Bartley, Adam C.

BACKGROUND: Patients who develop ARDS from medical or traumatic causes typically present after the inciting event has already occurred. Postoperative ARDS is unique in that the inciting insult potentially responsible for ARDS is known ahead of time, which provides an opportunity to study the early pathophysiology of ARDS. The objective of this study was to better understand the early pathophysiology of postoperative ARDS through a temporal analysis of key biomarkers of interest. METHODS: We performed a case-control study of adults undergoing elective thoracic, aortic vascular, or cardiac surgery, which placed them at increased risk of developing postoperative ARDS. Biomarkers were measured at baseline, 2 h, and 6 h after the key intraoperative event believed to be responsible for ARDS. RESULTS: Of the 467 subjects enrolled, 26 developed ARDS and were matched to non-ARDS controls 1:2 based on age, sex, surgical procedure, and surgical lung injury prediction score. Patients with ARDS were more likely to have lower preoperative albumin ( P = .029), longer surgery ( P = .007), larger amounts of intraoperative fluid ( P = .036), and higher intraoperative peak inspiratory pressures ( P = .006). Baseline plasminogen activator inhibitor-1 levels were higher in the ARDS group ( P = .03). Changes in postoperative biomarker levels from baseline were greater in the ARDS group for interleukin-8 (baseline to 6 h, P = .02) and surfactant protein-D (baseline to 2 h, P = .009). CONCLUSIONS: Our study supported the hypothesis that dysregulated coagulation, inflammation, and epithelial injury are pathophysiologic features of early postoperative ARDS. Interleukin-8, plasminogen activator-1, and surfactant protein-D may help predict development of postoperative ARDS.

AbstractBackgroundConflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development.MethodsWe conducted a retrospective, case–control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age‐ and sex‐matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date.ResultsThree hundred ninety‐nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non‐SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05–2.93).ConclusionsOur findings support an increased risk of SCC development in the setting of AD.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.

Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and socioeconomic burden. There is a paucity of literature regarding sex-based sociodemographic differences in VTE presentation and short-term outcomes. We aimed to compare clinical outcomes between men and women hospitalized for VTE management. We performed a retrospective analysis using data from the National Inpatient Sample (NIS) database from 2012 to 2013. Inclusion criteria were age 18 years and older and a primary discharge diagnosis of VTE. Sociodemographic features and medical comorbidities were analyzed, as were hospital length of stay and in-hospital mortality rates. A total of 107,896 patients met the inclusion criteria; 53% were female. Median age was 65 years (interquartile range 51–77) and women were older than men (65 vs 62 years, p<0.001). There were significant differences between men and women with respect to race, primary insurance payer and medical comorbidities, and small differences with respect to VTE location. Female sex was associated with a small but significantly longer hospital length of stay (mean ratio 1.04, 95% CI 1.03–1.05, p<0.001) but no significant difference in in-hospital mortality (2.2% vs 2.1%, p=0.15). In a multivariate model, there was no significant difference between women and men with respect to hospital length of stay or in-hospital mortality. In conclusion, we used data from the NIS to study over 100,000 patients hospitalized for VTE, and identified several sex-based disparities in sociodemographic factors and location of VTE. However, in a multivariable analysis correcting for these factors, sex was not associated with significant differences in clinical outcomes.

