Sepsis In Pediatric Patients Research Articles

Neutrophil-lymphocyte count ratio correlation to procalcitonin and PELOD-2 score in pediatric sepsis

Background Sepsis is a leading cause of children’s mortality worldwide. Procalcitonin (PCT) is a widely used infection marker, but has limitations in terms of cost and availability. The neutrophil-lymphocyte count ratio (NLCR) is easy to perform, low-cost, and widely used as a diagnostic and prognostic marker of various inflammatory processes.
 Objective To investigate possible correlations of NLCR to PCT and Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score among pediatric sepsis patients.
 Method A retrospective study was conducted by reviewing the Pediatric Sepsis Registry at Dr. Hasan Sadikin General Hospital, Bandung, West Java, from January 2019–June 2020. We recorded patients’ characteristics, PELOD-2 score, NLCR, and PCT results. Correlation analysis was conducted using Spearman’s Rank test with significance value of P<0.05.
 Results Ninety patients were included in the study. Most patients were male (56.7%), under 2 years of age (57.8%), and had lower respiratory tract infection (67.8%) as the most common source of infection. The NLCR value had significant, positive correlations to PCT (r=0.642; P<0.001) and PELOD-2 score (r=0.233; P=0.027) in pediatric sepsis patients.
 Conclusion The NLCR is directly proportional to PCT in pediatric sepsis patients. This result suggents that NLCR may have a potential role as an alternative marker for sepsis in emergency setting.

The Platelet-to-lymphocyte ratio, PELOD-2 score, and mortality rate in pediatric sepsis

Background Sepsis is life-threatening organ dysfunction caused by a regulated immune response to infection. Sepsis remains the most common cause of death in infants and children worldwide. The Pediatric Logistic Organ Dysfunction (PELOD-2) score, one of the most widely used scoring systems in pediatric sepsis patients, has been shown to be accurate in predicting mortality. The platelet-to-lymphocyte ratio (PLR) is a new clinical indicator of inflammation in a variety of diseases including sepsis.
 Objective To investigate the relationship between PLR, PELOD-2 score, and clinical outcomes in pediatric patients with sepsis.
 Methods This retrospective cohort study was conducted in the Pediatric Intensive Care Unit (PICU), Prof R.D. Kandou Hospital, Manado, North Sulawesi, from February to August 2020. Subjects’ PELOD-2 score and PLR were recorded once within the first 24 hours of PICU admission. We analyzed patients’ PELOD-2 score, PLR, and mortality rate, with 95% confidence interval (CI) for each value.
 Results Of 96 children with sepsis admitted to the PICU during the study period, 87 patients (46 boys; 52.9%) met the inclusion criteria. In total, 50 (57.47%) patients were non-survivors. Mean PLR values among survivors [77.54 (SD 50.08)] was significantly lower compared to the values among non-survivors [157.13 (SD 67.38)]; as well as the PELOD-2 score in the survivors group [12 (SD 1.32)] was significantly lower than its value in the non-survivors [14.65 (SD 2.09)]. Spearman’s analysis showed a moderately positive correlation between PLR and PELOD-2 score (r=0.444; 95%CI 0.44 to 1; P<0.01). Biserial point correlation analysis revealed a significant association between PLR and mortality rate (rpb=0.566; P<0.0001),with elevated PLR related to an increased risk of mortality.
 Conclusion There are positive correlations between PLR, PELOD-2 score, and mortality rate in pediatric patients with sepsis. Higher PLR and PELOD-2 score are associated with higher mortality.

Validity of Urine Syndecan-1 as A Predictor of Acute Kidney Injury In Pediatric Sepsis Patients

