Drug cost implications for antibiotic prophylaxis for dental procedures.

OBJECTIVE: To determine the potential economic impact from the practice of antibiotic prophylaxis for dental procedures. STUDY DESIGN: We estimated the prevalence of patients in the United States with 15 medical conditions and devices. We multiplied the prevalence for each patient population by the percentage of specialists recommending prophylaxis, then by the estimated number of dental office visits per year, and then by an average pharmacy cost to arrive at a total estimated range of annual cost for this practice. RESULTS: The 15 medical conditions and devices included in the present study involve upward of 20 million people and an estimated annual cost between $19,880,279 and $143,685,823. The actual cost may be far greater because of an underestimation of these prevalence figures and the use of antibiotic prophylaxis for additional patient populations. CONCLUSIONS: Our data suggest a significant cost for antibiotic prophylaxis in the dental practice setting and the need for evidence-based recommendations concerning this practice.

Cancer incidence among residents of the Three Mile Island accident area: 1982-1995.

BACKGROUND: The Pennsylvania Department of Health established a registry of the Three Mile Island (TMI) nuclear power plant accident in 1979. Over 93% of the population present on the day of the accident within a 5-mile radius was enrolled and interviewed. We used the registry to investigate the potential cancer risk from low-dose radiation exposure among the TMI population. METHODS: Cancer incidence data among the TMI cohort were available from 1982 to 1995. Because more than 97% of the population were white and few cancer cases were reported for those younger than 18 years of age, we included whites of age 18 years and older (10,446 men and 11,048 women) for further analyses. Cox regression models were used to estimate the relative risk (RR) per 0.1 mSv and 95% confident interval (CI) of cancer by radiation-related exposures. The cancers of interest were all malignant neoplasms, cancer of bronchus, trachea, and lung, cancer of lymphatic and hematopoietic tissues, leukemia, and female breast. RESULTS: Among men and women, there was no evidence of an increased risk for all malignant neoplasms among the TMI cohort exposed to higher maximum and likely γ radiation (RR=1.00, 95% CI=0.97, 1.01 and RR=0.99, 95% CI=0.94, 1.03, respectively) after adjusting for age, gender, education, smoking, and background radiation. Elevation in risk was noted for cancer of the bronchus, trachea, and lung in relation to higher background radiation exposure (RR=1.45, 95% CI=1.02-2.05 at 8.0-8.8 µR/h compared to 5.2-7.2 µR/h). An increased risk of leukemia was found among men exposed to higher maximum and likely γ radiation related to TMI exposure during the ten days following the accident (RR=1.15, 95% CI=1.04, 1.29 and RR=1.36, 95% CI=1.08, 1.71, respectively). This relationship was not found in women. CONCLUSION: Increased cancer risks from low-level radiation exposure within the TMI cohort were small and mostly statistically non-significant. However, additional follow-up on this population is warranted, especially to explore the increased risk of leukemia found in men.

The outcome of unintentional pediatric bupropion ingestions: a NPDS database review.

Unintentional bupropion pediatric exposures uncommonly report severe clinical effects such as seizures. We sought to determine the clinical effects and case outcomes for unintentional bupropion ingestions in children age

Skeletal traction versus external fixation in the initial temporization of femoral shaft fractures in severely injured patients.

