Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273.

BACKGROUND: BNT162b2 (Pfizer/BioNTech, Comirnaty) and mRNA-1273 (Moderna, Spikevax) are messenger RNA (mRNA) vaccines that elicit antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) and have been approved by the US Food and Drug Administration to combat the coronavirus disease 2019 (COVID-19) pandemic. Because vaccine efficacy and antibody levels waned over time after the 2-shot primary series, the US Food and Drug Administration authorized a booster (third) dose for both mRNA vaccines to adults in the fall of 2021. OBJECTIVE: To evaluate the magnitude and durability of S-RBD immunoglobulin (Ig)G after the booster mRNA vaccine dose in comparison to the primary series. We also compared S-RBD IgG levels after BNT162b2 and mRNA-1273 boosters and explored effects of age and prior infection. METHODS: Surrounding receipt of the second and third homologous mRNA vaccine doses, adults in an employee-based cohort provided serum and completed questionnaires, including information about previous COVID-19 infection. The IgG to S-RBD was measured using an ImmunoCAP-based system. A subset of samples were assayed for IgG to SARS-CoV-2 nucleocapsid by commercial assay. RESULTS: There were 228 subjects who had samples collected between 7 and 150 days after their primary series vaccine and 117 subjects who had samples collected in the same time frame after their boost. Antibody levels from 7 to 31 days after the primary series and booster were similar, but S-RBD IgG was more durable over time after the boost, regardless of prior infection status. In addition, mRNA-1273 post-boost antibody levels exceeded BNT162b2 out to 5 months. CONCLUSION: The COVID-19 mRNA vaccine boosters increase antibody durability, suggesting enhanced long-term clinical protection from SARS-CoV-2 infection compared with the 2-shot regimen.

Cluster analysis of nasal cytokines during rhinovirus infection identifies different immunophenotypes in both children and adults with allergic asthma.

BACKGROUND: Infection with rhinovirus (RV) is a major risk factor for disease exacerbations in patients with allergic asthma. This study analysed a broad set of cytokines in the noses of children and adults with asthma during RV infection in order to identify immunophenotypes that may link to virus-induced episodes. METHODS: Nasal wash specimens were analysed in children (n = 279 [healthy, n = 125; stable asthma, n = 64; wheeze, n = 90], ages 2-12) who presented to a hospital emergency department, and in adults (n = 44 [healthy, n = 13; asthma, n = 31], ages 18-38) who were experimentally infected with RV, including a subset who received anti-IgE. Cytokines were measured by multiplex bead assay and data analysed by univariate and multivariate methods to test relationships to viral load, allergic status, airway inflammation, and clinical outcomes. RESULTS: Analysis of a core set of 7 cytokines (IL-6, CXCL8/IL-8, IL-15, EGF, G-CSF, CXCL10/IP-10 and CCL22/MDC) revealed higher levels in children with acute wheeze versus those with stable asthma or controls. Multivariate analysis identified two clusters that were enriched for acutely wheezing children; one displaying high viral load ("RV-high") with robust secretion of CXCL10, and the other displaying high IgE with elevated EGF, CXCL8 and both eosinophil- and neutrophil-derived mediators. Broader assessment of 39 cytokines confirmed that children with acute wheeze were not deficient in type 1 anti-viral responses. Analysis of 18 nasal cytokines in adults with asthma who received RV challenge identified two clusters; one that was "RV-high" and linked to robust induction of anti-viral cytokines and anti-IgE; and the other associated with more severe symptoms and a higher inflammatory state featuring eosinophil and neutrophil factors. CONCLUSIONS: The results confirm the presence of different immunophenotypes linked to parameters of airway disease in both children and adults with asthma who are infected with RV. Such discrepancies may reflect the ability to regulate anti-viral responses.

Lower viral loads in subjects with rhinovirus-challenged allergy despite reduced innate immunity.

