Incidence of SARS-CoV-2 seropositivity in pediatric healthcare workers prior to widespread vaccination: A 5-month longitudinal cohort study.

OBJECTIVES: Determine SARS-CoV-2 IgG antibody incidence over time in unvaccinated pediatric healthcare workers (pHCWs). DESIGN: A prospective longitudinal cohort of unvaccinated pHCWs measuring the incidence of new infection after initial prevalence was established at 4.1% with seropositive predominance in emergency department (ED)-based pHCWs. Serum samples were collected at follow-up visits to detect new SARS-CoV-2 seropositivity. Univariate analysis was performed to estimate different incidence rates between participant demographics, job, employment location, and community risk factors. Anxiety levels about COVID-19 were collected. SARS-CoV-2 antibody decay postinfection and neutralization antibodies were evaluated. Log-linear Poisson regression models were used to estimate incidence. RESULTS: Of 642 initially enrolled, 390 pHCWs presented for at least one follow-up serology test after baseline analysis. The incidence of SARS-CoV-2 seropositivity was 8.2%. The seropositive cohort, like the negative one, consisted mainly of females in non-ED settings and nonphysician roles. There were no statistically significant differences in incidence across variables. Seropositive participants dropped antibody titers by 50% at 3 months. Neutralization antibodies correlated to SARS-CoV-2 binding antibodies (r = 0.43, P < 0.0001). CONCLUSION: The incidence of seropositivity was 8.2%. Although seropositivity was higher among ED staff during the early stages of the pandemic, this difference declined over time, likely due to the universal adoption of personal protective equipment.

Sensitivity of rapid antigen tests against SARS-CoV-2 Omicron and Delta variants.

Rapid antigen tests (RATs) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of 10 commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using both individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR cycle threshold (CT) value (a rough proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Sensitivity of Rapid Antigen Tests Against SARS-CoV-2 Omicron and Delta Variants.

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (C T ) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.

Safety and Efficacy of Insulin and Heparin in the Management of Hypertriglyceridemia-Induced Pancreatitis in a Patient without Diabetes: A Case Report.

Acute pancreatitis (AP) leads to a variety of complications, such as local or systemic inflammatory responses as well as organ failure. While choledocholithiasis and alcohol abuse are two of the most common causes of AP, hypertriglyceridemia causes AP with an incidence rate between 2 and 5%. The management of hypertriglyceridemia-induced pancreatitis (HTGIP) is focused on the lowering of triglyceride (TG) levels, and the efficacy of therapies for the management of HTGIP may vary based on the hypertriglyceridemia etiology. The aim of this article is to report a case of a 43-year-old female with a history of familial hypertriglyceridemia and without diabetes who was admitted for acute pancreatitis with a TG level elevated to 4,435 mg/dL. The patient was treated with a combination of insulin, heparin, atorvastatin, and omega-3-acid ethyl esters, and her TG level was reduced to 880 mg/dL after 9 days of therapy. Despite the successful treatment of the patient, standardization of the approach for the treatment of HTGIP is needed. Future research should aim to identify the appropriateness of insulin therapy specifically in patients without diabetes presenting with hypertriglyceridemia and the dosing associated with optimal safety.

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.

OBJECTIVE: Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations in UBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP. METHODS: Exome and targeted sequencing of UBA1 was performed in a prospective observational cohort of patients with RP. Clinical and immunologic characteristics of patients with RP were compared based on the presence or absence of UBA1 mutations. The random forest method was used to derive a clinical algorithm to identify patients with UBA1 mutations. RESULTS: Seven of 92 patients with RP (7.6%) had UBA1 mutations (referred to here as VEXAS-RP). Patients with VEXAS-RP were all male, were on average ≥45 years of age at disease onset, and commonly had fever, ear chondritis, skin involvement, deep vein thrombosis, and pulmonary infiltrates. No patient with VEXAS-RP had chondritis of the airways or costochondritis. Mortality was greater in VEXAS-RP than in RP (23% versus 4%; P = 0.029). Elevated acute-phase reactants and hematologic abnormalities (e.g., macrocytic anemia, thrombocytopenia, lymphopenia, multiple myeloma, myelodysplastic syndrome) were prevalent in VEXAS-RP. A decision tree algorithm based on male sex, a mean corpuscular volume >100 fl, and a platelet count <200 ×103 /µl differentiated VEXAS-RP from RP with 100% sensitivity and 96% specificity. CONCLUSION: Mutations in UBA1 were causal for disease in a subset of patients with RP. This subset of patients was defined by disease onset in the fifth decade of life or later, male sex, ear/nose chondritis, and hematologic abnormalities. Early identification is important in VEXAS given the associated high mortality rate.

Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based study.

BACKGROUND: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited. METHODS: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013-2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (<35, ≥35) and infant sex. RESULTS: We identified 13,376 cases of Down syndrome. Prevalence among all programs was 12.7 per 10,000 live births. Among these children, 75% had at least one reported co-occurring birth defect diagnosis code. Among 6,210 cases identified by active programs, 66% had a cardiovascular defect with septal defects being the most common: atrial (32.5%), ventricular (20.6%), and atrioventricular (17.4%). Defect prevalence differed by infant sex more frequently than by maternal age. For example, atrioventricular septal defects were more common in female children (20.1% vs. 15.1%) while limb deficiencies were more prevalent in male children (0.4% vs. 0.1%). CONCLUSIONS: Our study provides updated prevalence estimates for structural defects, including rare defects, among children with Down syndrome using one of the largest and most recent cohorts to date. These data may aid clinical care and surveillance.

Acculturation and selected birth defects among non-Hispanic Blacks in a population-based case-control study.

BACKGROUND: There are noted birth defects prevalence differences between race/ethnicity groups. For instance, non-Hispanic (NH) Black mothers are more likely to have an infant with encephalocele, although less likely to have an infant with anotia/microtia compared to NH Whites. When stratifying by nativity and years lived within the United States, additional variations become apparent. METHODS: Data from the National Birth Defects Prevention Study were used to calculate descriptive statistics and estimate crude/adjusted odds ratios (aORs) and 95% confidence intervals (95%CIs) among NH Blacks with one of 30 major defects and non-malformed controls. Total case/controls were as follows: U.S.- (2,773/1101); Foreign- (343/151); African-born (161/64). Study participants were also examined by number of years lived in the U.S. (≤5 vs. 6+ years). RESULTS: Compared to U.S.-born, foreign-born NH Black controls tended to be older, had more years of education, and were more likely to have a higher household income. They also had fewer previous livebirths and were less likely to be obese. In the adjusted analyses, two defect groups were significantly attenuated: limb deficiencies, aORs/95%CIs = (0.44 [0.20-0.97]) and septal defects (0.69 [0.48-0.99]). After stratifying by years lived in the United States, the risk for hydrocephaly (2.43 [1.03-5.74]) became apparent among those having lived 6+ years in the United States. When restricting to African-born mothers, none of the findings were statistically significant. CONCLUSIONS: Foreign-born NH Blacks were at a reduced risk for a few selected defects. Results were consistent after restricting to African-born mothers and did not change considerably when stratifying by years lived in the United States.

The prevalence of birth defects among non-Hispanic Asian/Pacific Islanders and American Indians/Alaska Natives in Texas, 1999-2015.

BACKGROUND: There is considerable variability in the prevalence of birth defects among racial/ethnic groups. This study estimated birth defect prevalence among the less studied non-Hispanic (NH) Asian/Pacific Islander (PI) and American Indian/Alaska Native (AI/AN) populations in Texas relative to NH Whites. METHODS: Data were obtained from the Texas Birth Defect Registry from 1999 to 2015 for deliveries to Texas-resident women who were NH White, NH Asian/PI, or AI/AN. This covers a live birth population of 2.6 million. Prevalence ratios and 95% confidence intervals (95% CIs) were calculated for NH Asian/PIs and AI/ANs (relative to NH Whites) for 44 birth defects using Poisson regression adjusting for maternal age. RESULTS: After adjustment there were 33 statistically significant prevalence ratios (aPRs). Among NH Asian/PIs, 23 defects had a lower aPR (0.38-0.86) and three defects had a higher aPR (1.19-2.50). AI/ANs had one defect with a significantly lower aPR (0.64) and six with a higher aPR (1.36-4.63). CONCLUSIONS: Non-Hispanic Asian/PIs generally have a lower prevalence ratio for many birth defects while AI/ANs have a higher prevalence ratio compared to NH Whites. These findings update the limited literature on this topic and warrant additional research to identify the true associations across a range of birth defects among these understudied racial/ethnic groups.

