Shun-Hwa Li

A Central Role for Induced Regulatory T Cells in Tolerance Induction in Experimental Colitis

In addition to thymus-derived or natural T regulatory (nTreg) cells, a second subset of induced T regulatory (iTreg) cells arises de novo from conventional CD4+ T cells in the periphery. The function of iTreg cells in tolerance was examined in a CD45RBhighCD4+ T cell transfer model of colitis. In situ-generated iTreg cells were similar to nTreg cells in their capacity to suppress T cell proliferation in vitro and their absence in vivo accelerated bowel disease. Treatment with nTreg cells resolved the colitis, but only when iTreg cells were also present. Although iTreg cells required Foxp3 for suppressive activity and phenotypic stability, their gene expression profile was distinct from the established nTreg “genetic signature,” indicative of developmental and possibly mechanistic differences. These results identified a functional role for iTreg cells in vivo and demonstrated that both iTreg and nTreg cells can act in concert to maintain tolerance.

A Meta-analytic Review of the Psychosocial Adjustment of Youth with Inflammatory Bowel Disease

OBJECTIVE To conduct a meta-analytic review of psychosocial adjustment of youth with inflammatory bowel disease (IBD). METHODS Nineteen studies with a total of 1167 youth with IBD (M age = 14.33, 50% female) were included. Effect size (ES) estimates were calculated for anxiety symptoms & disorders, depressive symptoms & disorders, internalizing symptoms & disorders, externalizing symptoms, quality of life (QOL), social functioning, and self-esteem. Separate ESs were calculated for comparisons between IBD and youth with chronic illnesses versus healthy youth. RESULTS Youth with IBD had higher rates of depressive disorders and internalizing disorders than youth with other chronic conditions. Youth with IBD had higher parent-reported internalizing symptoms, lower parent- and youth-reported QOL, and lower youth-reported social functioning compared to healthy youth. CONCLUSIONS Clinical attention to depressive disorders, QOL, and social functioning may be particularly salient in the context of pediatric IBD.

Association between Rainfall and Pediatric Emergency Department Visits for Acute Gastrointestinal Illness

Background Microbial water contamination after periods of heavy rainfall is well described, but its link to acute gastrointestinal illness (AGI) in children is not well known. Objectives We hypothesize an association between rainfall and pediatric emergency department (ED) visits for AGI that may represent an unrecognized, endemic burden of pediatric disease in a major U.S. metropolitan area served by municipal drinking water systems. Methods We conducted a retrospective time series analysis of visits to the Children’s Hospital of Wisconsin ED in Wauwatosa, Wisconsin. Daily visit totals of discharge International Classification of Diseases, 9th Revision codes of gastroenteritis or diarrhea were collected along with daily rainfall totals during the study period from 2002 to 2007. We used an autoregressive moving average model, adjusting for confounding variables such as sewage release events and season, to look for an association between daily visits and rainfall after a lag of 1–7 days. Results A total of 17,357 AGI visits were identified (mean daily total, 7.9; range, 0–56). Any rainfall 4 days prior was significantly associated with an 11% increase in AGI visits. Expected seasonal effects were also seen, with increased AGI visits in winter months. Conclusions We observed a significant association between rainfall and pediatric ED visits for AGI, suggesting a waterborne component of disease transmission in this population. The observed increase in ED visits for AGI occurred in the absence of any disease outbreaks reported to public health officials in our region, suggesting that rainfall-associated illness may be underestimated. Further study is warranted to better address this association.

