CoV-2/imunologia , Sensibilidade e EspecificidadeRESUMO
Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.
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COVID-19/epidemiologia , COVID-19/terapia , Hospitalização/estatística & dados numéricos , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Espanha/epidemiologia , Resultado do TratamentoRESUMO
High plasma triglyceride (TG) levels and chronic inflammation are important factors related to metabolic-associated fatty liver disease in patients at cardiovascular risk. Using nuclear magnetic resonance (1H-NMR), we aimed to study the triglyceride-rich lipoprotein (TRL) and acute-phase glycoprotein profiles of a cohort of patients with metabolic disease and their relationship with fatty liver. Plasma samples of 280 patients (type 2 diabetes, 81.1%; obesity, 63.3%; and metabolic syndrome, 91.8%) from the University Hospital Lipid Unit were collected for the measurement of small, medium and large TRL particle numbers and sizes and glycoprotein profiles (Glyc-A and Glyc-B) by 1H-NMR. Liver function parameters, including the fatty liver index (FLI) and fibrosis-4 (FIB-4) score, were assessed. Hepatic echography assessment was performed in 100 patients, and they were followed up for 10 years. TRL particle concentrations showed a strong positive association with Glyc-A and Glyc-B (ρ=0.895 and ρ=0.654, p<0.001, respectively) and with the liver function-related proteins ALT ρ=0.293, p<0.001), AST (ρ=0.318, p<0.001) and GGT (ρ=0.284, p<0.001). Likewise, TRL concentrations showed a positive association with FLI (ρ=0.425, p<0.001) but not with FIB-4. During the follow-up period of 10 years, 18 new cases of steatosis were observed among 64 patients who were disease-free at baseline. Baseline TRL particle numbers and glycoprotein levels were associated with the new development of metabolic-associated fatty liver disease (MAFLD) (AUC=0.692, p=0.018 and AUC=0.669, p=0.037, respectively). Overall, our results indicated that TRL number and acute-phase glycoproteins measured by 1H-NMR could be potential biomarkers of the development of hepatic steatosis in patients at metabolic risk.
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Diabetes Mellitus Tipo 2/metabolismo , Glicoproteínas/metabolismo , Lipoproteínas/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Triglicerídeos/metabolismo , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , UltrassonografiaRESUMO
Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.
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Aterosclerose , Lipopolissacarídeos , Animais , Humanos , Lipoproteínas , Lipoproteínas LDL , Lipoproteínas VLDL , Masculino , Mamíferos , UltracentrifugaçãoRESUMO
Purpose: Surgical stress is a phenomenon not completely understood from the biochemical point of view, although it produces alterations in the oxidative balance and inflammatory status. The present study aimed to investigate the alterations of the circulating levels of paraoxonase-1 (PON1)-related variables and markers of inflammation in hospitalized patients who underwent surgery. Methods: We recruited 285 hospitalized patients. Of those, 115 were hospitalized due to a surgical intervention and 170 for reasons other than surgery. The control group consisted of 128 healthy volunteers. A blood sample was obtained for the measurement of serum PON1-related variables, and C-reactive protein (CRP), chemokine (C-C motif) ligand 2 (CCL2), and procalcitonin concentrations. Results: Hospitalized patients had lower serum PON1 activities [paraoxonase: 215.6 (168.6 - 277.8) vs. 298.7 (229.7 - 382.6) U/L, p < 0.001; lactonase: 3.0 (2.3 - 3.7) vs. 5.7 (4.6 - 6.5) U/L, p < 0.001], and higher CCL2, CRP and procalcitonin concentrations than the healthy individuals. The days elapsed following surgery and the duration of the procedure itself inversely correlated with PON1-related variables, and directly correlated with CRP concentrations. Patients that were operated on by laparotomy had higher PON1 activity than patients operated on by laparoscopy. Local and regional anesthesia was associated with higher PON1 activities and lower CRP concentrations. Conclusion: These results show a decrease in PON1 activities and an increase in acute phase response in hospitalized patients undergoing surgery and support the hypothesis that these phenomena are related to post-surgical metabolic alterations.