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PURPOSE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19). METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect. RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness. CONCLUSION: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.
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Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Índice de Severidad de la Enfermedad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estados Unidos/epidemiología , Vacunación/efectos adversosRESUMEN
PURPOSE: Mpox is a rare infectious disease. Lack of knowledge among eye care professionals regarding mpox keratitis greatly reduces the likelihood of diagnosis and effective management. This report and review seek to increase the knowledge of mpox keratitis among eye care professionals. METHODS: We report a patient with mpox keratitis who underwent successful penetrating keratoplasty, with 20 years of follow-up. A systematic literature search and review of cases of mpox keratitis from 1970 to 2024 was performed. RESULTS: A total of 24 articles and 2 abstracts reporting 35 cases of mpox keratitis were identified. A frequency of 0.5% to 1.0% may be the lower range of mpox keratitis among symptomatic patients with a confirmed mpox diagnosis. Mpox keratitis occurred with and without systemic mpox. Initial misdiagnoses were common (40%). Polymerase chain reaction results aided clinical diagnosis. Corneal disease ranged from mild epitheliopathy to fulminant ulcerative keratitis. Outcomes ranged from 20/20 acuity to no light perception. In the absence of fulminant systemic disease, tecovirimat was associated with clinical improvement of mpox keratitis in almost all cases. Our case is the only known report of successful penetrating keratoplasty for mpox keratitis and the only case whereby monkeypox virus was cultured from the corneal surface. CONCLUSIONS: Mpox keratitis is rare but can result in severe vision loss and blindness. Systemic tecovirimat seems to be effective in treating mpox keratitis, although the low frequency of keratitis precludes clinical trials. Topical steroids may extend virus survival in the cornea. Polymerase chain reaction may help confirm mpox corneal involvement.
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Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42â¯156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34â¯524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13â¯494 (39.1%) during the second or third trimester, and 18â¯985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.
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Vacunas contra la COVID-19 , COVID-19 , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/epidemiología , Recién Nacido , Anomalías Congénitas/epidemiología , Anomalías Congénitas/prevención & control , Nacimiento Vivo/epidemiología , Vacunación/efectos adversos , Vacunación/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.
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Anticuerpos Antivirales , Pruebas de Inhibición de Hemaglutinación , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Vacunas de Productos Inactivados , Vacunas Sintéticas , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Adulto , Anticuerpos Antivirales/sangre , Adulto Joven , Gripe Humana/prevención & control , Gripe Humana/inmunología , Femenino , Masculino , Persona de Mediana Edad , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Adolescente , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Wisconsin , Vacunación/métodos , Virus de la Influenza B/inmunología , Inmunogenicidad Vacunal , Técnicas de Cultivo de Célula , Estados Unidos , Formación de Anticuerpos/inmunología , Inmunización Secundaria/métodos , HuevosRESUMEN
OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.
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Vacunas contra la COVID-19 , COVID-19 , Resultado del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/epidemiología , Recién Nacido , Nacimiento Prematuro/epidemiología , SARS-CoV-2 , Complicaciones Infecciosas del Embarazo/prevención & control , Recién Nacido Pequeño para la Edad Gestacional , Adulto Joven , Vacunación/estadística & datos numéricosRESUMEN
In this multisite, observational, matched cohort study of more than 80,000 pregnant people, receipt of an mRNA monovalent coronavirus disease 2019 (COVID-19) booster vaccination in pregnancy was not associated with increased risk for thrombocytopenia, myocarditis, venous thromboembolism, ischemic stroke, or other serious adverse events within 21 or 42 days after booster vaccination. The mRNA monovalent COVID-19 booster in pregnancy was associated with an increased risk for medically attended malaise or fatigue within 7 days of vaccination (adjusted rate ratio [aRR] 3.64, 95% CI 2.42-5.48) and lymphadenopathy or lymphadenitis within 21 days (aRR 3.25, 95% CI 1.67-6.30) or 42 days (aRR 2.18, 95% CI 1.33-3.58) of vaccination. Our findings are consistent with prior evaluations of the primary COVID-19 vaccine series and are reassuring with respect to COVID-19 booster vaccination in pregnancy.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Embarazo , Estudios de Cohortes , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ARN Mensajero , Vacunación/efectos adversosRESUMEN
BACKGROUND: Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. METHODS: Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. RESULTS: From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). CONCLUSIONS: Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.
