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INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.
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Fístula Anastomótica , Proteína C-Reativa , Neoplasias Ovarianas , Pró-Calcitonina , Humanos , Feminino , Fístula Anastomótica/sangue , Fístula Anastomótica/diagnóstico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/sangue , Estudos Prospectivos , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Idoso , Valor Preditivo dos Testes , Biomarcadores/sangue , Adulto , Espanha , Biomarcadores Tumorais/sangue , Procedimentos Cirúrgicos de Citorredução/efeitos adversosRESUMO
Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5' end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A-H. In clinical samples from 125 patients, the main genotypes were A, D, F and H in Caucasian, B and C in Asian and A and E in Sub-Saharan patients. Genotype mixtures were identified in 28 (22.40%) cases, and potential intergenotypic recombination was observed in 29 (23.20%) cases. Furthermore, we evaluated sequence conservation among haplotypes classified into genotypes A, C, D, and E by computing the information content. The preS haplotypes exhibited limited shared conserved regions, whereas the 5X haplotypes revealed two groups of conserved regions across the genotypes assessed. In conclusion, we developed an NGS-based HBV genotyping method utilizing the DB Rule for genotype classification. We identified two regions conserved across different genotypes at 5X, offering promising targets for RNA interference-based antiviral therapies.
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Genótipo , Haplótipos , Vírus da Hepatite B , Sequenciamento de Nucleotídeos em Larga Escala , Vírus da Hepatite B/genética , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hepatite B/virologia , Hepatite B/genética , Técnicas de Genotipagem/métodos , Sequência Conservada , Coinfecção/virologia , Genoma Viral , Masculino , Feminino , Filogenia , DNA Viral/genética , AdultoRESUMO
OBJECTIVES: The aim of this study was to harmonize the criteria for the Bhattacharya indirect method Microsoft Excel Spreadsheet for reference intervals calculation to reduce between-user variability and use these criteria to calculate and evaluate reference intervals for eight analytes in two different years. METHODS: Anonymized laboratory test results from outpatients were extracted from January 1st 2018 to December 31st 2019. To assure data quality, we examined the monthly results from an external quality control program. Reference intervals were determined by the Bhattacharya method with the St Vincent's hospital Spreadsheet firstly using original criteria and then using additional harmonized criteria defined in this study. Consensus reference intervals using the additional harmonized criteria were calculated as the mean of four users' lower and upper reference interval results. To further test the operation criteria and robustness of the obtained reference intervals, an external user validated the Spreadsheet procedure. RESULTS: The extracted test results for all selected laboratory tests fulfilled the quality criteria and were included in the present study. Differences between users in calculated reference intervals were frequent when using the Spreadsheet. Therefore, additional criteria for the Spreadsheet were proposed and applied by independent users, such as: to set central bin as the mean of all the data, bin size as small as possible, at least three consecutive bins and a high proportion of bins within the curve. CONCLUSIONS: The proposed criteria contributed to the harmonization of reference interval calculation between users of the Bhattacharya indirect method Spreadsheet.
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Valores de Referência , Humanos , Controle de QualidadeRESUMO
Importance: Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy. Objective: To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia. Design, Setting, and Participants: Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants. Interventions: Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group). Main Outcomes and Measures: Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%. Results: Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority. Conclusions and Relevance: Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio. Trial Registration: ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.
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Aspirina , Pré-Eclâmpsia , Nascimento Prematuro , Suspensão de Tratamento , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Biomarcadores/sangue , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Período Periparto , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/prevenção & controle , Complicações na Gravidez/sangue , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/prevenção & controle , Primeiro Trimestre da Gravidez , Nascimento Prematuro/sangue , Nascimento Prematuro/prevenção & controle , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangueRESUMO
Background Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Next-generation sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms. Here we compare two NGS panels for cfDNA: Oncomine™ Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360® (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory. Methods Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360® (G360) was requested as part of their clinical assistance. Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with Oncomine™ Pan-Cancer (OM) panel in an Ion GeneStudio S5™ System. Results cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01). Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM. Conclusions In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.
