RETICULAR DYSGENESIS IN A PRETERM INFANT: A Case Report

Reticular dysgenesis (RD) is a rare congenital immunodeficiency classified within the severe combined immunodeficiencies (SCIDs) and characterized by impairment of both lymphoid and myeloid cell development. Neutropenia unresponsive to recombinant human granulocyte colony-stimulating factor (rGCSF) is the hallmark of RD and the clinical course is rapidly fatal due to overwhelming infections. The authors report a female newborn at 32 weeks of gestation presenting with severe leukopenia at birth. The bone marrow showed a maturation arrest in the myeloid and lymphoid lineage. She had no response to granulocyte colony stimulating factor (rGCSF) treatment and died with sepsis at age of 2 months.     

Activation of the L-arginine nitric oxide pathway in severe sepsis

AIMS: To determine in children with sepsis syndrome and septic shock the time course of nitric oxide metabolites: nitrate and nitrite (nitrogen oxides). To determine whether serum concentrations of nitrogen oxides distinguished those children who died from sepsis from those who survived; those who required prolonged inotropic support compared with those who did not; and whether there was any relationship of the levels of nitrogen oxides to markers of tissue perfusion. METHODS: Nitrogen oxides were measured in 30 children with sepsis syndrome or septic shock at admission, 12, 24, and 48 hours. A non-septic control group had serum nitrogen oxides measured at admission. Markers of haemodynamics and tissue perfusion measured were mean arterial pressure, blood lactate, base deficit, gastric intramucosal pH, and deltaCO2 (DCO2: the difference between arterial and gastric intraluminal carbon dioxide tensions). Inotrope doses, number of organ systems failing at 48 hours, and outcome as survival were recorded. RESULTS: Children with sepsis had increased nitrogen oxide concentrations at presentation compared with a group of non-septic controls. Children with organ failure at 48 hours had higher serum nitrogen oxide concentrations than those with sepsis uncomplicated by organ failure at 48 hours. There was no difference in nitrogen oxide when patients were subgrouped according to the receipt of inotropes at 48 hours, and no association with markers of tissue perfusion, or survival. CONCLUSIONS: While this study shows that nitric oxide production is increased in sepsis in children, there was a limited relationship with clinically important markers of illness severity and no relationship to survival.     

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.     

Epidemiology of neonatal sepsis in South Korea

Background:  Neonatal sepsis is a severe clinical syndrome characterized by systemic signs of infection, shock and system organ failure; diagnosis is confirmed on positive culture from a normally sterile site(s). There are few reports comparing incidence, mortality, and risk factors between clinically diagnosed sepsis and that confirmed by culture.
Methods:  All infants diagnosed with early- (within first 72 h after birth) or late-onset (72 h–4 weeks after birth) neonatal sepsis between 1997 and 1999 from four neonatal centers in South Korea, were investigated.
Results:  The estimated incidence rate of neonatal sepsis during the 3 years was 30.5 per 1000 live births for clinical sepsis and 6.1 per 1000 live births for sepsis with positive culture, with case-fatality rates of 4.7% and 2.2%, respectively. When only early-onset sepsis was considered, the incidence and fatality rates were 25.1 per 1000 live births and 6.1% for clinical sepsis, and 4.3 per 1000 live births and 2.5% for culture-confirmed sepsis, respectively. For the 179 patients (185 causative organisms) of proven sepsis, Staphylococcus spp. including S. aureus were the most frequent isolates. In early-onset clinical sepsis, having very low birthweight (≤1500 g), a low Apgar score at 5 min (≤7), and being male were related to higher rates of case-fatality (relative risk: 11.3, 6.8 and 2.5, respectively)
Conclusions:  Clinical sepsis was more common than culture-confirmed sepsis and had a higher case-fatality rate. It seems prudent to take rapid and decisive steps toward better management of the high-risk group whether the sepsis is clinically diagnosed or culture confirmed.     

