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Background: The aims of the study were to assess the performance of a clinically available cell‐free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. Methods: Observational, non‐interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy‐associated plasma samples were used for cfDNA measurements. Pre‐determined cut points were tested for analytic performance. Results: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df‐cfDNA values between rejection [0.21% (IQR 0.12–0.69)] and healthy samples [0.05% (IQR 0.01–0.14), p <.0001]. The pediatric rejection group had a median df‐cfDNA value of 0.93% (IQR 0.28–2.84) compared to 0.09% (IQR 0.04–0.23) for healthy samples, p =.005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. Conclusion: The study suggests that pediatric patients with rejection show higher levels of circulating df‐cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance. [ABSTRACT FROM AUTHOR]

However, 16 patients were missing either the self-BAT or the physician BAT scores, so 63 patients were included in the final analyses. (B) Showing agreeability between physician BAT scores and electronic self-administered patient BAT scores. Exploration of the relationship between patient and physician BAT scores From the Bland-Altman plot (Figure 1A), self and Physician BAT scores appear to agree mainly within a difference of 2 but there are several with higher differences. [Extracted from the article]

Background: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell‐free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. Methods: Patients with heart transplantation were enrolled in two sequential, multi‐center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. Results: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p <.0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post‐therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p <.0001). Conclusion: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients. [ABSTRACT FROM AUTHOR]

Background: Cell‐free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell‐free DNA (ncfDNA) itself is largely unexplored. Objective: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. Methods: We conducted a multi‐center prospective study to investigate the value of cell‐free DNA in non‐invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints. Results: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection. Conclusions: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant. [ABSTRACT FROM AUTHOR]

Background: Donor specific antibody sum mean fluorescence intensity (MFI) values have been successfully used in transplant medicine to assess risk for organ rejection. However, little is known regarding whether MFI values could be similarly used to aid in platelet product selection. We have developed a novel protocol where MFI values are used to offer human leukocyte antigen (HLA)‐incompatible platelet products when HLA antigen‐matched products are not available. We aimed to evaluate the efficacy of this protocol. Methods: We performed a 4‐year retrospective chart review for all patients who received at least one MFI‐selected platelet product. A corrected count increment (CCI) was calculated for each transfusion event. A mixed effects model was used to investigate the association between CCIs for MFI‐selected, HLA antigen matched, and random donor platelet transfusions. A random effects expectation‐maximization regression tree was used to define the extent to which other patient variables, such as age, sex, and diagnosis impacted the CCI for each platelet transfusion. Results: Twenty highly HLA alloimmunized patients received a total of 591 platelets. MFI‐selected platelet (low MFI) transfusions had a significantly higher median CCI 0–6 hour post‐transfusion (13,559, interquartile range [IQR]: 8275–18,736) compared to random donor platelets (2121, IQR: 0–10,368, p < 0.0001). There was no significant difference in median CCI between HLA antigen matched and MFI selected platelet transfusions (p = 0.2). Mixed effects and regression modeling revealed that MFI‐selected platelet products had a significantly higher CCI than non‐matched platelets, even when accounting for other significant patient variables. Conclusion: MFI‐selected HLA‐incompatible platelet products could provide a comparable alternative to traditional HLA antigen‐matched platelet products. See editorial on page 2223–2228, in this issue [ABSTRACT FROM AUTHOR]

