Biomarker combinations in predicting sepsis in hospitalized children with fever.

Sepsis is among the leading causes of critical illness worldwide. It includes physiologic, pathologic, and biochemical abnormalities, induced by infection. Novel methods for recognizing a dysregulated inflammatory response and predicting associated mortality must be developed. Our aim was to investigate biomarkers that characterize a pro-inflammatory and anti-inflammatory response in patients with fever by comparing predictive validity for sepsis. 165 patients with fever were enrolled in this study, 55 of them had sepsis according to pSOFA criteria. All patients had blood samples drawn at the time of inclusion and after 24 h. CRP, PCT and also IL-6, IL-8 and sFAS levels were significantly higher in patients with sepsis. The AUC of CRP to predict sepsis was 0.799, all the other biomarkers had AUC's lower than that. Cytokines, when used as a single marker, did not show a significant diagnostic performance We analyzed various models of biomarker combinations. CRP combined with sFAS showed increase in sensitivity in predicting sepsis (88% vs. 83%). The highest AUC was achieved, when CRP, IL-6, sFAS and sVCAM-1 markers were combined 0.830 (95% CI 0.762-0.884) with a sensitivity of 70% and specificity of 84%. vs. 0.799 for CRP alone.

Invasive Pneumococcal Disease in Latvia in PCV10 Vaccination Era, 2012-2018.

In 2010 in Latvia, invasive pneumococcal disease (IPD) became a cause for concern and vaccination of infants with four doses of 7-valent pneumococcal conjugate vaccine (PCV7) commenced. In 2012, 10-valent pneumococcal conjugate vaccine (PCV10) (three doses at 2, 4, and 12-15 month of age) vaccination was introduced. We described incidence and serotype distribution of IPD in Latvia and investigated serotypes associated with death from IPD based on surveillance data. Adult vaccination against pneumococcal infection is not included in the national immunization program. Laboratory confirmed IPD cases are passively notified to the Center for Disease Prevention and Control of Latvia (CDPC) by laboratories and clinicians. We calculated incidence by age, sex, case fatality, and trend in serotypes by conducting a retrospective population-based cross-sectional study based on national IPD surveillance data. From 2012 to 2018 466 cases of IPD were reported. The highest notified incidence was in 2015 at 4.4/100,000, which fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in the elderly (6.0). PCV10 vaccine serotypes were the most prevalent in IPD cases up to 2015 with a decreasing trend from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend of odds = 0.000). PCV23nonPCV13 vaccine serotypes had an increasing trend and rose from 18% (7/40) to 34% (25/74) (chi2 test for trend of odds = 0.000). Non-Vaccine serotypes had an increasing trend and rose from 13% (5/40) to 27% (20/74) (chi2 test for trend of odds = 0.038). Reported total case fatality was 19% (87/466). The highest, at 36% (20/56), was reported in 2013. After adjusting for age, Streptococcus pneumoniae serotype 3 was associated with death from IPD (adjusted OR 2.3 95%CI 1.25-4.12 p 0.007). Surveillance data indicate evidence of serotype replacement with an increasing trend of serotype 19A and PPV23nonPCV13 and Non-Vaccine serotypes. Serotype 3 and age were associated with fatal IPD outcome. Further studies of S. pneumoniae carriage would be useful in providing more evidence to characterize serotypes' circulation.

Pediatric Readiness in the Emergency Department and Its Association With Patient Outcomes in Critical Care: A Prospective Cohort Study.

OBJECTIVES: Pediatric mortality in Latvia remains one of the highest among Europe. The purpose of this study was to assess the quality of pediatric acute care and pediatric readiness and determine their association with patient outcomes using a patient registry. DESIGN: This was a prospective cohort study. Pediatric readiness was measured using the weighted pediatric readiness score based on a 100-point scale. The processes of care were measured using in situ simulations to generate a composite quality score. Clinical outcome data-including PICU and hospital length of stay as well as 6-month mortality-were collected from the Pediatric Intensive Care Audit Network registry. The associations between composite quality score and weighted pediatric readiness score on patient outcomes were explored with mixed-effects regressions. SETTING: This study was conducted in all Latvian Emergency Departments and in the national PICU. PATIENTS: All patients who were transferred into the national PICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All (16/16) Latvian Emergency Departments participated with a mean composite quality score of 35.3 of 100 and a median weighted pediatric readiness score of 31 of 100. A total of 254 patients were included in the study and followed up for a mean of 436 days, of which nine died (3.5%). Higher weighted pediatric readiness score was associated significantly with lower length of stay in both the PICU and hospital (adjusted ß, -0.06; p = 0.021 and -0.36; p = 0.011, respectively) and lower 6-month mortality (adjusted odds ratio, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: These data provide a national assessment of pediatric emergency care in a European country. Pediatric readiness in the emergency department was associated with patient outcomes in this population of pediatric patients transferred to the national PICU.

Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker.

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as "life-threatening organ dysfunction due to a dysregulated host response to infection". In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.

Inflammatory Cytokine and Chemokine Patterns in Paediatric Patients with Suspected Serious Bacterial Infection.

Background and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.

Assessment of Immature Granulocytes Percentage to Predict Severe Bacterial Infection in Latvian Children: An Analysis of Secondary Data.

