Factors affecting the patency and complications of peripheral intravenous catheters in newborns.

BACKGROUND: Peripheral intravenous catheters (PICs) are necessary for medication, nutrient, and fluid administration in pediatric patients. However, PICs are uneasy to access and maintain in young infants. This study identified risk factors affecting the complications and patency of PICs. METHODS: This retrospective cohort study included neonates and infants aged <4 months. All PICs inserted in the neonatal intensive care unit and intermediate care nursery were analyzed more than 5 months. The variables included gestational age, age and body weight at PIC insertion, insertion site, methods to maintain PIC patency (continuous intravenous drip [CIVD] versus intermittent flushing), fluid infusion rate and osmolarity, and ampicillin and cefotaxime concentrations. The effects of these variables on PIC complications and lifespan were assessed using binary logistic regression analysis and a general linear model, respectively. RESULTS: In total, 315 PICs were analyzed. The mean indwelling time was 33.8 ± 21.5 h and complication rate was 82.2%. The most frequent complications were infiltration (55.9%) and leakage (22.2%). The infusion rate and method to maintain PICs significantly impacted PIC patency. A negative correlation was noted between the infusion rate and PIC patency, with the patency decreasing by 0.9 h (p = 0.047) on increasing the infusion rate by 1 mL/h. Notably, compared with intermittent flushing, CIVD using a hypertonic solution significantly decreased PIC patency by 14 h (p = 0.006). As the patients' age increased by a month, the complication risk decreased by 35% (p = 0.027). However, as the infusion rate increased by 1 mL/h, the complication risk increased by 17% (p = 0.018). CONCLUSIONS: Intermittent flushing may be preferred over CIVD to preserve PIC patency. An increased infusion rate is correlated with decreased PIC patency and increased complications. For the peripheral administration of ampicillin, we recommended preparing final concentrations below 50 mg/dL to prevent PIC complications.

Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants

The COVID-19 pandemic has highlighted how viral variants that escape monoclonal antibodies can limit options to control an outbreak. With the emergence of the SARS-CoV-2 Omicron variant, many clinically used antibody drug products lost in vitro and in vivo potency, including AZD7442 and its constituent, AZD1061 [VanBlargan2022, Case2022]. Rapidly modifying such antibodies to restore efficacy to emerging variants is a compelling mitigation strategy. We therefore sought to computationally design an antibody that restores neutralization of BA.1 and BA.1.1 while simultaneously maintaining efficacy against SARS-CoV-2 B.1.617.2 (Delta), beginning from COV2-2130, the progenitor of AZD1061. Here we describe COV2-2130 derivatives that achieve this goal and provide a proof-of-concept for rapid antibody adaptation addressing escape variants. Our best antibody achieves potent and broad neutralization of BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4, BA.5, and BA.5.5 Omicron subvariants, where the parental COV2-2130 suffers significant potency losses. This antibody also maintains potency against Delta and WA1/2020 strains and provides protection in vivo against the strains we tested, WA1/2020, BA.1.1, and BA.5. Because our design approach is computational--driven by high-performance computing-enabled simulation, machine learning, structural bioinformatics and multi-objective optimization algorithms--it can rapidly propose redesigned antibody candidates aiming to broadly target multiple escape variants and virus mutations known or predicted to enable escape.

Clinical significance of the fucosyltransferase 2 (FUT2) secretor status in children hospitalized with acute gastroenteritis in Taiwan.

BACKGROUND/PURPOSE: The FUT2 gene is a histo-blood group antigen (HBGA) that determines the susceptibility to Norovirus (NoV) infection. This study investigated the clinical significance of the FUT2 gene profile and HBGA expression in NoV infection. METHODS: Fecal specimens were collected from children in Chang-Gung Children's Hospital with acute gastroenteritis (AGE). The medical records were reviewed for clinical data. The viral etiology of gastroenteritis was validated using molecular methods. Genomic DNA was isolated from saliva or whole blood with the Puregene B Kit, according to the manufacturers' instructions. Single-nucleotide polymorphisms (SNPs) were determined by real-time PCR assays. RESULTS: FUT2 gene DNA was examined in 98 children with AGE. NoV was detected by RT-PCR in 44 patients (44.8%), while 54 (55.2%) had non-NoV AGE. Of the 44 NoV patients, 38 (86.3%) were secretors (no G428A mutation) and six (13.7%) were non-secretors (G428A mutation). Of the 54 non-NoV AGE patients, 28 (51.9%) were secretors and 20 (48.1%) were non-secretors. NoV-infected patients who were secretors had more frequent vomiting (P < 0.001), longer duration of diarrhea (P < 0.001), and greater overall disease severity score (P < 0.001) compared with non-secretors. Non-NoV infection secretor AGE patients had a longer duration of diarrhea (P < 0.001) than non-secretors. CONCLUSION: FUT2 secretor status affects NoV AGE in children. Secretor patients have prolonged diarrhea, more frequent vomiting, more severe disease, and greater infection transmissibility than non-secretors.