Introduction: AKI (Acute Kidney Injury) complications in sepsis patients generally occur 24 hours after admission to ICU. Creatine Serum Concentration is a standard parameter to diagnose AKI. Unfortunately, the changes in creatine serum concentration will only be seen several days after the decrease of renal function to 50%. The low detection ability has been linked with time loss before preventive therapy is commenced. Furthermore, this instigates the need for biomarkers to ensure early detection. Objective: This study aimed to identify cut-off points of urine syndecan-1 and to measure the prediction ability of urine syndecan-1 towards the AKI occurrence in pediatric sepsis patients. Materials and methods: This study was a prospective cohort study performed at a single center in Dr. Soetomo General Hospital, Surabaya. The inclusion criterion was all children admitted to the resuscitation room from October until December 2019. Furthermore, urine sampling is carried out at 0, 6, 12, and 24 hours for a syndecan-1 urine examination, and every procedure performed on the patient will be recorded. This action was continued up to the third day and aimed to evaluate some factors related to AKI at 48-72 hours of admission. Result and Discussion: Out of 41 pediatric sepsis patients, 30 patients fulfilled the inclusion criteria and 57% had AKI. The value of urine syndecan-1 at hour-0 and hour-6 was significantly featured a cut-off point. Conclusion: The value of urine syndecan-1 at hour-0 and hour-6 are valid parameters to predict the occurrence of AKI grades 1, 2, and 3 in pediatric septic patients at 48-72 hours after their hospital admission. The best cut-off value of urine syndecan-1 at the 0th hour was 0.67 ng/ml.

Prediction of Impending Septic Shock in Children With Sepsis.

Sepsis and septic shock are leading causes of in-hospital mortality. Timely treatment is crucial in improving patient outcome, yet treatment delays remain common. Early prediction of those patients with sepsis who will progress to its most severe form, septic shock, can increase the actionable window for interventions. We aim to extend a time-evolving risk score, previously developed in adult patients, to predict pediatric sepsis patients who are likely to develop septic shock before its onset, and to determine whether or not these risk scores stratify into groups with distinct temporal evolution once this prediction is made. Retrospective cohort study. Academic medical center from July 1, 2016, to December 11, 2020. Six-thousand one-hundred sixty-one patients under 18 admitted to the Johns Hopkins Hospital PICU. None. We trained risk models to predict impending transition into septic shock and compute time-evolving risk scores representative of a patient's probability of developing septic shock. We obtain early prediction performance of 0.90 area under the receiver operating curve, 43% overall positive predictive value, patient-specific positive predictive value as high as 62%, and an 8.9-hour median early warning time using Sepsis-3 labels based on age-adjusted Sequential Organ Failure Assessment score. Using spectral clustering, we stratified pediatric sepsis patients into two clusters differing in septic shock prevalence, mortality, and proportion of patients adequately fluid resuscitated. We demonstrate the applicability of our methodology for early prediction and stratification for risk of septic shock in pediatric sepsis patients. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children and are able to stratify pediatric sepsis patients using their risk score trajectories into low and high-risk categories.

Balanced Salt Solution Versus Normal Saline in Resuscitation of Pediatric Sepsis: A Randomized, Controlled Trial.

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576

TNF-Alpha Serum Level as Prognostic Factor in Pediatric Sepsis Patients

OBJECTIVE: The study aimed to investigate the role of TNFα-308 genetic polymorphism, association between TNF-α serum level and prognostic factor of mortality in pediatric sepsis. 
 
 METHODS: This was a prospective cohort study. Consecutive sampling method was used and samples were obtained from septic patients diagnosed based on the IPSC 2005 criteria. Serum TNF-α and genetic polymorphism were measuread and analyzed with ELISA and PCR plus sequencing, respectively.
 
 RESULT: One hundred and seventeen samples were included, 62 were in survivor grioup and 55 in non survivor group. A very significant association was found between TNF-α serum level and mortality (p<0.001). The optimal cut off point of TNFα serum level as prognostic factor for mortality was ≥ 500 pg/mL (p<0.001 and OR 16.6) sensitivity 78.1%, specificity 82%, Positive Predictive Value (PPV) 79.6%, Negative Predictive Value (NPV) 80.9%, Area Under Curve (AUC) 0.811. Two samples showed TNFα-308A polymorphism and mutation of GG allele to heterozygote GA allele. Neither TNFα polymorphism and TNFα serum level showed any association with mortality. There was no significant association between TNFα-308 polymorphism and TNF-α serum level p=0.461(p>0.05) and mortality p=0.219 (p>0.05), all sample who had TNFα-308 genetic polymorphism were in non survivor group and had TNF-α serum level ≥ 500 pg/mL. 
 