Recurrence Rates After Intussusception Enema Reduction: A Meta-analysis

BACKGROUND AND OBJECTIVE: Reported rates of recurrence after enema reduction for intussusception are variable. Concerns for recurrence influence postreduction management. The objective of this study was to conduct a systematic review and meta-analysis to estimate overall, 24-hour, and 48-hour recurrence rates after enema reduction in children. METHODS: PubMed, Cochrane Database, and OVID Medline were searched from 1946 through December 2011 using the search terms: intussusception, recurrence, and enema. Sixty-nine studies of patients age 0 to 18 years with radiographically proven intussusception reduced by enema that report the number of enema reductions and the number of recurrences were included. Extraction was done by the primary author (M.P.G.) with 10% of included studies independently audited to ensure concordance. RESULTS: Overall recurrence rates were 12.7% (95% confidence interval [CI]: 11.1%–14.4%, I2 = 28.8%) for contrast enema (CE), 7.5% (95% CI: 5.7%–9.8%, I2 = 52.4%) for ultrasound-guided noncontrast enema (UGNCE), and 8.5% (95% CI: 6.9%–10.4%, I2 = 50.1%) for fluoroscopy-guided air enema (FGAE). Recurrence rates within 24 hours were 3.9% (95% CI: 2.2%–6.7%, I2 = 47.0%) for CE, 3.9% (95% CI: 1.5%–10.1%, I2 = 0.0%) for UGNCE, and 2.2% (95% CI: 0.7%–6.5%, I2 = 59.8%) for FGAE. Recurrence rates within 48 hours were 5.4% (95% CI 3.7%–7.8%, I2 = 32.3%) for CE, 6.6% (95% CI: 4.0%–10.7%, I2 = 0.0%) for UGNCE, and 2.7% (95% CI: 1.2%–6.5%, I2 = 73.8%) for FGAE. Most included studies are retrospective and vary in quality of reporting. Few studies reported detailed patient characteristics including timing of recurrences. CONCLUSIONS: The risk of early (within 48 hours) recurrence after enema reduction is low, suggesting outpatient management of well-appearing patients should be considered.

Supplemental Written Information Improves Prenatal Counseling: A Randomized Trial

OBJECTIVE: To determine if maternal knowledge of prematurity is improved when verbal gestational age-specific counseling is supplemented with written gestational age-specific information. METHODS: Prospective, randomized study of 60 pregnant participants assessed to be at risk for premature delivery between 23 and 34 weeks’ gestation. Counseling in the control group consisted of gestational age–specific verbal information, and counseling in the intervention group consisted of written gestational age–specific information 1 hour before the verbal gestational age–specific information. Both groups completed a Prematurity Knowledge Questionnaire after counseling and the State-Trait Anxiety Inventory before and after counseling. The Prematurity Knowledge Questionnaire consisted of questions regarding short-term problems (immature lungs, intraventricular hemorrhage, retinopathy, feeding problems, infection, apnea, and jaundice), long-term problems (chronic lung disease, postdischarge respiratory infections, visual impairment, hearing impairment, brain damage, and learning and behavior problems), and numerical outcome data (probabilities of survival, survival without significant morbidity, severe intraventricular hemorrhage, severe retinopathy, and chronic lung disease). RESULTS: Knowledge of short-term problems was not statistically different between the intervention (82%) and control groups (67%). Knowledge of long-term problems was better in the intervention (71%) than the control group (45%). Knowledge of numerical data was better in the intervention (48%) than the control group (29%). State-Trait Anxiety Inventory scores decreased after counseling in the intervention group. CONCLUSIONS: Supplementation of face-to-face verbal counseling with written information improved knowledge of long-term problems and knowledge of numerical outcome data, and it also decreased anxiety in women expecting a premature delivery.

Factors predicting prolonged hospital stay for infants with bronchiolitis.

BACKGROUND Prior prediction models for length of stay (LOS) in bronchiolitis have focused more on birth- and disease-related risk factors than on early hospital course factors, particularly common clinical markers including respiratory status and caloric intake. OBJECTIVES 1) Study the associations of various clinical markers and LOS; and 2) develop a LOS prediction model. DESIGN Retrospective cohort study. SETTING Childrens Hospital of Wisconsin. PATIENTS Inclusion criteria were: age < 365 days old; admission between November 1, 2004 and April 15, 2005; final diagnosis of bronchiolitis; placement on the bronchiolitis treatment protocol; and lack of concurrent condition impacting LOS. RESULTS During the study period, 272/347 infants admitted with bronchiolitis met inclusion criteria. On hospital day 2, infants in the prolonged LOS group (≥ 108 hours) had a significantly greater number of hours on supplemental oxygen, maximum supplemental oxygen use, minimum supplemental oxygen use, maximum respiratory rate, mean respiratory score, and number of times suctioned. They had significantly lower minimum oxygen saturation and caloric intake. Recursive partitioning demonstrated five variables (hours of supplemental oxygen, maximum respiratory rate, minimum supplemental oxygen use, gestation, and caloric intake) to predict short or prolonged LOS with an area under the receiver-operator characteristic curve of 0.89/0.72 in the learning/test trees; sensitivity, 0.85; and specificity, 0.82. CONCLUSIONS There are important differences between infants with bronchiolitis having short and prolonged hospital stays, including several clinical markers identifiable on hospital day 2. This model may be a useful prediction tool for targeting early interventions for high-risk infants.

