Active observation versus interval appendicectomy after successful non-operative treatment of an appendix mass in children (CHINA study): an open-label, randomised controlled trial

BACKGROUND: Despite a scarcity of supporting evidence, most surgeons recommend routine interval appendicectomy after successful non-operative treatment of an appendix mass in children. We aimed to compare routine interval appendicectomy with active observation. METHODS: We enrolled participants in the CHildren's INterval Appendicectomy (CHINA) study, a multicentre, open-label, randomised controlled study at 19 specialist paediatric surgery centres, 17 of which were in the UK, one in Sweden, and one in New Zealand. 106 children aged 3–15 years were assigned (1:1) by weighted minimisation to interval appendicectomy or active observation with minimisation for age, trial centre, sex, and presence of a faecolith on imaging. Eligible children had acute appendicitis with an appendix mass and were successfully treated without appendicectomy or other surgical intervention. Children were excluded from the study if they had coexisting gastrointestinal disease or had a substantial coexisting medical condition or immune defect. Because of the nature of the interventions, blinding was not possible. The primary outcome was the proportion of children developing histologically proven recurrent acute appendicitis or a clinical diagnosis of recurrent appendix mass within 1 year of enrolment after successful non-operative treatment of appendix mass (active observation group) and incidence of severe complications related to interval appendicectomy. Data were analysed on an intention-to-treat basis. This study is registered with ISRCTN, number 93815412. FINDINGS: Between Aug 8, 2011, and Dec 31, 2014, we randomly assigned 106 patients, 52 patients to interval appendicectomy and 54 to active observation. Two children in the interval appendicectomy group were withdrawn due to withdrawal of consent; two in the active observation group were withdrawn because they became ineligible after allocation. Six children under active observation had histologically proven recurrent acute appendicitis. Three children in the interval appendicectomy group had severe complications. Thus, the proportion of children with histologically proven recurrent acute appendicitis under active observation was 12% (95% CI 5–23) and the proportion of children with severe complications related to interval appendicectomy was 6% (95% CI 1–17). INTERPRETATION: More than three-quarters of children could avoid appendicectomy during early follow-up after successful non-operative treatment of an appendix mass. Although the risk of complications after interval appendicectomy is low, complications can be severe. Adoption of a wait-and-see approach, reserving appendicectomy for those who develop recurrence or recurrent symptoms, results in fewer days in hospital, fewer days away from normal daily activity, and is cheaper than routine interval appendicectomy. These high-quality data will allow clinicians, parents, and children to make an evidence-based decision regarding the justification for interval appendicectomy. FUNDING: BUPA Foundation

Outcomes of truncal vascular injuries in children.

BACKGROUND: Pediatric truncal vascular injuries occur infrequently and have a reported mortality rate of 30% to 50%. This report examines the demographics, mechanisms of injury, associated trauma, and outcome of patients presenting for the past 10 years at a single institution with truncal vascular injuries. METHODS: A retrospective review (1997-2006) of a pediatric trauma registry at a single institution was undertaken. RESULTS: Seventy-five truncal vascular injuries occurred in 57 patients (age, 12 +/- 3 years); the injury mechanisms were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular complications occurred more frequently in patients with abdominal vascular injuries who were hemodynamically unstable on presentation. All patients with thoracic vascular injuries presenting with hemodynamic instability died. In patients with neck vascular injuries, 1 of 2 patients who were hemodynamically unstable died, compared to 1 of 12 patients who died in those who presented hemodynamically stable. Overall survival was 75%. CONCLUSIONS: Survival and complications of pediatric truncal vascular injury are related to hemodynamic status at the time of presentation. Associated injuries are higher with trauma involving the abdomen