Background: There are no pediatric norms for gastric emptying (GE) measured by nuclear scintigraphy. The 13C‐labeled, stable isotope GE breath test (GEBT) is a non‐radioactive alternative. We aimed to determine normative GEBT ranges in a cohort of healthy children and examine the influence of age, gender, puberty, and body surface area (BSA). Methods: Healthy children ages 8–18 years completed the [13C]‐Spirulina platensis GEBT after an overnight fast. Breath samples were collected at baseline, every 15 min × 1 h, then every 30 min for 4 h total. The 13CO2 excretion rate was determined by the change in 13CO2/12CO2 over time in each breath sample, expressed as kPCD (Percent 13C Dose excreted/min). A mixed model with random time was used for multivariable analysis and outcome fit into a quadratic model. Key Results: The 100 subjects completed the test meal within allotted time. Median (IQR) age was 13.5 (11.3–15.5) years; 51% were female. Females had lower 13CO2 excretion rates (slower GE) than males across time (p < 0.001) while decreased excretion rates correlated with higher BSA (p = 0.015). Gender differences were also noted within pubertal stages with females showing slower GE. Multivariable analysis suggested that pre‐pubertal children have faster GE than both peri‐ and post‐pubertal groups (p < 0.0001). Conclusions & Inferences: Gender, puberty, and BSA influence GE rates in healthy children more than age. Although further data are needed, pubertal stage and hormonal influences may be unique factors to consider when assessing GE in children. [ABSTRACT FROM AUTHOR]

Solid‐organ transplantation is the treatment of choice for end‐stage organ failure. Parents of pediatric transplant recipients who reported a lack of readiness for discharge had more difficulty coping and managing their child's medically complex care at home. In this paper, we describe the protocol for the pilot study of a mHealth intervention (myFAMI). The myFAMI intervention is based on the Individual and Family Self‐Management Theory and focuses on family self‐management of pediatric transplant recipients at home. The purpose of the pilot study is to test the feasibility of the myFAMI intervention with family members of pediatric transplant recipients and to test the preliminary efficacy on postdischarge coping through a randomized controlled trial. The sample will include 40 family units, 20 in each arm of the study, from three pediatric transplant centers in the United States. Results from this study may advance nursing science by providing insight for the use of mHealth to facilitate patient/family–nurse communication and family self‐management behaviors for family members of pediatric transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Partial normal saline replacement during plasma exchange procedures is a common practice to reduce procedure costs but may increase the risk of adverse events, such as hypotension and citrate reactions. The goal of this study was to compare adverse event rates for the patients that used albumin or albumin/saline as replacement. Study Design and Methods: A retrospective chart review was done of plasma exchange procedures that used all albumin or 80% albumin to 20% normal saline (80/20) as replacement. The procedure type (all albumin vs 80/20), the percent of normal saline used, age, gender, and adverse events during the procedure were recorded. Results: During the study period, 3624 procedures were documented for 401 patients (46% female), age range 0 to 93 years, of which 2453 (67.7%) used 80/20. Overall 91 procedures (2.5%) resulted in a hypotensive event, 26 (0.7%) of which were classified as moderate to severe hypotension, and 40 (1.1%) had reported citrate toxicity. After adjusting for age, gender, and diagnosis using a generalized linear mixed model and backward model selection, results showed that 100% albumin had a significantly lower risk of having hypotension than 80/20 (odds ratio (OR): 0.531 [0.298, 0.946], P = 0.032) and moderate to severe hypotension (odds ratio: 0.140 [95% confidence interval (CI): 0.031, 0.628], P = 0.010). Older age was also predictive of having hypotensive reactions (OR[95%CI] = 1.017,[1.0, 1.034], P = 0.047). Conclusion: Partial saline use as a replacement fluid with albumin during plasma exchange is associated with an increased risk of hypotension. Use of saline as replacement fluid during plasma exchange should be minimized especially in older patients. [ABSTRACT FROM AUTHOR]