BACKGROUND: Viral infections, especially those caused by rhinovirus, are the most common cause of asthma exacerbations. Previous studies have argued that impaired innate antiviral immunity and, as a consequence, more severe infections contribute to these exacerbations. OBJECTIVE: These studies explored the innate immune response in the upper airway of volunteers with allergic rhinitis and asthma in comparison to healthy controls and interrogated how these differences corresponded to severity of infection. METHODS: Volunteers with allergic rhinitis, those with asthma, and those who are healthy were inoculated with rhinovirus A16 and monitored for clinical symptoms. Tissue and nasal wash samples were evaluated for antiviral signature and viral load. RESULTS: Both subjects with allergic rhinitis and asthma were found to have more severe cold symptoms. Subjects with asthma had worsened asthma control and increased bronchial hyperreactivity in the setting of higher fractional exhaled breath nitric oxide and blood eosinophils. These studies confirmed reduced expression of interferons and virus-specific pattern recognition receptors in both cohorts with atopy. Nevertheless, despite this defect in innate immunity, volunteers with allergic rhinitis/asthma had reduced rhinovirus concentrations in comparison to the controls. CONCLUSION: These results confirm that the presence of an allergic inflammatory disorder of the airway is associated with reduced innate immune responsive to rhinovirus infection. Despite this, these volunteers with allergy have reduced viral loads, arguing for the presence of a compensatory mechanism to clear the infection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02910401.

Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma.

BACKGROUND: Allergic asthmatic subjects are uniquely susceptible to acute wheezing episodes provoked by rhinovirus. However, the underlying immune mechanisms and interaction between rhinovirus and allergy remain enigmatic, and current paradigms are controversial. OBJECTIVE: We sought to perform a comprehensive analysis of type 1 and type 2 innate and adaptive responses in allergic asthmatic subjects infected with rhinovirus. METHODS: Circulating virus-specific TH1 cells and allergen-specific TH2 cells were precisely monitored before and after rhinovirus challenge in allergic asthmatic subjects (total IgE, 133-4692 IU/mL; n = 28) and healthy nonallergic controls (n = 12) using peptide/MHCII tetramers. T cells were sampled for up to 11 weeks to capture steady-state and postinfection phases. T-cell responses were analyzed in parallel with 18 cytokines in the nose, upper and lower airway symptoms, and lung function. The influence of in vivo IgE blockade was also examined. RESULTS: In uninfected asthmatic subjects, higher numbers of circulating virus-specific PD-1+ TH1 cells, but not allergen-specific TH2 cells, were linked to worse lung function. Rhinovirus infection induced an amplified antiviral TH1 response in asthmatic subjects versus controls, with synchronized allergen-specific TH2 expansion, and production of type 1 and 2 cytokines in the nose. In contrast, TH2 responses were absent in infected asthmatic subjects who had normal lung function, and in those receiving anti-IgE. Across all subjects, early induction of a minimal set of nasal cytokines that discriminated high responders (G-CSF, IFN-γ, TNF-α) correlated with both egress of circulating virus-specific TH1 cells and worse symptoms. CONCLUSIONS: Rhinovirus induces robust TH1 responses in allergic asthmatic subjects that may promote disease, even after the infection resolves.

Understanding the asthmatic response to an experimental rhinovirus infection: Exploring the effects of blocking IgE.

BACKGROUND: Rhinovirus frequently causes asthma exacerbations among children and young adults who are allergic. The interaction between allergen and rhinovirus-induced symptoms and inflammation over time is unclear. OBJECTIVE: Our aim was to compare the response to an experimental inoculation with rhinovirus-16 in allergic asthmatics with the response in healthy controls and to evaluate the effects of administrating omalizumab before and during the infection. METHODS: Two clinical trials were run in parallel. In one of these trials, the response to an experimental inoculation with rhinovirus-16 among asthmatics with high levels of total IgE was compared to the response in healthy controls. The other trial compared the effects of administering omalizumab versus placebo to asthmatics in a randomized, double-blind placebo-controlled investigation. The primary outcome for both trials compared lower respiratory tract symptoms (LRTSs) between study groups over the first 4 days of infection. RESULTS: Frequent comparisons of symptoms, lung function, and blood eosinophil counts revealed differences that were more pronounced among allergic asthmatics than among controls by days 2 and 3 after virus inoculation. Additionally, an augmentation of upper respiratory tract symptom scores and LRTS scores occurred among the atopic asthmatics versus the controls during the resolution of symptoms (P < .01 for upper respiratory symptom tract scores and P < .001 for LRTS scores). The beneficial effects of administering omalizumab on reducing LRTSs and improving lung function were strongest over the first 4 days. CONCLUSIONS: LRTSs and blood eosinophil counts were augmented and lung function was reduced among allergic asthmatics early after rhinovirus inoculation but increased late in the infection during symptom resolution. The effect of administering omalizumab on the response to rhinovirus was most pronounced during the early/innate phase of the infection.