BACKGROUND: : Damage control with external fixation (DC-EF) of femoral shaft fractures in polytrauma patients is becoming standard treatment in many trauma centers. However, skeletal traction (ST) has long been used in the temporization of fractures. The purpose of this study was to compare the major physiologic clinical outcomes of provisional ST with DC-EF of femoral shaft fractures in severely injured patients. METHODS: : We retrospectively reviewed 205 patients sustaining blunt trauma, a femoral shaft fracture, and an Injury Severity Score > or =17 from 2001 to 2007 at a level I trauma center. Patients underwent definitive fixation in the first 24 hours with intramedullary nailing (IMN) (N = 126), initial DC-EF with delayed definitive treatment (N = 19), or initial ST with delayed definitive treatment (N = 60). Incidences of adult respiratory distress syndrome, multiple organ failure, sepsis, pneumonia, pulmonary embolism, and deep vein thrombosis were evaluated. Length of stay (LOS), intensive care unit LOS, days of mechanical ventilation, and mortality were also compared. RESULTS: : There were no significant differences between ST and DC-EF groups in age, mechanism of injury, Injury Severity Score, Glasgow Coma Scale score on arrival, mean time to definitive fixation (4.1 days versus 5.0 days, respectively), or Abbreviated Injury Scale for chest. However, the ST group had a higher Abbreviated Injury Scale-head (2.5 versus 1.0, p = 0.0026). There were no significant differences in subsequent rates of adult respiratory distress syndrome, multiple organ failure, pulmonary embolism, deep vein thrombosis, pneumonia, mechanical ventilation days, intensive care unit LOS, and death. However, the ST group had a lower rate of sepsis (8.3% versus 31.6%, p = 0.0194) and a shorter LOS (26.5 days versus 36.2 days, p = 0.0237) than the EF group. CONCLUSION: : DC-EF of femur fractures in severely injured patients offers no significant advantage in clinical outcomes compared with ST. Unless initially subjected to general anesthesia for life saving procedures, the use of ST as a temporization method remains a practical option.

Poor oral hygiene as a risk factor for infective endocarditis-related bacteremia.

BACKGROUND: Infective endocarditis (IE) often is caused by bacteria that colonize teeth. The authors conducted a study to determine if poor oral hygiene or dental disease are risk factors for developing bacteremia after toothbrushing or single-tooth extraction. METHODS: One hundred ninety-four participants in a study were in either a toothbrushing group or a single-tooth extraction with placebo group. The authors assessed the participants' oral hygiene, gingivitis and periodontitis statuses. They assayed blood samples obtained before, during and after the toothbrushing or extraction interventions for IE-associated bacteria. RESULTS: The authors found that oral hygiene and gingival disease indexes were associated significantly with IE-related bacteremia after toothbrushing. Participants with mean plaque and calculus scores of 2 or greater were at a 3.78- and 4.43-fold increased risk of developing bacteremia, respectively. The presence of generalized bleeding after toothbrushing was associated with an almost eightfold increase in risk of developing bacteremia. There was no significant association between any of the measures of periodontal disease and the incidence of bacteremia after toothbrushing. The oral hygiene or disease status of a tooth was not significantly associated with bacteremia after its extraction. CONCLUSION: Bacteremia after toothbrushing is associated with poor oral hygiene and gingival bleeding after toothbrushing. CLINICAL IMPLICATIONS: Improvements in oral hygiene may reduce the risk of developing IE.

Concomitant surgical treatment of dental and valvular heart diseases.

BACKGROUND: Invasive dental procedures are often indicated before cardiac valve surgery. The purpose of this case-control study was to determine the risks and benefits of concomitant dental and thoracic surgery. METHODS: Critically ill cardiac inpatients requiring cardiac valve surgery were referred by the Department of Thoracic and Cardiovascular Surgery to our Oral Medicine consult service. Those requiring dental extractions were considered for dental treatment during the same general anesthetic as the cardiac surgery. These study patients were compared with control patients who had extractions before valve surgery in a different setting. There was no attempt to analyze the impact of this practice on the development of infective endocarditis. All patients received broad-spectrum antibiotics during dental surgery. RESULTS: Twenty-one patients had concomitant oral and cardiac valve surgery. Seventeen patients were in the control group. There were no statistically significant differences between cases and controls in demographics, length of stay, nature of the dental surgery, mean number of teeth removed, oral bleeding, or postoperative infections. One patient in the control group developed prosthetic valve endocarditis versus none in the concomitant surgery group. CONCLUSIONS: This case-control study suggests that concomitant surgical procedures for dental and valvular heart disease can be accomplished without clinically significant oral complications. Given the risk from poor oral health following cardiac valve surgery, this approach should be considered for patients who would benefit by avoiding a second general anesthetic and/or a delay in cardiac surgery, and by having their oral surgery performed in the safest environment.