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Ácidos Nucleicos Livres/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Neoplasias/genética , HumanosRESUMO
The remarkable effectivity of current antiviral therapies has led to consider the elimination of hepatitis C virus (HCV) infection. However, HCV infection is highly underdiagnosed; therefore, a global strategy for eliminating it requires improving the effectiveness of HCV diagnosis to identify hidden cases. In this study, we assessed the effectiveness of a protocol for HCV diagnosis based on viral load reflex testing of anti-HCV antibody-positive patients (known as one-step diagnosis) by analyzing all diagnostic tests performed by a central laboratory covering an area of 1.5 million inhabitants in Barcelona, Spain, before (83,786 cases) and after (45,935 cases) the implementation of the reflex testing protocol. After its implementation, the percentage of anti-HCV-positive patients with omitted HCV RNA determination remarkably decreased in most settings, particularly in drug treatment centers and primary care settings, where omitted HCV RNA analyses had absolute reductions of 76.4 and 20.2%, respectively. In these two settings, the percentage of HCV RNA-positive patients identified as a result of reflex testing accounted for 55 and 61% of all anti-HCV-positive patients. HCV RNA results were provided in a mean of 2 days. The presence of HCV RNA and age of ≥65 years were significantly associated with advanced fibrosis, assessed using the serological FIB-4 index (odds ratio [OR], 5.92; 95% confidence interval [CI], 3.4 to 10.4). The implementation of viral load reflex testing in a central laboratory is feasible and significantly increases the diagnostic effectiveness of HCV infections, while allowing the identification of underdiagnosed cases.
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Hepacivirus , Hepatite C/diagnóstico , Hepatite C/virologia , Técnicas de Diagnóstico Molecular , Tomada de Decisão Clínica , Técnicas de Laboratório Clínico , Árvores de Decisões , Gerenciamento Clínico , Hepacivirus/genética , Hepatite C/complicações , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , RNA Viral , Sensibilidade e Especificidade , Espanha , Carga ViralRESUMO
Aluminum contamination in parenteral nutrition (PN) solutions can lead to neurotoxicity, reduced bone mass, and liver toxicity, especially in pediatric patients. Ingredients commonly used in PN compounding, such as vitamins, trace elements, calcium, and phosphate salts, contain significant amounts of aluminum. This study aimed to compare aluminum concentrations in multichamber-bag (MCB) and compounded PN for adults and pediatrics. A prospective study assessed aluminum concentrations in various types of MCB and compared them with compounded PN formulations with similar compositions. The types of MCB included Lipoflex® (without electrolytes), Omegaflex®, Finomel®, Smofkabiven® (with and without electrolytes), Olimel®, Clinimix®, and Numeta®. Overall, 80 aluminum determinations were included: 36 for MCBs and 44 for compounded PN. MCBs showed significantly lower aluminum concentrations than compounded PN: 11.37 (SD 6.16) vs. 21.45 (8.08) µg/L, respectively. Similar results were observed for adult (n = 40) and pediatric (n = 40) PN formulations (12.97 (7.74) vs. 20.78 (10.28) µg/L, and 9.38 (2.23) vs. 22.01 (5.82) µg/L, respectively). Significant differences were also found between MCBs depending on the manufacturing company. These findings suggest that MCBs PN offer a safer option for reducing aluminum contamination in PN. Harmonizing regulations concerning aluminum concentrations in PN solutions could help mitigate differences between PN formulations.
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Alumínio , Nutrição Parenteral , Adulto , Humanos , Criança , Estudos Prospectivos , Soluções de Nutrição Parenteral , EletrólitosRESUMO
BACKGROUND & AIMS: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). METHODS: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. RESULTS: Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057). CONCLUSIONS: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.
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Doença de Depósito de Glicogênio Tipo V , Glicogênio , Humanos , Glicemia , Suplementos Nutricionais , Cetonas , Músculos , Estudos Cross-OverRESUMO
Accurate measurement of sex steroids, particularly testosterone and estradiol, is relevant for the diagnosis and treatment of a wide range of conditions. Unfortunately, current chemiluminescent immunoassays have analytical limitations with important clinical consequences. This document reviews the current state of clinical assays for estradiol and testosterone measurements and their potential impact in different clinical situations. It also includes a series of recommendations and necessary steps to introduce steroid analysis by mass spectrometry into national health systems, a methodology recommended for more than a decade by international societies.
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Estradiol , Hormônios Esteroides Gonadais , Espectrometria de Massas/métodos , Testosterona , Esteroides/análiseRESUMO
Dasatinib is a tyrosine kinase inhibitor drug used for chronic myeloid leukaemia (CML) treatment. Chylothorax has been rarely reported as a secondary effect of dasatinib occurring especially in long-term treated patients, although its pathophysiology is not yet fully understood. Laboratory analysis of the pleural effusion is crucial for chylothorax diagnosis. We report a case of a 53-year-old male patient presenting a chylothorax after 14 years of dasatinib therapy where the clinical laboratory was key in the diagnosis.
