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Background: The primary goal of this study was to demonstrate that endotracheal tubes coated with antimicrobial lipids plus mucolytic or antimicrobial lipids with antibiotics plus mucolytic would significantly reduce pneumonia in the lungs of pigs after 72 hours of continuous mechanical ventilation compared to uncoated controls., Materials and Methods: Eighteen female pigs were mechanically ventilated for up to 72 hours through uncoated endotracheal tubes, endotracheal tubes coated with the antimicrobial lipid, octadecylamine, and the mucolytic, N-acetylcysteine, or tubes coated with octadecylamine, N-acetylcysteine, doxycycline, and levofloxacin (6 pigs per group). No exogenous bacteria were inoculated into the pigs, pneumonia resulted from the pigs' endogenous oral flora. Vital signs were recorded every 15 minutes and arterial blood gas measurements were obtained for the duration of the experiment. Pigs were sacrificed either after completion of 72 hours of mechanical ventilation or just prior to hypoxic arrest. Lungs, trachea, and endotracheal tubes were harvested for analysis to include bacterial counts of lung, trachea, and endotracheal tubes, lung wet and dry weights, and lung tissue for histology., Results: Pigs ventilated with coated endotracheal tubes were less hypoxic, had less bacterial colonization of the lungs, and survived significantly longer than pigs ventilated with uncoated tubes. Octadecylamine-N-acetylcysteine-doxycycline-levofloxacin coated endotracheal tubes had less bacterial colonization than uncoated or octadecylamine-N-acetylcysteine coated tubes., Conclusion: Endotracheal tubes coated with antimicrobial lipids plus mucolytic and antimicrobial lipids with antibiotics plus mucolytic reduced bacterial colonization of pig lungs after prolonged mechanical ventilation and may be an effective strategy to reduce ventilator-associated pneumonia., (Copyright © 2021. Published by Elsevier Inc.)

Mesenteric ischemia and reperfusion (I/R) injury can ensue from a variety of vascular diseases and represents a major cause of morbidity and mortality in intensive care units. It causes an inflammatory response associated with local gut dysfunction and remote organ injury. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of metabolic homeostasis. The catalytic α1 subunit is highly expressed in the intestine and vascular system. In loss-of-function studies, we investigated the biological role of AMPKα1 in affecting the gastrointestinal barrier function. Male knock-out (KO) mice with a systemic deficiency of AMPKα1 and wild-type (WT) mice were subjected to a 30 min occlusion of the superior mesenteric artery. Four hours after reperfusion, AMPKα1 KO mice exhibited exaggerated histological gut injury and impairment of intestinal permeability associated with marked tissue lipid peroxidation and a lower apical expression of the junction proteins occludin and E-cadherin when compared to WT mice. Lung injury with neutrophil sequestration was higher in AMPKα1 KO mice than WT mice and paralleled with higher plasma levels of syndecan-1, a biomarker of endothelial injury. Thus, the data demonstrate that AMPKα1 is an important requisite for epithelial and endothelial integrity and has a protective role in remote organ injury after acute ischemic events.

COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. To expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients, including matched analysis of the whole-blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate herein the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide., Competing Interests: Declaration of interests J.M.E. serves in the COVID Development Advisory Board for Elly Lilly and has provided consulting services to Gilead Sciences Inc. J.M.E. also serves on the Cell Reports Advisory Board. The remaining authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The national opioid epidemic is a public health crisis. Thoracic surgery has also been associated with high incidence of new persistent opioid use. Our purpose was to describe the incidence and predictors of opioid use after lung cancer resection., Methods: Retrospective review of lung cancer resections from 2015 to 2018 was performed using the Ohio Automated Rx Reporting System. Opioid dosing was recorded as milligram morphine equivalents (MME). Patients were stratified by preoperative opioid use. Chronic preoperative opioid users (opioid dependent) filled > 120 days supply of opioid pain medication in the 12 months prior to surgery; intermittent opioid users filled < 120 days. Chronic postoperative opioid users continued monthly use after 180 days postoperatively., Results: 137 patients underwent resection. 16.1% (n = 22) were opioid dependent preoperatively, 29.2% (n = 40) were intermittent opioid users, and 54.7% (n = 75) were opioid naïve. Opioid dependent patients had higher daily inpatient opioid use compared to intermittent users and opioid naïve (43[30.0-118.1] MME vs 17.9[3.5-48.8] MME vs 8.8[2.1-25.0] MME, p < 0.001). Twenty-six percent (n = 35) of all patients were opioid users beyond 180 days postoperatively. Variables associated with opioid use > 180 days were: chronic preoperative opioid use (OR 23.8, p < 0.01), daily inpatient opioid requirement (1.02, p < 0.01), and neoadjuvant chemotherapy (28.2, p < 0.01)., Conclusions: A quarter of patients are opioid dependent after lung cancer resection. This is due to both preexisting and new persistent opioid use. Improved strategies are needed to prevent chronic pain and opioid dependence after lung cancer resection.

