King, Katherine S.

Background Inhaled corticosteroids (ICSs) are important in asthma management, but there are concerns regarding associated risk of pneumonia. While studies in asthmatic adults have shown inconsistent results, this risk in asthmatic children is unclear. Objective Our aim was to determine the association of ICS use with pneumonia risk in asthmatic children. Methods A nested case-control study was performed in the Mayo Clinic Birth Cohort. Asthmatic children (<18 years) with a physician diagnosis of asthma were identified from electronic medical records of children born at Mayo Clinic from 1997 to 2016 and followed until 31 December 2017. Pneumonia cases defined by Infectious Disease Society of America were 1:1 matched with controls without pneumonia by age, sex and asthma index date. Exposure was defined as ICS prescription at least 90 days prior to pneumonia. Associations of ICS use, type and dose (low, medium and high) with pneumonia risk were analysed using conditional logistic regression. Results Of the 2108 asthmatic children eligible for the study (70% mild intermittent and 30% persistent asthma), 312 children developed pneumonia during the study period. ICS use overall was not associated with risk of pneumonia (adjusted OR: 0.94, 95% CI: 0.62 to 1.41). Poorly controlled asthma was significantly associated with the risk of pneumonia (OR: 2.03, 95% CI: 1.35 to 3.05; p<0.001). No ICS type or dose was associated with risk of pneumonia. Conclusion ICS use in asthmatic children was not associated with risk of pneumonia but poorly controlled asthma was. Future asthma studies may need to include pneumonia as a potential outcome of asthma management.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose- 13 C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Abstract Background As the use of antibiotics during the peripartum period increases, the incidence of autoimmune disorders and autism spectrum disorders (ASDs) is also increasing. In this study, we aim to assess if antibiotic exposure during the peripartum period affects the incidence of autoimmune diseases and ASD in the offspring. Methods We identified children (< 18 years of age) born in Olmsted County from January 1, 2003 through December 31, 2012. Offspring with celiac disease (CD), inflammatory bowel disease (IBD), or ASD diagnoses were matched to two controls on birth date, index date, mother’s age at delivery, and sex. Data from the mother’s medical records were retrieved to determine peripartum antibiotics use. Results A total of 242 cases and 484 matched controls were included in this study. Median age at the last follow-up was 11.3 years (range: 0.5–14.9), 73% were males in both groups. Odds of CD diagnosis was not statistically different between vaginal delivery with antibiotics compared with vaginal delivery with no antibiotics (odds ratio [OR] = 0.76, 95% confidence interval [CI]: 0.32–1.85), similarly in IBD (OR = 2.41, 95% CI: 0.53–10.98) and ASD (OR = 1.00, 95% CI:0.55–1.79). Preeclampsia or eclampsia was associated with offspring CD (OR = 3.20, 95% CI: 1.05–9.78). Smoking history and diabetes mellitus were associated with offspring ASD (OR = 1.84, 95% CI: 1.22–2.77 and OR = 2.01, 95% CI: 1.03–3.91, respectively). Conclusion In this cohort, we found no statistically significant association between peripartum antibiotics exposure and the development of CD, IBD, or ASD.

INTRODUCTION: Untreated symptomatic celiac disease (CD) adversely affects female reproduction; however, the effect of hidden CD autoimmunity is uncertain. METHODS: We identified women who were not previously diagnosed with CD and tested positive for tissue transglutaminase and endomysial antibodies between 2006 and 2011 in a community-based retrospective cohort study. We evaluated (i) the rate of adverse pregnancy outcomes and medical complications of pregnancy in successful singleton deliveries and (ii) reproductive characteristics in seropositive women without a clinical diagnosis of CD and age-matched seronegative women. RESULTS: Among 17,888 women whose serum samples were tested for CD autoimmunity, 215 seropositive and 415 seronegative women were included. We reviewed 231 and 509 live singleton deliveries of 117 seropositive and 250 seronegative mothers, respectively. Menarche and menopausal age, gravidity, parity, and age at first child were similar in seropositive and seronegative women. CD seropositivity was not associated with an increased risk of maternal pregnancy complications. Maternal seropositivity was associated with small for gestational age in boys (OR 3.77, 95% CI: 1.47–9.71; P = 0.006), but not in girls (OR 0.57, 95% CI: 0.15–2.17; P = 0.41). CD serum positivity was not associated with prematurity, small for gestational age (birth weight <10th percentile), or 5-minute Apgar score of less than 7. DISCUSSION: Although underpowered, the present study did not show any difference in reproductive characteristics or rates of adverse pregnancy outcomes in women with and without CD autoimmunity, except for birth weight in male offspring. Larger studies are needed to determine the effects of CD autoimmunity on female reproduction.

