Setting: A tertiary-referral urban children's hospital.Patients: A total of 131 patients younger than 18 years with a preoperative diagnosis of perforated appendicitis.Interventions: Early appendectomy (within 24 hours of admission) vs interval appendectomy (6-8 weeks after diagnosis).Main Outcome Measures: Time away from normal activities (days). Secondary outcomes included the overall adverse event rates and the rate of predefined specific adverse events (eg, intra-abdominal abscess, surgical site infection, unplanned readmission).Results: Early appendectomy, compared with interval appendectomy, significantly reduced the time away from normal activities (mean, 13.8 vs 19.4 days; PϽ.001). The overall adverse event rate was 30% for early appendectomy vs 55% for interval appendectomy (relative risk with interval appendectomy, 1.86; 95% confidence interval, 1.21-2.87; P=.003). Of the patients randomized to interval appendectomy, 23 (34%) had an appendectomy earlier than planned owing to failure to improve (n=17), recurrent appendicitis (n=5), or other reasons (n=1). Conclusions:Early appendectomy significantly reduced the time away from normal activities. The overall adverse event rate after early appendectomy was significantly lower compared with interval appendectomy.

BACKGROUND The authors prospectively evaluated the performance of a proprietary molecular testing platform using one-step nucleic acid amplification (OSNA) for the detection of metastatic carcinoma in sentinel lymph nodes (SLNs) in a large multicenter trial and compared the OSNA results with the results from a detailed postoperative histopathologic evaluation (reference pathology) and from intraoperative imprint cytology (IC). METHODS In total, 1044 SLN samples from 496 patients at 11 clinical sites were analyzed. Alternate 1-mm sections were subjected to either detailed histopathologic evaluation with hematoxylin and eosin and pancytokeratin immunostaining or the OSNA Breast Cancer System, which was calibrated to detect tumor deposits >0.2 mm by measuring cytokeratin 19 messenger RNA. At 7 sites, IC was performed before permanent section. The OSNA results were classified as negative (<250 copies/μL), micrometastases (from ≥250 to <5000 copies/μL), or macrometastases (≥5000 copies/μL). RESULTS The sensitivity and specificity of the OSNA breast cancer system compared with reference pathology were 77.5% (95% confidence interval, 69.7%-84.2%) and 95.8% (95% confidence interval, 94.3%-97.0%), respectively, before discordant case analyses (DCA). Sensitivity and specificity after DCA were 82.7% and 97.7%, and final concordance was 95.8%. Performance for invasive lobular carcinoma demonstrated 88.2% sensitivity (95% confidence interval, 63.6%-98.5%) and 98.5% specificity (95% confidence interval, 92%-100%). The sensitivity of OSNA was significantly better than that of IC (80% vs 63%; P =.0229). CONCLUSIONS The OSNA breast cancer system proved to be highly accurate for the detection of metastatic breast cancer in axillary SLNs. Sensitivity was comparable to that predicted for conventional postoperative histologic examination at 2-mm intervals and was significantly more sensitive than IC. Automation, semiquantitative results enabling the differentiation of macrometastasis and micrometastasis, and rapid results render the assay suitable for intraoperative and/or permanent evaluation of SLNs.

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Implementation of a clinical evaluation pathway emphasizing examination, early surgeon involvement, and utilization of ultrasound as the initial imaging modality for evaluation of abdominal pain concerning for appendicitis resulted in a marked decrease in the reliance on CT scanning without loss of diagnostic accuracy.

BACKGROUND The purpose of this study was to determine the relationship between timing and volume of crystalloid before blood products and mortality, hypothesizing that earlier transfusion and decreased crystalloid before transfusion would be associated with improved outcomes. METHODS A multi-institutional prospective observational study of pediatric trauma patients younger than 18 years, transported from the scene of injury with elevated age-adjusted shock index on arrival, was performed from April 2018 to September 2019. Volume and timing of prehospital, emergency department, and initial admission resuscitation were assessed including calculation of 20 ± 10 mL/kg crystalloid boluses overall and before transfusion. Multivariable Cox proportional hazards and logistic regression models identified factors associated with mortality and extended intensive care, ventilator, and hospital days. RESULTS In 712 children at 24 trauma centers, mean age was 7.6 years, median (interquartile range) Injury Severity Score was 9 (2–20), and in-hospital mortality was 5.3% (n = 38). There were 311 patients(43.7%) who received at least one crystalloid bolus and 149 (20.9%) who received blood including 65 (9.6%) with massive transfusion activation. Half (53.3%) of patients who received greater than one crystalloid bolus required transfusion. Patients who received blood first (n = 41) had shorter median time to transfusion (19.8 vs. 78.0 minutes, p = 0.005) and less total fluid volume (50.4 vs. 86.6 mL/kg, p = 0.033) than those who received crystalloid first despite similar Injury Severity Score (median, 22 vs. 27, p = 0.40). On multivariable analysis, there was no association with mortality (p = 0.51); however, each crystalloid bolus after the first was incrementally associated with increased odds of extended ventilator, intensive care unit, and hospital days (all p < 0.05). Longer time to transfusion was associated with extended ventilator duration (odds ratio, 1.11; p = 0.04). CONCLUSION Resuscitation with greater than one crystalloid bolus was associated with increased need for transfusion and worse outcomes including extended duration of mechanical ventilation and hospitalization in this prospective study. These data support a crystalloid-sparing, early transfusion approach for resuscitation of injured children. LEVEL OF EVIDENCE Therapeutic, level IV.

Quantification of intratumoral flow of a US contrast agent at gray-scale imaging shows promise for monitoring tumor vascular response to antiangiogenic therapy.

Type I interferons (a/b) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. An alternative dosing schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while maintaining its antitumor efficacy. We have tested a gene therapy approach in murine tumor models to treat malignancies that have shown responsiveness to interferon in clinical trials. The tumor cell lines used were moderately sensitive to the direct effects of human interferon-b (hIFN-b) in vitro. For in vivo testing, systemic delivery of hIFN-b was generated following liver-targeted delivery of adeno-associated virus (AAV) vector carrying the hIFN-b transgene. This prevented engraftment of subcutaneous human gliomas, and orthotopic, localized (intrarenal) and disseminated (primarily pulmonary) human renal cell carcinomas; and caused regression of established tumors at these sites. In a syngeneic, immunocompetent model of melanoma, AAV IFN-b treatment limited subcutaneous tumor growth and prevented disseminated disease. A significant decrease in mean intratumoral vessel density was demonstrated in hIFN-b-treated tumors, suggesting that in addition to a direct tumoricidal effect, the antitumor efficacy of AAV IFN-b in this study was due to its ability to inhibit angiogenesis.