Systemic host immuno-inflammatory response to dental extractions and periodontitis.

OBJECTIVES: Little is known about the host immuno-inflammatory response to dental extractions. The purpose of this pilot clinical study was to explore the effect of both periodontitis and dental extractions on the host systemic immuno-inflammatory response. STUDY DESIGN: We recruited and collected baseline blood samples on 41 essentially healthy patients. A subset of 22 subjects underwent single (n = 11) or multiple (n = 11) tooth extractions with additional blood samples taken at 1 hour following single tooth extraction and at 8 and 24 hours following multiple tooth extractions. Samples were used for determination of an array of 12 cytokines known to play key roles in innate and adaptive immunity. RESULTS: There was no significant difference in cytokine levels between the pre- and post-tooth extraction samples for either extraction group for the time points measured. Nor was there a positive relationship between the level of any of the cytokines and periodontal disease status as measured by mean probing depths and other periodontal disease parameters. CONCLUSION: Our pilot data suggest that the body is well adjusted to deal with the inflammation and bacteremia associated with dental extractions and periodontal disease.

Bacteremia associated with toothbrushing and dental extraction.

BACKGROUND: Antibiotic prophylaxis recommendations for the prevention of infective endocarditis are based in part on studies of bacteremia from dental procedures, but toothbrushing may pose a greater threat. The purpose of this study was to compare the incidence, duration, nature, and magnitude of endocarditis-related bacteremia from single-tooth extraction and toothbrushing and to determine the impact of amoxicillin prophylaxis on single-tooth extraction. METHODS AND RESULTS: In this double-blind, placebo-controlled study, 290 subjects were randomized to (1) toothbrushing, (2) single-tooth extraction with amoxicillin prophylaxis, or (3) single-tooth extraction with identical placebo. Blood was drawn for bacterial culturing and identification at 6 time points before, during, and after these interventions. The focus of our analysis was on bacterial species reported to cause infective endocarditis. We identified 98 bacterial species, 32 of which are reported to cause endocarditis. Cumulative incidence of endocarditis-related bacteria from all 6 blood draws was 23%, 33%, and 60% for the toothbrushing, extraction-amoxicillin, and extraction-placebo groups, respectively (P<0.0001). Significant differences were identified among the 3 groups at draws 2, 3, 4, and 5 (all P<0.05). Amoxicillin resulted in a significant decrease in positive cultures (P<0.0001). CONCLUSIONS: Although amoxicillin has a significant impact on bacteremia resulting from a single-tooth extraction, given the greater frequency for oral hygiene, toothbrushing may be a greater threat for individuals at risk for infective endocarditis.

Classification tree methods for development of decision rules for botulism and cyanide poisoning.

INTRODUCTION: Identification of predictors of potential mass poisonings may increase the speed and accuracy with which patients are recognized, potentially reducing the number ultimately exposed and the degree to which they are affected. This analysis used a decision-tree method to sort such potential predictors. METHODS: Data from the Toxic Exposure Surveillance System were used to select cyanide and botulism cases from 1993 to 2005 for analysis. Cases of other poisonings from a single poison center were used as controls. After duplication was omitted and removal of cases from the control sample was completed, there remained 1,122 cyanide cases, 262 botulism cases, and 70,804 controls available for both analyses. Classification trees for each poisoning type were constructed, using 131 standardized clinical effects. These decision rules were compared with the current case surveillance definitions of one active poison center and the American Association of Poison Control Centers (AAPCC). RESULTS: The botulism analysis produced a 4-item decision rule with sensitivity (Se) of 68% and specificity (Sp) of 90%. Use of the single poison center and AAPCC definitions produced Se of 19.5% and 16.8%, and Sp of 99.5% and 83.2%, respectively. The cyanide analysis produced a 9-item decision rule with Se of 74% and Sp of 77%. The single poison center and AAPCC case definitions produced Se of 10.2% and 8.6%, and Sp of 99.8% and 99.8%, respectively. CONCLUSIONS: These results suggest the possibility of improved poisoning case surveillance sensitivity using classification trees. This method produced substantially higher sensitivities, but not specificities, for both cyanide and botulism. Despite limitations, these results show the potential of a classification-tree approach in the detection of poisoning events.

