Supplementary Table S1. Differentially expressed genes

Supplementary Figures. Supplemental Figure S1: Representative sections showing changes in expression between baseline biopsy and post-treatment surgical specimens. Supplemental Figure S2: Correlogram showing the correlation between changes in protein expression immunoscore, metabolic activity on PET and tumor size by CT scan.

PURPOSE:Converting the nation's International Classification of Diseases (ICD) diagnosis coding system, from 14,025 ICD-9 to 69,823 ICD-10 codes, is projected to have enormous financial and operational implications. We aimed to assess the magnitude of impact that this code conversion will have on radiology claims.METHODS:The most frequently billed ICD-9 diagnosis codes for 588,523 radiology claims from five hospitals and affiliated outpatient sites during a 12-month period were mapped to matching ICD-10 codes using a Medicare-endorsed tool. The code-conversion impact factor was calculated for the entire radiology system, and each individual subspecialty division.RESULTS:Of all ICD-9 codes, only 3,407 (24.3%) were used to report any primary diagnosis. Of all claims, 50% were billed using just 37 (0.3%) primary codes; 75% with 131 (0.5%), and 90% with 348 (2.5%). Those 348 ICD-9 codes mapped onto 2,048 ICD-10 codes (5.9-fold impact), representing just 2.9% of all ICD-10 codes. By subspecialty, the conversion impact factor varied greatly, from 1.1 for breast (11 ICD-9 to 12 ICD-10 codes) to 28.8 for musculoskeletal imaging (146 to 4,199). The community division, reflecting a general practice mix, saw a conversion impact factor of 5.8 (254 to 1,471).CONCLUSIONS:Fewer than 3% of all ICD-9 and ICD-10 codes are used to report an overwhelming majority of all radiology claims. Although the number of commonly used codes will expand 5.9-fold overall, musculoskeletal imaging will experience a projected 28.8-fold explosion. Radiology practices should target their ICD educational and operational conversion efforts in an evidence-based manner.

OBJECTIVE:The purpose of this study was to identify opportunities for reducing epinephrine administration errors after a sentinel event entailing an overdose of i.v. epinephrine occurred in a radiology department.MATERIALS AND METHODS:A root cause analysis was performed that included review and analysis of current system protocols, a medication audit, and access to treatment algorithms. A proctored three-question multiple-choice test was administered to radiology attending physicians, fellows, residents, and nurses to gauge baseline knowledge of epinephrine use. Chi-square analysis was performed.RESULTS:Twelve of 13 radiology department central pharmacy automation system locations lacked epinephrine ampules. As a result, personnel had to access i.v. epinephrine stocked on hospital code carts designed for use during cardiac arrest. This led to errors related to appropriate dosing. Test participants included 46 attending physicians, 23 fellows, 28 residents, and 25 nurses (n = 122). Almost all (99%) correctly identified epinephrine as the medication to administer in this situation. Approximately one half (52%) correctly identified the dose of intramuscular epinephrine, but only 29% knew the dose and rate of administration of i.v. epinephrine (p < 0.001). Attending physicians were more likely to administer i.v. epinephrine correctly than were the other groups (p < 0.0001).CONCLUSION:Stocking and routine auditing of medication availability are essential. The use of epinephrine intended for cardiac arrest stocked on code carts should be avoided during contrast reactions. It would be optimal if first-line responders to contrast reactions included attending physicians, but this may not always be the case at academic institutions.

Orthotopic liver transplantation is becoming an increasingly routine procedure for a variety of benign and malignant diseases of the liver and biliary system. Continued improvements in surgical techniques and post-transplantation immunosuppression regimens have resulted in better graft and patient survival. A number of potentially treatable nonvascular complications of liver transplantation are visible at imaging, and accurate diagnosis of these complications allows patients to benefit from potential treatment options. Biliary complications include stricture (anastomotic and nonanastomotic), leak, biloma formation, and development of intraductal stones. Pathologic conditions, including hepatitis C infection, hepatocellular carcinoma, hepatic steatosis, and primary sclerosing cholangitis, may recur after liver transplantation. Transplant patients are at increased risk for developing de novo malignancy, including post-transplantation lymphoproliferative disorder, which results from immunosuppression. Patients are also at increased risk for systemic infection from immunosuppression, and patients with hepatic artery and biliary complications are at increased risk for liver abscess. Transplant recipients are typically followed with serial liver function testing; abnormal serum liver function test results may be the first indication that there is a problem with the transplanted liver. Ultrasonography is typically the first imaging test performed to try to identify the cause of abnormal liver function test results. Computed tomography, magnetic resonance imaging, angiography, and/or cholangiography may be necessary for further evaluation. Accurately diagnosing nonvascular complications of liver transplantation that are visible at imaging is critically important for patients to benefit from appropriate treatment.

