The quality and persistence of children's humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, ...we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.
The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with ...the reverse sequence in patients with newly diagnosed anaplastic gliomas.
Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence.
Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio HR = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O(6)-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm.
Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation.
Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. ...We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio OR 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Germinal matrix intraventricular hemorrhage (IVH) remains a severe and common complication in preterm infants. A neonatal care bundle (NCB) was implemented as an in-house guideline at a tertiary ...neonatal intensive care unit to reduce the incidence of IVH in preterm infants. The NCB was applied either to preterm infants <1250 g birth weight or <30 weeks gestational age or both, and standardized patient positioning, nursing care, and medical procedures within the first week of life. A retrospective cohort study was performed to investigate the effect of the NCB and other known risk factors on the occurrence and severity of IVH. Data from 229 preterm infants were analyzed. The rate of IVH was 26.2% before and 27.1% after implementing the NCB. The NCB was associated neither with reducing the overall rate of IVH (odds ratio (OR) 1.02; 95% confidence interval (CI) 0.57-1.84;
= 0.94) nor with severe IVH (OR 1.0; 95% CI 0.67-1.55;
= 0.92). After adjustment for group differences and other influencing factors, amnion infection syndrome and early intubation were associated with an increased risk for IVH. An NCB focusing on patient positioning, nursing care, and medical interventions had no impact on IVH in preterm infants. Known risk factors for IVH were confirmed.
Background Preterm delivery is a leading cause of neonatal morbidity and death. It often results from chorioamnionitis, which is a complication of bacterial vaginosis. Probiotics are effective in the ...treatment of bacterial vaginosis in women who were not pregnant; studies in pregnant woman are missing. Objective The purpose of this study was to evaluate whether an oral probiotic food supplement supports the maintenance or restoration of a normal vaginal microbiota during pregnancy. Study Design We conducted a randomized, placebo-controlled, triple-blind, parallel group trial. Oral Lactobacillus rhamnosus GR-1and L reuteri RC-14 (109 colony-forming units) or placebo were administered for 8 weeks to women with <12 completed weeks of pregnancy. Participants were enrolled at Tuebingen University Hospital and 10 recruiting gynecologic practices. Vaginal swabs were taken before and after intervention and analyzed according to the Nugent scoring system. Telephone interviews were performed before and after intervention and after delivery. Primary outcome was the proportion of swabs with normal Nugent score (<4) after intervention, compared by Fisher’s exact test in an intention-to-treat analysis. Results Three hundred twenty pregnant women were enrolled. Vaginal swabs were analyzed from 290 women before and 271 women after intervention. The proportion of normal vaginal microbiota decreased from 82.6 to 77.8% in the treatment group and from 79.1 to 74.3% in the placebo group, with no significant difference across groups after intervention ( P =.297). Conclusion Oral probiotics may be suitable for implementation in antenatal care but, as administered here, had no effect on vaginal health during mid gestation. Other application routes or probiotic preparations may be more effective in supporting vaginal microbiota during pregnancy.
Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low ...birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants.
In this randomized multicenter trial, 216 preterm infants born at 26 + 0-29 + 6 gestational weeks will be allocated to receive a higher (6-8 cmH
O) or a lower (3-5 cmH
O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO
(fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO
> 0.5 for > 1 h or pCO
≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart).
Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4-8 cmH
O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants.
drks.de DRKS00019940 . Registered on March 13, 2020.
Objectives:
To study the safety and efficacy of continuous intratympanic dexamethasone‐phosphate (Dex‐P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic ...anacusis after failure of systemic therapy.
Study Design:
Randomized, double‐blind, placebo controlled multicenter trial.
Methods:
Patients with ISSHL and insufficient recovery (mean 4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either Dex‐P (4mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the round window niche via a temporarily implanted catheter. For ethical reasons, intratympanic treatment was continued with Dex‐P in all patients for another 14 days after the placebo‐controlled study period. According to a two‐step adaptive study design an interim analysis was performed after inclusion of 23 patients.
Results:
Intention‐to‐treat analysis for the primary outcome criterion (4PTA: 0.5‐3kHz) during the placebo controlled study period (14 days) showed an average hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: −7.1–24.1) was statistically not significant (p = .26). Of the secondary outcome parameters, the largest benefit of local salvage therapy was found for maximum speech discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5% (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow‐up period (i.e. after all patients received intratympanic Dex‐P) hearing improvement in the two groups was very similar. No serious adverse events were observed. Sample size calculation after the interim analysis resulted in stopping of the trial.
Conclusions:
The tendency toward better hearing improvement in the treatment group, the rather conservative inclusion criteria, the limited placebo‐controlled observation period and the absence of serious adverse events supports further investigation local inner ear drug delivery as a first or second line treatment option for ISSHL. Laryngoscope, 119:359–369, 2009
Most extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic ...episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA. Closed-loop automated control of the inspiratory fraction of oxygen (FiO
-C) reduces time outside the hemoglobin oxygen saturation (SpO
) target range, number and duration of hypo- and hyperoxemic episodes and caregivers' workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied.
An outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO
-C (in addition to routine manual control (RMC) of FiO
), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO
-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks). FiO
-C is provided by commercially available and CE-marked ventilators with an FiO
-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age.
Short-term studies on FiO
-C showed improved time ELGANs spent within their assigned SpO
target range, but effects of FiO
-C on clinical outcomes are yet unknown and will be addressed in the FiO
-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO
-C may be implemented as standard therapy.
The study is registered at www.ClinicalTrials.gov: NCT03168516 , May 30, 2017.
Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent ...symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households.
1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires.
The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% 95% CI: 30.7–42.4% vs 14.2% 95% CI: 8.7–21.5%), infected men (22.9% 95% CI: 17.9–28.5% vs 10.3% 95% CI: 5.8–16.9%) and infected adolescent girls (32.1% 95% CI: 17.2–50.5% vs 8.9% 95%CI: 3.1–19.8%). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14–18 (9.7% 95% CI: 2.8–23.6% or in infected children <14 years (girls: 4.3% 95% CI: 1.2–11.0%; boys: 3.7% 95% CI: 1.1–9.6%) than in their exposed counterparts (adolescent boys: 0.0% 95% CI: 0.0–6.7%; girls < 14 years: 2.3% 95% CI: 0·7–6·1%; boys < 14 years: 0.0% 95% CI: 0.0–2.0%). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI 1.03–1.20).
In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful.
Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.
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