Management of oral epithelial dysplasia: a review.

One of the goals of the fourth meeting of The World Workshop on Oral Medicine (WWOM IV) included a review of the pathophysiology and future directions for the clinical management of patients with oral epithelial dysplasia, excluding the lips and oropharynx. In the pathophysiology review of dysplasia since WWOM III (1998-2006), a wide range of molecular changes associated with progression of dysplasia to squamous cell carcinoma were found. These include loss of heterozygosity, dysregulation of apoptosis, aberrant DNA expression, and altered expression of numerous tissue markers. Based on the literature search, no single molecular pathway has been identified as the primary factor in progression of dysplasia to squamous cell carcinoma. A systematic review of medical (i.e., nonsurgical) management strategies for the treatment of dysplastic lesions has shown promising results in short-term resolution of dysplasia in the small number of studies that met eligibility criteria for review. However, because of the limited periods of follow-up reported in these studies, it remains unclear as whether resolution of dysplasia would actually be a long-term benefit of these interventions. This question is particularly germane when it is considered in the context of prevention of future development of squamous cell carcinoma. Because of the lack of randomized controlled trials that have shown effectiveness in the prevention of malignant transformation, no recommendations can be provided for specific surgical interventions of dysplastic oral lesions either.

Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial.

BACKGROUND: Policosanol is one of the fastest growing over-the-counter supplements sold in the United States. The use of policosanol to treat elevated cholesterol is based on clinical trials conducted in Cuba, which showed sugar cane-derived policosanol to be similar in efficacy to statins. Recent studies have challenged these findings, but there have been no trials conducted in North America that have examined the ability of sugar cane-derived policosanol to lower cholesterol. OBJECTIVES: This study investigated the efficacy of sugar cane-derived policosanol in healthy adults with mild hypercholesterolemia. The primary outcome was the percentage change in LDL cholesterol after 8 wk of therapy. Secondary outcome measures included changes in total cholesterol, HDL cholesterol, triacylglycerols, C-reactive protein, and nuclear magnetic resonance-determined lipoprotein profile. Dietary habits, weight, and blood pressure were also monitored. DESIGN: Ambulatory, community-dwelling healthy adults with mild hypercholesterolemia (n = 40) were assigned to receive oral policosanol (20 mg) or placebo once daily for 8 wk. This was a double-blind, randomized controlled trial conducted from January through August 2005. RESULTS: No significant differences in the change in LDL cholesterol were observed between the placebo (n = 20) and policosanol (n = 20) groups. Also, no significant changes in secondary outcome measures, including total cholesterol, HDL cholesterol, triacylglycerol, C-reactive protein, and nuclear magnetic resonance spectroscopy-determined profiles were observed. Policosanol was well tolerated, and no significant adverse events were noted. CONCLUSION: Policosanol does not alter the serum lipid profile over an 8-wk period in adults with mild hypercholesterolemia.

Caregiver reports of common symptoms in children following a traumatic brain injury.

This study describes the common symptoms in children and adolescents following a traumatic brain injury (TBI) as reported by their primary caregivers. Utilizing data from a large-scale state demonstration project, 681 children who had sustained a TBI were ascertained from both Hospital Emergency Departments (n = 409) and Pediatric Inpatient settings (n = 272). The sample ranged in age from infancy to 18 years, was largely male (59.7%), and had equal numbers of Caucasian and minority patients. Most of the participants experienced a mild TBI (83%), with about 5.1% being moderate and 12% severe. Caregivers described the presence of current symptoms (neurological, neurocognitive, behavioral, school problems) using a series of dichotomous questions regarding their child via a structured telephone interview at 1, 4, and 10 months post-injury. Inpatient children were described as manifesting more symptoms at each of the follow-up time points than their ED counterparts. At 1 month inpatients were described as having more symptoms across all 4 domains. At 4 and 10 months, the inpatients were described as having more neurocognitive symptoms and as not returning to school on a full-time basis, with behavior problems approaching significance at the 10-month point. A large number of individuals from both groups also reported persistent symptoms 10 months post-injury including headaches, attention and memory problems, low frustration tolerance, sleep problems, personality changes, and new school problems. Practical implications of these findings for the ongoing management of these children are discussed.