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Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , COVID-19 , Miocarditis , Pericarditis , Vacuna nCoV-2019 mRNA-1273/efectos adversos , Vacuna BNT162/efectos adversos , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Masculino , Miocarditis/epidemiología , Miocarditis/etiología , Pericarditis/epidemiología , Pericarditis/etiología , ARN Mensajero , Vacunación/efectos adversosRESUMEN
BACKGROUND: The human papillomavirus (HPV) vaccine is recommended for all adolescents age 11-12 years. HPV vaccine coverage remains suboptimal in the United States though, particularly in rural areas. We surveyed adolescent immunization providers in two Midwestern states to assess rural vs. urban differences in HPV vaccine resources, practices, and attitudes. METHODS: A cross-sectional survey was sent to all licensed adolescent care providers in a subset of urban and rural counties in Minnesota and Wisconsin during 2019. Multivariable regression was used to identify attitudes and practices that differentiated rural vs. urban providers. RESULTS: There were 437 survey respondents (31% rural). Significantly fewer rural providers had evening/weekend adolescent vaccination appointments available (adjusted odds ratio (aOR) = 0.21 [95% confidence interval (CI): 0.12, 0.36]), had prior experience with adolescent vaccine quality improvement projects (aOR = 0.52 [95% CI: 0.28, 0.98]), and routinely recommended HPV vaccine during urgent/acute care visits (aOR = 0.37 [95% CI: 0.18, 0.79]). Significantly more rural providers had standing orders to administer all recommended adolescent vaccines (aOR = 2.81 [95% CI: 1.61, 4.91]) and reported giving HPV vaccine information to their patients/families before it is due (aOR = 3.10 [95% CI: 1.68, 5.71]). CONCLUSIONS: Rural vs. urban differences in provider practices were mixed in that rural providers do not implement some practices that may promote HPV vaccination, but do implement other practices that promote HPV vaccination. It remains unclear how the observed differences would affect HPV vaccine attitudes or adolescent vaccination decisions for parents in rural areas.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Niño , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Estados Unidos , VacunaciónAsunto(s)
Vacunas contra la COVID-19 , COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vacunación , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Embarazo , Vacunación/efectos adversosRESUMEN
Background: Studies have shown that adolescent vaccination rates with human papillomavirus (HPV) and quadrivalent meningococcal conjugate (MenACWY) vaccines are lower in rural areas of the U.S. than in urban areas. We sought to determine factors associated with vaccine acceptance in these two settings. Methods: We conducted a cross-sectional survey of 536 parents or guardians of teens age 13 through 15 years in select rural and urban counties of Minnesota and Wisconsin. We collected information on demographic variables, receipt of adolescent vaccines, and attitudes toward HPV vaccine in particular. Multivariable logistic regression models were used to assess associations between covariates and outcomes of interest (HPV vaccine receipt and MenACWY receipt). Results: Of the 536 respondents, 267 (50%) resided in a rural county. Most respondents were female (78%) and non-Hispanic White (88%). About half (52%) of teens of the surveyed parents received the three vaccines recommended specifically for adolescents: 90% received tetanus-diphtheria-acellular pertussis (Tdap), 84% received MenACWY, and 60% received one or more doses of HPV vaccine. Rural and urban parents surveyed differed on several covariates relating to teen's health services, parent's demographics, and household characteristics. Parent's perception of the importance that their healthcare providers placed on vaccination with HPV and MenACWY were independently associated with receipt of each of those vaccines (odds ratio [OR] 6.37, 95% confidence interval [CI] 2.90-13.96 and OR 2.15, 95% CI 1.07-4.31, respectively). Parents of vaccinated teens were less likely to report concerns about potential harm from the HPV vaccine or having heard stories about health problems caused by the HPV vaccine. Conclusion: Teen receipt of HPV vaccine and MenACWY appears to be influenced by parents' perception of vaccine importance, provider recommendations, and concerns regarding potential harm from the HPV vaccine. Continued education of providers and parents of the importance of adolescent vaccinations is warranted.
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A 5-week-old infant born at term was diagnosed with acute necrotizing encephalopathy associated with severe acute respiratory syndrome coronavirus 2 as evidenced by clinical presentation, neuroimaging, and cerebrospinal fluid studies. Our patient was treated with high-dose intravenous methylprednisolone, tocilizumab, and intravenous immunoglobulin with significant short-term clinical improvement but long-term sequelae.
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Encefalopatías , COVID-19 , Encefalopatías/diagnóstico , Encefalopatías/etiología , COVID-19/complicaciones , Progresión de la Enfermedad , Humanos , Lactante , Metilprednisolona/uso terapéutico , NeuroimagenRESUMEN
COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).
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Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Nacimiento Prematuro/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Seguridad del Paciente , Embarazo , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , SARS-CoV-2/inmunología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: Childhood asthma is known to be associated with risks of both respiratory and non-respiratory infections. Little is known about the relationship between asthma and the risk of Kawasaki disease (KD). We assessed associations of asthma status and asthma phenotype (e.g. atopic asthma) with KD. METHODS: We performed a population-based retrospective case-control study, using KD cases between January 1, 1979, and December 31, 2016, and two matched controls per case. KD cases were defined by the American Heart Association diagnostic criteria. Asthma status prior to KD (or control) index dates was ascertained by the two asthma criteria, Predetermined Asthma Criteria (PAC) and Asthma Predictive Index (API, a surrogate phenotype of atopic asthma). We assessed whether 4 phenotypes (both PAC + and API+; PAC + only; API + only, and non-asthmatics) were associated with KD. RESULTS: There were 124 KD cases during the study period. The group having both PAC + and API + was significantly associated with the increased odds of KD, compared to non-asthmatics (odds ratio [OR] 4.3; 95% CI: 1.3 - 14.3). While asthma defined by PAC was not associated with KD, asthma defined by PAC positive with eosinophilia (≥4%) was significantly associated with the increased odds of KD (OR: 6.7; 95% CI: 1.6 - 28.6) compared to non-asthmatics. Asthma status defined by API was associated with KD (OR = 4.7; 95% CI: 1.4-15.1). CONCLUSIONS: Atopic asthma may be associated with increased odds of KD. Further prospective studies are needed to determine biological mechanisms underlying the association between atopic asthma and increased odds of KD.
