ObjectivesTo evaluate the potential associations between fever without a source (FWS) in children and detection of human enterovirus (HEV), human parechovirus (HPeV), adenovirus (AdV) and human herpesvirus type 6 (HHV-6) in the plasma; and to assess whether the detection of viruses in the plasma is associated with a reduced risk of serious bacterial infection (SBI) and antibiotic use.Design and settingBetween November 2015 and December 2017, this prospective, single-centre, diagnostic study tested the plasma of children <3 years old with FWS. Real-time (reverse-transcription) PCR for HEV, HPeV, AdV and HHV-6 was used in addition to the standardised institutional work-up. A control cohort was also tested for the presence of viruses in their blood.ResultsHEV, HPeV, AdV and HHV-6 were tested for in the plasma of 135 patients of median age 2.4 months old. At least one virus was detected in 47 of 135 (34.8%): HEV in 14.1%, HHV-6 in 11.1%, HPeV in 5.9% and AdV in 5.2%. There was no difference in antibiotic use between patients with or without virus detected, despite a relative risk of 0.2 for an SBI among patients with viraemia. Controls were less frequently viraemic than children with FWS (6.0% vs 34.8%; p<0.001).ConclusionsHEV, HPeV, AdV and HHV-6 are frequently detected in the plasma of children with FWS. Antibiotic use was similar between viraemic and non-viraemic patients despite a lower risk of SBI among patients with viraemia. Point-of-care viral PCR testing of plasma might reduce antibiotic use and possibly investigations and admission rates in patients with FWS.Trial registration numberNCT03224026.
Rituximab (RTX) is an anti-CD20 monoclonal antibody that targets B cells—from the immature pre-B-cell stage in the bone marrow to mature circulating B cells—while preserving stem cells and plasma cells. It is used to treat autoimmune diseases, hematological malignancies, or complications after hematopoietic stem cell transplantation (HSCT). Its safety profile is acceptable; however, a subset of patients can develop persistent hypogammaglobulinemia and associated severe complications, especially in pediatric populations. We report the unrelated cases of two young men aged 17 and 22, presenting with persistent hypogammaglobulinemia more than 7 and 10 years after treatment with RTX, respectively, and administered after HSCT for hemolytic anemia and Epstein–Barr virus reactivation, respectively. Both patients’ immunological workups showed low levels of total immunoglobulin, vaccine antibodies, and class switched-memory B cells but an increase in naive B cells, which can also be observed in primary immunodeficiencies such as those making up common variable immunodeficiency. Whole exome sequencing for one of the patients failed to detect a pathogenic variant causing a Mendelian immunological disorder. Annual assessments involving interruption of immunoglobulin replacement therapy each summer failed to demonstrate the recovery of endogenous immunoglobulin production or normal numbers of class switched-memory B cells 7 and 10 years after the patients’ respective treatments with RTX. Although the factors that may lead to prolonged hypogammaglobulinemia after rituximab treatment (if necessary) remain unclear, a comprehensive immunological workup before treatment and long-term follow-up are mandatory to assess long-term complications, especially in children.
IMPORTANCELittle is known about the natural course of oxygen desaturation in acute bronchiolitis.Information on risk factors associated with desaturation as well as the time to desaturation in infants with bronchiolitis could help physicians better treat these infants before deciding whether to hospitalize them. OBJECTIVETo prospectively determine the frequency of desaturation in infants with bronchiolitis, along with the time to desaturation and risk factors associated with desaturation, and to compare infants who were hospitalized with those discharged home and evaluate risk factors for rehospitalization. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted during the 2017 to 2018 and 2018 to 2019 respiratory syncytial virus seasons in a tertiary care pediatric emergency department in Switzerland. Included individuals were 239 otherwise-healthy infants aged younger than 1 year, diagnosed with acute bronchiolitis and oxygen saturation of 90% or more on arrival. Data were analyzed from July 2019 to October 2020. EXPOSURES After receiving triage care, study participants admitted to the emergency department were equipped with a pulse oximeter to continuously record oxygen saturation (SpO 2 levels), regardless of subsequent hospitalization or discharge home. MAIN OUTCOMES AND MEASURESThe primary outcome was desaturation (ie, SpO 2 < 90%) during the first 36 hours. RESULTSOf 239 infants enrolled, with a median (interquartile range [IQR]) age of 3.9 (1.5-6.5) months, 116 (48.5%) were boys and desaturation occurred in 165 infants (69.0%). Median (IQR) time to desaturation was 3.6 (1.8-9.4) hours. The rate of desaturation was similar between infants hospitalized and those discharged home (137 of 200 infants [68.5%] vs 28 of 39 infants [71.8%]; difference, −3.3%; 95% CI, −18.8% to 12.2%; P = .85). A more severe initial clinical presentation with moderate or severe retractions was the only independent risk factor associated with desaturation (odds ratio, 2.73; 95% CI, 1.49 to 5.02; P = .001). Of 39 infants discharged home, 22 infants (56.4%) experienced major desaturations. However, infants with desaturations, including those with major desaturations, had rates of rehospitalization similar to those of infants without desaturations (8 of 28 infants [28.5%] vs 3 of 11 infants [27.3%]; difference, 1.2%; 95% CI, −29.9% to 32.5; P > .99). CONCLUSIONS AND RELEVANCEThese findings suggest that rates of desaturation in infants with acute bronchiolitis were high and similar between infants who were hospitalized and those discharged home. A more severe initial clinical presentation was the only risk factor associated with (continued) Key Points Question What are the frequency, timing, risk factors, and outcomes associated with oxygen desaturation in infants with acute bronchiolitis and initially normal oxygen saturation? Findings In this cohort study of 239 infants, desaturation occurred in most infants, regardless of whether they were hospitalized or discharged home. A more severe initial clinical presentation was the ...
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