Neutrophils are vital to both the inflammatory cascade and tissue repair after an injury. Neutrophil heterogeneity is well established but there is less evidence for significant, different functional roles for neutrophil subsets. OLFM4 (Olfactomedin-4) is expressed by a subset of neutrophils, and high expression of OLFM4 is associated with worse outcomes in patients with sepsis and acute respiratory distress syndrome. We hypothesized that an increased number of OLFM4 + neutrophils would occur in trauma patients with worse clinical outcomes. To test this, we prospectively enrolled patients who suffered a blunt traumatic injury. Blood was collected at the time of admission, Day 3, and Day 7 and analyzed for the percentage of neutrophils expressing OLFM4. We found that a subset of patients who suffered blunt traumatic injury upregulated their percentage of OLFM4 + neutrophils. Those who upregulated their OLFM4 had an increased length of stay, days in the ICU, and ventilator days. A majority of these patients also suffered from hemorrhagic shock. To establish a potential role for OLFM4 + neutrophils, we used a murine model of hemorrhagic shock because mice also express OLFM4 in a subset of neutrophils. These studies demonstrated that wild type mice had higher concentrations of cytokines in the plasma and myeloperoxidase in the lungs compared with OLFM4-null mice. In addition, we used an anti-OLFM4 antibody, which when given to wild type mice led to the reduction of myeloperoxidase in the lungs of mice. These findings suggest that OLFM4 + neutrophils are a unique subset of neutrophils that affect the inflammatory response after tissue injury.

Background: Salvage and delayed esophagectomy after chemoradiation therapy (CRT) have been associated with increased morbidity and mortality, but recent series have shown similar outcomes compared to timely esophagectomy. We aim to evaluate outcomes for delayed and salvage esophagectomy for esophageal adenocarcinoma utilizing a large national database., Methods: The National Cancer Database for 2004 to 2014 was queried for patients with clinical stage II or III esophageal adenocarcinoma who underwent preoperative CRT and esophagectomy. Patients who underwent surgery <90 days after CRT were defined as the timely esophagectomy group (n = 7822), and those who underwent surgery ≥90 days after CRT were defined as the delayed esophagectomy group (n = 667)., Results: A total of 8489 patients met our inclusion criteria. The median post-CRT interval was 49 days (range, 40-61 days) for the timely esophagectomy group and 109 days (range, 97-132 days) for the delayed esophagectomy group. The delayed group was more likely to be of black race (2.3% vs 1.2%; P < .01) and more likely to have Medicare (47.9% vs 39.8%; P < .001). There were no significant between-group differences in chemotherapy regimens (P = .17), radiation dose (P = .18), or surgical approach (P = .48). The delayed esophagectomy group had higher rates of pathological complete response (22.2% vs 18.6%; P = .043) and 90-day postoperative mortality (10.4% vs 7.8%; P < .01). On multivariate analysis, delayed esophagectomy was not independently associated with decreased overall survival., Conclusions: In this large retrospective database study, despite increased perioperative mortality, delayed and salvage esophagectomy for adenocarcinoma appear to have similar long-term survival as timely esophagectomy. Delayed and salvage esophagectomy may be offered to patients who do not receive timely esophagectomy after CRT., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Pediatric sepsis is a leading cause of morbidity and mortality in children. One of the most common and devastating morbidities is sepsis-related acute kidney injury (AKI). AKI was traditionally thought to be related to low perfusion and acute tubular necrosis. However, little acute tubular necrosis can be found following septic AKI, and little is known about the mechanism of septic AKI. Olfactomedin-4 (OLFM4) is a secreted glycoprotein that marks a subset of neutrophils. Increased expression of OLFM4 in the blood is associated with worse outcomes in sepsis. Here, we investigated a pediatric model of murine sepsis using murine pups to investigate the mechanisms of OLFM4 in sepsis. When sepsis was induced in murine pups, survival was significantly increased in OLFM4-null pups. Immunohistochemistry at 24 h after the induction of sepsis demonstrated increased expression of OLFM4 in the kidney, which was localized to the loop of Henle. Renal cell apoptosis and plasma creatinine were significantly increased in wild-type versus OLFM4-null pups. Finally, bone marrow transplant suggested that increased OLFM4 in the kidney reflects local production rather than filtered from the plasma. These results demonstrate renal expression of OLFM4 for the first time and suggest that a kidney-specific mechanism may contribute to survival differences in OLFM4-null animals.