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Asma , Síndrome Mucocutáneo Linfonodular , Asma/diagnóstico , Asma/epidemiología , Asma/etiología , Estudios de Casos y Controles , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.
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Agammaglobulinemia Tirosina Quinasa/genética , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Variación Genética , Mutación , Adulto , Agammaglobulinemia/enzimología , Agammaglobulinemia/inmunología , Linfocitos B/inmunología , Preescolar , Análisis Mutacional de ADN , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/enzimología , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Fenotipo , Adulto JovenRESUMEN
To assess the longitudinal incidence of Kawasaki disease (KD) within the well-defined predominantly White population of Olmsted County, MN. This retrospective cohort study used a population-based medical record linkage system and manual chart reviews to identify children with KD in Olmsted County, MN between January 1, 1979-December 31, 2016. Age- and gender-adjusted incidence rates were calculated using the 2010 U.S. White population. 124 children with KD were confirmed during the study period (median age 3.5, 61% male, 85% White, 9% Asian). The overall age- and gender-adjusted incidence rates for all ages and < 5 years old were 9.8 and 21.4 per 100,000 person-years, respectively. There was an overall increase in incidence up to 1994 followed by plateau, except among children between the ages of 1-5 years. There was also an overall increase in incidence among females compared to males. 24% of children had cardiac complications. While the overall incidence of KD in Olmsted County appears to be stable since 1994, the incidence of KD in subgroups of children 1-5 years old and females seems to have increased. Given the rising trends and one-quarter of children developing cardiac complications, further studies identifying factors driving these trends are warranted.
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Síndrome Mucocutáneo Linfonodular/epidemiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Minnesota/epidemiología , Estudios Retrospectivos , Población Blanca/estadística & datos numéricosRESUMEN
Severe combined immunodeficiency (SCID) includes a group of monogenic disorders presenting with severe T cell lymphopenia (TCL) and high mortality, if untreated. The newborn screen (NBS) for SCID, included in the recommended universal screening panel (RUSP), has been widely adopted across the US and in many other countries. However, there is a lack of consensus regarding follow-up testing to confirm an abnormal result. The Clinical Immunology Society (CIS) membership was surveyed for confirmatory testing practices for an abnormal NBS SCID result, which included consideration of gestational age and birth weight, as well as flow cytometry panels. Considerable variability was observed in follow-up practices for an abnormal NBS SCID with 49% confirming by flow cytometry, 39% repeating TREC analysis, and the remainder either taking prematurity into consideration for subsequent testing or proceeding directly to genetic analysis. More than 50% of respondents did not take prematurity into consideration when determining follow-up. Confirmation of abnormal NBS SCID in premature infants continues to be challenging and is handled variably across centers, with some choosing to repeat NBS SCID testing until normal or until the infant reaches an adjusted gestational age of 37 weeks. A substantial proportion of respondents included naïve and memory T cell analysis with T, B, and NK lymphocyte subset quantitation in the initial confirmatory panel. These results have the potential to influence the diagnosis and management of an infant with TCL as illustrated by the clinical cases presented herein. Our data indicate that there is clearly a strong need for harmonization of follow-up testing for an abnormal NBS SCID result.
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Infecciones Bacterianas , Síndrome de Job/diagnóstico , Factor de Transcripción STAT3/genética , Infecciones Bacterianas/complicaciones , Celulitis (Flemón)/microbiología , Niño , Diagnóstico Diferencial , Exantema/etiología , Genes Dominantes , Infecciones por Haemophilus/diagnóstico por imagen , Humanos , Hidrocefalia/complicaciones , Síndrome de Job/complicaciones , Síndrome de Job/genética , Masculino , Recurrencia , Streptococcus pyogenesRESUMEN
STUDY DESIGN: Basic science. OBJECTIVE: Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model. Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics. METHODS: K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed. RESULTS: Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals' cultures were significantly lower than all other groups (P < 0.0001) with negative culture results, except for one animal. The vancomycin-loaded MS-treated animals had lower bone bacterial counts than the controls (P < 0.0279); blank MS-treated animals had no differences in bacterial densities when compared to non-treated animals. CONCLUSION: Vancomycin powder and vancomycin-loaded MS were active against MRSE in vitro, in a rat MRSE implant model; however, vancomycin MS were inferior to the topical vancomycin powder. Vancomycin powder prevented MRSE infection in a rat spinal implant infection model.