Nasal continuous positive airway pressure versus nasal intermittent positive pressure ventilation for preterm neonates: a systematic review and meta-analysis

Aim: To determine whether nasal intermittent positive pressure ventilation (NIPPV) is more effective in preterm infants than nasal continuous positive airway pressure (NCPAP) in reducing the rate of extubation failure following mechanical ventilation, and reducing the frequency of apnoea of prematurity and subsequent need for endotracheal intubation. Methods: Randomized trials of NIPPV versus NCPAP were sought and their data extracted and analysed independently by the authors using the methodology of the Cochrane Collaboration. The analysis used relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals. Results: The three studies identified, comparing NIPPV with NCPAP in the postextubation period, all used synchronized NIPPV (SNIPPV), which was more effective than NCPAP in preventing failure of extubation [RR 0.21 (0.10, 0.45), RD 30.32 (30.45, 30.20), NNT 3 (2, 5)]. Two studies compared NIPPV versus NCPAP for the treatment of apnoea of prematurity. Although meta-analysis was not possible one trial showed a reduction in apnoea frequency with NIPPV and the other a trend favouring NIPPV. Conclusion: SNIPPV is an effective method of augmenting the beneficial effects of NCPAP in preterm infants in the postextubation period. Further research is required to delineate the role of NIPPV in the management of apnoea of prematurity.     

3-Day versus 5-Day Course of Intravenous Antibiotics for Suspected Early Onset Neonatal Sepsis: A Randomized Controlled Trial

Objective:

The objective of this randomized controlled trial was to compare the treatment failure of suspected early onset neonatal sepsis with either 3-day or 5-day course of empirical antibiotic therapy.

Methods:

Infants with birth weight over 1500 g and/or gestational age over 34 weeks within 7 days postnatal age with clinical symptoms of neonatal sepsis received empirical antibiotics (Ampicillin + Amikacin) in two neonatal intensive care units. After 72 hours if the result of blood culture was negative and symptoms resolved they were randomly allocated to 3-day or 5-day groups. The main outcome was treatment failure which was defined as reappearance of symptoms of sepsis within two weeks after discontinuation of antibiotics. Infants with congenital anomalies, localized infections, asphyxia, those undergoing surgery or when serum C-reactive protein levels remained abnormal despite treatment, were not included. Randomization was accomplished with simple randomization procedure.

Findings:

Sixty patients were randomized in a 1:1 ratio to either group. Baseline characteristics were similar between two groups. The follow-up period was 2 weeks with no lost to follow-up. One infant in 3-day group had treatment failure compared with no treatment failure in 5-day group (P=0.5). No serious harm was observed due to our empirical antibiotic regimen.

Conclusion:

The results of this study indicated no evidence that treatment failure differs between 3-day and 5-day course antibiotic therapy for suspected early onset uncomplicated neonatal sepsis in late preterm and term newborns.     

Plasma concentrations of defensins and lactoferrin in children with severe sepsis.

BACKGROUND: We hypothesized that systemic release of endogenous leukocyte-derived polypeptide antimicrobial defensins (polymorphonuclear leukocyte-specific) and lactoferrin (polymorphonuclear leukocyte and epithelial cell derived) occurs in nonneutropenic children with severe sepsis. METHODS: We performed a prospective cross-sectional and longitudinal study in a university children's hospital pediatric intensive care unit. Ninety-two consecutive children meeting criteria for sepsis and 14 critically ill children without sepsis (controls) were enrolled, and plasma defensins and lactoferrin concentrations were measured on Days 1 and 3 of sepsis. RESULTS: Nonneutropenic sepsis patients (n = 71) had increased defensins and lactoferrin plasma concentrations compared with critically ill control patients [defensins, 450 ng/ml vs. 150 ng/ml; lactoferrin, 332 ng/ml vs. 176 ng/ml (median values); P < 0.05] and neutropenic sepsis patients [n = 21; defensins, 450 ng/ml vs. 50 ng/ml; lactoferrin, 332 ng/ml vs. 20 ng/ml (median values); P < 0.05]. Neutropenic sepsis patients had similar plasma defensin concentrations and a decrease in plasma lactoferrin concentrations compared with control patients (P < 0.05). Defensins and lactoferrin plasma concentrations correlated to total white blood cell and absolute neutrophil count (P < 0.05). There was no association between plasma defensin concentration and organ failure or outcome; however, increased plasma lactoferrin concentrations were observed with the development of organ failure (P < 0.05). CONCLUSION: These data suggest that increased circulating defensins and lactoferrin release are dependent in part on neutrophil count and might play a role in host defense in children with severe sepsis.     