Change and predictors of change in communication, cognition, and social function between 1 and 5 years after traumatic brain injury.

OBJECTIVE: To study cognitive, communication, and social changes experienced by individuals between 1 and 5 years after traumatic brain injury (TBI). DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database with 927 eligible subjects using a cohort with complete 1- and 5-year data (N = 292). MAIN OUTCOME MEASURES: Change in Functional Independence Measure trade mark -Cognitive (FIM-Cog) items from Year 1 to Year 5 postinjury. RESULTS: On the FIM-Cog Total score, 26% individuals improved, 61% stayed the same, and 14% worsened by more than 1 point from Year 1 to Year 5. On the 2 FIM Communication items, 19% individuals improved, 68% stayed the same, and 13% worsened by greater than 1 point. On the FIM Social Interaction item, 12% individuals improved, 76% stayed the same, and 11% worsened. On the FIM Memory and Problem Solving items, 34% individuals improved, 48% stayed the same, and 19% worsened. Several variables predicted this improvement and worsening, some of which were available at the time of injury and most were those available at 1 year postinjury. The Memory and Problem Solving items, taken together, showed fewer participants at ceiling at Year 1 and more change between Year 1 and Year 5 compared to the Communication and Social Interaction items. CONCLUSIONS: Many individuals did not demonstrate meaningful change on FIM-Cog and its component items from Year 1 to Year 5. In particular, a high proportion of improvement was observed in Memory/Problem Solving, and worsening in Social Interaction. Demographic and functional indicators present at 1 year postinjury may be predictive of subsequent change.

Clinical use of fluorodeoxyglucose F 18 positron emission tomography for detection of renal cell carcinoma.

PURPOSE: We evaluate the role of fluorodeoxyglucose F 18 positron emission tomography (PET) in patients with renal cell carcinoma (RCC) by retrospective review. To our knowledge this series is the largest reviewing the use of PET in patients with RCC. MATERIALS AND METHODS: A total of 66 patients who underwent 90 PET scans for suspected or known RCC were identified. Dictated reports of PET, chest computerized tomography (CT), abdominal/pelvic CT and bone scan were examined with confirmation of results by histopathology or followup of at least 1 year. The accuracies of PET and conventional imaging modalities were compared. RESULTS: PET exhibited a sensitivity of 60% and specificity of 100% for primary RCC tumors (abdominal CT demonstrated 91.7% sensitivity and 100% specificity). For retroperitoneal lymph node metastases and/or renal bed recurrence, PET was 75.0% sensitive and 100.0% specific (92.6% sensitivity and 98.1% specificity for abdominal CT). PET had a sensitivity of 75.0% and a specificity of 97.1% for metastases to the lung parenchyma compared to 91.1% and 73.1%, respectively, for chest CT. PET had a sensitivity of 77.3% and specificity of 100.0% for bone metastases, compared to 93.8% and 87.2% for combined CT and bone scan. In 39 scans (32 patients) PET failed to detect RCC lesions identified by conventional imaging. CONCLUSIONS: The role of fluorodeoxyglucose F 18 PET in the detection of RCC is limited by low sensitivity. With superior specificity PET may have a complementary role as a problem solving tool in cases that are equivocal on conventional imaging.

Five years after traumatic brain injury: a study of individual outcomes and predictors of change in function.

