Consequences of low estimated glomerular filtration rate either before or early after kidney donation.

In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks. One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m2; 1.2% eGFR<30 mL/min/1.73m2; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m2 (N = 79) was 17 years, and eGFR<30 mL/min/1.73m2 (N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m2 (P < .0001) and eGFR<30 mL/min/1.73m2 (P < .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m2 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), but not CVD, hypertension, DM, or death.

Race, rituximab, and relapse in TTP.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Should children receive a kidney transplant before 2 years of age?

BACKGROUND: The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years. METHOD: We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased-donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis-free time was defined as graft survival time for cases and the sum of dialysis-free time on the waitlist and graft survival time for controls. RESULTS: We observed similar patient survival for posttransplant periods 0-3 and 4-12 months but higher survival for period >12 months for <2-year decreased-donor recipients (aHR: 0.32; 95% CI: 0.13-0.78; p = .01) compared with controls. Similarly, patient survival was higher for <2-year living-donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06-0.73; p = .01). The 5-year dialysis-free survival was higher for <2-year deceased- (difference: 0.59 years; 95% CI: 0.23-0.93) and living-donor (difference: 1.84 years; 95% CI: 1.31-2.25) recipients. CONCLUSION: Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years.

New Morbidities During Critical Illness and Associated Risk of ICU Readmission: Virtual Pediatric Systems Cohort, 2017-2020.

OBJECTIVES: To describe change in Functional Status Scale (FSS) associated with critical illness and assess associated development of new morbidities with PICU readmission. DESIGN: Retrospective, cross-sectional cohort study using the Virtual Pediatric Systems (VPS; Los Angeles, CA) database. SETTING: One hundred twenty-six U.S. PICUs participating in VPS. SUBJECTS: Children younger than 21 years old admitted 2017-2020 and followed to December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 40,654 patients, 86.2% were classified as having good function or mild dysfunction before illness. Most patients did not have a change in their FSS category during hospitalization. Survival with new morbidity occurred most in children with baseline good/mild dysfunction (8.7%). Hospital mortality increased across categories of baseline dysfunction. Of 39,701 survivors, 14.2% were readmitted within 1 year. Median time to readmission was 159 days. In multivariable, mixed-effects Cox modeling, time to readmission was most associated with discharge functional status (hazard ratio [HR], 5.3 [95% CI, 4.6-6.1] for those with very severe dysfunction), and associated with lower hazard in those who survived with new morbidity (HR, 0.7 [95% CI, 0.6-0.7]). CONCLUSIONS: Development of new morbidities occurs commonly in pediatric critical illness, but we failed to find an association with greater hazard of PICU readmission. Instead, patient functional status is associated with hazard of PICU readmission.

School Connectedness and Adolescent E-cigarette Susceptibility in an Urban Sample of Middle and High School Students.

Adolescent school connectedness generally protects from risk behaviors such as tobacco use; however, its relationship to e-cigarette use is unclear. This study examines the relationship between adolescent school connectedness and e-cigarette susceptibility in a diverse longitudinal sample. This secondary analysis of a school-based intervention surveyed 608 middle (66%) and high school (34%) students from 10 schools at 3 time points over 1 year. At baseline, respondents had a mean age of 14 years, 54% were female, and 71% were BIPOC (Black, Indigenous, People of Color). Logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and e-cigarette susceptibility over time. E-cigarettes represented the most prevalent form of current nicotine-containing product use in spring 2019 (2.3%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility remained relatively stable during the study. Higher baseline school connectedness levels were associated with lower odds of e-cigarette susceptibility over time. Similarly, higher concurrent school connectedness scores were associated with lower odds of e-cigarette susceptibility over time: spring 2019 (OR, 0.39; 95% CI, 0.32, 0.47), fall 2019 (OR, 0.49; 95% CI, 0.34, 0.72), and spring 2020 (OR, 0.64; 95% CI, 0.47, 0.87). Findings were similar for middle and high school students and did not differ significantly after adjusting for other covariates. Adolescents' school connectedness appears to protect from e-cigarette susceptibility over time, underscoring the importance of promoting positive school experiences to reduce adolescent risk e-cigarette use.