Background: Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC., Methods: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed., Results: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA., Conclusion: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

Olfactomedin-4 (OLFM4) identifies a subset of neutrophils conserved in both mouse and man, associated with worse outcomes in several inflammatory conditions. We investigated the role of OLFM4-positive neutrophils in murine intestinal ischemia/reperfusion (IR) injury. Wild-type (WT) C57Bl/6 and OLFM4 null mice were subjected to intestinal IR injury and then monitored for survival or tissues harvested for further analyses. In vivo intestinal barrier function was determined via functional assay of permeability to FITC-dextran. OLFM4 null mice had a significant 7-d survival benefit and less intestinal barrier dysfunction compared with WT. Early after IR, WT mice had worse mucosal damage on histologic examination. Experiments involving adoptive transfer of bone marrow demonstrated that the mortality phenotype associated with OLFM4-positive neutrophils was transferrable to OLFM4 null mice. After IR injury, WT mice also had increased intestinal tissue activation of NFκB and expression of iNOS, 2 signaling pathways previously demonstrated to be involved in intestinal IR injury. In combination, these experiments show that OLFM4-positive neutrophils are centrally involved in the pathologic pathway leading to intestinal damage and mortality after IR injury. This may provide a therapeutic target for mitigation of intestinal IR injury in a variety of common clinical situations.-Levinsky, N. C., Mallela, J., Opoka, A., Harmon, K., Lewis, H. V., Zingarelli, B., Wong, H. R., Alder, M. N. The olfactomedin-4 positive neutrophil has a role in murine intestinal ischemia/reperfusion injury.

