Association of timing of congenital diaphragmatic hernia repair with survival and morbidity for patients not requiring extra-corporeal life support.

BACKGROUND: While physiologic stabilization followed by repair has become the accepted paradigm for management of congenital diaphragmatic hernia (CDH), few studies have examined the effect of incremental changes in operative timing on patient outcomes. We hypothesized that later repair would be associated with higher morbidity and mortality. METHODS: Data were queried from the CDH Study Group (CDHSG) from 2007-2020. Patients with chromosomal or cardiac abnormalities and those who were never repaired or required pre-repair extra-corporeal life support (ECLS) were excluded. Time to repair was analyzed both as a continuous variable and by splitting the cohort into top/bottom percentiles. The primary outcome of interest was in-hospital mortality. Secondary outcomes included need for and duration of post-repair ventilatory and nutritional support. RESULTS: A total of 4,104 CDH infants were included. Median time to repair was 4 days (IQR 2-6). On multivariable analysis, high-risk (CDHSG stage C/D) defects and lower birthweight predicted later repair. Overall, in-hospital mortality was 6%. On univariate analysis, there was no difference in the number of days to repair between survivors and non-survivors. On risk-adjusted analysis, single-day changes in day of repair were not associated with increased mortality. Later repair was associated with longer time to reach full oral feeds, increased post-repair ventilator days, and increased need for tube feeds and supplementary oxygen at discharge. CONCLUSIONS: For infants with isolated CDH not requiring pre-operative ECLS, there is no difference in mortality based on timing of repair, but single-day delays in repair are associated with increased post-repair duration of ventilatory and nutritional support.

The preparation of fully active chymopapain free of contaminating proteinases.

Chymopapain (EC 3.4.22.6) was purified from commercially available dried latex of papaya (Carica papaya) by extraction at acidic pH, cation-exchange chromatography and active site-directed affinity chromatography on immobilized alanyl-phenyl-alaninaldehyde semicarbazone, with elution by mercuric chloride. The product was found by immunoassay to be essentially free of the other cysteine proteinases from papaya, including papaya proteinase IV, and was fully active. The rate of alkylation of the active site cysteine of chymopapain by iodoacetate was found to be sufficiently rapid and selective for this reagent to be used as an active-site titrant.