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Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, and liver fibrosis is the strongest predictor of morbimortality. We aimed to assess the performance of a sequential algorithm encompassing the Fibrosis 4 (FIB-4) and Enhanced Liver Fibrosis (ELF) scores for identifying patients at risk of advanced fibrosis. This cross-sectional study included one hospital-based cohort with biopsy-proven NAFLD (n = 140) and two primary care cohorts from different clinical settings: Type 2 Diabetes (T2D) follow-up (n = 141) and chronic liver disease (CLD) initial study (n = 138). Logistic regression analysis was performed to assess liver fibrosis diagnosis models based on FIB-4 and ELF biomarkers. The sequential algorithm retrieved the following accuracy parameters in predicting stages F3-4 in the biopsy-confirmed cohort: sensitivity (85%), specificity (73%), negative predictive value (79%) and positive predictive value (81%). In both T2D and CLD cohorts, a total of 28% of patients were classified as stages F3-4. Furthermore, of all F3-4 classified patients in the T2D cohort, 80% had a diagnosis of liver disease and 44% were referred to secondary care. Likewise, of all F3-4 classified patients in the CLD cohort, 71% had a diagnosis of liver disease and 44% were referred to secondary care. These results suggest the potential utility of this algorithm as a liver fibrosis stratifying tool in primary care, where updating referral protocols to detect high-risk F3-4 is needed. FIB-4 and ELF sequential measurement is an efficient strategy to prioritize patients with high risk of F3-4 in populations with metabolic risk factors.
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PURPOSE: Changes in the myocardial extracellular matrix (ECM) identified using T1 mapping cardiovascular magnetic resonance (CMR) have been only reported in obese adults, but with opposite conclusions. The objectives are to assess the composition of the myocardial ECM in an obese pediatric population without type 2 diabetes by quantifying native T1 time, and to quantify the pericardial fat index (PFI) and their relationship with cardiovascular risk factors. METHODS: Observational case-control research of 25 morbidly obese adolescents and 13 normal-weight adolescents. Native T1 and T2 times (ms), left ventricular (LV) geometry and function, PFI (g/ht3) and hepatic fat fraction (HFF, %) were calculated by 1.5-T CMR. RESULTS: No differences were noticed in native T1 between obese and non-obese adolescents (1000.0 vs. 990.5 ms, p0.73), despite showing higher LV mass values (28.3 vs. 22.9 g/ht3, p0.01). However, the T1 mapping values were significantly higher in females (1012.7 vs. 980.7 ms, p < 0.01) while in males, native T1 was better correlated with obesity parameters, particularly with triponderal mass index (TMI) (r = 0.51), and inflammatory cells. Similarly, the PFI was correlated with insulin resistance (r = 0.56), highly sensitive C-reactive protein (r = 0.54) and TMI (r = 0.77). CONCLUSION: Female adolescents possess myocardium peculiarities associated with higher mapping values. In males, who are commonly more exposed to future non-communicable diseases, TMI may serve as a useful predictor of native T1 and pericardial fat increases. Furthermore, HFF and PFI appear to be markers of adipose tissue infiltration closely related with hypertension, insulin resistance and inflammation.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Obesidade Mórbida , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Tecido Adiposo/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Pericárdio/diagnóstico por imagem , Valor Preditivo dos Testes , Caracteres Sexuais , Função Ventricular Esquerda , Estudos de Casos e ControlesRESUMO
BACKGROUND: This study aimed to determine the effect of different carbohydrate (CHO) doses on exercise capacity in patients with McArdle disease-the paradigm of "exercise intolerance", characterized by complete muscle glycogen unavailability-and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell (in vitro) level. METHODS: Patients with McArdle disease (nâ¯=â¯8) and healthy controls (nâ¯=â¯9) underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo. In a randomized, double-blinded, cross-over design, patients repeated the tests after consuming either 75 g or 150 g of CHO (glucose:fructose = 2:1). Cardiorespiratory, biochemical, perceptual, and electromyographic (EMG) variables were assessed. Additionally, glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations (0.35, 1.00, 4.50, and 10.00 g/L). RESULTS: Compared with controls, patients showed the "classical" second-wind phenomenon (after prior disproportionate tachycardia, myalgia, and excess electromyographic activity during submaximal exercise, all p < 0.05) and an impaired endurance exercise capacity (-51% ventilatory threshold and -55% peak power output, both p < 0.001). Regardless of the CHO dose (p < 0.05 for both doses compared with the placebo), CHO intake increased blood glucose and lactate levels, decreased fat oxidation rates, and attenuated the second wind in the patients. However, only the higher dose increased ventilatory threshold (+27%, pâ¯=â¯0.010) and peak power output (+18%, pâ¯=â¯0.007). In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes, whereas a dose-response effect was observed in McArdle myotubes. CONCLUSION: CHO intake exerts beneficial effects on exercise capacity in McArdle disease, a condition associated with total muscle glycogen unavailability. Some of these benefits were dose dependent.