Comparison of viral load in individuals with and without asthma during infections with rhinovirus.

RATIONALE: Most virus-induced attacks of asthma are caused by rhinoviruses (RVs). OBJECTIVES: To determine whether people with asthma are susceptible to an increased viral load during RV infection. METHODS: Seventy-four children (4-18 yr old) were enrolled; 28 with wheezing, 32 with acute rhinitis, and 14 without respiratory tract symptoms. Nasal washes were evaluated using quantitative polymerase chain reaction for RV to judge viral load along with gene sequencing to identify strains of RV. Soluble intercellular adhesion molecule-1, IFN-λ1, and eosinophil cationic protein in nasal washes, along with blood eosinophil counts and total and allergen-specific IgE in sera, were also evaluated. Similar assessments were done in 24 young adults (16 with asthma, 8 without) who participated in an experimental challenge with RV (serotype 16). MEASUREMENTS AND MAIN RESULTS: Fifty-seven percent of wheezing children and 56% with acute rhinitis had nasal washes testing positive for RV. The geometric mean of viral loads by quantitative polymerase chain reaction in washes from wheezing children was 2.8-fold lower, but did not differ significantly from children with rhinitis (7,718 and 21,612 copies of viral RNA per microliter nasal wash, respectively; P = 0.48). The odds for wheezing were increased if children who tested positive for RV were sensitized to one or more allergens (odds ratio, 3.9; P = 0.02). Similarly, neither peak nor cumulative viral loads differed significantly in washes from adults with asthma compared with those without asthma during the experimental RV challenge. CONCLUSIONS: During acute symptoms, children infected with RV enrolled for wheezing or acute rhinitis had similar viral loads in their nasal washes, as did adults with and without asthma infected with RV-16 experimentally.

Mammalian Meat Allergy and IgE to Alpha-gal in in Central Virginia: findings from a COVID-19 vaccine and patient cohort.

BACKGROUND: IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked with tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The "alpha-gal syndrome" (AGS) is recognized as being common in the southeastern USA, however prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. OBJECTIVE: Here we characterized the prevalence, as well as presentation and risk factors, of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regards to history of allergic disease. METHODS: Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. ImmunoCAP was used for IgE assays and ABO blood group was assessed by reverse typing using stored serum. Biobanked serum from COVID-19 patients was also investigated. RESULTS: Of 267 enrollees, median age was 42, 76% were female and 43 (16%) were sensitized to alpha-gal (cut-off 0.1 IU/mL), of which mammalian meat allergy was reported by 7 (2.6%). Sensitized subjects were i) older, ii) had higher total IgE levels but similar frequency of IgE to common respiratory allergens, and iii) were more likely to report tick bites than non-sensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat allergic than non-allergic subjects (GM 9.0 vs 0.5 IU/mL, P<0.001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. CONCLUSION: In central Virginia AGS is a dominant cause of adult food allergy with a prevalence approaching or exceeding 2%.

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19.

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.

High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus.

BACKGROUND: The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear. OBJECTIVE: We sought to examine the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden. METHODS: The children enrolled (n= 287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, IgE, allergen-specific IgE antibody, and fraction of exhaled nitric oxide levels. RESULTS: Sixty-four percent of wheezing children compared with 13% of children with stable asthma and 13% of nonasthmatic control subjects had positive test results for rhinovirus (P< .001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides species) were common and correlated significantly with total IgE and fraction of exhaled nitric oxide levels. The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite of 17.5 IU/mL or greater who tested positive for rhinovirus (odds ratio for wheezing, 31.5; 95% CI, 8.3-108; P< .001). CONCLUSIONS: High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.