Background Detection of small renal calculi has benefitted from recent advances in computed tomography (CT) scanner design. Information regarding observer performance when using state-of-the-art CT scanners for this application is needed. Purpose To assess observer performance and the impact of radiation dose for detection and size measurement of <4 mm renal stones using CT with integrated circuit detectors and iterative reconstruction. Material and Methods Twenty-nine <4 mm calcium oxalate stones were randomly placed in 20 porcine kidneys in an anthropomorphic phantom. Four radiologists used a workstation to record each calculus detection and size. JAFROC Figure of Merit (FOM), sensitivity, false positive detections, and calculus size were calculated. Results Mean calculus size was 2.2 ± 0.7 mm. The CTDI vol values corresponding to the automatic exposure control settings of 160, 80, 40, 25, and 10 Quality Reference mAs (QRM) were 15.2, 7.9, 4.2, 2.7, and 1.3 mGy, respectively. JAFROC FOM was ≥ 0.97 at ≥ 80 QRM, ≥ 0.89 at ≥ 25 QRM, and was inferior to routine dose (160 QRM) at 10 QRM (0.72, P < 0.05). Per-calculus sensitivity remained ≥ 85% for every reader at ≥ 25 QRM. Mean total false positive detections per reader were ≤ 3 at ≥ 80 QRM, but increased substantially for two readers ( ≥ 12) at ≤ 40 QRM. Measured calculus size significantly decreased at ≤ 25 QRM ( P ≤ 0.01). Conclusion Using low dose renal CT with iterative reconstruction and ≥ 25 QRM results in high sensitivity, but false positive detections increase for some readers at very low dose levels (≤ 40 QRM). At very low doses with iterative reconstruction, measured calculus size will artifactually decrease.

311 Background: Previous population-based studies have shown variations in disease incidence and overall survival (OS) among multiple myeloma (MM) patients (pts) from different ethnic and racial backgrounds. However, the impact of race and ethnicity on early mortality (EM) or death in the first year after the diagnosis of MM is less well known. Methods: Pts with MM diagnosed from 2000-2011 were identified in the NCDB. We obtained data associated with socio-demographics, type and location of care facility, as well as the use of autologous stem cell transplant (ASCT) as an initial treatment option. Two cohorts were created based on the use of ASCT: 1) The group who received an upfront ASCT and 2) Pts who were 75 years or older who are unlikely to have ever received an ASCT. The rate of early mortality (EM) was estimated using the 1-year OS and assessed for all pts based on racial/ethnic background and the use of ASCT in their therapy. Results: There were a total of 108,352 pts who were included in this analysis. The median age of this cohort was 65 years (Range: 20 – 90). Of these 58,223 (54%) were male. The racial distributions of these cohorts were as follows: 78,589 (73%) White non-Hispanic (WNH), 21,292 (20%) Black non-Hispanic (BNH), 1,943 (2%) Asian Pacific-Islander (API), 293 (< 1%) Native-American (NA) and 6,235 (5%) Hispanics-any race (HIS). The estimated 1-yr OS (95% CI) was 71% (71 – 72) for WNH, 74% (73 – 74) for BNH, 77% (75 – 79) for API, 73% (68 – 78) for NA and 75% (74 – 76) for HIS. Amongst patients who received an upfront ASCT, the estimated 1-yr OS (95% CI) was 97% (97 – 98) for WNH (Reference), 98% (97 – 98) for BNH (P = 0.99), 99% (99 – 100) for API (P = 0.96) and 98% (97 – 99) for HIS (P = 0.99). Whereas amongst pts who likely never received an ASCT (75 years or older), the estimated 1-yr OS (95% CI) was 55% (54 – 56) WNH (Reference), 57% (56 – 59) for BNH (P = 0.03), 62% (58 – 67) for API (P = 0.02), 55% (43 – 72) for NA (P = 0.99) and 55% (52 – 58) for HIS (P = 0.99). Conclusions: In general, WNHs have a worse 1-yr OS compared to BNH and API. However, this disparity appears significant only among pts unlikely to get an ASCT. Further studies are required to identify explanations for such disparate outcomes based on race and use of ASCT.