Selected acculturation factors and birth defects in the National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Acculturation has been examined with respect to various pregnancy adverse outcomes, including birth defects. Given the mixed and limited findings on the association between nativity and birth defects, we sought to further explore parental nativity and years lived in the U.S. across a range of defects. METHODS: Data from the National Birth Defects Prevention Study were used for this analysis. Infants with one of 46 major isolated birth defects (30 noncardiac/16 cardiac conditions) and infants without birth defects (controls) born during 1997-2011 were included. We examined parental nativity (foreign-born mothers, fathers, and both parents combined compared to a referent of both U.S.-born parents) and the number of years lived in the U.S. (≤5/6+ years). Descriptive statistics and logistic regression analyses were performed to estimate crude/adjusted odds ratios and 95% confidence intervals. RESULTS: Compared to U.S.-born mothers, foreign-born mothers tended to be older (25+ years), of Hispanic or Other race/ethnicity and were less likely to have reported drinking, smoking, illicit drug use, or having taken folic acid. In the adjusted analysis, seven findings among both parents reporting a foreign-birth were significant, including an increased association with spina bifida, anotia/microtia, and diaphragmatic hernia (aORs range: 1.3-1.7), and a reduced association with craniosynostosis and gastroschisis (aORs = 0.7). A generally protective effect was observed among foreign-born subjects living in the U.S. ≤5 years. CONCLUSIONS: We found that nativity was associated with some selected isolated defects, although the direction of effect varied by phenotype and by a number of years residing in the U.S.

Janus kinases to jakinibs: from basic insights to clinical practice.

Cytokines are critical mediators of diverse immune and inflammatory diseases. Targeting cytokines and cytokine receptors with biologics has revolutionized the treatment of many of these diseases, but targeting intracellular signalling with Janus kinase (JAK) inhibitors (jakinibs) now represents a major new therapeutic advance. We are still in the first decade since these drugs were approved and there is still much to be learned about the mechanisms of action of these drugs and the practical use of these agents. Herein we will review cytokines that do, and just as importantly, do not signal by JAKs, as well as explain how this relates to both efficacy and side effects in various diseases. We will review new, next-generation selective jakinibs, as well as the prospects and challenges ahead in targeting JAKs.

JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis.

Janus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoid cells (ILCs) is still lacking. Herein, we observed that, in mice, the homeostatic pool of liver ILC1 was less affected by JAK inhibitors compared to the pool of NK cells present in the liver, spleen and bone marrow. JAK inhibition had overlapping effects on the transcriptome of both subsets, mainly affecting genes regulating cell cycle and apoptosis. However, the differential impact of JAK inhibition was linked to the high levels of the antiapoptotic gene Bcl2 expressed by ILC1. Our findings provide mechanistic explanations for the effects of JAK inhibitors on NK cells and ILC1 which could be of major clinically relevance.

Spontaneous dissection of the left main coronary artery treated with percutaneous coronary stenting.

Spontaneous coronary artery dissection is a rare and often fatal cause of acute myocardial ischemia occurring predominantly in young or middle-aged and otherwise healthy patients. We report a case of spontaneous dissection of the left main coronary artery in a young woman who was successfully treated with percutaneous coronary stent implantation.

Mycotic pseudoaneurysm of the left circumflex coronary artery: a fatal complication following drug-eluting stent implantation.

Coronary artery stent infection is a rare complication of percutaneous intervention. We report a case of fulminant coronary stent infection with Staphylococcus aureus presenting as a pseudoaneurysm of the left circumflex artery following repeated implantation of drug-eluting stents in the setting of multiple episodes of recurrent in-stent restenosis. We speculate that sirolimus- and paclitaxel-eluting stents may be more likely to predispose to infection than bare metal stents because of their immunomodulating and antiproliferative effects.