Trajectory of IgG to SARS-CoV-2 After Vaccination With BNT162b2 or mRNA-1273 in an Employee Cohort and Comparison With Natural Infection.

Three COVID-19 vaccines have received FDA-authorization and are in use in the United States, but there is limited head-to-head data on the durability of the immune response elicited by these vaccines. Using a quantitative assay we studied binding IgG antibodies elicited by BNT162b2, mRNA-1273 or Ad26.COV2.S in an employee cohort over a span out to 10 months. Age and sex were explored as response modifiers. Of 234 subjects in the vaccine cohort, 114 received BNT162b2, 114 received mRNA-1273 and six received Ad26.COV2.S. IgG levels measured between seven to 20 days after the second vaccination were similar in recipients of BNT162b2 and mRNA-127 and were ~50-fold higher than in recipients of Ad26.COV2.S. However, by day 21 and at later time points IgG levels elicited by BNT162b2 were lower than mRNA-1273. Accordingly, the IgG decay curve was steeper for BNT162b2 than mRNA-1273. Age was a significant modifier of IgG levels in recipients of BNT162b2, but not mRNA-1273. After six months, IgG levels elicited by BNT162b2, but not mRNA-1273, were lower than IgG levels in patients who had been hospitalized with COVID-19 six months earlier. Similar findings were observed when comparing vaccine-elicited antibodies with steady-state IgG targeting seasonal human coronaviruses. Differential IgG decay could contribute to differences observed in clinical protection over time between BNT162b2 and mRNA-1273.

Management of Hypoparathyroidism.

Hypoparathyroidism (HypoPT) is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. HypoPT is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to nonsurgical causes. In both groups of patients, conventional therapy includes calcium and active vitamin D analogue therapy aiming to maintain serum calcium concentration in the low normal or just below the normal reference range and normalize serum phosphorus, magnesium concentrations, and urine calcium levels. The limitations of conventional therapy include wide fluctuations in serum calcium, high pill burden, poor quality of life, and renal complications. Parathyroid hormone (PTH) replacement therapy may improve the biochemical profile in those in whom conventional therapy proves unsatisfactory. Based on a systematic review and meta-analysis of the literature, the panel made a graded recommendation suggesting conventional therapy as first line therapy rather than administration of PTH (weak recommendation, low quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers use of PTH. Because pregnancy and lactation are associated with changes in calcium homeostasis, close monitoring is required during these periods with appropriate adjustment of calcium and active vitamin D analogue therapy to ensure that serum calcium remains in the mid to low normal reference range in order to avoid maternal and fetal complications. Emerging therapies include molecules with prolonged PTH action as well as different mechanisms of action that may significantly enhance drug efficacy and safety. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Factors associated with children's anticipated responses to ambiguous teases.

The authors used two studies involving 5th- and 6th-grade children to examine factors potentially associated with individual differences in children's perceptions of and anticipated responses to ambiguous teases. Study 1 assessed the extent to which the children would expect recipients to feel hurt in response to a series of ambiguous teases and whether the children would perceive those teases as more like antisocial or prosocial teases. In Study 2 the children were asked to evaluate emotional and behavioral responses to ambiguous teases with various gender compositions of the teaser-target dyad. Despite some gender of participant differences, the studies demonstrated that children with relatively negative attitudes toward teases and relatively negative experiences as recipients of teases tended to interpret ambiguous teases as if they were meant to be hostile and antisocial.

Benefit of a Stroke Management Program.

Hospital participation in stroke bundle programs presents financial risk. There are limited comparative data on the success of such programs. The authors aimed to assess the success of a management program in reducing the number of patients admitted to a skilled nursing facility (SNF), average length of stay, and the number of patients discharged to inpatient rehabilitation units. Three program metrics included reduction in number of stroke patients admitted to SNF, reduction in length of stay at SNFs, and reduced 90-day hospital readmission rates. The program was implemented during a 3-year period from October 1, 2015, through September 30, 2018, included 803 patients in the data, and demonstrated financial gain with positive patient outcomes. There was a 0.5% reduction in the number of stroke patients admitted to SNF. Sending patients home with a high-quality home care agency for rehabilitation and navigation assistance were the goals for this metric. A 1.65-day reduction in length of stay for overall SNF providers was noted. This was achieved by utilizing a preferred network of skilled facilities and community partners that the nurse navigator interfaced with weekly. The proportion of patients discharged to inpatient rehabilitee units was 2.2% less than in the baseline years. With the implementation of a stroke nurse navigator, hospital readmissions as a percentage of admissions for stroke decreased by 4%. Overall return on investment was greater than 400% after accounting for additional staffing and data/license fees.

