Factors influencing creatine kinase-MM concentrations in newborns and implications for newborn screening for Duchenne muscular dystrophy.

INTRODUCTION: Newborn screening for Duchenne muscular dystrophy can be performed via a first-tier creatine kinase-MM measurement followed by reflex testing to second-tier molecular analysis of the DMD gene. In order to establish appropriate cut-offs for the creatine kinase-MM screen, factors that influence creatine kinase-MM in newborns were investigated. MATERIALS AND METHODS: Creatine kinase-MM data from a consented pilot study in New York State were collected over a two-year period and combined with de-identified validation data and analyzed. Univariate analysis and multiple linear regression analysis were performed. RESULTS: The analysis indicated that age of newborn at specimen collection, gestational age and birth weight were significant influencers of CK-MM levels in newborns. In addition, to a lesser extent, sex, race/ethnicity and seasonal temperature also affect CK-MM levels in newborns. CONCLUSIONS: To reduce false positive and false negative cases, newborn screening programs should be cognizant of factors that influence CK-MM when determining cut-offs for the assay. Variability based on age at specimen collection and birth weight are primarily observed within the first week of life. Therefore, particularly during this time period, multi-tiered cut-offs based on age of collection and lower cut-offs for premature and low birth weight babies are recommended. Other cut-off determinants may include sex, race/ethnicity and seasonal temperature.

Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.

Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by immunoglobulin G (IgG), with an IgG subclass ratio skewed toward elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2-specific antibody binding to the inflammatory receptor FcÉ£RIIIa. Based on these correlational studies, we propose that spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy.

The Impact of Seasonal Changes on Thyroxine and Thyroid-Stimulating Hormone in Newborns.

Newborn screening for congenital hypothyroidism (CH) is performed by measuring the concentration of thyroxine (T4) and/or thyroid-stimulating hormone (TSH) in dried blood spots. Unfortunately, the levels of T4 and TSH vary due to multiple factors, and therefore the false-positive rate for the test is a challenge. We analyzed screening data from 2008 to 2017 to determine the effect of seasonal changes and manufacturer kit lot changes on T4 and TSH values and on numbers of infants referred. Over a 10-year period, we screened 2.4 million infants using commercially available fluoroimmunoassays to measure T4 and TSH concentrations in dried blood spots. During colder months, daily mean T4 and TSH values were higher and referral rates and false-positive rates were higher. However, there was no significant difference between the number of confirmed CH cases. Furthermore, in rare instances, we observed differences in T4 daily mean values during the 10-year period when manufacturer kit lot changes were made. Seasonal temperature variations influence measured T4 and TSH values and consequently lower the positive predictive value for CH testing in colder months. Newborn screening (NBS) programs should be aware that manufacturer kit lot changes may also influence T4 values.

HIV test offers and acceptance: New York State findings from the behavioral risk factor surveillance system and the National HIV behavioral surveillance, 2011-2012.

BACKGROUND: The New York State HIV testing law requires that patients aged 13-64 years be offered HIV testing in health care settings. We investigated the extent to which HIV testing was offered and accepted during the 24 months after law enactment. METHODS: We added local questions to the Behavioral Risk Factor Surveillance System (BRFSS) and the National HIV Behavioral Surveillance (NHBS) surveys asking respondents aged 18-64 years whether they were offered an HIV test in health care settings, and whether they had accepted testing. Statewide prevalence estimates of test offers and acceptance were obtained from a combined 2011-2012 BRFSS sample (N = 6,223). Local estimates for 2 high-risk populations were obtained from NHBS 2011 men who have sex with men (N = 329) and 2012 injection drug users (N = 188) samples. RESULTS: BRFSS data showed that 73% of New Yorkers received care in any health care setting in the past 12 months, of whom 25% were offered an HIV test. Sixty percent accepted the test when offered. The levels of test offer increased from 20% to 29% over time, whereas acceptance levels decreased from 68% to 53%. NHBS data showed that 81% of men who have sex with men received care, of whom 43% were offered an HIV test. Eighty-eight percent accepted the test when offered. Eighty-five percent of injection drug users received care, of whom 63% were offered an HIV test, and 63% accepted the test when offered. CONCLUSIONS: We found evidence of partial and increasing implementation of the HIV testing law. Importantly, these studies demonstrated New Yorkers' willingness to accept an offered HIV test as part of routine care in health care settings.