 CONCLUSION: Genetic polymorphism of TNF-α-308 showed no statistic significant on mortality, but all subjects with TNFα-308 polymorphism had higher TNF-α serum and were all in non-survivor group.

Effectiveness of a central line associated blood stream infection protocol in a pediatric population

BackgroundCentral line associated bloodstream infections are a common cause of bacteremia and sepsis in pediatric patients with intestinal failure, secondary to long-term CVC use. MethodsAn IRB approved retrospective chart review was conducted on TPN-dependent patients with IF who had an identified CLABSI and presented to Children's of Alabama's emergency department (ED) and were admitted to the hospital. ResultsForty-four patients were included in the study, 28 in the first 18-month period and 26 in the second, with 10 in both populations. After implementation, mean time from ED presentation to antibiotic ordered and ED admission to antibiotic administered were lower. Mean time between antibiotic administration and admission to the floor was greater, and number of infectious disease consultations was greater. Floor-ICU transfers were lower, readmissions within 30 days was similar, and mean length of stay was similar. ConclusionA collaborative, multidiscipline-supported protocol for the care of patients with IF presenting to the ED enhances efficiency of antibiotic ordering/administration, as well as reduces the number of unplanned floor-ICU transfers.

Triggering receptor expressed on myeloid cells-1 as pediatric sepsis biomarker.

Triggering receptor expressed on myeloid cells-1 concentration can be used as a predictive, diagnostic, and prognostic marker in patients with sepsis. The objective of this study was to determine the validity of triggering receptor expressed on myeloid cells-1 levels as a biomarker of sepsis in pediatric patients. This was an integrative literature review. PubMed, ScienceDirect, LILACS, MEDLINE, and VHL databases were searched for papers published between 2015 and 2020, using the keywords triggering receptor expressed on myeloid cells-1, sepsis, and child. The review included ten studies, of which four used triggering receptor expressed on myeloid cells-1 as a predictive biomarker; four, as a diagnostic biomarker; and two, as a prognostic biomarker. A total of 1,409 and 1,628 patients were included in primary and review studies, respectively. There was a predominance of significant results for the validity of triggering receptor expressed on myeloid cells-1 levels in the prediction, diagnosis, and prognosis of sepsis in pediatric patients. Triggering receptor expressed on myeloid cells-1 is a valid predictive, diagnostic, and prognostic biomarker of sepsis with good sensitivity and specificity in the pediatric population.

Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort.

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

New PELOD-2 cut-off score for predicting death in children with sepsis

Background According to the most recent Sepsis-3 Consensus, the definition of sepsis is life-threatening organ dysfunction caused by dysregulated immune system against infection. Currently, one of the most commonly used prognostic scoring system is pediatric logistic organ damage-2 (PELOD-2) score.
 Objective To determine and validate the pediatric logistic organ dysfunction-2 (PELOD-2) cut-off score to predict mortality in pediatric sepsis patients.
 Methods A prospective cohort study was conducted in the intensive care units of Cipto Mangunkusumo Hospital, Jakarta. We assessed subjects with PELOD-2 and calculated the predicted death rate (PDR) using SFAR software. The Hosmer-Lemeshow goodness-of-fit test was used to evaluate calibration and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) to estimate discrimination.
 Results Of 2,735 children admitted to the emergency department, 52 met the inclusion criteria. Patients had various types of organ dysfunction: 53.8% respiratory, 28.8% neurological, 15.4% cardiovascular, 1.9% hematological. The mortality rate in this study was 38.5%. Mean PELOD-2 score was higher in patients who died than in those who survived [13.9 (SD 4.564) vs. 7.59 (SD 3.025), respectively, P=0.000]. The discrimination of PELOD-2 score with the lactate component had an AUC of 85.5% (95%CI 74.5 to 96.5), while PELOD-2 without lactate had an AUC of 85.4% (95%CI 74.5 to 96.3%). We propose a new PELOD-2 cut-off score to predict organ dysfunction and death of 10, with 75% sensitivity, 72% specificity, 62.5% PPV, and 82% NPV. PELOD-2 score > 10 had a moderate, statistically significant correlation to mortality (r=0.599; P<0.001).
 Conclusion A PELOD-2 score > 10 is valid for predicting life-threatening organ dysfunction in pediatric patients with sepsis.