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Objectives: Congenital X-linked adrenal hypoplasia is a rare disease with a known genetic basis characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and a wide variety of clinical manifestations. Case presentation: We present the case of a 26-day old male newborn with symptoms consistent with adrenal insufficiency, hyponatremia, and hyperkalemia. Following NaCl and fludrocortisone supplementation, the patient remained clinically stable. 17-OH-progesterone testing excluded congenital adrenal hyperplasia. The rest of hormones were within normal limits, except for adrenocorticotropic hormone (ACTH), which was significantly elevated, and aldosterone, which was below the reference value. Further testing included very long chain fatty acids to exclude adrenoleukodystrophy, the CYP11B2 gene (aldosterone synthase), and an MRI to screen for other morphological abnormalities. All tests yielded normal results. Finally, after cortisol deficiency was detected, expanded genetic testing revealed a mutation in the NR0B1 gene, which led to a diagnosis of congenital adrenal hypoplasia. Conclusions: Diagnosis of congenital adrenal hypoplasia is challenging due to the heterogeneity of both clinical manifestations and laboratory abnormalities. As a result, diagnosis requires close monitoring and genetic testing.
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Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55-0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57-0.84) for SOFA and 0.70 (0.58-0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.
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BACKGROUND AND AIMS: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. METHOD: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. RESULTS: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. CONCLUSIONS: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.
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Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency. Design: Prospective, observational, single-center study. Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021. Patients: Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included. Interventions: Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients. Measurement: Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L). Main results: Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients. Conclusion: This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.
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Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in western countries. Insulin resistance (IR), type 2 diabetes (T2D), and the polymorphisms patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 are independent risk factors of NASH. Nevertheless, little is known about the interaction between IR and T2D with these polymorphisms in the pathogenesis of NASH and the development of advanced fibrosis. Thus, our study aimed to investigate this relationship. This is a cross-sectional study including NASH patients diagnosed by liver biopsy, at the Vall d'Hebron University Hospital. A total of 140 patients were included (93 T2D, 47 non-T2D). T2D (OR = 4.67; 95%CI 2.13−10.20; p < 0.001), PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms (OR = 3.94; 95%CI 1.63−9.54; p = 0.002) were independently related with advanced liver fibrosis. T2D increased the risk of advance fibrosis on top of the two polymorphisms (OR = 14.69; 95%CI 3.03−77.35; p = 0.001 for PNPLA3 rs738409 and OR = 11.45; 95%CI 3.16−41.55; p < 0.001 for TM6SF2 rs58542926). In non-T2D patients, the IR (HOMA-IR ≥ 5.2, OR = 14.33; 95%CI 2.14−18.66; p = 0.014) increased the risk of advanced fibrosis when the polymorphisms were present (OR = 19.04; 95%CI 1.71−650.84; p = 0.042). The T2D and IR status increase the risk of advanced fibrosis in patients with NASH carrying the PNPLA3 rs738409 and/or TM6SF2 rs58542926 polymorphisms, respectively.
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Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): RT-PCR-confirmed SARS-CoV-2 positive (Groups 1−4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and 'SARS-CoV-2 unexposed' patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.
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Objectives: Administration of busulfan is extending rapidly as a part of a conditioning regimen in patients undergoing hematopoietic stem cell transplantation (HSCT). Monitoring blood plasma levels of busulfan is recommended for identifying the optimal dose in patients and for minimizing toxicity. The aim of this research was to validate a simple, rapid, and cost-effective analytical tool for measuring busulfan in human plasma that would be suitable for routine clinical use. This novel tool was based on liquid chromatography coupled to mass spectrometry. Methods: Human plasma samples were prepared using a one-step protein precipitation protocol. These samples were then resolved by isocratic elution in a C18 column. The mobile phase consisted 2 mM ammonium acetate and 0.1% formic acid dissolved in a 30:70 ratio of methanol/water. Busulfan-d8 was used as the internal standard. Results: The run time was optimized at 1.6 min. Standard curves were linear from 0.03 to 5 mg/L. The coefficient of variation (%CV) was less than 8%. The accuracy of this method had an acceptable bias that fell within 85-115% range. No interference between busulfan and the interfering compound hemoglobin, lipemia, or bilirubin not even at the highest concentrations of compound was tested. Neither carryover nor matrix effects were observed using this method. The area under the plasma drug concentration-time curves obtained for 15 pediatric patients who received busulfan therapy prior to HSCT were analyzed and correlated properly with the administered doses. Conclusions: This method was successfully validated and was found to be robust enough for therapeutic drug monitoring in a clinical setting.