Abstract Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non–small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples. Results: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, −21%, −24%; P = 0.014), tumor size (10.1%, 5.8%, −11.6%; P = 0.047), and modulation of S6 (−36.1, −13.7, −77.0; P = 0.071) and pS6 (−41.25, −61.57, −47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity. Conclusions: This “window-of-opportunity” study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC. Clin Cancer Res; 21(8); 1859–68. ©2015 AACR.

Optimizing workflow efficiency is key to improving the performance of any system. Optimized workflows in health care benefit patients by reducing unnecessary waits and delays. Additionally, optimized workflows benefit health care organizations by allowing the production of more units during a fixed period of time and with fixed resources.

Posttransplantation lymphoproliferative disease (PTLD) is the second most common tumor in adult transplant recipients. Most cases of PTLD are attributed to Epstein-Barr virus. Decreased levels of immunosurveillance against this tumor virus as a result of immunosuppressive regimens are thought to account for most cases of PTLD. Histologically, PTLD ranges from relatively benign lymphoid hyperplasia to poorly differentiated lymphoma, and tissue sampling is required to establish the subtype. The frequency of PTLD varies depending on the type of allograft and immunosuppressive regimen. PTLD has a bimodal manifestation, with most cases occurring within the first year after transplantation and a second peak occurring 4-5 years after transplantation. Patients are often asymptomatic or present with nonspecific symptoms, and a mass visible at imaging may be the first clue to the diagnosis. Imaging plays an important role in identifying the presence of disease, guiding tissue sampling, and evaluating response to treatment. The appearance of PTLD at imaging can vary. It may be nodal or extranodal. Extranodal disease may involve the gastrointestinal tract, solid organs, or central nervous system. Solid organ lesions may be solitary or multiple, infiltrate beyond the organ margins, and obstruct organ outflow. Suggestive imaging findings should prompt tissue sampling, because knowledge of the PTLD subtype is imperative for appropriate treatment. Treatment options include reducing immunosuppression, chemotherapy, radiation therapy, and surgical resection of isolated lesions.

