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by studies in experimental animals in which neutrophil C-X-C chemokines are potent chemoattractants that depletion before a hepatic insult can limit tissue injury. 1,6,7 are believed to mediate neutrophilic inflammation in For neutrophils to emigrate from the circulation to the heseveral organs. Recent studies suggest a role for C-X-C patic parenchyma, they must respond to a specific chemotacchemokines in the pathogenesis of neutrophilic hepatitic signal. We and others have shown that liver cells are tis but do not prove causation. We investigated the biocapable of producing neutrophil chemoattractants belonging logical consequences of hepatic chemokine production to the C-X-C family of chemokines. [8][9][10][11][12] Among the C-X-C in vivo by transiently overexpressing cytokine-induced chemokines produced by liver cells are interleukin (IL)-8 and neutrophil chemoattractant (CINC), a member of the Ca related compound in the rat called cytokine-induced neutro-X-C chemokine family, in intact rats. Rats were injected phil chemoattractant (CINC). IL-8 and CINC are 47% homolintraportally with a replication-defective recombinant ogous in nucleotide sequence; from a functional point of view, adenovirus containing the CINC complementary DNA the two are almost identical. Each compound has the ability (cDNA). Within 4 days, treated animals had high levels to attract neutrophils from humans and rats, respectively, in of CINC in both liver tissue and plasma. Rats overexnanomolar concentrations in vitro. 13pressing CINC exhibited an eightfold increase in circuHigh levels of IL-8 or CINC have been reported in humans lating neutrophils; they also developed severe hepatic and rats with neutrophilic hepatitis, 4,5 which documents an injury, characterized by a 6-to 25-fold increase in plasma association between hepatic chemokine production and neutransaminases and marked hepatic inflammation on bitrophilic liver injury in vivo. However, the precise role of opsy. Liver disease in CINC-producing rats correlated chemokines in the pathogenesis of neutrophilic hepatitis repositively with the number of neutrophils sequestered mains unresolved, because these compounds represent but in the hepatic parenchyma. Tissue injury was attributed one of many inflammatory mediators produced locally in liver directly to chemokine overproduction, because control injury. Indeed, neutrophilic hepatitis is accompanied not only rats infected with adenoviruses lacking the CINC cDNA by hepatic chemokine induction but also by local upregulation did not produce CINC and developed only minor hepatic of IL-1, IL-6, tumor necrosis factor, and platelet-activating abnormalities. These experiments provide direct evifactor. 11,15,16 Oxyradicals and arachidonic acid metabolites dence that C-X-C chemokines, when expressed in suffialso accumulate in acute inflammatory liver disease. 17,18cient quantity in the liver in vivo, induce neutrophil reThese too may enhance neutrophil recruitment and liver cruitment and tissue invasion and provoke severe liver damage. In such...

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Widespread preoperative imaging did not eliminate unnecessary pediatric appendectomies. Controlling for factors potentially associated with referral bias, a CT scan was more likely to be performed in children initially evaluated at community hospitals compared with the children's hospital. Broadly-applicable strategies to systematically maximize diagnostic accuracy for childhood appendicitis, while minimizing ionizing radiation exposure, are urgently needed.

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for the Midwest Pediatric Surgery Consortium IMPORTANCE Nonoperative management with antibiotics alone has the potential to treat uncomplicated pediatric appendicitis with fewer disability days than surgery.OBJECTIVE To determine the success rate of nonoperative management and compare differences in treatment-related disability, satisfaction, health-related quality of life, and complications between nonoperative management and surgery in children with uncomplicated appendicitis. DESIGN, SETTING, AND PARTICIPANTS Multi-institutional nonrandomized controlled intervention study of 1068 children aged 7 through 17 years with uncomplicated appendicitis treated at 10 tertiary children's hospitals across 7 US states between May 2015 and October 2018 with 1-year follow-up through October 2019. Of the 1209 eligible patients approached, 1068 enrolled in the study. INTERVENTIONS Patient and family selection of nonoperative management with antibiotics alone (nonoperative group, n = 370) or urgent (Յ12 hours of admission) laparoscopic appendectomy (surgery group, n = 698). MAIN OUTCOMES AND MEASURESThe 2 primary outcomes assessed at 1 year were disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care (expected difference, 5 days), and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year (lowest acceptable success rate, Ն70%). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome assessments. RESULTS Among 1068 patients who were enrolled (median age, 12.4 years; 38% girls), 370 (35%) chose nonoperative management and 698 (65%) chose surgery. A total of 806 (75%) had complete follow-up: 284 (77%) in the nonoperative group; 522 (75%) in the surgery group. Patients in the nonoperative group were more often younger (median age, 12.3 years vs 12.5 years), Black (9.6% vs 4.9%) or other race (14.6% vs 8.7%), had caregivers with a bachelor's degree (29.8% vs 23.5%), and underwent diagnostic ultrasound (79.7% vs 74.5%). After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.31%; P = .86). Nonoperative management was associated with significantly fewer patient disability days at 1 year than did surgery (adjusted mean, 6.6 vs 10.9 days; mean difference, −4.3 days (99% CI, −6.17 to −2.43; P < .001). Of 16 other prespecified secondary end points, 10 showed no significant difference.CONCLUSION AND RELEVANCE Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not stat...

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