Background Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However, their concurrent impact in humans is unclear. Methods Our aim was to determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. Age- and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent ( NAlc) and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection. The groups were compared regarding (i) inflammation/intestinal barrier: systemic tumor necrosis factor levels, intestinal inflammatory cytokine (duodenum, ileum, sigmoid), and ileal antimicrobial peptide expression; (ii) microbiota composition: 16Sr RNA sequencing of duodenal, ileal, and colonic mucosal and fecal microbiota; and (iii) microbial functionality: duodenal fluid and fecal bile acid ( BA) profile (conjugation and dehydroxylation status), intestinal BA transporter ( ASBT, FXR, FGF-19, SHP) expression, and stool metabolomics using gas chromatography/mass spectrometry. Results Alc patients demonstrated a significant duodenal, ileal, and colonic mucosal and fecal dysbiosis, compared to NAlc and controls with lower autochthonous bacterial taxa. BA profile skewed toward a potentially toxic profile (higher secondary and glycine-conjugated BAs) in duodenal fluid and stool in Alc patients. Duodenal fluid demonstrated conjugated secondary BAs only in the Alc group. There was a greater expression of all ileal BA transporters in Alc patients. This group also showed higher endotoxemia, systemic and ileal inflammatory expression, and lower amino acid and bioenergetic-associated metabolites, without change in antimicrobial peptide expression. Conclusions Despite cirrhosis, continued alcohol misuse predisposes patients to widespread dysbiosis with alterations in microbial functionality such as a toxic BA profile, which can lead to intestinal and systemic inflammation. [ABSTRACT FROM AUTHOR]

Background To determine prevalence, clinical implication, and risk factors for aortic root dilation ( ARD) in pediatric heart transplant recipients. Methods Serial echocardiograms were reviewed in all pediatric heart transplant recipients from 1999 to 2014 to assess maximal systolic diameter at the aortic annulus, aortic sinus, aortic sino-tubular ( ST) junction, and ascending aorta. ARD was defined by a sinus/annulus ratio >1.56, ST junction/annulus ratio >1.28, and/or ascending aorta/annulus ratio >1.35. Results A total of 147 subjects (53% male) were evaluated; 50% had congenital heart disease ( CHD). Of the 74 with CHD, 38 had prior aortic arch reconstruction. The median age at transplant was 3 years (7 days-20.3 years) with a median duration of follow-up of 3.88 years (3 months-15 years). Prevalence of ARD significantly increased in the cohort from 15.6% at the initial echocardiogram to 49.6% at later follow-up ( P<.0001). The median duration to development of ARD was 7.6 months. There were no significant differences in prevalence of ARD or days to maximum ratio based on the pretransplant diagnosis. Aortic regurgitation was very rare (7 with ≤mild) and did not correlate with ARD or require any interventions. Conclusion During intermediate follow-up, ARD commonly develops in children post-heart transplant, and prevalence increases with time after transplant. Within 1 year after transplant, almost 50% had developed abnormalities in aortic root size that were not apparent at the initial posttransplant echocardiogram. Preexisting CHD or need for prior arch reconstruction did not increase the risk of ARD. [ABSTRACT FROM AUTHOR]

Objective Controversy exists regarding which febrile children with sickle cell disease ( SCD) should receive a chest x-ray ( CXR). Our goal is to provide data informing the decision of which febrile children with SCD presenting to the emergency department ( ED) require a CXR to evaluate for acute chest syndrome ( ACS). Methods Retrospective chart review of children ages 3 months to 21 years with SCD presenting to the ED at one of two academic children's hospitals with fever ≥38.5°C between January 1, 2010, and December 31, 2012. Demographic characteristics, respiratory symptoms, and laboratory results were abstracted. The primary outcome was the presence of ACS. Binary recursive partitioning was performed to determine predictive factors for a diagnosis of ACS. Results A total of 185 (10%) of 1,837 febrile ED visits met ACS criteria. The current National Heart, Lung, and Blood Institute ( NHLBI) consensus criteria for obtaining a CXR (shortness of breath, tachypnea, cough, or rales) identified 158 (85%) of ACS cases, while avoiding 825 CXRs. Obtaining a CXR in children with NHLBI criteria or chest pain and in children without those symptoms but with a white blood cell ( WBC) count ≥18.75 × 109/L or a history of ACS identified 181 (98%), while avoiding 430 CXRs. Conclusion Children with SCD presenting to the ED with fever and shortness of breath, tachypnea, cough, rales, or chest pain should receive a CXR due to high ACS rates. A higher WBC count or history of ACS in a child without one of those symptoms may suggest the need for a CXR. Prospective validation of these criteria is needed. [ABSTRACT FROM AUTHOR]