In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m2) with fasting normoglycemia (n = 40) or dysglycemia (impaired fasting glucose + diabetes; n = 20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: We conducted this ‘window- of-opportunity’ study to characterize the biologic activity of everolimus, an allosteric inhibitor of mTOR pathway, in patients with surgically resectable NSCLC. Methods: Patients with surgically resectable NSCLC (Stage I-III) underwent baseline tumor biopsy and FDG PET/CT scan followed by treatment with everolimus (5 or 10mg daily for up to 28 days). A repeat PET/CT scan was obtained 24 hours prior to surgery. Blood samples for pharmacokinetic (PK) assay for drug levels were collected at 0.5, 1, 2, 5, 8 and 24 hours post drug ingestion on Days 1, 8 and 21. Control patients not treated with everolimus also had paired FDG PET/CT scans prior to surgery. Target modulation by everolimus was assessed in vivo by PET and ex vivo by immunohistochemical detection of total and phosphorylated mTOR, Akt, S6, eIF4e and 4EBP1 in pretreatment and posttreatment tissue samples. Alterations in common driver mutations in NSCLC were assessed using SnapShot minisequencing technique. Results: We enrolled 33 patients; 23 on everolimus and 10 on the control arm. Median age: 64 yrs (range 36-77), gender: (14/19 -M/F), stage (I - 14; II - 13; IIIA - 6); histology (adenocarcinoma - 22; squamous - 7; others - 4). Treatment was tolerated well with mostly grade 1/2 toxicities (hyperglycemia, hypertriglyceridemia, anemia and fatigue) and 32 of 33 patients proceeded with surgery on schedule. Compared to controls, there was significant reduction in SUVmax and median anatomic tumor size in a dose-dependent manner in everolimus-treated patients (15.38 vs. -21.74 vs. -23.23; p=0.012 and 4.39 vs. 0 vs.-13.33; p=0.039 in the control, 5mg and 10mg cohorts respectively). There was a similar trend in reduced metabolic activity in Ras mutant tumors treated with 10mg everolimus compared to control (88% vs. -28%). Comparison of baseline biopsy samples and resected tumor specimens in control and everolimus-treated patients showed reduction of S6 (-27.38 vs. 0 vs. -78.95; p=0.0536), pS6 (-20 vs. -29.17 vs. -57.14; p=0.0233) and p4EBP1 (-45.83 vs. 0 vs. -75; p=0.057) with greatest reduction observed in patients treated with higher dose of everolimus. Conclusions: Everolimus exerts a measurable, dose-dependent biologic activity in NSCLC tumors. ‘Window of opportunity’ studies in early stage NSCLC provide strong mechanistic insights and guide development of novel targeted agents. Acknowledgements: This study was supported by NCI grant P01 CA116676. Everolimus was provided by Novartis Oncology. TKO, GS, SS, SSR and FRK are Georgia Cancer Coalition Distinguished Cancer Scholars. Citation Format: Taofeek Kunle Owonikoko, Daniel L. Miller, Seth Force, Gabriel Sica, Scott Kono, Madhusmita Behera, Jennifer Mendel, Zhengjia Chen, Allan Pickens, Robert W. Fu, William F. Auffermann, Jaqueline Rogerio, William E. Torres, Haian Fu, John Hohneker, Shi-Yong Sun, Anthony A. Gal, Suresh S. Ramalingam, Fadlo R. Khuri. Window of opportunity preoperative interrogation of mTOR pathway in patients with resectable non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-194. doi:10.1158/1538-7445.AM2013-LB-194

Experience with 47 Treated Lesions Sherif G Nour, David A Kooby, Shishir K Maithel, Charles A Staley, Hiroumi D Kitajims, William C Small, and William E Torres Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, Interventional MRI Program, Emory University, Atlanta, GA, United States, Surgical Oncology, Emory University, Atlanta, GA, United States, School of Medicine, Emory University, Atlanta, GA, United States

Individuals who are severely obese have an increased risk of type 2 diabetes (T2DM), which may be undiagnosed. Earlier detection and treatment of diabetes can prevent the progression to serious complications. We have shown that sagittal abdominal diameter (SAD)—the height of the abdominal region—is a good estimate of visceral adiposity (VAT) in severely obese women. In this current study we determined whether SAD and VAT could predict T2DM or prediabetes. Eligible subjects were consecutively enrolled females, who were scheduled for bariatric surgery (n=60). Subjects were categorized as having normal fasting glucose (NFG), impaired fasting glucose (IFG), or T2DM as defined by the American Diabetes Association. VAT volume (in cm3) was measured by multislice computer tomography. SAD (in cm) was measured in the supine position by sliding-beam caliper. Receiver operating curve analysis was used to estimate optimal cut-points for detecting T2DM or IFG. Forty subjects were NFG, seven had IFG, and thirteen had T2DM. Both SAD and VAT volumes were greater (p<0.05) in IFG (31.6±0.8, 5,410±710, respectively) or T2DM (30.1±0.8, 5,460±520) subjects compared to NFG subjects (29.3±0.4, 3,520±240); BMI did not differ between groups (mean, 46.0±0.7 kg/m2). The VAT cut-off for detecting T2DM or prediabetes was 4,950 cm3, area-under-the-curve (AUC) = 0.75. The SAD cut-off for detection was 30.2 cm, AUC = 0.66. Increased VAT and SAD are good predictors of diabetes or prediabetes in severely obese women. SAD is a low-cost and simple anthropometric measure that can be used to identify those at risk of diabetes among severely obese women.