Pandemic Care Through Collaboration: Lessons From a COVID-19 Field Hospital.

During the surge of Coronavirus Disease 2019 (COVID-19) infections in March and April 2020, many skilled-nursing facilities in the Boston area closed to COVID-19 post-acute admissions because of infection control concerns and staffing shortages. Local government and health care leaders collaborated to establish a 1000-bed field hospital for patients with COVID-19, with 500 respite beds for the undomiciled and 500 post-acute care (PAC) beds within 9 days. The PAC hospital provided care for 394 patients over 7 weeks, from April 10 to June 2, 2020. In this report, we describe our implementation strategy, including organization structure, admissions criteria, and clinical services. Partnership with government, military, and local health care organizations was essential for logistical and medical support. In addition, dynamic workflows necessitated clear communication pathways, clinical operations expertise, and highly adaptable staff.

Measurement of Patients' Perceptions of the Quality of Acute Stroke Services: Development and Validation of the STROKE Perception Report.

INTRODUCTION: Patients' perceptions of healthcare quality have become an important part of quality measurement. We explored patients' and family's lived experiences during acute stroke hospitalization to develop a quantitative instrument. METHODS: Focus groups were conducted using open-ended scripted questions. Interview data were coded and analyzed using an inductive approach to thematic analysis. Symmetric patient and family instruments were developed based on qualitative domains and serially refined to a set of 30 survey items, 12 stroke knowledge test items, and 5 subject demographic fields. Scales were evaluated for internal consistency reliability using Cronbach α; construct validity with exploratory factor analysis using principal components with varimax rotation was performed to determine the extent to which items in a scale measure the same underlying factor. Feasibility of an electronic cloud-based survey was also tested. RESULTS: Three main themes emerged: fast action to diagnose and treat stroke, genuine caring, and education to prevent and respond to stroke. A total of 1029 subjects completed the final instrument with no differences in perception found by race, ethnicity, or length of stay. Scales showed satisfactory internal consistency reliability (Cronbach α scores, .89-.94); factor loadings across each scale ranged from 0.55 to 0.87. Data entry by electronic pad was perceived by 77% to be more confidential than paper surveys; median score for difficulty was 4 ("easy to use"). CONCLUSION: The STROKE Perception Report enables understanding of patients' and family's beliefs about the quality of acute stroke care in essential new domains never explored before.

Long-term efficacy and safety of sirolimus-eluting vs bare-metal stents.

BACKGROUND: Although previous studies have documented persistent clinical benefit of sirolimus-eluting stents (SES)in reducing the need for target vessel revascularization without an increase in myocardial infarction (MI) or mortality, the long-term safety and efficacy of CYPHER stent use in routine clinical practice, including off-label stent implantation, remains uncertain. METHODS: We compared long-term clinical outcomes in 2,550 patients treated with one or more SES with 1,022 patients treated with one or more bare metal or heparin-coated stents (BMS). The study groups included 1,058 SES patients (41.5%) and 488 BMS patients (47.7%) with off-label indications. A propensity-score method was utilized to adjust for differences in baseline characteristics. Patients were followed for up to five years for the occurrence of all-cause mortality, MI and repeat target vessel revascularization. RESULTS: Compared to BMS patients, SES patients demonstrated significantly improved event-free survival with respect to all-cause mortality (RR, 1.39; 95% CI, 1.07 to 1.80, P = 0.014) and repeat target vessel revascularization (RR, 2.72; 95% CI, 1.99 to 3.73, P < 0.001), with no significant difference in the incidence of cumulative MI. A landmark analysis, examining composite adverse events occurring six months after stent implantation in the two study groups, demonstrated no increased late hazard associated with SES use (relative risk, 1.08; 95% CI, 0.80 to 1.46). CONCLUSIONS: Use of SES in routine clinical practice, including off-label indications, is associated with improved long-term mortality, reduced need for repeat target vessel revascularization and no increase in MI compared to BMS.