Background: The impact of recent preoperative opioid exposure on outcomes of colorectal surgery is unclear. Our aim was to evaluate the impact of preoperative opioid use on outcomes and opioid prescribing patterns after colorectal surgery., Methods: We performed a retrospective review of all patients undergoing elective resection at a single institution from 2015 to 2017. Primary outcomes included in-hospital narcotic use and cost. Secondary outcomes included postoperative surgical outcomes and discharge prescribing patterns., Results: A total of 390 patients underwent elective colorectal surgery, of whom 63 (16%) had a recent history of preoperative opioid use. Opioid users had similar age, sex, American Society of Anesthesiologists score, and operative indication compared with opioid-naïve patients (P > .05 for each). Postoperatively, the 30-day readmission rate was greater among opioid users (18% vs 9%, P = .03). Opioid users had greater total narcotic use (218 morphine milligram equivalents vs 111 morphine milligram equivalents, P = .04) and direct costs ($11,165 vs $8,911, P < .01). These patients were also more likely to require an opioid prescription on discharge (90% vs 68%, P < .01) and an opioid refill within 30 days (54% vs 21%, P < .01)., Conclusion: Recent preoperative opioid exposure among colorectal surgery patients was associated with increased opioid consumption and costs. Moreover, unadjusted analysis was pertinent for more readmissions after surgery among preoperative opioid users. This work underscores the negative impact of preoperative, chronic opioid use on surgical outcomes and highlights the need for developing protocols to minimize perioperative narcotics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Enhanced recovery protocols are associated with improved recovery. However, data on outcomes following the implementation of an enhanced recovery protocol in colorectal cancer are limited. We set out to study the postoperative outcomes, opioid use patterns, and cost impact for patients undergoing colon or rectal resection for cancer., Methods: A retrospective review of all elective colorectal cancer resections from January 2015 to June 2018 at a single institution was performed. Patient demographics, operative details, and postoperative outcomes were collected. Colon and rectal patients were studied separately, with comparison of patients before and after the implementation of an enhanced recovery protocol., Results: One hundred ninety-two patients underwent elective colorectal resection for cancer. In January 2016, an enhanced recovery protocol was implemented for all elective resections - 71 patients (33 colon and 38 rectal) underwent surgery before implementation and 121 patients (56 colon and 65 rectal) underwent surgery after implementation of the enhanced recovery protocol. There were no differences with regard to age, gender, or body mass index before or after implementation (all P > .05). For both colon and rectal cancer patients, the enhanced recovery protocol reduced time to regular diet (both P < .05) and length of stay (colon: 3 vs 4 days; rectal: 4 vs 6 days; both P < .01). Enhanced recovery protocol patients also consumed fewer total narcotics (colon: 44 vs 184 morphine milligram equivalents, P < .01; rectal: 121 vs 393 morphine milligram equivalents, P < .01)., Conclusions: Enhanced recovery protocol use reduced length of stay and narcotic use with similar total costs and no difference in 30-day complications for both colon and rectal cancer resections., (© 2019 Published by Elsevier Inc.)

Background: A disconnected distal pancreas (DDP) remnant is a morbid sequela of necrotizing pancreatitis. Definitive surgical management can be accomplished by either fistulojejunostomy (FJ) or distal pancreatectomy (DP). It is unclear which operative approach is superior with regard to short- and long-term outcomes., Methods: Between 2002 and 2014, patients undergoing either FJ or DP for DDP were retrospectively identified at a center specializing in pancreatic diseases. Patient demographics, perioperative, and postoperative variables were evaluated., Results: Forty-two patients with DDP secondary to necrotizing pancreatitis underwent either a FJ (n = 21) or DP (n = 21). Between the two cohorts, there were no significant differences in overall lengths of stay, pancreatic leak rates, or readmission rates (all p > 0.05). DP was associated with higher estimated blood loss, increased transfusion requirements, and worsening endocrine function (all p < 0.05). At a median follow-up of 18 months, four patients that underwent a FJ developed a recurrent fluid collection requiring re-intervention. Overall, FJ was successful in 80% of patients as compared to a 95% success rate for DP (p = 0.15)., Conclusions: Although DP was associated with higher intraoperative blood loss, increased transfusion requirements, and worsening of preoperative diabetes, this procedure provides superior long-term resolution of a DDP when compared to FJ.

Background and Objectives: In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT., Methods: Between 2005 and 2015, 38 patients at a tertiary care referral center underwent NT followed by pancreaticoduodenectomy for borderline resectable pancreas cancer. Radiographic response after the completion of NT and pathologic response after surgery were graded according to RECIST and Evans' criteria, respectively., Results: Preoperatively, 50% of patients underwent chemotherapy alone and 50% underwent chemotherapy and chemoradiation. Radiographically, one patient demonstrated a complete radiologic response, 68.4% (n = 26) of patients had stable disease (SD), 26.3% (n = 10) demonstrated a partial response, and one patient had progressive. Among patients without radiographic response, 77.7% (n = 21) achieved a R0 resection. Of patients with SD on imaging, 26.9% (n = 7) had Evans grade IIB or greater pathologic response., Conclusions: Our data indicate that approximately one-fourth of patients who did not have a radiologic response had a grade IIB or greater pathologic response. In the absence of metastatic progression, lack of radiographic down-staging following NT should not preclude surgery., (© 2017 Wiley Periodicals, Inc.)