Meconium-stained amniotic fluid and meconium aspiration syndrome: a prospective study

BACKGROUND: The incidence of meconium aspiration syndrome (MAS), associated perinatal factors, morbidity and deaths varies widely. This study aimed to assess the perinatal attributes and morbidity associated with MAS. METHODS: Over a 2-year period, all neonates born through meconium-stained amniotic fluid (MSAF) were observed for respiratory distress (RD). Birth details, chest radiograph (CXR) and clinical course were documented. Neonates with consistent CXR findings whose RD could not otherwise be explained were defined as MAS. RESULTS: Of 409 neonates born through MSAF, meconium was thick in 196 (47.9%). Fifty-five (13.4%) had RD and 45 (11.3%) were consistent with MAS. Six (1.5%) neonates died. Mean (SD) birthweight and gestation of MAS infants were 2721.9 (510.2) g and 38.67 (1.09) weeks, respectively. About one-third were of low birthweight and 28 were born by caesarean section. On univariate analysis, caesarean delivery, meconium in the trachea and thick meconium were the significant perinatal factors for the development of MAS. On multiple regression analysis, thick meconium was the only independent factor for MAS (OR 7.08, 95% CI 3.08-16.27, p<0.001). An Apgar score of 相似文献   

Group B <Emphasis Type="Italic">Streptococcus</Emphasis> causes severe sepsis in term neonates: 8 years experience of a major Chinese neonatal unit

Background:In contrast to industrialized countries,the clinical characteristics of neonatal sepsis caused by Group B Streptococcus (GBS) are largely unexplored in China.Methods:A retrospective case series study was performed at a high-capacity neonatal unit in Shanghai,China from January 2008 to December 2015.Clinical characteristics of neonates with culture-proven GBS sepsis and antibiotic susceptibility of isolated strains were analyzed.Results:Forty-three term neonates were included during the study period.The majority (74.4％) had early-onset sepsis with symptoms of respiratory distress.Meningitis was significantly more common in lateonset sepsis than in early-onset sepsis (81.5％ vs.18.8％,P＜0.0001).Approximately one third of all patients (n=16)developed severe sepsis,defined as sepsis with organ dysfunctions,and respiratory dysfunction/failure was the most common (32.6％).The in-hospital mortality rate of GBS sepsis was 4.7％.Neonates who progressed to severe sepsis had significantly lower pH level at the onset of symptoms than those who did not (7.26±0.12 vs.7.39±0.05,P=-0.006).Treatment of severe GBS sepsis required lots of medical resources including extracorporeal membrane oxygenation.All tested GBS strains were susceptible to penicillin,but the rate of resistance to clindamycin (84.0％) and erythromycin (88.0％) was high.Conclusions:GBS as a pathogen for neonatal sepsis has been receiving little attention in China.Our data demonstrated that GBS sepsis was likely to be fulminant.Early recognition followed by antibiotics and adequate supportive therapies was critical for successful treatment.Chinese clinicians should be aware of GBS infection when treating neonatal sepsis,especially in the absence of universal maternal GBS screening.     

Attention deficit hyperactivity disorder with reading disabilities: preliminary genetic findings on the involvement of the ADRA2A gene

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) and reading disability (RD) tend to co-occur and quantitative genetic studies have shown this to arise primarily through shared genetic influences. However, molecular genetic studies have shown different genes to be associated with each of these conditions. Neurobiological studies have implicated noradrenergic function in the aetiology of ADHD that is comorbid with RD. This paper examines the neurobiological evidence and presents preliminary testing of the hypothesis that the ADRA2A receptor gene is contributing to ADHD and comorbid RD. METHODS: One hundred and fifty-two children (140 boys, 12 girls) of British Caucasian origin, aged between 6 and 13 years and with a diagnosis of ADHD, were recruited. The children's reading ability was tested. Children were identified as having ADHD or ADHD plus RD (n=82). DNA was available for 110 parent child trios and 42 parent child duos. Genotyping was undertaken for an ADRA2A polymorphism. RESULTS: For those with ADHD plus RD there was evidence of association with the alpha 2A adrenergic receptor (ADRA2A) polymorphism with the G allele being preferentially transmitted. CONCLUSIONS: The preliminary evidence together with other neurobiological research findings suggests that the ADRA2A gene may contribute to comorbid ADHD and RD and needs to be properly examined.     