Background: Detection of small proportion of serious bacterial infections (SBI) with a potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections that were admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) infected patients with no suspicion of SBI (n = 75); (2) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC), and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without-the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC, and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86% (95% CI 77%⁻93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore, IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Health-related quality of life of the parents of children hospitalized due to acute rotavirus infection: a cross-sectional study in Latvia.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in young children and infants worldwide, representing a heavy public health burden. Limited information is available regarding the impact of rotavirus gastroenteritis on the quality of life of affected children and their families. The objectives of study were to estimate the impact of rotavirus infection on health-related quality of life (HRQL), to assess the social and emotional effects on the families of affected children. METHODS: This study enrolled all (n = 527) RotaStrip®-positive (with further PCR detection) cases (0-18 years of age) hospitalized from April 2013 to December 2015 and their caregivers. A questionnaire comprising clinical (filled-in by the medical staff) and social (filled by the caregivers) sections was completed per child. RESULTS: Main indicators of emotional burden reported by caregivers were compassion (reported as severe/very severe by 91.1% of parents), worry (85.2%), stress/anxiety (68.0%). Regarding social burden, 79.3% of caregivers reported the need to introduce changes into their daily routine due to rotavirus infection of their child. Regarding economic burden, 55.1% of parents needed to take days off work because of their child's sickness, and 76.1% of parents reported additional expenditures in the family's budget. Objective measures of their child's health status were not associated with HRQL of the family, as were the parent's subjective evaluation of their child's health and some sociodemographic factors. Parents were significantly more worried if their child was tearful (p = 0.006) or irritable (p < 0.001). Parents were more stressful/anxious if their child had a fever (p = 0.003), was tearful (p < 0.001), or was irritable (p < 0.001). Changes in parents' daily routines were more often reported if the child had a fever (p = 0.02) or insufficient fluid intake (p = 0.04). CONCLUSION: Objective health status of the child did not influence the emotional, social or economic burden, whereas the parents' subjective perception of the child's health status and sociodemographic characteristics, were influential. A better understanding of how acute episodes affect the child and family, will help to ease parental fears and advise parents on the characteristics of rotavirus infection and the optimal care of an infected child.

High-mobility group box-1 protein, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study.

INTRODUCTION: Even though sepsis is one of the common causes of children morbidity and mortality, specific inflammatory markers for identifying sepsis are less studied in children. The main aim of this study was to compare the levels of high-mobility group box-1 protein (HMGB1), Lipopolysaccharide-binding protein (LBP), Interleukin-6 (IL-6) and C-reactive protein (CRP) between infected children without systemic inflammatory response syndrome (SIRS) and children with severe and less severe sepsis. The second aim was to examine HMGB1, LBP, IL6 and CRP as markers for of bacteraemia. METHODS: Totally, 140 children with suspected or proven infections admitted to the Children's Clinical University Hospital of Latvia during 2008 and 2009 were included. Clinical and demographical information as well as infection focus were assessed in all patients. HMGB1, LBP, IL-6 and CRP blood samples were determined. Children with suspected or diagnosed infections were categorized into three groups of severity of infection: (i) infected without SIRS (n = 36), (ii) sepsis (n = 91) and, (iii) severe sepsis (n = 13). They were furthermore classified according bacteraemia into (i) bacteremia (n = 30) and (ii) no bacteraemia (n = 74). RESULTS: There was no statistically significant difference in HMGB1 levels between children with different levels of sepsis or with and without bacteraemia. The levels of LBP, IL-6 and CRP were statistically significantly higher among patients with sepsis compared to those infected but without SIRS (p < 0.001). Furthermore, LBP, IL-6 and CRP were significantly higher in children with severe sepsis compared to those ones with less severe sepsis (p < 0.001). Median values of LBP, IL6 and CRP were significantly higher in children with bacteraemia compared to those without bacteraemia. The area under the receiver operating curve (ROC) for detecting bacteraemia was 0.87 for both IL6 and CRP and 0.82 for LBP, respectively. CONCLUSION: Elevated levels of LBP, IL-6 and CRP were associated with a more severe level of infection in children. Whereas LBP, IL-6 and CRP seem to be good markers to detect patients with bacteraemia, HMGB1 seem to be of minor importance. LBP, IL-6 and CRP levels may serve as good biomarkers for identifying children with severe sepsis and bacteraemia and, thus, may be routinely used in clinical practice.

Prevalence of systemic inflammatory response syndrome (SIRS) in hospitalized children: a point prevalence study.

BACKGROUND: In accordance with the 1st International pediatric sepsis consensus conference, where sepsis was defined as SIRS associated with suspected or proven infection, we have identified the need to assess the prevalence of SIRS and sepsis in children with abnormal temperatures hospitalized in The Children's Clinical University Hospital in Latvia. METHODS: A descriptive prospective point prevalence study (using two time periods, each 24 h, randomly chosen) was conducted on all children (n = 943) treated in the hospital. All children with abnormal temperatures - fever or hypothermia (n = 92) - were included in the study. Questionnaires evaluating age-specific SIRS criteria were completed. The prevalence of SIRS was detected with 95% CI. RESULTS: Out of a total of 943 patients treated in the hospital, 10% (n = 92) had abnormal temperatures. In all these cases the abnormal temperature was a fever; hypothermia was not established in any patient. Of the children with fever, 72% (n = 66) had SIRS. Of the SIRS patients, 8% (n = 5) developed sepsis, 5% (n = 3) severe sepsis and 2% (n = 1) septic shock. Seventy-six percent (n = 50) of the SIRS patients had fever in combination with respiratory rate >2 SD above normal for age; 50% (n = 33) had fever with abnormal leukocyte count; 15% (n = 10) had fever with tachycardia >2 SD above normal for age. Most of the SIRS patients (39%, n = 25) were aged 2-5 years. Twenty-one percent (n = 14) of the children with SIRS and 50% (n = 2) of those with severe sepsis and septic shock had an underlying disease. In no case was SIRS and sepsis recognized by doctors and the diagnoses were not recorded on the patients' cards. CONCLUSION: Our results would indicate a high risk for sepsis development in children with SIRS. Early SIRS diagnosis and awareness of risk of developing sepsis could change the medical approach to the patient in everyday clinical practice, eventually leading to early, goal-directed therapy for sepsis.