Objectives: Home visiting programs promote the education and health of Early Head Start (EHS) children and pregnant women. However, EHS's oral health component is unevenly implemented. We conducted an educational intervention to improve oral health knowledge and motivational interviewing techniques among Wisconsin EHS home visitors.Methods: A questionnaire assessing oral health-related knowledge and confidence was administered to home visitors before and after an educational session. Changes between pre/post-responses were analyzed with McNemar's test and Wilcoxon Signed Rank test.Results: After the intervention there were increases in both knowledge and confidence related to oral health communication. Knowledge increases were observed in such topics as fluoridation, dental caries, and caregivers' role in assisting and supervising children's tooth brushing.Conclusions: A brief educational intervention was associated with increased home visitor knowledge and confidence in communicating oral health messages to EHS caregivers and pregnant women. [ABSTRACT FROM AUTHOR]

Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy. [ABSTRACT FROM AUTHOR]

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care. [ABSTRACT FROM AUTHOR]

Background Continuous opioid infusion ( COI) remains the mainstay of analgesic therapy in the neonatal intensive care unit ( NICU). Parent/nurse-controlled analgesia ( PNCA) has been accepted as safe and effective for pediatric patients, but few reports include use in neonates. This study sought to compare outcomes of PNCA and COI in postsurgical neonates and young infants. Methods Twenty infants treated with morphine PNCA were retrospectively compared with 13 infants treated with fentanyl COI in a Midwestern pediatric hospital in the United States. Outcome measures included opioid consumption, pain scores, frequency of adverse events, and subsequent methadone use. Results The PNCA group (median 6.4 μg·kg−1·h−1 morphine equivalents, range 0.0-31.4) received significantly less opioid ( P < 0.001) than the COI group (median 40.0 μg·kg−1·h−1 morphine equivalents; range 20.0-153.3), across postoperative days 0-3. Average daily pain scores (based on 0-10 scale) were low for both groups, but median scores differed nonetheless (0.8 PNCA vs 0.3 COI, P < 0.05). There was no significant difference in the frequency of adverse events or methadone use. Conclusion Results suggest PNCA may be a feasible and effective alternative to COI for pain management in postsurgical infants in the NICU. Results also suggest PNCA may provide more individualized care for this vulnerable population and in doing so, may potentially reduce opioid consumption; however, more studies are needed. [ABSTRACT FROM AUTHOR]

To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single-blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m2 or ranitidine 60 mg/m2 when gastric pH < 4.0 >1 hour with serial blood sampling following first dose. Twenty-four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty-four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours ( p > 0.2). No difference between drugs in clearance, volume of distribution and half-life ( p > 0.05). Ratio of AUC pH to AUC drug concentration 0-12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect. [ABSTRACT FROM AUTHOR]