Relationship between Procalcitonin and C-Reactive Protein on Pelod Score in Pediatric Surgery Sepsis Patients at Dr Soetomo General Hospital Surabaya

The incidence of sepsis in the world was estimated around 1.8 million cases / year , whereas 25-38% ofthem requiring treatment in intensive care unit , with mortality of 1,400 cases / day . In Indonesia, child’smortality rate due to sepsis is still very high, around 50% -70%, and if accompanied with septic shock andmultiple organs dysfunction, the rate is increased (80%) . One of the scoring system that can describe theseverity degree of multiple organs dysfunction in children is PELOD (Pediatric Logistic Organ Dysfunction)score. But this assessment is time consuming, because many parameters that have to be calculated. One ofthe ways to shorten the time is by using diagnostic markers such as procalcitonin (PCT) and C-ReactiveProtein (CRP).Method: The research is a study of analytic observational to determine the relationship between PELODscore with a value of procalcitonin and CRP in patients of children with sepsis and determine the cutoff pointof procalcitonin and CRP can be associated with incidence of septic shock. Research carried out for threemonths started in January 2020 until April 2020. Patients who meet the criteria for inclusion and exclusionrequested approval. Laboratory blood tests were done from day 1-3 of the sepsis.Results: In the study it was obtained the result that the age of majority is in the category of 5-10 years thatas many as 11 patients (36.7%). In the category of the type of sex the most are men - men that 19 patients(63.3%) and patients mostly great suffering sepsis that 23 patients (76.7%). Analysis between CRP withPELOD Score by using the chi-square test , the obtained results that there is a relationship that significantbetween CRP with PELOD Sc ore on a day to 1-3 with a value of p value of each 0,001 ( p < 0,05) ; 0.002( p < 0.05) ; 0.004 ( p < 0.05), which means that there is significant relationship between CRP with PELODScore . Analysis between PCT with PELOD Score by using the chi-square test , the obtained results thatthere is a relationship that significant between PCT with PELOD Score on a day to 1-3 with a value ofp value respectively 0.005 ( p < 0,05) ; 0.001 ( p> 0.05) ; 0.016 ( p> 0.05), which means that there is arelationship which is significantly meaningful between PCT with PELOD Score. In research it obtained thevalue of the boundary between the groups of patients with sepsis with shock, sepsis is Pelod score value of29 is the boundary between groups of sepsis and shock, sepsis, CRP value of 88 is the boundary betweengroups of sepsis and shock, sepsis, PCT value 9 is the boundary between groups of sepsis and shock sepsis .Conclusion: There is a significant relationship between the PCT with PELOD Score and significantrelationship between the CRP with PELOD Score.

Early Detection and Initial Management of Sepsis in Pediatric Patients.

Background: Sepsis and septic shock being the most common cause of death in infants and children worldwide, Therefore, we aim to look into the pediatric sepsis that both medical students and new physicians face in the recognition, diagnosis, and management of these conditions. Targeted population: sepsis that is requiring urgent management in the Emergency Department (ED), with Emergency Physicians for teaching approach protocol. Aim of the study: Appropriate identification of pediatric sepsis, severe sepsis and septic shock and their management by training protocol to Emergency Physicians. Based on the child’s age, site, severity and source of infection. Methods: Collection of all possible available data about pediatric sepsis at the emergency department. By many research questions to achieve these aims so a midline literature search was performed with the keywords “critical care”, “emergency medicine”, “Pediatric sepsis principals in emergencies, Pediatric sepsis and management”. Literature search included an overview of recent definition, causes and recent therapeutic interventions strategies. Results: All studies introduced that initial diagnosis of different emergencies situations of pediatric sepsis and their interventions are serious conditions that face pediatric patients in ED. Conclusion: The early recognition of sepsis in pediatric would help to start the initial management promptly, thus will prevent sepsis to complicate into worse stages and have a better prognosis.