Optimization of recombinant ligninolytic enzyme production in Pichia pastoris

Manganese peroxidase (MnP) is a heme containing enzyme produced by white-rot fungi for the degradation of lignin in wood. This enzyme has potential applications in the biobleaching of wood pulp as an environmentally friendly alternative to chemical bleaching methods. To increase production of MnP above levels achievable with the native white-rot fungus, the mnp1 gene, encoding MnP, has been cloned into the yeast Pichia pastoris . Research is reported here on the production of recombinant MnP (rMnP) using shake flask and bench scale fermentors, and on the purification and concentration of the rMnP for use in pulp bleaching experiments. Active recombinant MnP (rMnP) could be produced in shake-flasks provided the pH was maintained between 6 and 7. At lower pH, no active enzyme was produced, even though the yeast cells grew at the same rate down to pH 4. Use of protease inhibitors or a protease deficient strain did not appear to increase the concentration of rMnP produced below pH 6, and no increase in rMnP concentrations in fermentations at pH 6 resulted from addition of casamino acids or peptone as protease competitive inhibitors, use of pure O 2 to reduce agitation speed and release of proteases via cell lysis, and production at a lower temperature to decrease protease activity. Amendment of the medium with heme (0.1 to 1 g/L) increased the concentration of rMnP. The rMnP concentration was increased from approximately 100 μmoles/min/L in shake flasks to greater than 3,000 moles/min/L in the fermentors using a protease deficient P. pastoris strain ( P. pastoris αMP 1-1) containing the mnp1 gene with a constitutive glyceraldehydes-3-phosphate dehydrogenase (pGAP) promoter and yeast secretion signal. A batch and fed-batch approach was employed with a basal salts medium and glucose as the carbon source. Heme was added at the beginning of fed-batch. Batch and fed-batch cultivation using glucose as the growth substrate was modeled and the kinetic parameters were determined. The model predictions agree well with the experimental data. Due to the low aqueous solubility of heme, it formed a fine dispersion in the medium. To separate the rMnP from the medium and concentrate the enzyme, centrifugation (10,000x g , 5 minutes) was employed to remove the yeast cells and the heme, and then the enzyme was precipitated using acetone. Approximately 75% of the rMnP could be precipitated and recovered using 40% acetone, and the enzyme concentrate was found to be of adequate purity and concentration for use in pulp bleaching experiments

Association of Emergency Department Pediatric Readiness With Mortality to 1 Year Among Injured Children Treated at Trauma Centers

Importance: There is substantial variability among emergency departments (EDs) in their readiness to care for acutely ill and injured children, including US trauma centers. While high ED pediatric readiness is associated with improved in-hospital survival among children treated at trauma centers, the association between high ED readiness and long-term outcomes is unknown. Objective: To evaluate the association between ED pediatric readiness and 1-year survival among injured children presenting to 146 trauma centers. Design, setting, and participants: In this retrospective cohort study, injured children younger than 18 years who were residents of 8 states with admission, transfer to, or injury-related death at one of 146 participating trauma centers were included. Children cared for in and outside their state of residence were included. Subgroups included those with an Injury Severity Score (ISS) of 16 or more; any Abbreviated Injury Scale (AIS) score of 3 or more; head AIS score of 3 or more; and need for early critical resources. Data were collected from January 2012 to December 2017, with follow-up to December 2018. Data were analyzed from January to July 2021. Exposures: ED pediatric readiness for the initial ED, measured using the weighted Pediatric Readiness Score (wPRS; range, 0-100) from the 2013 National Pediatric Readiness Project assessment. Main outcomes and measures: Time to death within 365 days. Results: Of 88 071 included children, 30 654 (34.8%) were female; 2114 (2.4%) were Asian, 16 730 (10.0%) were Black, and 49 496 (56.2%) were White; and the median (IQR) age was 11 (5-15) years. A total of 1974 (2.2%) died within 1 year of the initial ED visit, including 1768 (2.0%) during hospitalization and 206 (0.2%) following discharge. Subgroups included 12 752 (14.5%) with an ISS of 16 or more, 28 402 (32.2%) with any AIS score of 3 or more, 13 348 (15.2%) with a head AIS of 3 or more, and 9048 (10.3%) requiring early critical resources. Compared with EDs in the lowest wPRS quartile (32-69), children cared for in the highest wPRS quartile (95-100) had lower hazard of death to 1 year (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.56-0.88). Supplemental analyses removing early deaths had similar results (aHR, 0.75; 95% CI, 0.56-0.996). Findings were consistent across subgroups and multiple sensitivity analyses. Conclusions and relevance: Children treated in high-readiness trauma center EDs after injury had a lower risk of death that persisted to 1 year. High ED readiness is independently associated with long-term survival among injured children