Recombinant human activated protein C for the treatment of severe sepsis: is there a role in pediatrics?

Sepsis with organ failure (severe sepsis) remains an important cause of morbidity and mortality among children. The clinical pathophysiology of severe sepsis reflects a coordinated activation of the innate immune response, including elaboration of proinflammatory cytokines and the induction of the extrinsic pathway of coagulation (sepsis-induced coagulopathy). These proinflammatory and procoagulant pathways are linked, and are similarly coregulated by a number of proteins and factors, including protein C. However, at least 80% of children and adults with severe sepsis develop acquired deficiency of protein C because of factor consumption. This deficiency is associated with poor outcomes, including multiple organ failure and mortality. Recently, recombinant activated protein C was shown to reduce the mortality of adults with severe sepsis, and is now approved for such use in the United States and Europe. The rationale for pediatric applications of protein C and ongoing clinical trials in children are reviewed.     

The relationship between attention, executive functions and reading domain abilities in attention deficit hyperactivity disorder and reading disorder: a comparative study

BACKGROUND: Co-morbidity of attention deficit hyperactivity disorder (ADHD) and reading disorder (RD) is frequent. The objective of this investigation was to assess the potential uniqueness of co-morbid ADHD + RD and extend existing findings to the Hebrew language. METHOD: A parallel group design with post-hoc analysis of group differences was employed comparing four groups of children (19 ADHD, 17 RD, 27 ADHD + RD, and 23 controls) on reading measures, attention and executive functions (EF) as well as functions of phonemic awareness and rapid naming. Forward stepwise regressions were run in order to delineate significant relationships between phonemic awareness, rapid naming, attention and EF with outcome variables of reading. RESULTS: The co-morbid group shared the basic characteristic impairments in attention and executive functions with the pure ADHD group and in reading domain functions with the pure RD group. In addition, this group showed unique deficits in rapid naming and a more severe impairment in working memory. Forward stepwise regression pointed to associations between executive functions and word reading accuracy in children with ADHD, in contrast to associations between linguistic functions and word accuracy in non-ADHD. CONCLUSION: The combination of cognitive deficits in the subgroup of children with both ADHD and RD and the relationship between accuracy in word decoding and executive functions shown for the ADHD groups point to a distinct clinical profile of the co-morbid condition. Attention and EF should be considered in the diagnosis of RD and in the remediation protocol.     

Kana reading disability and Das–Naglieri Cognitive Assessment System findings in children with attention deficit hyperactivity disorder

Background: Epidemiological and clinical studies suggest that attention deficit hyperactivity disorder (ADHD) and reading disability co‐occur more frequently than would be expected by chance. The purposes of this study were to (i) assess the frequency of Japanese syllabary (Kana) reading disability (RD) and (ii) measure the psychometric properties of the Das–Naglieri Cognitive Assessment System (DN‐CAS) in a clinic‐referred sample of Japanese children with ADHD. Methods: Twenty children with ADHD aged 8–13 years were evaluated using both Kana reading tasks and the DN‐CAS. Results: Seven children (35%) showed excessive reading time in at least two of four Kana reading tasks and were diagnosed as ADHD plus RD. The children with ADHD plus RD took significantly longer to read a single mora, four‐syllable words, and short sentences. There was no significant difference in the time it took the children with ADHD plus RD to read four‐syllable non‐words compared to the children with ADHD only. The children with ADHD plus RD had significantly lower simultaneous‐processing scores in the DN‐CAS compared to children with ADHD but not RD. Conclusion: Children with ADHD should be given Kana reading tasks because RD is highly comorbid with ADHD. DN‐CAS is a useful method for evaluating cognitive processing in children with ADHD with or without RD.     