Qigong in Injured Military Service Members.

BACKGROUND: Wounded, ill, and injured (WII) Military Service members experience significant stress and are at risk for developing chronic conditions including posttraumatic stress disorder and depression. Qigong, a meditative movement practice, may positively affect their ability to engage in successful rehabilitation. PURPOSE: We assessed the feasibility of Qigong practice in WII Service members returning from combat; effects on stress, sleep, and somatic symptoms; satisfaction; and participants' experience with the practice. DESIGN: Single-group, pre- and posttest, mixed methods approach. METHOD: Twenty-six WII were enrolled. The program was designed to include 20 classes over 10 weeks. Participants completed self-report questionnaires, practice logs, and an exit interview. FINDINGS: Average attendance was 8.14 classes ( SD = 4.9); mean engagement was 5.7 ( SD = 3.5) weeks. Participants endorsed a high level of satisfaction with the practice. Qualitative themes included coping with stress; feeling more resilient and empowered; improvement in symptoms including sleep and physical function; and factors affecting practice. Participant-reported facilitators included accessibility and portability of the practice; barriers included scheduling conflicts and personal challenges. Participants recommended offering shorter programs with flexible scheduling options, increasing program awareness, and including significant others in future classes. CONCLUSION: Qigong was safe, portable, and easily adapted for WII Service members.

Rhinovirus infection results in stronger and more persistent genomic dysregulation: Evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence.

BACKGROUND: Rhinovirus (HRV) is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined. METHODS: Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis. RESULTS: At baseline, 57 genes were differentially expressed between asthmatics and controls, and the asthmatics had decreased expression of viral replication inhibitors and increased expression of genes involved in inflammation. At 36 hours (before the emergence of peak symptoms), 1329 genes were significantly altered from baseline in the asthmatics compared to 62 genes in the controls. At this time point, asthmatics lacked an increase in IL-10 signaling observed in the controls. At 7 days following HRV inoculation, 222 genes were significantly dysregulated in the asthmatics, whereas only 4 genes were dysregulated among controls. At this time point, the controls but not asthmatics demonstrated upregulation of SPINK5. CONCLUSIONS: As judged by the magnitude and persistence of dysregulated genes, asthmatics have a substantially different host response to HRV-A16 infection compared with non-asthmatic controls. Gene expression differences illuminate biologically plausible mechanisms that contribute to a better understanding of the pathogenesis of HRV-induced asthma exacerbations.

Comparison of results of percutaneous coronary intervention for non-ST-elevation acute myocardial infarction or unstable angina pectoris in men versus women.

Previous randomized trials have addressed the impact of gender on outcomes, showing worse results in women assigned to invasive strategies compared with men with non-ST-elevation (NSTE) acute coronary syndrome (ACS). However, there is still a significant amount of controversy on strategies of treatment on the basis of gender. This study evaluated the impact of gender on treatment strategies and outcomes in patients with NSTE ACS in a high-volume, single-site tertiary center. We identified 1,197 consecutive patients with NSTE ACS (381 women, 816 men) who underwent percutaneous coronary intervention during their index hospitalizations. Patients were stratified by gender and baseline clinical and angiographic characteristics, and in-hospital and 9-month clinical outcomes were compared between the 2 groups. There were clear differences in baseline characteristics between men and women with ACS at presentation. Women were, on average, slightly older than men, with more hypertension and morbid obesity, but there were no differences in racial backgrounds or the prevalence of diabetes or dyslipidemia, nor were there treatment disparities in pharmacologic interventions. Women and men with ACS had similar rates of percutaneous coronary intervention on index admission. Women had a greater incidence of bleeding complications requiring blood transfusions. Overall, in-hospital and 9-month event-free survival were equivalent for the 2 genders. In conclusion, in this single-site observational study, patients with NSTE ACS who underwent angiography followed by percutaneous coronary intervention demonstrated no significant gender differences in treatment or in-hospital or 9-month event-free survival. From these results, interventional strategies should not be based on gender.