Citations

Background: Perinatal factors including gestational age, birthweight, size for gestational age, delivery route, maternal parity, maternal age, maternal education, socioeconomic status, race, and sex, are associated with the future risk of obesity and co-morbid conditions. This study evaluated the relationship of birthweight for gestational age and perinatal factors with severe obesity and dyslipidemia in adulthood. Methods: We conducted a population-based, retrospective birth cohort study of infants born to residents of Olmsted County, MN between 1976 and 1982. Outcomes were assessed after age 18 years until October 2020, including severe obesity (BMI ≥ 40 kg/m 2 ) and dyslipidemia (total cholesterol ≥200 mg/dL, non-high density lipoprotein [non-HDL] cholesterol ≥145 mg/dL or HDL cholesterol <40 mg/dL). We obtained mother’s age, education level, and parity as well as newborn sex, race, type of delivery, single/multiple birth, gestational age, and birthweight from birth certificate data. Individual-level socioeconomic status (SES) of the household at birth was determined with the HOUSES index. Results: Of 10 938 birth cohort subjects, 7394 had clinic visits after age 18 years and were included, with 2630 having severe obesity (n = 798) or dyslipidemia (n = 2357) as adults. In multivariable models, female sex, singleton birth, less maternal education, and lower SES defined by HOUSES were independently associated with an increased risk of severe obesity in adulthood. Non-white race, singleton birth, and lower birthweight were independently associated with adult dyslipidemia. Birthweight for gestational age was not associated with severe obesity or dyslipidemia. Conclusion: Perinatal factors were associated with both severe obesity and dyslipidemia in adulthood. Lower SES at birth was predictive of severe obesity in adulthood, highlighting the opportunity to investigate modifiable perinatal social determinants to reduce the risk of severe obesity.

AbstractBackgroundIn‐transit metastases (ITM) are a form of locoregional relapse representing intralymphatic metastatic spread and occur in approximately 4–9% of patients with melanoma >1 mm Breslow thickness. Our objective was to evaluate a combination of clinicopathologic risk factors and gene expression biomarkers predictive of ITM risk.MethodsWe used PCR to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 854 consecutive thin and intermediate thickness primary cutaneous melanomas. The outcome of interest was ITM >90 days after a melanoma diagnosis. Cox proportional hazard models were fit to estimate each clinicopathologic and molecular characteristic’s association with the risk of ITM.ResultsThe 5‐year cumulative incidence of ITM was 3.2%. Clinical factors univariately associated with an increased risk of ITM were older age, greater Breslow thickness, greater mitotic rate, lower extremity location, ulceration, and a positive SLN biopsy. Of 108 genes tested, five were significantly upregulated and five significantly downregulated when evaluated in Cox models adjusted for age, Breslow thickness, mitotic rate, and lower extremity location. Among the upregulated genes, the strongest association was observed for interleukin‐8 (IL8).ConclusionA subset of gene expression biomarkers was identified as independently associated with the risk of ITM after adjusting for key covariates. Once sufficiently validated, our results may lead the way to regional therapy trials for a small, selected group of high‐risk patients.

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age ( P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0–3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4–7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1–0.8) and ustekinumab (OR 0.2, 95% CI 0.05–0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.