Neuropsychological profiles of adolescents with ADHD: effects of reading difficulties and gender

BACKGROUND: Executive function, particularly behavioral inhibition, has been implicated as a core deficit specific to Attention-Deficit/Hyperactivity Disorder (ADHD) whereas rapid naming has been implicated as a core deficit specific to reading disabilities (RD). Females may be less impaired in executive function although adolescent females with ADHD have yet to be studied. METHOD: Neuropsychological profiles of four adolescent groups aged 13-16 with equal female representation were investigated: 35 ADHD, 12 RD, 24 ADHD+RD, and 37 normal controls. A semi-structured interview (K-SADS-PL), the Conners Rating Scales and the Ontario Child Health Study Scales were used to diagnose ADHD. RD was defined as a standard score below 90 on at least one of the following: Reading or Spelling of the WRAT3 or Word Attack or Word Identification of the WRMT-R. The WISC-III, Rapid Automatized Naming, Stroop and Stop tasks were used as measures of cognitive and executive function. RESULTS: The two ADHD groups (ADHD, ADHD+RD) showed deficits in processing speed, naming of objects, poor behavioral inhibition and greater variability in reaction times whereas the two RD groups (RD, RD+ADHD) showed verbal working memory deficits and slower verbal retrieval speed. Only the comorbid group was slower with naming of numbers and colors and had slower reaction times. Regression analyses indicated that incongruent color naming (Stroop) and variability in go reaction time were the best predictors of hyperactive/impulsive ADHD symptoms whereas variability in go reaction time and processing speed were the best predictors of inattentive ADHD symptoms. Speed of letter naming and verbal working memory accounted for the most variability in composite achievement scores. No gender differences were found on any of the cognitive tests. CONCLUSIONS: This study challenges the importance of behavioral inhibition deficits in ADHD and that naming deficits are specific to RD. Further investigation into cognitive deficits in these groups is required.     

Increasing incidence of respiratory distress in neonates

AIM: To document the change in the incidence of respiratory distress (RD), related interventions and mortality in neonates admitted to primary, secondary and tertiary neonatal units within a geographically defined population over a period of 30 years. METHODS: RD was defined as a clinical picture irrespective of the etiology. Information was collected retrospectively for 1974, 1984, 1994 and 2004 from all neonatal units in Switzerland. RESULTS: In the 30 years studied the proportion of infants hospitalized with RD increased from 1.9% to 3.8% of the whole neonatal population and from 30% to 53% of all infants admitted to a neonatal unit. Treatment of RD changed significantly. Mechanical ventilation decreased from 31% to 16%, nasal CPAP increased from almost 0% to 26% and surfactant administration increased from 0% to 53% in infants with hyaline membrane disease. Overall mortality decreased in infants with RD from 15.5% to 3.5%. CONCLUSIONS: The incidence of RD in infants admitted to neonatal units doubled over the last 30 years in a geographically defined neonatal population. This rise can predominantly be ascribed to infants with birth weight >2500 g and may reflect the corresponding increase in the rate of caesarean section.     

Linkage of speech sound disorder to reading disability loci

BACKGROUND: Speech sound disorder (SSD) is a common childhood disorder characterized by developmentally inappropriate errors in speech production that greatly reduce intelligibility. SSD has been found to be associated with later reading disability (RD), and there is also evidence for both a cognitive and etiological overlap between the two disorders. The present study tested whether SSD is linked to replicated risk loci for RD. METHOD: One hundred and eleven probands with SSD and their 76 siblings were tested with measures of speech, phonological memory (Nonword Repetition-NWR), and phonological awareness and genotyped for linkage markers on chromosomes 1p36, 6p22, and 15q21. Both single point and multipoint linkage were tested with multiple methods. RESULTS: The speech and NWR phenotypes were linked to the RD loci on chromosomes 6 and 15, with suggestive results for the RD locus on chromosome 1. CONCLUSIONS: It now appears that several RD loci are pleiotropic for SSD, extending the findings of Stein et al. (2004) for the RD locus on Chromosome 3.     