Our aim is to develop and validate an accurate method for estimating TCV using standard echocardiographic imaging that can be easily employed to aid in donor-recipient size matching in pediatric heart transplantation. Thirty patients who underwent Echo and cardiac magnetic resonance imaging ( cMRI) were identified. TCV was measured on cMRI. TCV was determined echocardiographically by two methods: a volume measurement using the modified Simpson's method on a four-chamber view of the heart; and a calculated volume measurement which assumed a true-elliptical shape of the heart. These two methods where compared with the value obtained by cMRI using the concordance correlation coefficient (CCC). TCV by method 1 correlated well with cMRI (CCC = 0.98%, CI = 0.97, 0.99). TCV by method 2 had a CCC = 0.90 (CI = 0.9464, 0.9716) when compared to cMRI. Left ventricular end-diastolic volume (LVEDV) also correlated as a predictor of TCV in patients with structurally normal hearts and could be described by the equation: TCV = 6.6 (LVEDV) + 12 (R2 = 0.97). Echocardiographic assessment of TCV for recipients and their potential donors is a simple process and can be prospectively applied as part of donor evaluation. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to explore pediatric nurses' knowledge of pressure ulcer prevention, investigate their beliefs and practices, and identify the barriers and facilitators to providing evidence-based pressure ulcer preventive practices. Design and Methods. An exploratory, descriptive, and cross-sectional survey was taken of registered nurses in a freestanding children's hospital. Results. Nurses have adequate knowledge of general pressure ulcer prevention; however, they struggle with individualization. Further, analysis revealed that nursing knowledge did not always correlate with nursing practice. Practice Implications. Nurses require education on individualized interventions and access to user-friendly, interactive, and comprehensive resources, including unit-based champions and order sets. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Children with neurologically impaired (NI) swallow can undergo tonsillectomy safely and effectively. Study Design: Retrospective review. Methods: Forty-five children with documented dysphagia were compared to age- and procedure-matched normal children for operating room and clinical experience. Three further studies were limited to the NI children only: preoperative and postoperative video swallow studies (VSS), and polysomnography (PSG) for sleep-disordered breathing history. Long-term telephone follow-up of clinical outcomes was performed. Results: There were no differences between the two groups measured by tonsil size or intraoperative or late post-tonsillectomy hemorrhage, but lowest measured oxygen levels were statistically different. No intraoperative complications, early post-tonsillectomy hemorrhage, hospital readmission, or mortality occurred in either group. Three NI children each had an episode of aspiration pneumonia (early or late) without sequelae. Of the 32 VSS available for review, postoperative aspiration incidence was significantly improved, but with new-onset aspiration occurring in five children. Of available matched pre- and postoperative PSG, 91% confirmed resolution of identified preoperative obstructive sleep apnea. Long-term telephone follow-up of 20 NI children revealed improved breathing (95%), communication (90%), and feeding efficiency (55%). Conclusions: This study suggests tonsillectomy in NI children can be performed safely with appropriate monitoring and precautions with a 48-hour hospital postoperative stay recommended. Swallowing safety appears to improve both objectively and subjectively in most NI children following tonsillectomy. Both preoperative and postoperative VSS are recommended for any NI child undergoing tonsillectomy. Long-term follow-up identified improved quality of life measures for the majority of the NI children queried. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than 50% response rate, prevalence of physician-diagnosed asthma was comparable to other studies in public school settings. Prevalence of symptoms in cases identified as current is suggestive of poor asthma control. Improved systems for case identification of children with asthma are needed in schools. Efforts should focus on strategies to improve asthma control.(J Sch Health. 2006;76(6):223-226) [ABSTRACT FROM AUTHOR]

Several cytokines have been reported to have hepato-protective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme-linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N-acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity. [ABSTRACT FROM PUBLISHER]

Inflammation appears to play an important role in the repair and regeneration of skeletal muscle after damage. We tested the hypothesis that the severity of the inflammatory response in muscle after an acute bout of resistance exercise is associated with single nucleotide polymorphisms (SNPs) previously shown to alter interleukin-1 (IL-1) activity. Using a double-blind prospective design, sedentary young men were screened (n = 100) for enrolment (n = 24) based upon having 1 of 4 haplotype patterns composed of five polymorphic sites in the IL-1 gene cluster: IL-1A (+4845), IL-1B (+3954), IL-1B (-511), IL-1B (-3737) and IL-1RN (+2018). Subjects performed a standard bout of resistance leg exercise and vastus lateralis biopsies were obtained pre-, and at 24, and 72 h post-exercise. Inflammatory marker mRNAs (IL-1β, IL-6 and tumor necrosis factor-α (TNF-α)) and the number of CD68+ macrophages were quantified. Considerable variation was observed in the expression of these gene products between subjects. At 72 h post-exercise, IL-1β had increased in a number of subjects (n = 10) and decreased (n = 4) or did not change (n = 10) in others. Inflammatory responses were significantly associated with specific haplotype patterns and were also influenced by individual SNPs. Subjects with genotypes 1.1 at IL-1B (+3954) or 2.2 at IL-1B (-3737) had approximately a 2-fold higher median induction of several markers, but no increase in macrophages, suggesting that cytokine gene expression is elevated per macrophage. The IL-1RN (+2018) SNP maximized the response specifically within these groups and was associated with increased macrophage recruitment. This is the first report that IL-1 genotype is associated with the inflammation of skeletal muscle following acute resistance exercise that may potentially affect the adaptations to chronic resistance exercise. [ABSTRACT FROM AUTHOR]