A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative.

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithm's parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.

Prolonged Elevations of Factor VIII and von Willebrand Factor Antigen After Multisystem Inflammatory Syndrome in Children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019 infection, with less characterization in MIS-C. Here we describe novel findings of nearly universal severe and prolonged factor VIII (FVIII) and von Willebrand factor antigen elevations in an institutional cohort of patients with MIS-C ages younger than or 21 years old (N=31). All patients had elevated acute phase reactants and D-dimer at presentation and met published criteria for MIS-C. FVIII was high at presentation in 97% of patients but continued to rise during the ensuing weeks of treatment to a mean 429%, peaking on median day 17 of illness as an outpatient. FVIII levels were >600% in multiple patients. von Willebrand factor antigen was measured less frequently but showed similar trends. These escalations occurred amidst resolving cardiac dysfunction and acute phase reactant normalization and despite patients receiving multimodal anti-inflammatory treatments and aspirin and enoxaparin thromboprophylaxis. No thrombotic events occurred. Endothelial dysfunction represented by very elevated FVIII levels may persist longer than other acute phase reactants may reflect.

Neuroimaging and biomarker evidence of neurodegeneration in asthma.

BACKGROUND: Epidemiologic studies have shown that Alzheimer's disease (AD) and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. OBJECTIVE: To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (phosphorylated tau 181, p-Tau181), neurodegeneration (neurofilament light chain, NfL), and glial activation (glial fibrillary acidic protein, GFAP). METHODS: dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration, and glial activation, indexed by plasma p-Tau181, NfL, and GFAP, respectively. Additional relationships were tested with cognitive function. RESULTS: Asthma participants had widespread and large-magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and which were robustly associated with GFAP and, to a lesser extent, NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn were associated with slower processing speed, a test of cognitive performance. CONCLUSIONS: Asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration, and may be a potential risk factor for neural injury and cognitive dysfunction. There is a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects.

Health topics emerged from brief-motivational interviewing: A randomized clinical trial.

OBJECTIVE: The goal of this study was to analyse transcription of audio recordings to determine health topics that emerged from brief-motivational interviewing (MI) compared to traditional oral hygiene instructions (OHI). METHODS: Fifty-eight periodontal maintenance patients were randomized to a brief-MI or traditional OHI group for a longitudinal 1-year clinical trial. Both groups received four patient education sessions per their assigned group. Audio recordings were transcribed and coded. The overarching themes and subthemes emerged were quantified and reported as the number of instances per participant. Global scores and behavioural counts were compared across baseline, 4, 8, and 12-month research visits using mixed-effect models. RESULTS: Of the six overarching themes, the brief-MI group evoked more topics toward total health. Oral home care behaviours (15 vs. 10.2) and oral diseases/conditions (3.3 vs. 1.9) were discussed more in the brief-MI group compared to the traditional OHI group. This positive outcome for the average number of times a health topic was discussed in the brief-MI group compared to the traditional OHI group continued for the remaining major themes: lifestyle behaviours (1.0 vs. 0.4), nutrition (2.6 vs. 0.8), emotional/mental health (1.8 vs. 0.8) and general health (1.2 vs. 0.4). CONCLUSION: This study identified that brief-MI was a more successful communication approach to increase discussions of oral home care behaviours, oral diseases/conditions, lifestyle behaviours, nutrition, emotional/mental health and general health compared to traditional OHI in individuals with periodontitis.

Mucus Plugs in Asthma at CT Associated with Regional Ventilation Defects at 3He MRI.