小儿严重脓毒症并发多器官功能障碍综合征的研究

目的 小儿脓毒症是PICU的常见疾病,具有较高的病死率.本研究旨在了解小儿脓毒症的临床特点及转归,探寻儿童严重脓毒症的死亡危险因素.方法 分析2008年1月至12月收入我院PICU的脓毒症病例,对严重脓毒症患儿作单因素分析,并建立Logistic回归模型,探寻儿童严重脓毒症的死亡危险因素.结果 纳入脓毒症患儿103例,病死率16.5%.严重脓毒症45例,其死亡危险因素是PRISM Ⅲ评分(OR 1.502;95%CI 1.131～1.995)和病程中外周血血小板计数最高值(OR 0.991;95%CI0.982～1.000).小儿严重脓毒症伴随1、2、3、4个及4个以上脏器功能障碍的病死率分别为10.0%、11.1%、44.4%、68.8%,差异具有非常显著性(P＜0.001).最常受累的是心血管系统(75.6%)和呼吸系统(66.7%),严重脓毒症伴发MODS死亡危险因素是呼吸系统(OR 23.179;95%CI2.095～256.522)和肾脏(OR 9.637;95%CI 1.698～54.703)功能受累.结论 小儿严重脓毒症的死亡危险因素是PRISM Ⅲ评分和病程中外周血血小板计数最高值.小儿脓毒症合并MODS提示预后不良,其病死率与发生功能障碍的脏器数目呈正相关,呼吸系统和肾脏功能受累是儿童脓毒症死亡的危险因素.     

Allogeneic hemopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission-similar outcomes after matched related and unrelated donor transplant: a study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon)

The authors report the results of 58 children with ALL in 2CR after related (n = 31) or unrelated (n = 27) AHSCT. Characteristics at diagnosis and initial and after relapse antileukemic treatment were similar in the related donor (RD) and the unrelated donor (UD) groups. Conditioning consisted of TBI/CY +/- VP-16 for patients > or = 3 years old (n = 43) and Bu/CY for the rest. Median recipient age was 8 years (range 1-17) in the RD and 9 years (range 3-14) in the UD group. Median follow-up was 54 months (range 24-80) and 52 months (range 22-85) in the RD and the UD groups repectively. The 5-year EFS probability was 43 +/- 9% for the RD group and 36 +/- 9% in the UD group (p = .25). The transplant-related mortality was 16% in the RD and 37% in the UD group (p = .016). In the RD group 36.7% of patients relapsed versus 18.6% in the UD group (p = .05). GvHD associated with organ failure or infection caused most of the transplant-related deaths in both groups. Survivor quality of life for both groups was good (Lansky score < or = 90).     

sFas and sFas ligand and pediatric sepsis-induced multiple organ failure syndrome

The Fas-Fas ligand system is important for apoptosis of activated immune cells. Perturbation of this system occurs in diseases with dysregulated inflammation. Increased soluble Fas (sFas) occurs in systemic inflammatory response syndrome (SIRS) and can block apoptosis. Increased shedding of FasL (sFasL) occurs in viral infection and hepatitis. Although dysregulated inflammation is associated with sepsis-induced multiple organ failure (MOF) in children, a role for Fas has not been established. We hypothesize that 1) sFas will be increased in children with severe and persistent sepsis-induced MOF and will correlate with inflammatory markers suggesting a role for sFas in inflammatory dysregulation in severe sepsis, and 2) sFasL will be increased when viral sepsis or sepsis-induced liver failure-associated MOF is present in children. Plasma sFas, sFasL, IL-6, IL-10, nitrite + nitrates, and organ failure scores were measured on d 1 and d 3 in 92 children with severe sepsis and 12 critically ill control children. sFas levels were increased in severe sepsis, continued to increase in persistent MOF and nonsurvivors, and were correlated with serum inflammatory markers (IL-6, IL-10, nitrite + nitrate levels). In contrast, sFasL was not increased in severe sepsis and did not correlate with inflammation. sFasL was, however, increased in liver failure-associated MOF and in nonsurvivors, and was associated with viral infection. At autopsy, hepatocyte destruction and lymphocyte infiltration were associated with increased sFas and sFasL levels. sFas may interfere with activated immune cell death and contribute to dysregulation of inflammation, worsening outcome from severe sepsis. sFasL may contribute to hepatic injury and the development of liver failure-associated MOF.