OBJECTIVE: Study functional changes between one and five years after traumatic brain injury (TBI). DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model Systems National Database subjects using cohort with complete one and five year data (n = 301). MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) Level of Functioning and Employability Items. RESULTS: On Level of Functioning, 53 (18%) individuals improved, 228 (76%) stayed the same, and 20 (7%) worsened by more than one point from Year 1 to Year 5. On Employability, 50 (17%) individuals improved, 237 (79%) stayed the same, and 14 (5%) worsened by greater than one point. Level of Functioning improvement was predicted by FIM-Motor, FIM-Cognitive, Rey Auditory Verbal Learning Test, Symbol Digit Modalities Test (written and oral), and Wechsler Adult Intelligence Scale-Revised Block Design, and worsening predicted by Symbol Digit Modalities Test (written and oral). Improvement in Employability was predicted by race, while Glasgow Coma Scale Eye Opening was predictive of worsening. CONCLUSIONS: Although the majority did not demonstrate meaningful change on the DRS items from year 1 to 5, some individuals made dramatic gains and a minority declined. There are demographic and functional indicators present at one-year post-injury that may be predictive of subsequent change.

Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure.

OBJECTIVE: Antipyrine metabolism is a "gold standard" measure of mixed cytochrome P450 (CYP) mediated drug metabolism in humans. Cytokines (e.g., interleukin-6) and nitric oxide reduce CYP 450 activity in vitro and in vivo. Because interleukin-6 and nitric oxide production increases in children with sepsis-induced multiple organ failure, we hypothesized impaired CYP 450 mediated drug metabolism in this population. METHODS: Fifty-one consecutive children with sepsis and six critically ill children without sepsis were enrolled and given 18 mg/kg antipyrine per NG. Plasma antipyrine elimination rate, elimination half-life, and apparent oral clearance were measured and calculated. Plasma interleukin-6 and nitrite plus nitrate levels were measured and organs failing scored on days 1-3 of sepsis. RESULTS: Children with sepsis had a twofold reduction in antipyrine clearance. Children with persistent failure of three or more organs had a fourfold reduction in antipyrine clearance. Antipyrine clearance was inversely correlated to circulating interleukin-6 and nitrite plus nitrate levels and to number of organ failures. CONCLUSIONS: Interpretation CYP 450 mediated drug metabolism is decreased in children with sepsis, related in part to the degree of inflammation and organ failure. For drugs metabolized by CYP 450 enzymes there is an urgent need to reevaluate the use of standard drug dosage schedules in the sepsis population

Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis.

OBJECTIVE: To examine the relationships between procalcitonin, bacterial infection, sepsis-induced multiple organ failure, and mortality rate in children. DESIGN: Cohort study. SETTING: A multidisciplinary, tertiary-care pediatric intensive care unit. PATIENTS: Seventy-eight children meeting criteria for sepsis or septic shock and 12 critically ill children without sepsis. INTERVENTIONS: Venous or arterial blood sampling. MEASUREMENTS AND MAIN RESULTS: Demographic, epidemiologic, and outcome data were recorded. Plasma from children with sepsis were collected on days 1 and 3, and procalcitonin concentrations were measured by immunoluminometric assay. Organ failure index scores were determined, and multiple organ failure was defined as organ failure index > or = 3. Persistent multiple organ failure was defined by presence of multiple organ failure on day 3. Procalcitonin concentrations (median [25th percentile-75th percentile]) were increased among children with sepsis on day 1 (2.4 ng/mL [0.2-24.2], p < .01) but not on day 3 (0.8 ng/mL [0.1-8.1], p = nonsignificant) vs. controls (0.2 ng/mL [0.1-0.5]). This increase in procalcitonin concentration was particularly robust among children with bacterial sepsis on day 1 (7.1 ng/mL [0.9-44.8], p < .001) and on day 3 (2.9 ng/mL [0.1-32.4], p < .05). Procalcitonin concentrations were not increased among children with fungal, viral, or culture-negative sepsis vs. controls. Procalcitonin concentrations were persistently increased over time among patients with bacterial sepsis who had persistent multiple organ failure (p < .05) and who died (p < .01) but not among patients with nonbacterial sepsis. CONCLUSIONS: Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Further study is needed to better delineate this differential procalcitonin response to bacterial vs. nonbacterial sepsis and to characterize any mechanistic role that procalcitonin might play in the development of bacterial sepsis-induced multiple organ failure and mortality.

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.