EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease

https://www.journal-of-hepatology.eu/article/S0168-8278(14)00933-7/pdf

NAFLD: A multisystem disease

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

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Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

Statistical Methods in Medical Research.

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia.

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Dyslipidemia in Obesity: Mechanisms and Potential Targets

We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates

Background: Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection.

Methods: The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life.

Results: Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6.

Conclusions: Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.

C-Reactive Protein, Interleukin-6, and Procalcitonin in the Immediate Postnatal Period: Influence of Illness Severity, Risk Status, Antenatal and Perinatal Complications, and Infection

The evaluation of tests for neonatal sepsis is important because the infection may present a very serious threat to the baby. There is an urgent need to know whether the baby has sepsis to institute treatment as quickly as possible. Confirmation of the diagnosis may take time, and diagnostic tests are used to obtain a rapid indication of the infection status. These tests are not perfect. Some real cases of infection will produce negative test results, whereas some babies without infection will test positive. The potential usefulness of the test will depend, above all, on the clinical condition of the baby. If the baby is really very sick, the test will not give very much additional information. Similarly, if the baby is evidently well, a clinical examination will be sufficient and a positive test result would not dramatically increase the probability that the baby is infected. It is in situations in which the clinical picture leaves the physician in doubt about the infection status that a diagnostic test is likely to be most useful. Thus, the result of a diagnostic test must be evaluated in the light of the clinical condition of the baby.

Extensive literature exists on single laboratory tests or combinations of tests, as well as tests used together with risk factors and/or clinical signs, to diagnose neonatal sepsis. In many instances, the results of the evaluations have been conflicting. There are several possible explanations for the divergent results, and the purpose of this review is to update readers on the topic and raise issues that should be addressed in the future.

Throughout pregnancy and until the membranes rupture, the fetus is relatively protected from the microbial flora of the mother by the chorioamniotic membranes, the placenta, and poorly understood antibacterial factors in amniotic fluid (1). However, there …

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Diagnosis of Neonatal Sepsis: A Clinical and Laboratory Challenge

Objectives: Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D3 (25(OH)D3) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. Methods: We determined serum 25(OH)D3 concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima‐media thickness (cIMT) ‐ two markers of subclinical atherosclerosis. Results: Higher 25(OH)D3 was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D3 levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (!17 ng/ml) compared with the highest tertile (O27 ng/ml) of 25(OH)D3 for hypertension was 1.72 (1.02‐2.92), and for MetS, it was 2.30 (1.20‐4.40). A similar pattern of association between 25(OH)D3, high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D3 concentrations and either FMD or cIMT. Conclusions: Low 25(OH)D3 levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

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Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents

Background: There is a wide range of reported sensitivities and specificities for C-reactive protein (CRP) and interleukin-6 (IL-6) in the detection of early-onset neonatal infection. This prompted us to assess reference intervals for CRP and IL-6 during the 48-h period immediately after birth and to identify maternal and perinatal factors that may affect them.

Methods: CRP and IL-6 values were prospectively obtained for 148 healthy babies (113 term, 35 near-term) at birth and at 24 and 48 h of life, and from their mothers at delivery.

Results: Upper reference limits for CRP at each neonatal age were established. At birth, CRP was significantly lower than at 24 and 48 h of life. Rupture of membranes ≥18 h, perinatal distress, and gestational hypertension significantly affected the neonatal CRP dynamics, but at specific ages. There was no correlation between CRP concentrations in mothers and their offspring at birth. The IL-6 values observed in the delivering mothers and in their babies at all three neonatal ages were negatively associated with gestational age. In the immediate postnatal period, IL-6 dynamics for term babies were significantly different from those for near-term babies. Maternal IL-6 concentrations correlated with babies’ IL-6 concentrations only for term deliveries. Apgar score had a significant effect on babies’ IL-6 values at birth.

Conclusions: The patterns of CRP and IL-6 responses in the healthy neonate should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.

/pdf/serial-measurements-of-c-reactive-protein-and-interleukin-6-31v8zoqai9.pdf

Serial Measurements of C-Reactive Protein and Interleukin-6 in the Immediate Postnatal Period: Reference Intervals and Analysis of Maternal and Perinatal Confounders

John Frederick Osborn

Papers

Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates

C-Reactive Protein, Interleukin-6, and Procalcitonin in the Immediate Postnatal Period: Influence of Illness Severity, Risk Status, Antenatal and Perinatal Complications, and Infection

Diagnosis of Neonatal Sepsis: A Clinical and Laboratory Challenge

Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents

Serial Measurements of C-Reactive Protein and Interleukin-6 in the Immediate Postnatal Period: Reference Intervals and Analysis of Maternal and Perinatal Confounders