297 Background: Unlike acute lymphoblastic leukemia, no studies have examined the effect of race on survival among AML in AYA using national data. Methods: We studied patients in the US National Cancer Data Base aged 15-39 diagnosed with AML from 2001-2011 (excluding acute promyelocytic leukemia). AMLs harboring inv(16) or t(8;21) were defined as good-risk. We examined overall survival (OS) according to race/ethnicity and survival trends over three time-periods: 2001-2004, 2005-2008, and 2009-2011. Results: We identified 8,986 patients, with a mean follow-up of 37 months. The median OS according to race/ethnicity was 56, 49, 41, and 22 months for Asians/Pacific Islanders (A/PI), Hispanics, Whites, and Blacks respectively (P < 0.001). OS improved over time among Whites only, with respective median OS of 31, 43, and 49 months (P < 0.001). Multivariate analysis adjusting for socio-demographics, travel distance, and AML type, showed that, compared to Whites, Blacks had a significantly worse and Hispanics a significantly better OS (Table). Conclusions: We found significant disparities in OS among racial/ethnic subgroups in AYA with AML despite adjustment for socio-demographic factors. Blacks had the worse and Hispanics the best outcome. In the past decade, OS improved only among the Whites. Further studies should examine provider and patient care delivery factors that may contribute to these disparities. [Table: see text]

284 Background: MM is an uncommon cancer with annual incidence of only 27,000 cases in the US. Our study determined the extent to which the number of MM patients treated annually in a treatment facility affected all-cause mortality. Methods: We used the National Cancer Data Base (NCDB) to identify adult patients with MM diagnosed from 2003-2011. NCDB is sourced from over 1,500 Commission on Cancer-accredited cancer registries representing 70% of cancer cases in the US. We classified treatment facilities by quartiles based on facility volume (mean patients/year): Quartile 1 (Q1: < 3.6), Quartile 2 (Q2: 3.6-6.1), Quartile 3 (Q3: 6.1-10.3) and Quartile 4 (Q4: > 10.3). We used hot deck imputation to account for missing data, Cox regression to analyze the association between facility volume and time-to-death, and random intercepts to adjust for multiple patients per facility. Results: There were 94,722 MM patients cared for at 1,333 facilities. Most patients (73.5%) were diagnosed and treated in the same facility. The median age at diagnosis was 67 years and 54.7% were males. The median annual facility volume was 6.1 patients/year (IQR: 3.6-10.3; range: 0.2-109.9). The distribution of patients according to facility volume was Q1 (5.2%), Q2 (12.6%), Q3 (21.9%) and Q4 (60.3%). The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months and Q4: 49.1 months. After multivariable analysis adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location), co-morbidity (Charlson-Deyo score), and disease-specific (year of diagnosis) factors, we show that facility volume remains an independent predictor of all-cause mortality. Compared to patients treated at Q4 facilities, patients treated at lower quartile facilities had a higher risk of death (Q3 HR: 1.16 [95% CI, 1.12-1.20]; Q2: 1.21 [1.17-1.26]; Q1: 1.27 [1.22-1.34]). We observed an inverse volume-outcome relationship up to an annual facility volume of approximately 60 patients. Conclusions: MM patients treated at higher volume facilities had lower risk of mortality compared to those treated at lower volume facilities.

Purpose To determine the association between the number of patients with multiple myeloma (MM) treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods Using the National Cancer Database, we identified patients diagnosed with MM between 2003 and 2011. We classified the facilities by quartiles (Q; mean patients with MM treated per year): Q1: < 3.6; Q2: 3.6 to 6.1, Q3: 6.1 to 10.3, and Q4: > 10.3. We used random intercepts to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location, travel distance), and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results There were 94,722 patients with MM treated at 1,333 facilities. The median age at diagnosis was 67 years, and 54.7% were men. The median annual facility volume was 6.1 patients per year (range, 0.2 to 109.9). The distribution of patients according to facility volume was: Q1: 5.2%, Q2: 12.6%, Q3: 21.9%, and Q4: 60.3%. The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months, and Q4: 49.1 months ( P < .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a higher risk of death (Q3 hazard ratio [HR], 1.12 [95% CI, 1.08 to 1.16]; Q2 HR, 1.17 [95% CI, 1.12 to 1.21]; Q1 HR, 1.22 [95% CI, 1.17 to 1.28]). Conclusion Patients who were treated for MM at higher-volume facilities had a lower risk of mortality compared with those who were treated at lower-volume facilities.