AbstractOBJECTIVESFunctional tricuspid regurgitation (fTR) has been amenable to tricuspid valve repair (TVr), with fewer patients needing tricuspid valve replacement (TVR). We sought to review our experience of tricuspid valve surgery for fTR.METHODSA retrospective analysis of adult patients (≥18 years) who underwent primary tricuspid valve surgery for fTR (n = 926; mean age 68.6 ± 12.5 years; 67% females) from January 1993 through June 2018 was conducted. There were 767 (83%) patients who underwent TVr (ring annuloplasty, 67%; purse-string annuloplasty, 33%) and 159 (17%) underwent TVR (bioprosthetic valves, 87%; mechanical valves, 13%). The median follow-up was 8.2 years [95% confidence interval (CI) 7.2–8.9 years].RESULTSA greater proportion of patients who underwent TVR had severe right ventricular dysfunction (P &lt; 0.001), severe tricuspid regurgitation (P &lt; 0.001) and congestive heart failure (P = 0.001) while the TVr cohort had a greater proportion with severe mitral valve (MV) regurgitation (P &lt; 0.001) and concomitant cardiac procedures. Early mortality (TVR, 9% vs TVr, 3%; P = 0.004), renal failure (TVR, 10% vs TVr, 5%; P = 0.014) and hospital stay (TVR, 15 ± 15 days vs TVr, 12 ± 11 days; P &lt; 0.001) were greater in TVR patients. The TVR cohort had worse survival [hazard ratio (HR) 1.57; 95% CI 1.23–1.99]. Multivariable analysis identified congestive heart failure (HR 1.37; 95% CI 1.10–1.72), renal failure (HR 1.79; 95% CI 1.14–2.82), previous MV surgery (HR 1.35; 95% CI 1.05–1.72) and TVR (HR 1.36; 95% CI 1.03–1.79) as independent risk factors for late mortality.CONCLUSIONSTricuspid repair for fTR appears to have better early and late outcomes. Since previous MV surgery and TVR are identified as independent risk factors for late mortality, concomitant TVr at the time of index MV surgery may be considered. Early referral before the onset of advanced heart failure may improve outcomes.

Background – The impact of post-operative complications on long-term survival is not well characterized. We sought to study the prevalence of post-operative complications after cardiac surgery and their impact on long-term survival. Methods – Operative survivors (n=26,221) who underwent coronary artery bypass grafting (CABG) (n=13054, 49.8%), valve surgery (n=8667, 33.1%) or combined CABG and valve surgery (n=4500, 17.2%) from 1993 to 2019 were included in the study. Records were reviewed for post-operative complications and long-term survival. The associations between post-operative complications and survival were assessed using a Cox-proportional model. Results – Complications occurred in 17,463 (66.6%) of 26,221 operative survivors. A total of 17 post-operative complications were analyzed. Post-operative blood product use was the commonest (n=12397, 47.3%), followed by atrial fibrillation (n=8399, 32.0%), prolonged ventilation (n=2336, 8.9%), renal failure (n=870, 3.3%), re-operation for bleeding (n=859, 3.3%) and pacemaker/ICD insertion (n=795, 3.0%). Stroke (HR 1.55, 95%CI 1.36-1.77), renal failure (HR 1.45, 95% CI 1.33-1.58) anticoagulant-related events (HR 1.26, 95%CI 1.02-1.56) and pneumonia (HR 1.23, 95%CI 1.11-1.36) had the strongest impact on long-term survival. Long-term survival decreased as the number of post-operative complications increased. Conclusions – Post-operative complications after cardiac surgery significantly impact outcomes that extend beyond the post-operative period. The presence, number and type of post-operative complications adversely impact long-term survival. Stroke, renal failure, anticoagulant-related events and pneumonia are particularly associated with poor long-term survival.