Background: Sequencing therapy for patients with periampullary malignancy is controversial. Clinical trial data report high rates of adjuvant therapy completion, though contemporary, real-world rates remain incomplete. We sought to identify patients who failed to receive adjuvant therapy and those at risk for early recurrence (ER) who might benefit most from neoadjuvant therapy (NT)., Methods: We retrospectively reviewed medical records of 201 patients who underwent pancreaticoduodenectomy for periampullary malignancies between 1999 and 2015; patients receiving NT were excluded. Univariate and multivariate analyses were performed to identify predictors of failure to receive adjuvant therapy and ER (within 6 months) as the primary end points., Results: The median age at the time of surgery was 65.5 years (interquartile range 57-74 years). The majority of tumors were pancreatic ductal adenocarcinoma (76.6 %), and 71.6 % of patients received adjuvant therapy after resection. Univariate predictors of failure to undergo adjuvant therapy were advanced age, age-adjusted Charlson comorbidity index, operative transfusion, reoperation, length of stay, and 30- to 90-day readmissions (all p < 0.05). Advanced age, specifically among patients >70 years, persisted as a significant preoperative predictor on multivariate analysis (p < 0.01). Patients who failed to receive adjuvant therapy and/or developed ER had significantly worse overall survival rates compared to all other patients (27.8 vs. 9.7 months; p < 0.01)., Conclusions: Approximately one-third of surgery-first patients undergoing pancreaticoduodenectomy at our institution did not receive adjuvant therapy and/or demonstrated ER. This substantial subset of patients may particularly benefit from NT, ensuring completion of multimodal therapy and/or avoiding futile surgical intervention., Competing Interests: The authors declare no conflict of interest.