Background: Ethanol intake during pregnancy alters offspring facial morphology. However, significant variation that may be due to genetic diversity in ethanol metabolizing enzymes occurs. The alcohol dehydrogenase 1B*3 (ADH1B*3) allele is protective for offspring developmental outcome after maternal alcohol drinking in pregnancy and may explain the spectrum of facial morphology. Methods: Faces of infants with knownADH1B genotype, whose mothers' ADH1B genotypes and ethanol intake were determined during pregnancy, were photographed using uniform procedures. Photographs were scanned and the inner canthal distance, palpebral fissure length, and distance from the bridge of the nose to the bottom of the upper lip were measured by an investigator who was blinded to genotype and ethanol exposure. Results: Among 247 photographed infants, each facial measurement varied >2-fold. Median absolute ethanol daily intake was 0.5 oz among mothers who reported drinking in the periconceptional period (N = 173) and 0.17 oz among mothers who reported drinking before the first prenatal visit (N = 62). Controlling for the amount of maternal ethanol intake just before the first prenatal visit and infant sex, the three-way interaction among the absence of a maternal and offspring ADH1B*3 allele and the presence of ethanol consumption just before the first prenatal visit was associated with smaller facial measurements (p = 0.002, MANCOVA). Conclusions: These are the first observations of a significant gene–environment interaction explaining variation in facial morphology associated with ethanol use in pregnancy. This positive effect of ADH1B*3 is consistent with its known positive effect on offspring birth weight and developmental outcome after in utero ethanol exposure. [ABSTRACT FROM AUTHOR]

Background: Nausea frequently co‐exists with functional abdominal pain disorders (FAPDs) and may be linked to a higher disease burden. This study aimed to prospectively compare multisystem symptoms, quality of life, and functioning in FAPDs with and without nausea. Methods: Adolescents ages 11‐18 years fulfilling Rome III criteria for a FAPD were grouped by the presence or absence of chronic nausea. Subjects completed validated instruments assessing nausea (Nausea Profile Questionnaire = NPQ), quality of life (Patient‐Reported Outcome Measurement Information System), functioning (Functional Disability Inventory), and anxiety (State‐Trait Anxiety Inventory for Children). Group comparisons were performed for instruments, multisystem symptoms, school absences, and clinical diagnoses. Key Results: A total of 112 subjects were included; 71% reported chronic nausea. Patients with Nausea compared to No Nausea had higher NPQ scores (P ≤ 0.001), worse quality of life (P = 0.004), and greater disability (P = 0.02). State and trait anxiety scores were similar (P = 0.57, P = 0.25). A higher NPQ score correlated with poorer quality of life, more disability, and higher anxiety. Specific comorbidities were more common in Nausea vs No Nausea group: dizziness (81% vs 41%; P ≤ 0.001), concentrating difficulties (68% vs 27%; P ≤ 0.001), chronic fatigue (58% vs 20%; P = 0.01), and sleep disturbances (73% vs 48%; P = 0.02). The Nausea group reported more school absences (P = 0.001) and more commonly met criteria for functional dyspepsia (P = 0.034). Conclusion and Inferences: Nausea co‐existing with FAPDs is associated with a higher extra‐intestinal symptom burden, worse quality of life, and impaired functioning in children. Assessing and targeting nausea therapeutically is essential to improve outcomes in FAPDs. [ABSTRACT FROM AUTHOR]