METHODS: A systematic review and Delphi consensus panel (consisting of eight8 international pediatric allergists and gastroenterologists) was conducted to evaluate evidence supporting growth, tolerability, and effectiveness of pHF in non-exclusively breastfed infants.
RESULTS: None of the studies reviewed identified potential harm of pHF use compared with CMP in non-exclusively breastfed infants. There was an expert consensus that pHF use is likely as safe as intact CMP formula, given studies suggesting these have comparable nutritional parameters. No high-quality studies were identified evaluating the use of pHF to prevent allergic disease in non-exclusively breastfed infants who are not at risk for allergic disease (e.g., lacking a parental history of allergy). Limited data suggest that pHF use in non-exclusively breastfed infants may be associated with improved gastric emptying, decreased colic incidence, and other common functional gastrointestinal symptoms compared with CMP. However, because the data are of insufficient quality, the findings from these studies have to be taken with caution. No studies were identified that directly compared the different types of pHF, but there was an expert consensus that growth, allergenicity, tolerability, effectiveness, and clinical role among such pHF products may differ.
CONCLUSIONS: Limited data exist evaluating routine use of pHFs in non-exclusively breastfed infants, with no contraindications identified in the systematic review. An expert consensus considers pHFs for which data were available to be as safe as CMP formula as growth is normal. The preventive effect on allergy of pHF in infants who are not at risk for allergic disease has been poorly studied. Cost of pHF versus starter formula with intact protein differs from country to country. However, further studies in larger populations are needed to clinically confirm the benefits of routine use of pHF in non-exclusively breastfed infants. These studies should also address potential consumer preference bias.
METHODS: We analyzed by digital droplet PCR (ddPCR) to determine presence of the MYD88 L265P and CD79B Y196 hotspot mutations in cfDNA isolated from plasma of 24 PCNSL patients with active disease. Corresponding tumor samples were available for 14 cases. Based on the false positive rate observed in 8 healthy control samples, a stringent cut-off for the MYD88 L265P and CD79B Y196 mutation were set at 0.3% and 0.5%, respectively.
RESULTS: MYD88 L265P and CD79B Y196 mutations were detected in 9/14 (64%) and 2/13 (15%) tumor biopsies, respectively. In cfDNA samples, the MYD88 L265P mutation was detected in 3/24 (12.5%), while the CD79B Y196 mutation was not detected in any of the 23 tested cfDNA samples. Overall, MYD88 L265P and/or CD79B Y196 were detected in cfDNA in 3/24 cases (12.5%). The detection rate of the combined analysis did not improve the single detection rate for either MYD88 L265P or CD79B Y196.
CONCLUSION: The low detection rate of MYD88 L265P and CD79B Y196 mutations in cfDNA in the plasma of PCNSL patients argues against its use in routine diagnostics. However, detection of MYD88 L265P by ddPCR in cfDNA in the plasma could be considered in challenging cases.