Background Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. Purpose To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 (3He) MRI. Materials and Methods In this secondary analysis of a Health Insurance Portability and Accountability Act-compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized 3He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. Results Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th-75th percentile, 7.3%-38.3%) versus 1.4% (25th-75th percentile, 0.1%-5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments (P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th-75th percentile, 7.1%-18.9%) versus 3.1% (25th-75th percentile, 1.1%-4.4%) in those without plugs (P < .001). Conclusion Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

The mixed spongiotic and interface reaction pattern: A study of clinical and histopathologic findings.

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern. METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified. RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04). CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

Racial disparities and trends in kidney transplant outcomes in patients with Alport syndrome.

BACKGROUND: Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown. MATERIALS AND METHODS: We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models. RESULTS: The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race. CONCLUSION: We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection.Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P < 0.001, χ2) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A; P < 0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (P < 0.0001), CDHR3 genotype (P < 0.05), and wheezing illnesses (P < 0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time.Conclusions: Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.

Developmental patterns in the nasopharyngeal microbiome during infancy are associated with asthma risk.

BACKGROUND: Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. OBJECTIVES: In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. METHODS: Children participating in the Childhood Origins of Asthma study (N = 285) provided nasopharyngeal mucus samples in the first 2 years of life, during routine healthy study visits (at 2, 4, 6, 9, 12, 18, and 24 months of age), and during episodes of respiratory illnesses, all of which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and we correlated these with presence of asthma at 6, 8, 11, 13, and 18 years of age. RESULTS: Of the 4 microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. CONCLUSION: In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma.

Ensemble Analysis Identifies Nasal 15-Keto-PGE2 as a Predictor of Recovery in Experimental Rhinovirus Colds.

BACKGROUND: Symptom intensity during a common cold is highly variable, particularly after the illness peaks, contributing to delay in recovery. Rhinoviruses frequently cause colds and, during acute infections, generate leukotriene B4 and prostaglandin E2 (PGE2). PGE2 is known to initiate oxylipin class switching and resolution of acute inflammation. Thus, we hypothesized that during acute rhinovirus colds, oxylipins with pro-resolving capabilities reduce symptom severity and speed recovery. METHODS: Four groups of healthy volunteers were inoculated with placebo or 3 different doses of rhinovirus A16. Participants kept daily records of symptoms and contributed serial nasal lavage fluid samples. We collected semi-quantitative mass spectrometry data for 71 oxylipins in these acute samples from all participants. An ensemble analysis approach was used to further reduce this dataset. RESULTS: Levels of 15-keto-PGE2 at day 3 of the cold were consistently among the top candidates in these models of recovery symptoms. 15-keto-PGE2 was the only oxylipin with an interaction between inoculum dose and time. Acute 15-keto-PGE2 levels were inversely associated with symptoms during cold recovery in a multivariable analysis (P = .0043). CONCLUSIONS: These findings show that high 15-keto-PGE2 levels during the acute cold are associated with fewer symptoms during recovery.

Use of expanded-criteria donors and > 85 KDPI kidneys for pediatric kidney transplantation in the United States.

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.

Comparison of prenatal anti-D titration testing by gel and tube methods: A review of the literature.

BACKGROUND: Antenatal titration testing is traditionally performed using a manual tube test. Tube testing has limitations; it is a manual, time-consuming method with wide interobserver variability. Gel-based testing is an attractive alternative because it is more precise and can be automated. This study's objective was to summarize the published literature that assessed the relationship between titrations performed by tube and gel for anti-D alloimmunized pregnancies. STUDY DESIGN AND METHODS: A comprehensive literature search was performed. Articles were selected if research was original and compared at least five pairs of anti-D titration tests performed by gel and tube. Differences in the number of dilutions between gel and tube methods were compared overall by study and cell type using linear models. RESULTS: A total of 512 articles were identified; eight were included, and titer data from 384 tube and gel pairs were abstracted. The median anti-D titer in tube was 8 (range 0-2048) and by gel was 64 (range 0-4096). Anti-D gel titration results were 2.1 (95% CI; 1-3.3) additional dilutions greater than in tube. Most studies utilized double-dose reagent cells for testing. At a tube titer of 16, the sensitivity and specificity of gel titrations is maximal (91% and 94% respectively) at a gel titer of 64. CONCLUSION: Overall, titrations performed by gel were two dilutions higher than the corresponding tube titer. For titrations, double-dose reagent cells should be considered to standardize practice. A rigorous prospective study is needed to compare tube titrations with gel titrations using a standardized process.