Background: There is growing concern about the rising incidence and prevalence of food allergy globally. We previously reported the incidence of food allergy in Olmsted County, Minnesota, between 2002 and 2011. We sought to update the incidence and temporal trends of food allergies in our region through 2018. Methods: By using the Rochester Epidemiology Project, all Olmsted County residents, with an incident diagnosis of food allergy between January 2, 2012, and December 31, 2018, were identified and their medical records were reviewed. These cases were combined with the previously collected incidence cases from January 2, 2002, and December 31, 2011, to understand longitudinal trends in food allergy incidence rates. Results: Over the 17-year study period, 1076 patients (58.0% male patients, 72.1% white) were diagnosed with an incident food allergy. The median (interquartile range) age at first diagnosis was 2.0 years (1.1-8.4 years). The overall annual incidence rate for all ages was 3.9 (95% confidence interval [CI], 3.6‐4.1) per 10,000 person-years and was significantly higher in male than in female patients (4.4 [95% CI, 4.0‐4.7] and 3.3 [95% CI, 3.0‐3.6], respectively; p < 0.001). The most common food allergen was egg in infancy (57.7%), peanuts in ages 1‐4 years (58.3%), tree nuts in ages 5‐18 years (57.4%), and seafood in adults (≥19 years) (45.3%). Conclusion: The incidence of food allergy in Olmsted County steadily increased from 2002 to 2008, then remained relatively stable between the years 2008 and 2013, and again presented a rising trend over the next 5 years until 2018. This warrants further investigations into the effects of changes in guidelines for early introductions of allergenic foods and other factors that affect causality.

Abstract Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P &lt; .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age &lt;50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

Mitogen-Activated Protein 3 Kinase 7 (MAP3K7, MIM 602614) encodes the ubiquitously expressed transforming growth factor β (TGF-β)–activated kinase 1 (TAK1), which plays a crucial role in many cellular processes. Variants in the MAP3K7 gene have been linked to 2 distinct disorders: frontometaphyseal dysplasia type 2 (FMD2, MIM #617137) and cardiospondylocarpofacial syndrome (CSCF, MIM #157800). The fact that different variants can induce 2 distinct phenotypes suggests a phenotype/genotype correlation, but no side-by-side comparison has been done thus far to confirm this. Here we significantly expand the cohort and the description of clinical phenotypes for individuals with CSCF and FMD2 who carry variants in MAP3K7. We show that in contrast to FMD2-causing variants, CSCF-causing variants in MAP3K7 have a loss-of-function effect. Additionally, patients with pathogenic variants in MAP3K7 are at risk for cardiac disease, have symptoms associated with connective tissue disease and we show overlap in clinical phenotypes of CSCF with Noonan syndrome. Together, we provide evidence for a molecular fingerprint of FMD2- versus CSCF-causing MAP3K7 variants and conclude that variants in MAP3K7 should be considered in the differential diagnosis of patients with syndromic congenital cardiac defects and/or cardiomyopathy, syndromic connective tissue disorders and in the differential diagnosis of Noonan syndrome.

OBJECTIVES We aimed to describe the intellectual ability and ratio of boys to girls with average or higher IQ within autism spectrum disorder (ASD) cases identified in a population-based birth cohort. We hypothesized that research-identified individuals with ASD would be more likely to have average or higher IQ, compared to clinically diagnosed ASD. We also hypothesized the male to female ratio would decrease as the definition of ASD broadened. METHODS ASD incident cases were identified from 31 220 subjects in a population-based birth cohort. Research-defined autism spectrum disorder, inclusive criteria (ASD-RI) was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, autistic disorder (AD), Asperger Disorder, and pervasive developmental disorder not otherwise specified criteria. Research-defined autism spectrum disorder, narrow criteria (ASD-RN) was a narrower definition based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision AD criteria. Clinical diagnoses of ASD were abstracted from medical and school records. Intellectual ability was based on the last IQ score or on documented diagnoses of intellectual disability if no scores available. Average or higher IQ was defined as IQ ≥86. RESULTS A total of 59.1% of those with ASD-RI (n = 890), 51.2% of those with ASD-RN (n = 453), and 42.8% of those with clinically diagnosed autism spectrum disorder (n = 187) had average or higher IQ. Within the ASD-RI and ASD-RN groups, boys were more likely than girls to have an average or higher IQ (62.0% vs 51.3% [P = .004] and 54.1% vs. 42.5% [P = .03], respectively). CONCLUSION Our data suggest that nearly half of individuals with ASD have average or higher IQ. Boys with ASD are more likely to have average or higher IQ than girls. Patients with ASD and higher IQ remain at risk for not being identified.