Background: For patients with chronic pancreatitis, duodenum-sparing head resections and pancreaticoduodenectomy are effective operations to relieve abdominal pain. For patients who develop recurrent symptoms after their index operation, the long-term management remains controversial., Methods: Between 2002 and 2014, patients undergoing operative intervention for chronic pancreatitis were identified retrospectively. Patients requiring reoperation after their index operation were reviewed., Results: A total of 121 patients with chronic pancreatitis underwent an index operation. At a median time of 33 months, 85 patients underwent no further operative intervention, while 36 patients underwent reoperation. A reoperative procedure was completed with acceptable perioperative morbidity and blood loss. After a revision operation, 25% of patients became narcotic independent. Narcotic requirements decreased from 143 morphine equivalent milligrams per day (MEQ/d) to 80 MEQ/d, and 58% of patients required less than 50 MEQ/d. Insulin requirements were not increased from preoperative levels. Multivariate analysis demonstrated only narcotic requirement and exocrine insufficiency after the index operation to be predictive for the need for a revision operation., Conclusion: Our data demonstrate the following: (1) A significant number of patients undergoing duodenum-sparing head resections (26%) or pancreaticoduodenectomy (29%) required reoperation for recurrent abdominal pain; and (2) a revisional operation can be effective in relieving recurrent abdominal symptoms. Patients with recurrent symptoms should be considered for additional operative intervention., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Traditional decompressive and/or pancreatic resection procedures have been the cornerstone of operative therapy for refractory abdominal pain secondary to chronic pancreatitis. Management of patients that fail these traditional interventions represents a clinical dilemma. Salvage therapy with completion pancreatectomy and islet cell autotransplantation (CPIAT) is an emerging treatment option for this patient population; however, outcomes after this procedure have not been well-studied., Methods: All patients undergoing CPIAT after previous decompressive and/or pancreatic resection for the treatment of chronic pancreatitis at our institution were identified for inclusion in this single-center observational study. Study end points included islet yield, narcotic requirements, glycemic control, and quality of life (QOL). QOL was assessed using the Short Form (SF)-36 health questionnaire., Results: Sixty-four patients underwent CPIAT as salvage therapy. The median age at time of CPIAT was 38 years (interquartile range [IQR], 14.7-65.4). The most common etiology of chronic pancreatitis was idiopathic pancreatitis (66%; n = 42) followed by genetically linked pancreatitis (9%; n = 6) and alcoholic pancreatitis (8%; n = 5). All of these patients had previously undergone prior limited pancreatic resection or decompressive procedure. The majority of patients (50%; n = 32) underwent prior pancreaticoduodenectomy, whereas the remainder had undergone distal pancreatectomy (17%; n = 11), Frey (13%; n = 8), Puestow (13%; n = 8), or Berne (8%; n = 5) procedures. Median time from initial surgical intervention to CPIAT was 28.1 months (IQR, 13.6-43.0). All of these patients underwent a successful CPIAT. Mean operative time was 502.2 minutes with average hospital duration of stay of 13 days. Islet cell isolation was feasible despite previous procedures with a mean islet yield of 331,304 islet cell equivalents, which totaled an islet cell autotransplantation of 4,737 ± 492 IEQ/kg body weight. Median patient follow-up was 21.2 months (IQR, 7.9-36.8). Before CPIAT, all patients required a mean of 120.8 morphine equivalent milligrams per day (MEQ/d), which improved to 48.5 MEQ (P < .001 compared with preoperative requirements) at most recent follow-up. Of these patients, 44% (n = 28) achieved narcotic independence. All patients were able to achieve stable glycemic control with a mean insulin requirement of 16 units per day. Of these patients, 20% (n = 13) were insulin independent after CPIAT. Mean postoperative glycosylated hemoglobin was 7.8% (range, 4.6-12.5). Islet cell viability was confirmed with endocrine testing and mean C-peptide levels 6 months after CPIAT were 0.91 ng/mL (range, 0.1-3.0). The SF-36 QOL survey administered postoperatively demonstrated improvement in all tested modules., Conclusion: This study is the first to examine the results of salvage therapy with CPIAT for patients with refractory chronic pancreatitis. Patients undergoing CPIAT achieved improved postoperative narcotic requirements, stable glycemic control, and improved QOL., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Acute appendicitis continues to be a common general surgical problem. Little is known about whether the contribution to margin has been affected by changes in technology., Study Design: Patients undergoing appendectomy for acute appendicitis from June 2005 to May 2007 were evaluated for demographics, diagnostic and treatment alternatives, and outcomes. Financial outcomes were assessed. Efficiency, including admission to emergency department bed to incision (bed to knife time [BTK]), operative length, and hospital length of stay (LOS) were assessed., Results: During the 2 years of the study, there were no differences in demographics, insurance status, case length, diagnostic accuracy, pathology, LOS, or outcomes. Both laparoscopy and CT use increased between the 2 study years (odds ratio [OR]: 1.68, p = 0.06; 95% CI, 0.98-2.89 and OR: 1.83, p = 0.06, CI, 0.98-3.45, respectively). Mean BTK time increased by about 1 hour: 465 minutes versus 521 minutes (p = 0.032; 95% CI, 0.08-1.78) in univariate analysis. However, multivariate analysis demonstrated no difference in BTK time between years (p = 0.136). After controlling for gender, year of operation, and insurance status, obtaining a CT study added 3.5 hours to BTK time (p < 0.001; 95% CI, 2.41-4.45). Women had BTK times 55 minutes longer than men when controlling for similar covariates (p = 0.027; 95% CI, 0.11-1.74). Laparoscopy contributed to shorter mean LOS (-0.78 days, p = 0.04), and gangrenous appendicitis (1.80 days, p < 0.001) and complications (4.23 days, p < 0.001) increased LOS. Mean contribution to margin decreased from $6,347 to $4,295 (p = 0.068)., Conclusions: Increasing use of CT scanning in acute appendicitis increases cost of care, decreases contribution to margin, prolongs patient's stay in the emergency department, and delays time to operation., (Copyright 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)