Sepsis in Children with Acute Lymphoblastic Leukemia

Background: Sepsis is the leading cause of morbidity and mortality in children worldwide, with around 75,000 inpatients each year and nearly 50% dying in pediatric hospitals. Acute lymphoblastic leukemia (ALL) in childhood is a malignancy originating from lymphoid progenitor cells, usually at the age of 2–6 years. Children with ALL contribute 30% to childhood cancer cases under 15 years old. Sepsis in pediatric patients increases mortality significantly. A previous study showed that the prevalence of sepsis in pediatrics is still high. Thus, this study aims to report ALL patients with sepsis in our institution.Methods: This study was a descriptive cross-sectional study at the National Cancer Center (NCC) - Dharmais Cancer Hospital. We recruited acute lymphoblastic leukemia (ALL) patients aged 2-18 years with suspected or documented sepsis based on Systemic Inflammatory Response Syndrome (SIRS) by The International Consensus Conference on Pediatric Sepsis. The data were collected by medical records from January 2014 to December 2018.Results: A total of 94 pediatric patients in the study included 57 males and 37 females with an average age of 5 years. The age range was 1–18 years with a median age of 5 years. The prevalence of sepsis in pediatric with ALL was 11 patients (11.7%) and 45.5% of deaths. The clinical conditions were as follows: abnormal temperature (8 [72.7%]), abnormal blood pressure, systolic (7 [63.6%]) and diastolic (7 [63.6%]), abnormal pulse rate (9 [81.8%]), abnormal respiratory rate (8 [72.7%]), and normal saturation (6 [54.5%]). We also did a laboratory check followed by all sepsis patients who had abnormal leukocytes (11 [100%]), and abnormal lymphocytes count (8 [72.7%]).Conclusions: The mortality rate and prevalence of sepsis in children with ALL in our institution are still high. Further prospective studies are required to explore the risk factors and predictors of sepsis based on its severity and adherence of health workers to implement guidelines on patients with sepsis in the hospital.

Molecular characterization of Staphylococcus aureus isolated from hospital acquired sepsis in pediatrics, relation to antibiotics, resistance and virulence genes.

The objective of this study was to determine the prevalence of antibiotic resistance genes mecA, vanA, B, C and virulence genes Panton-Valentine Leucocidin (PVL) and fibronectin-binding protein (fnBPA) among S. aureus isolates from hospital-acquired sepsis from pediatric intensive care units. The study was a retrospective cross-sectional study, including 250 unique isolates of S. aureus obtained from pediatric patients with hospital-acquired sepsis. The isolates were subjected to study of antibiotic susceptibility by disc diffusion method and molecular analysis of antibiotic resistance genes and certain virulence genes (PVL and fnBPA genes). Methicillin resistant S. aureus represented 178 (71%) of the isolated S. aureus and reduced susceptibility to vancomycin was detected by minimum inhibitory concentration in 39 (22%) isolates. It was found that there was a strong association between the MRSA strains and resistance to some antibiotics, devices association (p<0.001) and patient outcomes (p=0.003). There was a significant association between reduced vancomycin susceptibility (p=0.010), the presence of a central line catheter (p=0.000) and fnBPA gene (p<0.001) and mortality rate. The present study highlights that major S. aureus strains isolated from sepsis in pediatric patients were methicillin resistant with a substantial proportion of reduced susceptibility to vancomycin. Although none of the isolates had van genes responsible for vancomycin resistance, this finding warrants a considerable attention for study as it was a risk factor for mortality in those patients. The virulence genes fibronectin-binding protein and Panton-Valentine Leucocidin were not uncommon in S. aureus.

LncRNA SOX2OT rs9839776 Polymorphism Reduces Sepsis Susceptibility in Southern Chinese Children.

BackgroundSepsis in children is one of the main causes of death in pediatric intensive care units (PICUs); however, the pathogenesis of sepsis is not fully clear. Previous studies revealed that many genetic variations were related to sepsis susceptibility. A long non-coding RNA SOX2 overlapping transcript (SOX2OT) may play a role in mitochondrial homeostasis and antioxidative activity, but the relationship between the lncRNA SOX2OT polymorphism and sepsis susceptibility has not been reported.MethodsIn this study, 474 pediatric sepsis patients and 678 healthy controls were recruited from southern China. After genotyping, the strength of the associations was evaluated through odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe SOX2OT rs9839776 T allele was associated with decreased susceptibility to sepsis in southern Chinese children (TT/CT vs CC adjusted OR = 0.778, 95% CI = 0.610–0.992; P = 0.0431). Moreover, the difference in susceptibility was greater in children of age >60 months (adjusted OR = 0.458, 95% CI = 0.234–0.896; P = 0.0225), survivors (adjusted OR = 0.758, 95% CI = 0.585–0.972; P = 0.0358), males (adjusted OR = 0.655, 95% CI = 0.479–0.894; P = 0.0077) and the sepsis subgroup (adjusted OR = 0.548, 95% CI = 0.343–0.876; P = 0.0120).ConclusionThe rs9839776 T allele may contribute to decreased sepsis risk in Chinese children. Future studies with a larger sample size are needed to verify these results.