Expression of High-Affinity IgE Receptor on Human Peripheral Blood Dendritic Cells in Children

Background In a mouse model of viral induced atopic disease, expression of FcεRI on dendritic cells is critical. While adult human conventional (cDC) and plasmacytoid (pDC) dendritic cells have been shown to express FcεRI, it is not known if this receptor is expressed in childhood and how its expression is governed by IgE. Methods Following informed consent of subjects (n = 27, aged 12–188 months), peripheral blood was stained for surface expression of CD19, ILT7, CD1c, IgE, FcεRI and analyzed by flow cytometry (cDC: CD19− ILT7− CD1c+; pDC: CD19− ILT7+ CD1c−). Total and specific serum IgE levels to food and inhalant allergens were determined by ImmunoCAP, and the relationship between FcεRI expression on dendritic cells and sensitization, free IgE, cell bound IgE, and age was determined. Results Independent of sensitization status, FcεRI expression was noted on cDC and pDC as early as 12 months of age. Serum IgE level correlated with expression of FcεRI on cDC, but not pDC. Based on the concentration of IgE, a complex relationship was found between surface bound IgE and expression of FcεRI on cDC. pDC exhibited a linear relationship of FcεRI expression and bound IgE that was consistent through all IgE concentrations. Conclusions In children, FcεRI expression on cDC and pDC is modulated differently by serum and cell bound IgE. IgE governance of FcεRI expression on cDC depends upon a complex relationship. Further studies are needed to determine the functional roles of FcεRI on cDC and pDC.

Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men.

Background/Objectives:Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM).Subjects/Methods:Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured.Results:No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04).Conclusions:No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Introduction of a Novel Swine-Origin Influenza A (H1N1) Virus into Milwaukee, Wisconsin in 2009

On 17 April 2009, novel swine origin influenza A virus (S-OIV) cases appeared within the United States. Most influenza A diagnostic assays currently utilized in local clinical laboratories do not allow definitive subtype determination. Detailed subtype analysis of influenza A positive samples in our laboratory allowed early confirmation of a large outbreak of S-OIV in southeastern Wisconsin (SEW). The initial case of S-OIV in SEW was detected on 28 April 2009. All influenza A samples obtained during the 16 week period prior to 28 April 2009, and the first four weeks of the subsequent epidemic were sub typed. Four different multiplex assays were employed, utilizing real time PCR and end point PCR to fully subtype human and animal influenza viral components. Specific detection of S-OIV was developed within days. Data regarding patient demographics and other concurrently circulating viruses were analyzed. During the first four weeks of the epidemic, 679 of 3726 (18.2%) adults and children tested for influenza A were identified with S-OIV infection. Thirteen patients (0.34%) tested positive for seasonal human subtypes of influenza A during the first two weeks and none in the subsequent 2 weeks of the epidemic. Parainfluenza viruses were the most prevalent seasonal viral agents circulating during the epidemic (of those tested), with detection rates of 12% followed by influenza B and RSV at 1.9% and 0.9% respectively. S-OIV was confirmed on day 2 of instituting subtype testing and within 4 days of report of national cases of S-OIV. Novel surge capacity diagnostic infrastructure exists in many specialty and research laboratories around the world. The capacity for broader influenza A sub typing at the local laboratory level allows timely and accurate detection of novel strains as they emerge in the community, despite the presence of other circulating viruses producing identical illness. This is likely to become increasingly important given the need for appropriate subtype driven anti-viral therapy and the potential shortage of such medications in a large epidemic.

The effect of a high-fat meal on postprandial arterial stiffness in men with obesity and Type 2 diabetes

CONTEXT Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. OBJECTIVE The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). DESIGN AND SETTING Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). RESULTS AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 +/- 1204, 2764 +/- 1102, and 1187 +/- 429% . min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 +/- 68 min) compared with lean subjects (161 +/- 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). CONCLUSIONS Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.