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Browsing by Author "Loftis, Laura"
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Item A biomarker panel for risk of early respiratory failure following hematopoietic cell transplantation(American Society of Hematology, 2022) Rowan, Courtney M.; Smith, Lincoln; Sharron, Matthew P.; Loftis, Laura; Kudchadkar, Sapna; Duncan, Christine N.; Pike, Francis; Carpenter, Paul A.; Jacobsohn, David; Bollard, Catherine M.; Cruz, Conrad Russell Y.; Malatpure, Abhijeet; Farag, Sherif; Renbarger, Jamie; Little, Morgan R.; Gafken, Phillip R.; Krance, Robert A.; Cooke, Kenneth R.; Paczesny, Sophie; Pediatrics, School of MedicinePlasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF. Six candidate proteins, from this discovery cohort or identified in the literature, were measured by enzyme-linked immunosorbent assay in day-7 and day-14 post-HCT samples from the training (n = 213) and validation (n = 119) cohorts. Cox proportional-hazard analyses with biomarkers dichotomized by Youden's index, as well as landmark analyses to determine the association between biomarkers and RF, were performed. Of the 6 markers, Stimulation-2 (ST2), WAP 4-disulfide core domain protein 2 (WFDC2), interleukin-6 (IL-6), and tumor necrosis factor receptor 1 (TNFR1), measured at day 14 post-HCT, had the most significant association with an increased risk for RF in the training cohort (ST2: hazard ratio [HR], 4.5, P = .004; WFDC2: HR, 4.2, P = .010; IL-6: HR, 6.9, P < .001; and TFNR1: HR, 6.1, P < .001) and in the validation cohort (ST2: HR, 23.2, P = .013; WFDC2: HR, 18.2, P = .019; IL-6: HR, 12.2, P = .014; and TFNR1: HR, 16.1, P = .001) after adjusting for the conditioning regimen. Using cause-specific landmark analyses, including days 7 and 14, high plasma levels of ST2, WFDC2, IL-6, and TNFR1 were associated with an increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality from RF. ST2, WFDC2, IL-6 and TNFR1 levels measured early posttransplantation improve risk stratification for RF and its related mortality.Item Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak(American Medical Association, 2023-08-01) Halasa, Natasha; Zambrano, Laura D.; Amarin, Justin Z.; Stewart, Laura S.; Newhams, Margaret M.; Levy, Emily R.; Shein, Steven L.; Carroll, Christopher L.; Fitzgerald, Julie C.; Michaels, Marian G.; Bline, Katherine; Cullimore, Melissa L.; Loftis, Laura; Montgomery, Vicki L.; Jeyapalan, Asumthia S.; Pannaraj, Pia S.; Schwarz, Adam J.; Cvijanovich, Natalie Z.; Zinter, Matt S.; Maddux, Aline B.; Bembea, Melania M.; Irby, Katherine; Zerr, Danielle M.; Kuebler, Joseph D.; Babbitt, Christopher J.; Glas Gaspers, Mary; Nofziger, Ryan A.; Kong, Michele; Coates, Bria M.; Schuster, Jennifer E.; Gertz, Shira J.; Mack, Elizabeth H.; White, Benjamin R.; Harvey, Helen; Hobbs, Charlotte V.; Dapul, Heda; Butler, Andrew D.; Bradford, Tamara T.; Rowan, Courtney M.; Wellnitz, Kari; Allen Staat, Mary; Aguiar, Cassyanne L.; Hymes, Saul R.; Randolph, Adrienne G.; Campbell, Angela P.; RSV-PIC Investigators; Pediatrics, School of MedicineImportance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, setting, and participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main outcomes and measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.Item Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-Control Investigation(Wolters Kluwer, 2023) Zambrano, Laura D.; Wu, Michael J.; Martin, Lora; Malloch, Lacy; Chen, Sabrina; Newhams, Margaret M.; Kucukak, Suden; Son, Mary Beth; Sanders, Cameron; Patterson, Kayla; Halasa, Natasha; Fitzgerald, Julie C.; Leroue, Matthew K.; Hall, Mark; Irby, Katherine; Rowan, Courtney M.; Wellnitz, Kari; Sahni, Leila C.; Loftis, Laura; Bradford, Tamara T.; Staat, Mary; Babbitt, Christopher; Carroll, Christopher L.; Pannaraj, Pia S.; Kong, Michele; Schuster, Jennifer E.; Chou, Janet; Patel, Manish M.; Randolph, Adrienne G.; Campbell, Angela P.; Hobbs, Charlotte V.; Overcoming COVID-19 investigators; Pediatrics, School of MedicineBackground: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. Methods: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. Results: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. Conclusions: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C.