Comparison of pediatric scoring systems for mortality in septic patients and the impact of missing information on their predictive power: a retrospective analysis.

BackgroundScores can assess the severity and course of disease and predict outcome in an objective manner. This information is needed for proper risk assessment and stratification. Furthermore, scoring systems support optimal patient care, resource management and are gaining in importance in terms of artificial intelligence.ObjectiveThis study evaluated and compared the prognostic ability of various common pediatric scoring systems (PRISM, PRISM III, PRISM IV, PIM, PIM2, PIM3, PELOD, PELOD 2) in order to determine which is the most applicable score for pediatric sepsis patients in terms of timing of disease survey and insensitivity to missing data.MethodsWe retrospectively examined data from 398 patients under 18 years of age, who were diagnosed with sepsis. Scores were assessed at ICU admission and re-evaluated on the day of peak C-reactive protein. The scores were compared for their ability to predict mortality in this specific patient population and for their impairment due to missing data.ResultsPIM (AUC 0.76 (0.68–0.76)), PIM2 (AUC 0.78 (0.72–0.78)) and PIM3 (AUC 0.76 (0.68–0.76)) scores together with PRSIM III (AUC 0.75 (0.68–0.75)) and PELOD 2 (AUC 0.75 (0.66–0.75)) are the most suitable scores for determining patient prognosis at ICU admission. Once sepsis is pronounced, PELOD 2 (AUC 0.84 (0.77–0.91)) and PRISM IV (AUC 0.8 (0.72–0.88)) become significantly better in their performance and count among the best prognostic scores for use at this time together with PRISM III (AUC 0.81 (0.73–0.89)). PELOD 2 is good for monitoring and, like the PIM scores, is also largely insensitive to missing values.ConclusionOverall, PIM scores show comparatively good performance, are stable as far as timing of the disease survey is concerned, and they are also relatively stable in terms of missing parameters. PELOD 2 is best suitable for monitoring clinical course.

Evaluating the Therapeutic Efficacy and Safety of Landiolol Hydrochloride for Management of Arrhythmia in Critical Settings: Review of the Literature.

BackgroundLandiolol hydrochloride, a highly cardio-selective beta-1 blocker with an ultra-short-acting half-life of 4 minutes, was originally approved by Japan for treatment of intraoperative tachyarrhythmias. This review aims to provide an integrated overview of the current state of knowledge of landiolol hydrochloride in the management of arrhythmia in critical settings.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library to retrieve relevant articles with a total of 65 records identified.ResultsThe high β1 selectivity (β1/β2 ratio of 255:1) of landiolol causes a more rapid heart rate (HR) decrease compared to esmolol while avoiding decreases in mean arterial blood pressure. Recently, it has been found useful in left ventricular dysfunction patients and fatal arrhythmia requiring emergency treatment. Recent random clinical trials (RCT) have revealed therapeutic and prophylactic effects on arrhythmia, and very low-dose landiolol might be effective for preventing postoperative atrial fibrillation (POAF) and sinus tachycardia. Likewise, landiolol is an optimal choice for perioperative tachycardia treatment during cardiac surgery. The high β1 selectivity of landiolol is useful in heart failure patients as a first-line therapy for tachycardia and arrhythmia as it avoids the typical depression of cardiac function seen in other β-blockers. Application in cardiac injury after percutaneous coronary intervention (PCI), protection for vital organs (lung, kidney, etc.) during sepsis, and stabilizing hemodynamics in pediatric patients are becoming the new frontier of landiolol use.ConclusionLandiolol is useful as a first-line therapy for the prevention of POAF after cardiac/non-cardiac surgery, fatal arrhythmias in heart failure patients and during PCI. Moreover, the potential therapeutic effect of landiolol for sepsis in pediatric patients is currently being explored. As positive RCT results continue to be published, new clinical uses and further clinical studies in various settings by cardiologists, intensivists and pediatric cardiologists are being conducted.

Long noncoding RNA and messenger RNA abnormalities in pediatric sepsis: a preliminary study

BackgroundSepsis represents a complex disease with dysregulated inflammatory response and high mortality rate. Long noncoding RNAs (lncRNAs) have been reported to play regulatory roles in a variety of biological processes. However, studies evaluating the function of lncRNAs in pediatric sepsis are scarce, and current knowledge of the role of lncRNAs in pediatric sepsis is still limited. The present study explored the expression patterns of both lncRNAs and mRNAs between pediatric sepsis patients and healthy controls based on a comprehensive microarray analysis.MethodsLncRNA and mRNA microarray was used to detect the expression of lncRNAs and mRNAs in the septic and control groups. Aberrantly expressed mRNAs and lncRNAs identified were further interpreted by enrichment analysis, receiver operating characteristic (ROC) curve analysis, co-expression network analysis, and quantitative real-time PCR (qPCR).ResultsA total of 1488 differetially expressed lncRNAs and 1460 differentially expressed mRNAs were identified. A co-expression network of the identified lncRNAs and mRNAs was constructed. In this network, lncRNA lnc-RP11-1220 K2.2.1–7 is correlated with mRNA CXCR1 and CLEC4D; lncRNA lnc-ANXA3–2 is correlated with mRNA CLEC4D; lncRNA lnc-TRAPPC5–1 is correlated with mRNA DYSF and HLX; lncRNA lnc-ZNF638–1 is correlated with mRNA DYSF and HLX. Significantly different expressions between pediatric sepsis patients and controls were validated by qPCR for the 4 lncRNAs and 4 co-expressed mRNAs, validating the microarray results.ConclusionsOur study contributes to a comprehensive understading of the involvment of lncRNAs and mRNAs in pediatric sepsis, which may guide subsequent experimental research. Furthermore, our study may also provide potential candidate lncRNAs and mRNAs for the diagnosis and treatment of pediatric sepsis.

Bacterial and Fungal Etiology of Sepsis in Children in the United States: Reconsidering Empiric Therapy.

Timely empiric antimicrobial therapy is associated with improved outcomes in pediatric sepsis, but minimal data exist to guide empiric therapy. We sought to describe the prevalence of four pathogens that are not part of routine empiric coverage (e.g., Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium difficile, and fungal infections) in pediatric sepsis patients in a contemporary nationally representative sample. This was a retrospective cohort study using administrative data. We used the Nationwide Readmissions Database from 2014, which is a nationally representative dataset that contains data from nearly half of all discharges from nonfederal hospitals in the United States. Discharges of patients who were less than 19 years old at discharge and were not neonatal with a discharge diagnosis of sepsis. None. Of the 19,113 pediatric admissions with sepsis (6,300 [33%] previously healthy and 12,813 [67%] with a chronic disease), 31% received mechanical ventilation, 19% had shock, and 588 (3.1%) died during their hospitalization. Among all admissions, 8,204 (42.9%) had a bacterial or fungal pathogen identified. S. aureus was the most common pathogen identified in previously healthy patients (n = 593, 9.4%) and those with any chronic disease (n = 1,430, 11.1%). Methicillin-resistant S. aureus, P. aeruginosa, C. difficile, and fungal infections all had high prevalence in specific chronic diseases associated with frequent contact with the healthcare system, early surgery, indwelling devices, or immunosuppression. In this nationally representative administrative database, the most common identified pathogen was S. aureus in previously healthy and chronically ill children. In addition, a high proportion of children with sepsis and select chronic diseases had infections with methicillin-resistant S. aureus, fungal infections, Pseudomonas infections, and C. difficile. Clinicians caring for pediatric patients should consider coverage of these organisms when administering empiric antimicrobials for sepsis.

Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches. Retrospective, observational cohort study. PICU and cardiac ICU, Seattle Children's Hospital, Seattle, WA. A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction. None. Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis. The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.