Roux‐en‐y gastric bypass (RYGB) surgery is associated with dramatic improvements in obesity‐related comorbidity, but also with nutritional deficiencies. Vitamin D concentrations are depressed in the severely obese, but the impact of weight loss via RYGB is unknown. We determined associations between adiposity and systemic 25‐hydroxyvitamin D (25(OH)D) during weight loss and the immediate and longer‐term effects of RYGB. Plasma 25(OH)D concentrations and fat mass (FAT) were determined by immunoassay and air displacement plethysmography, respectively, at 0 (before RYGB surgery), and at 1, 6, and 24 months in severely obese white and African American (AA) women ( n = 20). Decreases in adiposity were observed at 1, 6, and 24 months following RYGB ( P < 0.05). Plasma 25(OH)D concentrations increased at 1 month ( P = 0.004); a decreasing trend occurred over the remainder months after surgery ( P = 0.02). Despite temporary improvement in vitamin D status, a high prevalence of vitamin D insufficiency was observed (76, 71, 67, and 82%, at baseline, 1, 6, and 24 months, respectively), and plasma 25(OH)D concentrations were lower in AA compared to white patients ( P < 0.05). Strong positive baseline and 1 month cross‐sectional correlations between FAT and plasma 25(OH)D were observed, which remained after adjustment for age and race subgroup (β = 0.76 and 0.61, respectively, P = 0.02). In conclusion, 25(OH)D concentrations increased temporarily and then decreased during the 24 months following RYGB. The acute increase and the positive associations observed between adipose tissue mass and systemic 25(OH)D concentrations suggest storage in adipose tissue and release during weight loss.

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue ( SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 +/- 0.8 kg/m(2) to 43.3 +/- 0.8 kg/m(2) (1 month), 35.2 +/- 0.8 kg/m(2) (6 months), and 30.2 +/- 1.2 kg/m(2) (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6-month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6-month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high-density lipoprotein (HDL) at 1 and 6 months after surgery (r = -0.38 and -0.42). This study found longitudinal associations between general, and more specifically intra-abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.

ObesityVolume 16, Issue S1 p. S47-S95 Free Access Oral Presentations Plenary Oral Abstracts First published: 06 September 2012 https://doi.org/10.1038/oby.2008.371Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume16, IssueS1Special Issue: OBESITY 2008 Abstract SupplementOctober 2008Pages S47-S95 RelatedInformation

Obesity-related glucose intolerance is a function of hepatic (homeostatic model assessment-insulin resistance [HOMA-IR]) and peripheral insulin resistance (S(i)) and beta-cell dysfunction. We determined relationships between changes in these measures, visceral (VAT) and subcutaneous (SAT) adipose tissue, and systemic adipocytokine biomarkers 1 and 6 months after surgical weight loss. HOMA-IR decreased significantly (-50%) from baseline by 1 month and decreased further (-67%) by 6 months, and S(i) was improved by 6 months (2.3-fold) weight loss. Plasma concentrations of leptin decreased and adiponectin increased significantly by 1 month, and decreases in interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-alpha were observed at 6 months of weight loss. Longitudinal decreases in CRP (r = -0.53, P < 0.05) were associated with increases in S(i), and decreases in HOMA-IR were related to increases in adiponectin (r = -0.37, P < 0.05). Decreases in VAT were more strongly related to increases in adiponectin and decreases in CRP than were changes in general adiposity or SAT. Thus, in severely obese women, specific loss of VAT leads to acute improvements in hepatic insulin sensitivity mediated by increases in adiponectin and in peripheral insulin sensitivity mediated by decreases in CRP.

HomeRadiologyVol. 245, No. 1 PreviousNext Reviews and CommentaryPerspectivesNonphysician Providers in Radiology: The Emory University ExperienceMichael A. Bowen, William E. Torres, William C. SmallMichael A. Bowen, William E. Torres, William C. SmallAuthor Affiliations1From the Division of Abdominal Imaging, Department of Radiology, Emory University School of Medicine, 1364 Clifton Rd NE, Atlanta, GA 30322. Received March 28, 2007; final version accepted April 25.Address correspondence to W.C.S. (e-mail: [email protected]). Michael A. BowenWilliam E. TorresWilliam C. SmallPublished Online:Oct 1 2007https://doi.org/10.1148/radiol.2451070575MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References1 Thrall JH. Reinventing radiology in the digital age. III. Facilities, work process, and job responsibilities. Radiology 2005; 237: 790–793. Google Scholar2 Dunnick NR. 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