Aerosol Generation from the Respiratory Tract with Various Modes of Oxygen Delivery.

Rationale: Aerosol generation with modes of oxygen therapy such as high-flow nasal cannula and noninvasive positive-pressure ventilation is a concern for healthcare workers during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The amount of aerosol generation from the respiratory tract with these various oxygen modalities is unknown.Objectives: To measure the size and number concentration of particles and droplets generated from the respiratory tract of humans exposed to various oxygen delivery modalities.Methods: Ten healthy participants with no active pulmonary disease were enrolled. Oxygen modalities tested included nonhumidified nasal cannula, face mask, heated and humidified high-flow nasal cannula, and noninvasive positive-pressure ventilation. Aerosol generation was measured with each oxygen mode while participants performed maneuvers of normal breathing, talking, deep breathing, and coughing. Testing was conducted in a negative-pressure room. Particles with a diameter between 0.37 and 20 µm were measured using an aerodynamic particle spectrometer.Measurements and Main Results: Median particle concentration ranged from 0.041 to 0.168 particles/cm3. Median diameter ranged from 1.01 to 1.53 µm. Cough significantly increased the number of particles measured. Measured aerosol concentration did not significantly increase with the use of either humidified high-flow nasal cannula or noninvasive positive-pressure ventilation. This was the case during normal breathing, talking, deep breathing, and coughing.Conclusions: Oxygen delivery modalities of humidified high-flow nasal cannula and noninvasive positive-pressure ventilation do not increase aerosol generation from the respiratory tract in healthy human participants with no active pulmonary disease measured in a negative-pressure room.

Patterns of farm exposure are associated with reduced incidence of atopic dermatitis in early life.

BACKGROUND: Farm exposures may reduce the risk of atopic dermatitis (AD) in children, but this is controversial and US data are limited. OBJECTIVE: This study was conducted to identify patterns of farm exposure in Wisconsin family farms that modify AD incidence and prevalence in early childhood. METHODS: Environmental exposures, health history, and clinical outcomes were prospectively recorded for 111 farm families and 129 non-farm families enrolled in the Wisconsin Infant Study Cohort birth cohort study. Exposures from the prenatal and early postnatal (2-month) visits were evaluated together with parental report of AD diagnosis by a health care provider through age 24 months. Latent class analysis was performed with prenatal and early postnatal farm-exposure variables to assign farm children to 3 classes. RESULTS: Overall, children of farm families had reduced AD incidence (P = .03). Within farm families, exposures including poultry (3% vs 28%; P = .003), pig (4% vs 25%; P = .04), feed grain (13% vs 34%; P = .02), and number of animal species were inversely associated with AD incidence. Among the latent class groups, children in families with diverse or more intense farm exposures (classes A and B) had reduced AD incidence, whereas low-exposure (class C) infants had AD incidence similar to that in nonfarm children. CONCLUSIONS: Infants in Wisconsin farm families had reduced AD incidence, and patterns of farm exposures further defined AD risk. These findings suggest that exposure to diverse farm animals, feed, and bedding during the prenatal period and in early infancy reduce the risk of early-onset AD, a phenotype associated with multiple other atopic diseases.

Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency.

BACKGROUND: There is an unmet need for an objective biomarker to predict asthma exacerbations. OBJECTIVE: Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging. METHODS: Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations. RESULTS: A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n = 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n = 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI = 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response. CONCLUSION: VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations.