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Objective: The aim of this study was to characterize preoperative super-utilizers and examine the effect of surgery on service utilization among patients undergoing major elective surgery., Summary Background Data: Rising healthcare costs are becoming increasingly burdensome for Medicare. Super-utilizers have been increasingly identified and studied as this subset of patients consume a disproportionate amount of healthcare services compared with the majority of the population., Methods: Patients aged 65 or older who underwent any of the following general elective surgeries: abdominal aortic aneurysm repair (AAA), coronary artery bypass graft (CABG), colectomy, or hip replacement were identified using 100% Medicare Inpatient and Outpatient Standard Analytic Files (SAFs) from years 2012 to 2016. Medicare inpatient and outpatient expenditures the year before surgery, around the time of surgery, and the year after surgery were examined., Results: Among 603,105 Medicare beneficiaries, 32,145 patients (5.3%) were categorized as super-utilizers. Compared with low-utilizers, super-utilizers were more likely to be male (low-utilizer vs super-utilizer: 47.9% vs 54.2%) and African American (4.0% vs 7.2%), whereas 58.8% (n = 208,080) of low-utilizers presented without any comorbidity [Charlson Comorbidity Index (CCI) = 0] and 49.8% (n = 16,007) of super-utilizers presented with a CCI score of ≥3. Total preoperative spending among super-utilizers was approximately $1.7 billion with a median of $3,159 [interquartile range (IQR): $554-$15,181] per beneficiary. Spending among super-utilizers accounted for 39.6% of total spending for all Medicare beneficiaries versus only 8.4% among low-utilizers. Although the median spending per Medicare beneficiary in the year after surgery was higher for super-utilizers compared with low-utilizers [$1,837 (IQR: $341-$11,390) vs $18,223 (IQR: $3,466-$43,356)], super-utilizers accounted for 13.5% of total postoperative spending. The reduction in adjusted average annual Medicare expenditure ranged from >$15,000 per year for patients undergoing CABG to approximately $30,000 per year for patients undergoing a hip replacement., Conclusions: Although super-utilizers accounted for only 5.3% of patients, these patients accounted for 39.6% of total Medicare expenditures in the year before surgery. Among a subset of super-utilizers, surgical intervention was associated with a reduction in annual Medicare expenditure in the year after surgery.

Background: A retrospective study was performed to characterize trends in centralization of care and compliance with National Comprehensive Cancer Network (NCCN) guidelines for resected cholangiocarcinoma (CCA), and their impact on overall survival (OS)., Methods: Using the National Cancer Database (NCDB) 2004-2015 we identified patients undergoing resection for CCA. Receiver Operating Characteristic (ROC) analyses identified time periods and hospital volume groups for comparison. Propensity score matching provided case-mix adjusted patient cohorts. Cox hazard analysis identified risk factors for OS., Results: Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p < 0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p < 0.001). Using ROC analyses, a hospital volume of 14 operations/year was the most sensitive and specific value associated with mortality. Surgery at high volume hospitals [HR] = 0.92, 95% CI: 0.88-0.97, p < 0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p < 0.001) were independently associated with improved OS., Conclusions: Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Current readmission rates do not account for readmissions to nonindex hospitals and may underestimate the actual burden of readmissions., Objective: Using a nationally representative database, we sought to characterize nonindex readmissions following bariatric surgery and identify risk factors associated with readmission to a nonindex hospital., Setting: Patients in the United States undergoing elective bariatric surgery., Methods: The Nationwide Readmissions Database was used to identify a weighted sample of 545,377 patients undergoing elective bariatric surgery between 2010 and 2014. Multivariable logistic regression analysis was used to identify factors associated with readmission to a nonindex hospital., Results: Among all patients, 5.6% were readmitted at least once within 30 days. Within the subgroup of patients who were readmitted, 17.6% were readmitted to a different hospital than the index admission hospital. Factors independently associated with higher odds of readmission to a nonindex hospital were primary payor (Medicare: odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.24-1.75; Medicaid: OR = 1.56, 95% CI: 1.26-1.95), All Patients Refined Diagnosis Related Group severity of illness score (extreme versus minor: OR = 1.48; 95% CI: 1.04-2.09), primary procedure (laparoscopic sleeve gastrectomy versus laparoscopic gastric bypass: OR = 1.23; 95% CI: 1.05-1.44), hospital bed size (reference: small hospital, medium: OR = .52, 95% CI: .39-.70; large: OR = .47, 95% CI: .35-.63), hospital ownership (reference: private, nonprofit hospital, government: OR = 1.77, 95% CI: 1.32-2.37; private, investor-owned: OR = 1.33, 95% CI: 1.07-1.64), and hospital location (reference: metropolitan area >1 million population, metropolitan <1 million population: OR = .44, 95% CI: .34-.56; micropolitan/rural: OR = .44, 95% CI: .27-.73)., Conclusion: Failure to account for readmissions to different hospitals may underestimate readmission rates by approximately 18%., (Copyright © 2019 American Society for Bariatric Surgery. All rights reserved.)

Background: Because of the rarity of desmoplastic small round cell tumors (DSRCT), there is a lack of data describing patterns of care and survival for these patients. Using a national tumor registry, the current study sought to describe patterns of care and clinical outcomes for patients with DSCRT., Methods: Data from the National Cancer Database were used to identify 491 patients aged 18 years or older diagnosed with DSRCT between 2004 and 2014. Multivariable Cox proportional hazards regression analysis was used to identify factors associated with overall survival (OS)., Results: Among all patients, 41.2% (n = 200), underwent surgical resection of their primary tumor, chemotherapy was administered to 86.5% (n = 415) of patients, while radiation therapy was administered to 13.0% (n = 63) of patients. Over the study, 69.7% of patients died with a median OS of 25.9 months (interquartile range [IQR]: 22.7-27.5); 1-, 3-, and 5-year OS were 78.6%, 32.3%, and 18.4%, respectively. On multivariable analysis, stage IV disease (Hazard Ratio [HR] = 2.12, 95% CI: 1.41-3.18), receipt of surgery (HR = 0.68, 95% CI: 0.50-0.91), chemotherapy (HR = 0.52, 95% CI: 0.35-0.78), or radiation therapy (HR = 0.55, 95% CI: 0.33-0.92) were independently associated with OS., Conclusions: Although receipt of multimodality treatment may lead to improved survival, further research and clinical trials are required to establish best practices for the care of DSRCT., (© 2019 Wiley Periodicals, Inc.)

Background: Patient blood management (PBM) programs represent a perioperative bundle of care that aim to reduce or eliminate unnecessary transfusions., Objective: To evaluate the impact of a PBM program on transfusion practices and clinical outcomes at a single surgical department at a tertiary care hospital in the United States., Methods: This pre-post, cross-sectional study was performed using data from 17,114 patients undergoing gastrointestinal surgery between 2010 and 2013. Multivariable regression analysis was used to evaluate the impact of implementing a PBM program on transfusion practices and perioperative clinical outcomes., Results: Implementation of the PBM program was associated with a reduction in the proportion of patients receiving packed red blood cell (PRBC) using a liberal trigger hemoglobin concentration (pre-PBM vs post-PBM: trigger ≥8.0 g/dL: 20.2% vs 15.3%, P < 0.001), as well as an increase in the proportion of patients receiving PRBC using a restrictive trigger hemoglobin concentration (trigger <7.0 g/dL: 37.1% vs 46.4%, P < 0.001). The proportion of patients overtransfused to a target hemoglobin concentration of 9.0 g/dL (54.8% vs 43.9%, P < 0.001) or 10.0 g/dL (22.3% vs 15.8%, P < 0.001) also decreased following implementation of the PBM program. On multivariable analysis, implementation of the PBM program was associated with 23% lower odds of receiving PRBC transfusion (odds ratio = 0.77, 95% confidence interval 0.657-0.896, P = 0.001); hospital length-of-stay, postoperative morbidity, and postoperative mortality were unchanged (all P > 0.05)., Conclusions: Implementation of a PBM program was associated with fewer patients receiving PRBC transfusion using a liberal trigger hemoglobin concentration and fewer patients being "overtransfused," without any detectable change in length-of-stay, morbidity or mortality. PBM programs can be safely implemented across hospitals and should be used to improve quality and reduce unnecessary transfusions.

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8 + cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1 + tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1 + tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8 + T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC., (©2019 American Association for Cancer Research.)

Background: An understanding of the overall routine intensive care unit utilization, and characterization of the factors associated with a routine intensive care unit stay, may help identify ways to decrease overutilization of this resource after pancreatic surgery., Methods: Patients undergoing major pancreatic resection were identified in the Truven Health Analytics (Ann Arbor, MI) MarketScan Commercial Claims and Encounters Database from 2010 to 2014. Routine postoperative intensive care unit admission was defined as an admission to the intensive care unit of 24 hours or less on postoperative day zero. The association between routine intensive care unit admission and postoperative outcomes, including extended length of stay, failure to rescue, and total inpatient costs were evaluated., Results: Of 3,280 patients who underwent a major pancreatic resection, 1,715 patients (52.3%) had a routine intensive care unit admission, which trended down over time (2010, n = 349; 53.0% versus 2014, n = 299; 47.5%; P = .019). The incidence of failure to rescue among patients who were routinely admitted to the intensive care unit (3.7%) was comparable to those admitted to the floor (1.7%, P = .098). Patients who were routinely admitted to the intensive care unit after major pancreatic resection had a median length of stay of 10 days (IQR: 7-15 days) versus 8 days (IQR: 7-12 days) for patients who were not admitted to the ICU (P < .001). Routine intensive care unit admission was not associated with higher overall payments (ratio of adjusted total payments: 1.02, 95% CI: 0.98-1.06, P = .297)., Conclusion: Routine intensive care unit admission was associated with a longer length of stay but did not translate into lower failure to rescue among patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The objective of the current study was to compare outcomes among patients combined colon (CR) and liver resection (LR) for the treatment of simultaneous colorectal liver metastasis (CRLM) versus patients undergoing two-stage CR and LR., Methods: Patients undergoing surgery for CRLM between 2004 and 2014 were identified using the Nationwide Inpatient Sample (NIS). Propensity-score matching was used to compare patients undergoing CR + LR with patients undergoing two-stage CR and LR., Results: Among 83,410 patients, CR + LR was performed in 5659 (6.7%), stage C + LR was performed in 5659 (6.7%), while isolated CR and LR was performed in 70,177 (84.0%) and 7574 (9.3%) patients, respectively. The number of patients undergoing CR + LR increased from 423 in 2004 to 580 in 2014 (Δ = +37%). Patients undergoing CR + LR had lower postoperative morbidity (CR + LR vs. two-staged CR and LR: 38.5% vs. 61.2%), shorter LOS (median LOS: 8 days [IQR: 7-12] vs. 14 days [IQR: 10-21]), and lower postoperative mortality (3.1% vs. 5.9%) versus patients undergoing two-stage CR and LR. Compared with patients undergoing two-staged CR and LR, median hospital costs were $13,093 lower for patients undergoing CR + LR (median costs: $36,775 [IQR: 26,416-54,245] vs. $23,682 [IQR: 16,299-32,996])., Conclusion: CR + LR was increasingly performed for treatment of CRLM. Compared with two-staged CR and LR, CR + LR was associated with improved outcomes and lower costs., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Sarcomas represent a heterogeneous group of tumors, and there is lack of data describing contemporary changes in patterns of care. We evaluated the epidemiology of sarcomas over 12 recent years., Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for sarcoma cases from 2002-2014. Patient, tumor and treatment factors, and trends over time were studied overall and by subtype. Univariable and multivariable logistic regression models and 5-year survival and cause-specific mortality (CSM) were summarized., Results: There were 78,527 cases of sarcomas with an overall incidence of 7.1 cases per 100,000 people, increasing from 6.8 in 2002 to 7.7 in 2014. Sarcoma NOS(14.8%) and soft tissue(43.4%) were the most common histology and primary site, respectively. A majority of tumors were high-grade(33.6%) and >5 cm(51.3%). CSM was 28.6% and 5-year survival was 71.4%. Many patients had unknown-grade(42.2%), which associated with 2.6 times increased odds of no surgical intervention., Conclusions: This comprehensive national study highlights important trends including increasing incidence, changing histologic types, and underestimation of true incidence. A large proportion of sarcomas are inadequately staged (unknown-grade 42.2%) with lack of appropriate surgical treatment. Our study highlights need for standardization of care for sarcomas., Competing Interests: CONFLICTS OF INTEREST No relevant conflict of interest disclosures. Dr. Nita Ahuja has received grant funding from Cepheid and Astex and has served as consultant to Ethicon. She has licensed methylation biomarkers to Cepheid.

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend chemotherapy for patients with inoperable biliary tract cancers (BTC), as well as patients following resection of BTC with lymph node metastasis (N1)/positive margins (R1). We sought to define overall adherence, as well as long-term outcomes, with the NCCN guidelines for BTC using the National Cancer Database (NCDB)., Methods: A total of 176,536 patients diagnosed with BTC at a hospital participating in the NCDB between 2004 and 2015 were identified., Results: Among all patients, 63% of patients received medical therapy (chemotherapy or best supportive care), 11% underwent surgical palliation, and 26% underwent curative-intent surgery. According to the NCCN guidelines, 86% (n = 152,245) of patients were eligible for chemotherapy, yet, only 42.2% (n = 64,615) received chemotherapy. Factors associated with a lower adherence with NCCN guidelines included patient age (> 65 years: OR = 1.02), ethnicity (Black: OR = 1.14, Hispanic: OR = 1.21, Asian: OR = 1.24), and insurance status (non-private: OR = 1.45, all p < 0.001). A smaller subset of patients was either recommended chemotherapy but refused (n = 9269, 10.6%) or had medical factors that contraindicated chemotherapy (n = 8275, 9.4%). On multivariable analysis, adjusting for clinical and tumor-specific factors, adherence with NCCN guidelines was associated with a survival benefit for patients receiving medical therapies (HR = 0.74) or undergoing curative-intent surgery (HR = 0.73, both p < 0.001)., Conclusion: Less than half of patients with BTC received systemic chemotherapy in adherence with NCCN guidelines. While a subset of patients had contraindications or refused chemotherapy, other factors such as insurance status and ethnicity were associated with adherence. Adherence with chemotherapy guidelines may influence long-term outcomes.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have been shown to improve clinical outcomes among select patients presenting with peritoneal carcinomatosis. The aim of the present study was to describe temporal trends in clinical outcomes among patients undergoing CRS/HIPEC., Materials and Methods: Patients who underwent CRS/HIPEC were identified using the American College of Surgeons National Surgical Quality Improvement Program databases from 2005 to 2013. A multivariable logistic regression analysis was performed to identify risk factors associated with postoperative morbidity and mortality., Results: A total of 889 patients were identified who met the inclusion criteria. The most common primary tumor sites were the peritoneum (59.8%), followed by the appendix (13.7%) and colon (6.4%). The median operative time for all patients was 438 min (interquartile range: 328-550); postoperative morbidity was 41.3%, and 2.0% of patients died within 30 d of surgery. Over the time evaluated, a statistically significant decrease was observed in the median operative time (2005 versus 2013, 600 versus 403 min), postoperative morbidity (50.0% versus 36.1%), and length of stay (13.5 versus 8 d; all P < 0.05). On multivariable analysis, age > 65 y (odds ratio [OR] = 1.51; 95% confidence interval [CI]: 1.02-2.24; P = 0.037), a low preoperative hematocrit (OR = 1.66; 95% CI: 1.19-2.33; P = 0.003), and preoperative serum albumin < 3 g/dL (OR = 2.10; 95% CI: 1.13-3.90; P = 0.019) were independently associated with greater odds for developing a postoperative complication and/or postoperative death., Conclusions: Operative time, postoperative morbidity, and length of stay after CRS/HIPEC were observed to improve over the study period. Careful patient selection may result in favorable outcomes for select patients undergoing CRS/HIPEC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There are few studies regarding severe chronic upper-airway disease (SCUAD) that represents an important socioeconomic problem for the treatment of rhinitis and associated comorbidities, particularly asthma., Objectives: The aim of our study is to evaluate the prevalence of this pathology in patients with allergic rhinitis (AR) in real life, to phenotype allergic patients with SCUAD, and to identify which factors are related to the severity of the disease., Methods: We studied 113 patients with uncontrolled AR despite optimal adherence to therapy according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in a multicenter Italian study, analyzing comorbidity, use of additional drugs, not scheduled visits, and the number of emergency room admissions., Results: Our data suggest that polysensitization is the only statistically significant factor correlating with SCUAD. Asthma does not seem to represent a correlating factor. An important finding is the poor use (20%) of allergy immunotherapy (AIT), although patients were suffering from AR and the ARIA guidelines recommend the use of AIT in moderate/severe AR., Conclusions: The SCUAD population seems not to have a specific phenotype; there is a greater presence of SCUAD in polysensibilized patients, perhaps a sign of greater inflammation., (© 2019 S. Karger AG, Basel.)

Background: Our objective was to determine the association between indicators of surgical quality - incidence of major complications and failure-to-rescue - and hospital market concentration in light of differences in costs of care., Methods: Patients undergoing coronary artery bypass graft (CABG), colon resection, pancreatic resection, or liver resection in the 2008-2011 Nationwide Inpatient Sample were identified. The effect of hospital market concentration on major complications, failure-to-rescue, and inpatient costs was estimated at the lowest and highest mortality hospitals using multivariable regression techniques., Results: A weighted total of 527,459 patients were identified. Higher market concentration was associated with between 4% and 6% increased odds of failure-to-rescue across all four procedures. Across procedures, more concentrated markets had decreased inpatient costs (average marginal effect ranging from -$3064 (95% CI: -$5812 - -$316) for CABG to -$4876 (-$7773 - -$1980) for liver resection., Conclusion: In less competitive (more concentrated) hospital markets, higher overall risk of failure-to-rescue after complications was accompanied by lower inpatient costs, on average. These data suggest that market controls may be leveraged to influence surgical quality and costs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There is a lack of evidence for the association between intensive statin therapy and outcomes following vascular surgery. The aim of this study was to evaluate the association between perioperative statin intensity and in-hospital mortality following open abdominal aortic aneurysm (AAA) repair., Methods: Patients undergoing open AAA repair between 2009 and 2015 were identified from the Premier Healthcare Database. Statin use was classified into low, moderate and high intensity, based on American College of Cardiology/American Heart Association guidelines. Supratherapeutic intensity was defined as doses higher than the recommended guidelines. Multivariable logistic regression analyses were undertaken to assess the association between statin intensity and postoperative major adverse events and in-hospital mortality., Results: Of 6497 patients undergoing open AAA repair, 3217 (49·5 per cent) received perioperative statin. Statin users were more likely to present with three or more co-morbidities than non-users (26·5 versus 21·8 per cent; P  < 0·001). Unadjusted postoperative mortality was significantly lower in statin users (2·6 versus 6·3 per cent; P  < 0·001); however, there was no difference in the risk of developing major adverse events. Multivariable analysis showed that statin use was associated with lower odds of death (odds ratio 0·41, 95 per cent c.i. 0·31 to 0·54). Moderate, high and supratherapeutic statin intensities were not associated with lower odds of death or major adverse events compared with low-intensity statin therapy., Conclusion: Statin use is associated with lower odds of death in hospital following open AAA repair. High-intensity statins were not associated with lower morbidity or mortality.

Background: Variations in hospital billing practices may reflect differences in patient risk or may represent the "upcoding" of patients in response to payer incentives/policies. The current study sought to assess whether coding practices for gastrointestinal surgery have changed over time and to evaluate the association between upcoding and in-hospital costs., Methods: A total of 1,344,152 patients aged >18 years undergoing a gastrointestinal operation between 2001 and 2011 were identified using the National Inpatient Sample. Coding practices were compared by hospital and patient characteristics. Multivariable analysis was performed to evaluate the association between coding practices and in-hospital costs., Results: The mean and median number of codes per admission were 8.8 (standard deviation = 4.58) and 9 (interquartile range: 5-11), respectively. Over time, the proportion of admissions being upcoded (>9 codes/admission) increased from 14.1% to 32.9% (∆ = +133.3%, P < .001). This trend was observed for each gastrointestinal operation and was greatest for hepatectomy (∆ = +73.3%). Although admissions that were upcoded were more likely to be for patients with greater comorbidity and Medicare enrollees, an increase in the proportion of patients upcoded was also observed regardless of the primary payer, among patients presenting without comorbidity, and among patients undergoing an elective operation (all P < .001). On adjusted analysis, admissions that were upcoded were independently associated with a $13,754 (95% confidence interval: $13,638-$13,870) greater in-hospital cost., Conclusion: The number of "upcoded" patients was observed to increase with time. Greater education, regulation, and scrutiny are required of coding practices., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology., (© 2018 John Wiley & Sons Ltd.)

Background and Objectives: A lack of consensus exists on the prognosis of extraskeletal Ewing sarcoma (EES) relative to its skeletal (ES) counterpart in adults. This study sought to characterize outcome differences between the two diagnoses., Methods: From 2004 to 2014, the NCDB identified 2,660 Ewing Sarcoma patients. Cox proportional hazards regression analysis was used to identify risk factors for overall survival (OS)., Results: EES patients were older, more likely to be female, and have smaller tumors. Among patients with ES, 4.0% received no treatment, 2.5% received local therapy only (surgery and/or radiation), 16.8% received chemotherapy only, while 52.2% received combination therapy (local and chemotherapy), and 17.0% recieived triple therapy (surgery, radiation and chemotherapy). Among patients with EES, 4.3% recived no treatment, 5.6% received local therapy only, 15.6% received chemotherapy only, while 47.0% received combination therapy, and 21.6% received triple therapy. No difference in OS was observed between the two groups (P = 0.816). Factors independently associated with OS for ES included age (HR = 1.26, P = 0.01), Charlson-Deyo Score (CDS) ≥2 (HR = 3.66, P < 0.001), combination therapy (HR = 0.39, P < 0.001) and triple therapy (HR = 0.34, P < 0.001). For EES, factors for OS were age (HR = 1.52, P < 0.001), CDS ≥2 (HR = 1.90, P = 0.02), combination therapy (HR = 0.44, P < 0.001), triple therapy (HR = 0.34, P < 0.001) and PNET histology (HR = 1.33, P = 0.02)., Conclusions: Demographic, histological, and treatment characteristics differ between adult patients diagnosed with ES and ESS. However, survival and independent predictors of survival are consistent between the two diagnoses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: The Affordable Care Act established a Center for Medicare/Medicaid Services based 10% reimbursement bonus for general surgeons in Health Professional Shortage Areas. We sought to assess the impact of the Affordable Care Act Surgery Incentive Payment on surgical procedures performed in Health Professional Shortage Areas., Methods: Hospital utilization data from the California Office of Statewide Health Planning and Development between January 1, 2006, and December 31, 2015, were used to categorize hospitals according to Health Professional Shortage Area location. A difference-in-differences analysis measured the effect of the Surgery Incentive Payment on year-to-year differences for inpatient and outpatient surgical procedures by hospital type pre- (2006-2010) versus post- (2011-2015) Surgery Incentive Payment implementation., Results: Among 409 unique hospitals that performed surgical procedures for at least 1 year of the study period, 2 performed surgery in a designated Health Professional Shortage Area. The two Health Professional Shortage Area -designated hospitals were located in a rural area, were non-teaching hospitals, and had 196 and 202 hospital beds, respectively. After the enactment of the Surgery Incentive Payment, while non- Health Professional Shortage Areas had only a modest relative decrease in total inpatient procedures (Pre-Surgery Incentive Payment: 4,666,938 versus Post-Surgery Incentive Payment: 4,451,612; Δ-4.6%), the proportional decrease in inpatient surgical procedures at Health Professional Shortage Area hospitals was more marked (Pre-Surgery Incentive Payment: 25,830 versus Post-Surgery Incentive Payment: 21,503; Δ-16.7%). In contrast, Health Professional Shortage Area hospitals proportionally had a greater increase in total outpatient procedures (Pre-Surgery Incentive Payment: 17,840 versus Post-Surgery Incentive Payment: 22,375: Δ+25.4%) versus non- Health Professional Shortage Area hospitals (Pre-Surgery Incentive Payment: 5,863,300 versus Post-Surgery Incentive Payment: 6,156,138; Δ+4.9%). Based on the difference-in-differences analysis, the increase in the trend of surgical procedures at Health Professional Shortage Area hospitals was much more notable after Surgery Incentive Payment implementation (Δ+75.2%)., Conclusion: The Medicare Surgery Incentive Payment program was associated with an increase in the number of surgical procedures performed at Health Professional Shortage Area hospitals relative to non-Health Professional Shortage Area hospitals during the study period, reversing the trend from negative to positive., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although well described for gastrointestinal and pelvic cancers, use of minimally invasive surgery (MIS) for the management of retroperitoneal soft tissue sarcoma (RPS) remains unknown. The current study aimed to describe patterns of MIS use and assess the association between MIS and clinical outcomes among patients undergoing surgery for RPS., Methods: Patients undergoing a primary resection for RPS between 2010 and 2014 were identified using the National Cancer Database. Multivariable logistic and Cox proportional hazards models were used to assess the association between use of MIS and clinical outcomes. Sensitivity analysis was performed using propensity score-matching (PSM)., Results: This study identified 3844 patients who met the inclusion criteria. Of these patients, 89.3% (n = 3432) underwent an open surgery, whereas 10.7% (n = 412) underwent MIS. The patients undergoing MIS were more likely to present with smaller tumors (open vs MIS: median tumor size, 17 cm; interquartile range [IQR, 9.8-26.0] vs 10.5 cm [IQR, 6.5-18.0]) and to undergo surgery at community hospitals (26.8% vs 36.1%; both P < 0.001). Although MIS was associated with a shorter hospital length of stay [LOS] (median LOS, 6 days [IQR, 5-9 days] vs 4 days [IQR, 2-7]; P < 0.001), postoperative mortality and overall survival were comparable between the two treatment groups (all P > 0.05). These findings were confirmed using PSM., Conclusions: MIS was associated with a shorter LOS, however, postoperative mortality and overall survival were comparable by operative approach. Future research is required to evaluate the use of MIS for the management of RPS. Policies are required to ensure that patients receive care in accordance with best practices and recommended guidelines.

Background: Margin negative resection offers the best chance of long-term survival in retroperitoneal sarcoma (RPS). En-bloc resection of adjacent structures, including the inferior vena cava (IVC), is often required to achieve negative margins. We review our 20-year experience of en-bloc IVC and RPS resection., Methods: Retrospective review of patients with RPS resection involving the IVC were matched 1:3 by age and histology to RPS without IVC resection. Prognostic factors for overall survival (OS) and disease free survival (DFS) were assessed., Results: Thirty-two patients underwent RPS resection en-bloc with IVC. They were matched with 96 cases of RPS without IVC resection. Median OS of 59 months and DFS 18 months in IVC resection group was comparable to RPS resection without vascular involvement: median OS 65 months, DFS 18 months (P = 0.519, P = 0.604). On multivariate analyses, R2 margin (OS: HR = 6.52 [95%CI: 1.18-36.09], P = 0.032) was associated with inferior OS. R2 margin and increased number of organs resected (DFS: HR = 5.07, [1.15-22.27], P = 0.031, HR = 1.28 [1.01-1.62], P = 0.014) were associated with inferior DFS. Reconstructions included graft (n = 19, 59%), patch (n = 4, 13%), primary repair (n = 6, 19%), and ligation (n = 4, 13%)., Conclusions: RPS resection en-bloc with IVC can achieve equivalent rates of DFS and OS to patients without vascular involvement., (© 2018 Wiley Periodicals, Inc.)

Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease., Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC)., Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3., Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm -2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm -2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells., Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy., (© 2018 The Association for the Publication of the Journal of Internal Medicine.)

Background: Despite growing evidence to support use of preoperative mechanical bowel preparation (MBP) plus oral antibiotic bowel preparation (OABP) compared with MBP alone or no bowel preparation before colorectal surgery, evidence supporting use of MBP plus OABP relative to OABP alone is lacking. This study aimed to investigate whether the addition of MBP to OABP was associated with improved clinical outcomes after colorectal surgery compared with outcomes following OABP alone., Methods: Patients who underwent colorectal surgery and preoperative bowel preparation with either OABP alone or MBP plus OABP were identified using the American College of Surgeons' National Surgical Quality Improvement Program Colectomy Targeted Participant Use Data File for 2012-2015. Thirty-day postoperative outcomes were compared, estimating the average treatment effect with propensity score matching and inverse probability-weighted regression adjustment., Results: In the final study population of 20 594 patients, 90·2 per cent received MBP plus OABP and 9·8 per cent received OABP alone. Patients who received MBP plus OABP had a lower incidence of superficial surgical-site infection (SSI), organ space SSI, any SSI, postoperative ileus, sepsis, unplanned reoperation and mortality, and a shorter length of hospital stay (all P < 0·050). After propensity score matching and inverse probability-weighted regression adjusted analysis, MBP plus OABP was associated with a reduction in superficial SSI, any SSI, postoperative ileus and unplanned reoperation (all P < 0·050)., Conclusions: Use of MBP plus OABP before colectomy was associated with reduced SSI, postoperative ileus, sepsis and unplanned reoperations, and shorter length of hospital stay compared with OABP alone.

Background: Although a growing body of literature recommends the early initiation of palliative care (PC), the use of PC remains variable., Objective: The current study sought to describe the use of PC and to identify factors associated with the use of inpatient PC., Design: Retrospective, cross-sectional analysis of data from the National Inpatient Sample., Setting and Subjects: Patients admitted with a primary diagnosis of gastrointestinal and/or thoracic cancer from 2012 to 2013., Measurements: In-hospital length of stay (LOS), morbidity, mortality, and total charges., Results: A total of 282,899 patients were identified who met inclusion criteria of whom, 24,100 (8.5%) patients received a PC consultation during their inpatient admission. Patients who received PC were more likely to have a longer LOS (LOS >14 days: 5.4% vs. 9.4%) and were more likely to develop a postoperative complication (28.3% vs. 45.9%, both p < 0.001). Inpatient mortality was significantly higher among patients who had received PC than those who did not (5.4% vs. 44.1%, p < 0.001). On multivariable analysis, patient age (age ≥75 years: Odds Ratio [OR] = 2.54, 95% CI: 2.33-2.78), comorbidity (CCI >6: OR = 2.60, 95% CI: 2.48-2.74), and admission to larger hospitals (reference small: OR = 1.20, 95% CI: 1.14-1.25) were associated with greater odds of receiving PC (all p < 0.05). Patients who underwent a major operation during their inpatient admission demonstrated 79% lower odds of receiving PC (OR = 0.21, 95% CI: 0.20-0.22, p < 0.001)., Conclusions: Among patients admitted for cancer, PC services were used in 8.5% of patients during their inpatient admission with surgical patients being 79% less likely to receive a PC consultation. Further research is required to delineate the barriers to the use of PC so as to promote the use of PC among high-risk patients.

Objective: The aim of this study is to assess the financial burden associated with treatment options for resectable pancreatic cancer., Background: As the volume of cancer care increases in the United States, there is growing interest among both clinicians and policy-makers to reduce its financial impact on the healthcare system. However, costs relative to the survival benefit for differing treatment modalities used in practice have not been described., Methods: Patients undergoing resection for pancreatic cancer were identified in the Truven Health MarketScan database. Associations between chemoradiation therapies and survival were performed using parameterized multivariable accelerated failure time models. Median payments over time were calculated for surgery, chemoradiation, and subsequent hospitalizations., Results: A total of 2408 patients were included. Median survival among all patients was 21.1 months [95% confidence interval (CI): 19.8-22.5 months], whereas median follow-up time was 25.1 months (95% CI: 23.5-26.5 months). After controlling for comorbidity, receipt of neoadjuvant therapy, and nodal involvement, a longer survival was associated with undergoing combination gemcitabine and nab-paclitaxel [time ratio (TR) = 1.26, 95% CI: 1.02-1.57, P = 0.035) or capecitabine and radiation (TR = 1.25, 95% CI: 1.04-1.51, P = 0.018). However, median cumulative payments for gemcitabine with nab-paclitaxel were highest overall [median $74,051, interquartile range (IQR): $38,929-$133,603)., Conclusions: Total payments for an episode of care relative to improvement in survival vary significantly by treatment modality. These data can be used to inform management decisions about pursuing further care for pancreatic cancer. Future investigations should seek to refine estimates of the cost-effectiveness of different treatments.

A fast analytical method for the simultaneous detection of 24 β 2 -agonists in human urine was developed and validated. The method covers the therapeutic drugs most commonly administered, but also potentially abused β 2 -agonists. The procedure is based on enzymatic deconjugation with β-glucuronidase followed by SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak resolution and rapid chromatographic separation, with reduced time and costs. The method was fully validated according ISO 17025:2005 principles. The following parameters were determined for each analyte: specificity, selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, matrix effect, recovery and carry-over. The method was tested on real samples obtained from patients subjected to clinical treatment under chronic or acute therapy with either formoterol, indacaterol, salbutamol, or salmeterol. The drugs were administered using pressurized metered dose inhalers. All β 2 -agonists administered to the patients were detected in the real samples. The method proved adequate to accurately measure the concentration of these analytes in the real samples. The observed analytical data are discussed with reference to the administered dose and the duration of the therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Allergic Rhinitis (AR) is a high-prevalence disease. In Europe about 25% of the general population is affected, and in Italy the prevalence is estimated to be 19.8%. The Allergic Rhinitis and its Impact on Asthma (ARIA) international document underlined that the prevalence of severe or refractory or overlapping rhinitis is increasing and represents a non-negligible socio-economic burden. In general, despite the social healthcare costs, allergic rhinitis remains underestimated, not sufficiently controlled and often undertreated., Aim of the Study: In this multi-center Italian observational and prospective study we assessed the control of AR in patients (> 16 years) without previous asthma diagnosis, referred to Allergy Centers., Methods: Patients of both sexes and older than 16 with rhinitis symptoms and without asthma were studied. A Visual Analogue Scale (VAS) and the CARAT (Control of Allergic Rhinitis and Asthma Test) were used as patient reported outcome. The possible causes of poor control of AR, as per protocol, were assessed accordingly., Results: We observed 250 patients in a real-life setting: more than 60% of them had an uncontrolled AR, only about 50% used multiple medications, and only a minority were receiving allergen immunotherapy., Conclusion: This survey, conducted in a real-life setting, confirmed that AR is overall poorly controlled. The VAS assessment well correlates with the structured CARAT questionnaire and with the relevant symptoms of AR.

Background: Acute kidney injury (AKI) after major cardiac operations is a potentially avoidable complication associated with increased morbidity, death, and costly long-term treatment. The financial impact of AKI at the population level has not been well defined. We sought to determine the incremental index hospital cost associated with the development of AKI., Methods: All patients undergoing coronary artery bypass grafting (CABG) or valve replacement operations, or both (clinical classification software codes 43 and 44), between 2008 and 2011 were identified from the Nationwide Inpatient Sample. AKI was identified using International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes (584.xx); patients with chronic renal failure were excluded. Mean total index hospitalization costs were compared between patients with and without AKI., Results: At the population level, 1,078,036 individuals underwent major cardiac procedures from 2008 to 2011, with AKI developing in 105,648 (9.8%). Specifically, AKI developed in 8.0% of CABG, 11.4% of valve replacement, and 17.0% of CABG plus valve replacement patients (p < 0.001). Death was more common among patients with AKI vs those without (13.9% vs 1.3%, p < 0.001). Mean total index hospitalization cost was $77,178 for patients with AKI vs $38,820 for those without (p < 0.001). At the national level, the overall incremental annual index hospitalization cost associated with AKI was $1.01 billion., Conclusions: AKI developed in 1 in every 10 patients nationwide after a cardiac operation. Achieving a 10% reduction in AKI in this population would likely result in an annual savings of approximately $100,000,000 in index-hospital costs alone. Support for research on mechanisms to detect impending damage and prevent AKI may lead to reduced patient morbidity and death and to substantial health care cost savings., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Diminished use and worse outcomes after immediate breast reconstruction (IBR) have been documented for Medicaid beneficiaries. However, to the authors' knowledge, the contribution of patient clustering at hospitals with a high percentage of Medicaid patients to these inequalities in IBR delivery is unknown., Methods: A cross-sectional analysis of patients undergoing IBR after mastectomy using the 2007 to 2011 Nationwide Inpatient Sample database was performed. Hospital Medicaid status was calculated as the percentage of all patients with Medicaid as a primary payer. Tertile groupings were generated to enable statistical analysis. Hierarchical regression models were used to investigate the link between Medicaid status and IBR use, outcomes, and costs. A subgroup of patients undergoing IBR for noninvasive cancer or those with increased genetic risk were used to study IBR use., Results: A total of 30,086 IBR cases in 1199 hospitals were analyzed. Hierarchical regression analysis demonstrated an association between high Medicaid burden hospitals and significantly decreased odds of IBR among patients with in situ disease and/or an elevated risk of cancer (odds ratio, 0.64; 95% confidence interval [95% CI], 0.507-0.806). Increasing age, obesity, being nonwhite, having more comorbid conditions, and having government insurance were found to be associated with diminished odds of IBR (P<.001 in all instances). In-hospital surgical and medical complication rates were comparable across the 3 strata of hospital Medicaid status. Log-adjusted costs of care were found to be positively associated with a higher hospital Medicaid burden status (coefficient of 0.038 [95% CI, 0.011-0.066] for medium Medicaid burden hospitals and coefficient of 0.053 [95% CI, 0.015-0.093] for high Medicaid burden hospitals)., Conclusions: High Medicaid burden hospital status is associated with an attenuation of IBR use and increased total inpatient costs. Structures of care such as hospital resources partially explain disparities in IBR delivery. Cancer 2018;124:346-55. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: While bundled payments aim to reduce variations in health care spending across the continuum of care, data reporting on variations in payments for privately insured patients undergoing treatment for colon cancer (CC) are lacking. The current study sought to characterize variations in payments received for the treatment of CC using a cohort of commercially insured patients., Methods: Patients who underwent a colectomy for CC were identified using the MarketScan Database for 2010-2014. Multivariable regression analysis was used to calculate and compare risk-adjusted payments between patients., Results: A total of 18,337 patients were identified who met inclusion criteria. The median risk-adjusted payment for surgery was $26,408 (IQR: $19,193-$38,037) ranging from $19,762 (IQR: $15,595-$25,636) among patients in the lowest quartile of payments to $33,809 (IQR: $24,783-$48,254) for patients in the highest (+△71.1%). The median risk-adjusted payment for chemotherapy was $70,090 (IQR: $57,813-$83,216); compared with patients in the lowest quartile of payments, payments associated with chemotherapy were 40.4% higher among patients in the highest quartile of payments (Q1 versus Q4: $56,827 [IQR: 49,173-65,353] versus $79,801 [IQR: 67,270-90,999]). When stratified by treatment type, patients in the highest two quartiles of risk-adjusted payments accounted for a total of 58.5% of all payments, whereas patients in the lower two quartiles of risk-adjusted payments accounted for only 41.5% of all payments. A younger patient age, increasing patient comorbidity and undergoing an open operation were associated with higher overall payments., Conclusions: Wide variations in payments exist for the treatment for colon cancer. Episode-based bundle payments for surgery and chemotherapy may differentially impact reimbursement for CC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although the relationship between laparoscopic surgery and improved clinical outcomes has been well established across a variety of procedures, the effect of operative experience with laparoscopic surgery remains less defined. The present study sought to assess the comparative benefit of laparoscopic colorectal surgery relative to surgeon volume., Methods: Commercially insured patients aged 18 to 64 years undergoing a colorectal resection were identified using the MarketScan Database from 2010-2014. Multivariable logistic regression analysis was used to calculate and compare postoperative mortality/morbidity by operative approach relative to surgeon volume., Results: A total of 21,827 patients were identified who met inclusion criteria. The median age among patients was 53 years (interquartile range: 46-59) with a slight majority of patients being female (n = 11,248, 51.5%). Laparoscopic operations were performed in 49.2% of patients (n = 10,756), whereas 50.7% (n = 11,071) underwent an open colorectal resection. On multivariable analysis, laparoscopic surgery was associated with 64% decreased odds of developing a postoperative complication or mortality (odds ratio = 0.36, 95% confidence interval, 0.32-0.41, P < .001). Patients who underwent colectomy performed by a higher operative volume surgeon (high versus low: odds ratio = 0.68, 95% confidence interval, 0.61-0.77, P < .001) demonstrated decreased odds of developing a postoperative complication/mortality. Interestingly the potential decrease in risk-adjusted morbidity/mortality between laparoscopic and open surgery was somewhat greater among high-operative-volume surgeons (odds ratio = 0.29, 95% confidence interval, 0.25-0.34, P < .001) and intermediate-operative-volume surgeons (odds ratio = 0.30, 95% confidence interval, 0.25-0.36, P < .001) compared with low-operative-volume surgeons (odds ratio = 0.36, 95% confidence interval, 0.32-0.41, P < .001)., Conclusion: Although laparoscopic surgery was associated with improved postoperative clinical outcomes, the effect of laparoscopic surgery varied somewhat according to surgeon volume., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Firearm-related deaths are the third leading cause of injury-related deaths in the United States. Yet limited data exist on contemporary epidemiological trends and risk factors for firearm-related injuries. Using data from the Nationwide Emergency Department Sample, we report epidemiological trends and quantify the clinical and financial burden associated with emergency department (ED) visits for firearm-related injuries. We identified 150,930 patients-representing a weighted total of 704,916 patients nationally-who presented alive to the ED in the period 2006-14 with firearm-related injuries. Such injuries were approximately nine times more common among male than female patients and highest among males ages 20-24. Of the patients who presented alive to the ED, 37.2 percent were admitted to inpatient care, while 8.3 percent died during their ED visit or inpatient admission. The mean per person ED and inpatient charges were $5,254 and $95,887, respectively, resulting in an annual financial burden of approximately $2.8 billion in ED and inpatient charges. Although future research is warranted to better understand firearm-related injuries, policy makers might consider implementing universal background checks for firearm purchases and limiting access to firearms for people with a history of violence or previous convictions to reduce the clinical and financial burden associated with these injuries., (Project HOPE—The People-to-People Health Foundation, Inc.)

Background: Although previous research on advance care planning (ACP) has associated ACP with improved quality of care at the end of life, the appropriate use of ACP remains limited., Objective: To evaluate the impact of a pilot program using the "Honoring Choices Wisconsin" (HCW) model for ACP in a tertiary care setting, and to understand barriers to system-wide implementation., Design: Retrospective review of prospectively collected data., Setting/subjects: Patients who received medical or surgical oncology care at Froedtert and the Medical College of Wisconsin., Measurements: Patient demographics, disease characteristics, patient satisfaction, and clinical outcomes., Results: Data from 69 patients who died following the implementation of the HCW program were reviewed; 24 patients were enrolled in the HCW program while 45 were not. Patients enrolled in HCW were proportionally less likely to be admitted to the ICU (12.5% vs. 17.8%) and were more likely to be "do not resuscitate" (87.5% vs. 80.0%), as well as have a completed ACP (83.3% vs. 79.1%). Furthermore, admission to a hospice was also higher among patients who were enrolled in the HCW program (79.2% vs. 25.6%), with patients enrolled in HCW more likely to die in hospice (70.8% vs. 53.3%). The HCW program was favorably viewed by patients, patient caregivers, and healthcare providers., Conclusions: Implementation of a facilitator-based ACP care model was associated with fewer ICU admissions, and a higher use of hospice care. System-level changes are required to overcome barriers to ACP that limit patients from receiving end-of-life care in accordance with their preferences.

Background: Pancreatic cancer has higher concentrations of angiotensin II compared with other cancers. This study sought to assess the effect of angiotensin II receptor blockers (ARBs) on survival of patients undergoing resection using a large, nationally representative dataset., Methods: Patients undergoing pancreatic cancer resection were identified in the Truven Health MarketScan database. Multivariable Cox proportional hazards regression was used to assess the effect of ARB use on overall survival., Results: A total of 4299 patients were identified, among whom 479 (11.1%) filled a prescription for an ARB. Mean patient age was 54.5 years (SD = 8.6 years); 2187 (51.1%) were female. Exactly 49.4% (n = 2125) of patients had a Charlson comorbidity index >2 at the time of surgery (n = 2125, 49.4%) and 59.6% (n = 2563) underwent a pancreaticoduodenectomy. Kaplan-Meier estimates of survival at 1, 2, and 4 years were 62.8% (95% CI: 61.3-64.2%), 38.2% (95% CI: 36.6-39.8%), and 19.0% (95% CI: 17.1-21.0%), respectively. On multivariable analysis, ARB use was associated with a 24% decreased risk of death over the 5-year period in which patients were under observation (HR = 0.76, 95% CI: 0.67-0.87, p < 0.001)., Conclusions: ARB use was associated with improved survival in patients undergoing resection of pancreatic cancer. Further research is required into the differential effect of ARBs in the treatment of pancreatic cancer.

Background: Data evaluating the financial implications of volume-based referral are lacking. This study sought to compare in-hospital costs for pancreatic surgery by annual hospital volume., Methods: Eleven thousand and eighty-one patients aged ≥18 years undergoing an elective pancreatic resection for cancer were identified using the Nationwide Inpatient Sample 2002-2011. Multivariable regression analysis was performed to compare length-of-stay (LOS), postoperative morbidity and mortality, failure-to-rescue (FTR), and inpatient costs by annual hospital volume group., Results: Patients undergoing surgery at high-volume hospitals (HVH) demonstrated 23% lower odds (odds ratio [OR] = 0.77, 95% confidence interval [95%CI] 0.63-0.95) of developing a postoperative complication, 59% lower odds of experiencing an LOS > 14 days (OR = 0.41, 95%CI 0.34-0.50), 51% lower odds of postoperative mortality (OR = 0.49, 95%CI 0.34-0.71), and 47% lower odds of FTR (OR = 0.53, 95%CI 0.37-0.76; all p<0.05). The overall mean in-hospital cost was $39,012 (SD = $15,214) with minimal differences observed across hospital volume groups. Rather, postoperative complications (no complication vs. complication $26,686 [SD = $5762] vs. $44,633 [SD = $11,637]) and FTR (rescue vs. FTR $42,413 [SD = $8481] vs. $69,546 [SD = $13,131]) were determinant of higher in-hospital costs. While this pattern was observed at all hospital volume groups, costs varied minimally between hospital volume groups after this stratification., Conclusions: Annual hospital surgical volume was not associated with in-hospital costs among patients undergoing pancreatic surgery.

Background: Severe asthma might be associated with overexpression of T h 17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways., Objective: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate., Methods: Inflammatory cells and IL-17A + , IL-17F + , IL-21 + , IL-22 + , and IL-23 + cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization., Results: Higher number (P < .05) of neutrophils, IL-17A + , IL-17F + , and IL-21 + cells in bronchial biopsies and higher numbers (P < .01) of IL-17F + and IL-21 + cells in nasal biopsies were observed in SAs compared with MAs. Bronchial IL-17F + cells correlated with bronchial neutrophils (r = 0.54), exacerbation rate (r = 0.41), and FEV 1 (r = -0.46). Nasal IL-17F + cells correlated with bronchial IL-17F (r = 0.35), exacerbation rate (r = 0.47), and FEV 1 (r = -0.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4 + /CD8 + cells and bronchial/nasal IL-17F + cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4 + /CD8 + cells., Conclusions: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines for transfusion focus on nadir levels of hemoglobin. Hemoglobin triggers may not be helpful, however, in defining appropriate intraoperative use of packed red blood cells. We sought to define the use of intraoperative packed red blood cells relative to quantitative physiologic factors at the time of operation., Methods: Prospective intraoperative data on patients undergoing a major gastrointestinal operation between 2010 and 2014 were analyzed. Risk of intraoperative transfusion was assessed with multivariable extended Cox models using baseline clinical covariates and time-varying intraoperative covariates., Results: Among 2,316 patients, the mean preoperative hemoglobin was 12.6 g/dL (standard deviation = 2.0 g/dL), while the median estimated blood loss was 200 mL (interquartile range: 100-55 mL). Overall, 357 (15.4%) patients received a transfusion intraoperatively. A greater hazard of transfusion was associated with a greater American Society of Anesthesiologists class (ref: American Society of Anesthesiologists class I-II; American Society of Anesthesiologists class III-IV; hazard ratio = 1.44, 95% confidence interval, 1.18-1.77, P < .001), and a lesser preoperative hemoglobin level (per 1 g/dL increase; hazard ratio = 0.70, 95% confidence interval, 0.65-0.74, P < .001). In addition, an increase in heart rate of 10 beats/min above the cumulative average at any measurement was associated with up to a 30% increased probability of transfusion (hazard ratio = 1.30, 95% confidence interval, 1.15-1.47, P < .001); similarly, an increase in mean arterial pressure of 10 mm Hg was associated with an 8% decreased likelihood of transfusion (hazard ratio = 0.92, 95% confidence interval, 87-0.99, P = .017). In contrast, nadir hemoglobin was not associated with the risk of receiving a transfusion (hazard ratio = 1.10, 95% confidence interval, 0.97-1.23, P = .129). Among patients who received an intraoperative transfusion, 9.2% (n = 33) never had a hemoglobin nadir below 10 g/dL, nor an average mean arterial pressure less than 65 mm Hg or a heart rate greater than 100 beats/min around the time of transfusion., Conclusion: Among the intraoperative factors, heart rate, and mean arterial pressure were strongly associated with the likelihood of receiving a transfusion, despite the observation that 9.2% of patients never had a physiologic indicator for transfusion or a nadir hemoglobin below 10 g/dL, suggesting a subset of patients could benefit from a decrease in intraoperative rate of transfusion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Given the increasing number of elderly and comorbid patients undergoing surgery, there is increased interest in preoperatively identifying patients at high risk of morbidity and mortality following liver resection. We sought to develop and validate the use of a frailty index (FI) to predict poor postoperative outcomes following liver surgery., Methods: Patients undergoing a liver resection were identified using the National Surgical Quality Improvement Program Hepatectomy-targeted database for 2014 and randomized into a training or validation cohort. Multivariable logistic regression analysis was performed to develop a revised frailty index (rFI) to predict adverse postoperative clinical outcomes. Leave one out cross-validation was performed to validate the proposed rFI., Results: A total of 2714 patients were identified who met the inclusion criteria. Postoperatively, 826 patients (30.4%) developed a postoperative complication, while 39 patients died within 30 days of surgery. Five preoperative variables (ASA class, BMI, serum albumin, hematocrit, underlying pathology, and type of liver resection) were used to develop the rFI. The rFI demonstrated good discrimination (AUROC = 0.68) and outperformed the previously proposed modified frailty index (mFI; AUROC = 0.53, p < 0.001) when evaluated among patients included in the training cohort. On validation, the rFI demonstrated good model discrimination (AUROC = 0.68) and was accurately able to risk-stratify patients within the validation cohort at risk for developing a postoperative complication, prolonged length-of-stay, and postoperative mortality (all p < 0.05)., Conclusion: Frailty, as measured by the rFI, was predictive of increased risk of morbidity and mortality following liver surgery and can be used to guide patient decision-making.

Background: Peritoneal carcinomatosis represents widespread metastatic disease throughout the abdomen and/or pelvis. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves the overall survival compared to standard therapy alone. The role palliative care (PC) plays however, remains poorly studied among these patients., Methods: Patients who had previously undergone HIPEC and who underwent an inpatient admission from 7/1/2013 to 6/30/2014 were identified to determine which patients were referred for inpatient or outpatient palliative consultation. Multivariable logistic regression analysis was performed to identify risk factors associated with the use of PC., Results: Of the 60 patients analyzed, 23 (38.3%) had a PC consultation with a median time to PC referral of 310 (IQR: 151-484 days). Patients who were prescribed opioids (no PC referral versus PC referral: 46.0% versus 91.3%, P < 0.001), patients who reported the use of a cancer-related emetic (35.1% versus 87.0%, P < 0.001), patients reporting the use of total parenteral nutrition (16.2% versus 39.1%, P = 0.046), and patients dependent on a gastric tube for nutrition (5.4% versus 43.5%, P < 0.001) were more likely to be referred to a PC consultation. On multivariable analysis, use of opioids, use of a cancer-related antiemetic, and the use of a G-tube were independently associated with a greater odds for being referred to PC (all P < 0.05)., Conclusions: Approximately one-third of patients were referred to PC following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy. Palliative care referrals were most commonly used for patients with chronic symptoms, which are difficult to manage, especially toward the end of life., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Data evaluating trends in hospital volume are lacking. The current study sought to examine trends in outcomes relative to hospital volume following liver surgery., Methods: A total of 14,296 patients >18 years undergoing an elective liver resection (LR) for cancer were identified using the National Inpatient Sample from 2001 to 2011. Multivariable logistic regression analysis was performed to compare postoperative morbidity and mortality relative to hospital volume over time., Results: Over time, the proportion of patients undergoing a LR at a high-volume hospital (HVH) increased from 24.4 to 45.0 %, while the proportion of patients undergoing a LR at a low-volume hospital (LVH) decreased from 40.4 to 22.7 %. On multivariable analysis, patients undergoing a LR at high-volume hospitals demonstrated a 29 % lower odds of mortality (OR = 0.71, 95 % CI = 0.59-0.86, p < 0.001) compared with patients undergoing a LR at a LVH. The rate of regionalization, however, was not equal among all patients as older patients, patients belonging to a racial minority, and those presenting with substantial comorbidity were less likely to undergo a LR at a HVH., Conclusion: An increase in the regionalization of liver surgery was observed over time. Trends in regionalization were, however, associated with discrepancies in access to HVH among specific patient populations.

Introduction: Post-operative bile leak (BL) and post hepatectomy liver failure (PHLF) are the major potential sources of morbidity among patients undergoing liver resection. We sought to define the incidence of BL and PHLF among a large cohort of patients, as well as examine the prognostic impact of model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) scores to predict these short-term outcomes., Materials and Methods: Patients who underwent a hepatectomy between January 1, 2014 and December 31, 2014 were identified using the National Surgical Quality Improvement Program (NSQIP) liver-targeted database. Risk factors for BL and PHLF were identified using multivariable logistic regression., Results: Among the 3064 patients identified, median age was 60 years (IQR 50-68). Most patients underwent surgery (78.9 %) for malignant lesions. Post-operatively, 250 (8.5 %) patients experienced a BL while PHLF occurred in 149 cases (4.9 %). Both MELD (MELD <10 4.9 %; MELD ≥10, 10 %; P = 0.001) and ALBI (grade 1, 4.0 %; grade 2, 7.2 %; grade 3, 10.0 %; P = 0.001) were associated with PHLF occurrence, while only ALBI predicted PHLF severity (P = 0.008). Moreover, ALBI was associated with BL (grade 1, 7.1 %; grade 2, 11.5 %; grade 3, 14.0 %; P < 0.001), whereas MELD was not (MELD <10, 8.4 %; MELD ≥10, 11.2 %; P = 0.13). On multivariable analysis, ALBI grade 2/3 was associated with PHLF (OR 1.57, 95 % CI 1.08-2.27; P = 0.02), PHLF severity (OR 3.06, 95 % CI 1.50-6.23; P = 0.003), and the development of a BL (OR 1.35, 95 % CI 1.02-1.80; P = 0.04)., Conclusion: The ALBI score was associated with short-term post-operative outcomes following hepatic resection and represents a useful pre-operative risk-assessment tool to identify patients at risk for adverse post-operative outcomes.

Background: Data-assessing trends and perioperative outcomes relative to surgical approach for colorectal cancer (CRC) surgery are lacking. We report national trends of CRC surgery and compare postoperative outcomes by surgical approach., Methods: A total of 261,886 patients undergoing surgery for CRC were identified using the Nationwide Inpatient Sample from 2009 to 2012. Trends in surgical approach were assessed using the Cochrane-Armitage test of trends. Multivariable logistic and linear regression analyses were performed to compare length of stay (LOS), postoperative complications, and cost by surgical approach., Results: At the time of surgery, 57.5% underwent an open procedure, whereas 42.4% underwent either a laparoscopic (39.9%) or robotic (2.5%) colorectal surgery. The use of minimally invasive surgery increased over time (2009 versus 2012: 37.3% versus 46.8%; P < 0.001). Postoperative morbidity was 15.9% and was higher after open surgery (open versus laparoscopic versus robotic: 18.4% versus 12.4% versus 13.3%; P < 0.001). Patients who underwent a minimally invasive surgery had shorter LOS (laparoscopic: OR, 0.55, 95% CI, 0.52-0.58; robotic: OR, 0.58; 95% CI, 0.49-0.69; both P < 0.001). Robotic surgery was consistently associated with the highest mean costs followed by laparoscopic and open surgery (P < 0.001)., Conclusions: Patients undergoing minimally invasive colorectal surgery had a lower postoperative morbidity and shorter LOS compared with patients undergoing open colorectal surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite cost containment efforts, the price for surgery is not subject to any regulations. We sought to characterize and compare variability in pricing for commonly performed major surgical procedures across the United States., Methods: Medicare claims corresponding to eight major surgical procedures (aortic aneurysm repair, aortic valvuloplasty, carotid endartectomy, coronary artery bypass grafting, esophagectomy, pancreatectomy, liver resection, and colectomy) were identified using the Medicare Provider Utilization and Payment Data Physician and Other Supplier Public Use File for 2013. For each procedure, total charges, Medicare-allowable costs, and total payments were recorded. A procedure-specific markup ratio (MR; ratio of total charges to Medicare-allowable costs) was calculated and compared between procedures and across states. Variation in MR was compared using a coefficient of variation (CoV)., Results: Among all providers, the median MR was 3.5 (interquartile range: 3.1-4.0). MR was noted to vary by procedure; ranging from 3.0 following colectomy to 6.0 following carotid endartectomy (P < 0.001). MR also varied for the same procedure; varying the least after liver resection (CoV = 0.24), while coronary artery bypass grafting pricing demonstrated the greatest variation in MR (CoV = 0.53). Compared with the national average, MR varied by 36% between states ranging from 1.8 to 13.0. Variation in MR was also noted within the same state varying by 15% within the state of Arkansas (CoV = 0.15) compared with 51% within the state of Wisconsin (CoV = 0.51)., Conclusions: Significant variation was noted for the price of surgery by procedure as well as between and within different geographical regions. Greater scrutiny and transparency in the price of surgery is required to promote cost containment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Reducing unwanted variations has been identified as an avenue for cost containment. We sought to characterize variations in hospital costs after major surgery and quantitate the variability attributable to the patient, procedure, and provider., Methods: A total of 22,559 patients undergoing major surgical procedure at a tertiary-care center between 2009 and 2013 were identified. Hierarchical linear regression analysis was performed to calculate risk-adjusted fixed, variable and total costs., Results: The median cost of surgery was $23,845 (interquartile ranges, 13,353 to 43,083). Factors associated with increased costs included insurance status (Medicare vs private; coefficient: 14,934; 95% CI = 12,445.7 to 17,422.5, P < .001), preoperative comorbidity (Charlson Comorbidity Index = 1; coefficient: 10,793; 95% CI = 8,412.7 to 13,174.2; Charlson Comorbidity Index ≥2; coefficient: 24,468; 95% CI = 22,552.7 to 26,383.6; both P < .001) and the development of a postoperative complication (coefficient: 58,624.1; 95% CI = 56,683.6 to 60,564.7; P < .001). Eighty-six percent of total variability was explained by patient-related factors, whereas 8% of the total variation was attributed to surgeon practices and 6% due to factors at the level of surgical specialty., Conclusions: Although inpatient costs varied markedly between procedures and providers, the majority of variation in costs was due to patient-level factors and should be targeted by future cost containment strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Accumulating evidence suggests that the eye can be used in the assessment of early on-set Alzheimer's disease (AD). The eye offers a natural window to the brain through the retina. The retina and brain share common developmental origins and patho-physiological origins and mechanisms, having been sequestered from it during early development, but retaining its connections with the brain via the optic nerve. Therefore, it is well understood that neurological abnormalities have a direct profound impact on the retina. Recent studies suggest an array of physiological and pathological changes in the retina in dementia and specifically in AD. There are also reports on imaging the two hallmark proteins of the disease, extracellular amyloid beta peptides and intracellular hyper phosphorylated tau protein, as a proxy to neuroimaging., Results: In this review, we summarise retinal structural, functional and vascular changes reported to be associated with AD. We also review techniques employed to image these two major hall mark proteins of AD and their relevance for early detection of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To evaluate the impact of transfused packed red blood cell (PRBC) age on perioperative morbidity among patients undergoing major gastrointestinal surgery., Background: Patients undergoing major surgery often receive PRBC transfusions. The effect of PRBC age (ie, storage duration before transfusion) on perioperative surgical outcomes remains poorly defined., Methods: In this study, 1365 patients were identified who underwent a hepato-pancreatic or colorectal resection and received ≥1 unit of PRBCs between 2009 and 2014 at the Johns Hopkins Hospital. Data regarding the storage duration of PRBCs, clinicopathologic characteristics, and perioperative outcomes were obtained and analyzed. Multivariable modified Poisson regression analyses were performed to assess the effect of PRBC age on perioperative morbidity., Results: A total of 5901 PRBC units were transfused for a median of 2 (interquartile range 2-4) units transfused per patient. In all, 936 (68.6%) patients received only units of blood that had been stored for less than 35 days ("fresh" blood), whereas 429 (31.4%) patients received at least 1 unit of PRBC that had been stored for ≥35 days ("older" blood). Overall postoperative morbidity was 32.8%. The incidence of postoperative complications (42.7% vs 28.3%) was higher among patients who received "older" vs "fresh" blood (P < 0.001). After adjusting for confounders on multivariable analysis, transfusion of "older" blood remained independently associated with an increased risk of perioperative morbidity (Relative Risk 1.20, P = 0.03)., Conclusions: The use of "older" blood was an independent predictor of postoperative morbidity among patients undergoing hepato-pancreatic or colorectal procedures. Transfusion of "older" blood products may contribute to a higher risk of postoperative complications.

Background: While physician attitudes about treatment goals have been examined around end-of-life care, surgeon attitudes regarding communication of therapeutic goals prior to cancer-directed operations have not been investigated. We examined how surgeons discuss the potential for cancer "cure" prior to operative treatment and how surgeons perceive patient priorities and treatment goals., Methods: Surgeons were invited to complete a Web-based survey about attitudes and practices when discussing cancer-directed operations, including how they defined cancer cure and whether and how they discussed cure as a treatment goal., Results: A total of 551 e-mail invitations were sent and opened; 205 responses were received (response rate 37.2%). While 44.9% of surgeons reported being asked about cure in all or most discussions, only 37.6% used the word cure as often. When discussing cure, an equal number of surgeons reported using qualitative versus quantitative language to express probability of cure (45.7% and 47.4%, respectively). Roughly one third of surgeons (n = 65, 31.7%) defined cure as 5-year, disease-free survival; 36.1% (n = 74) defined cure as absence of recurrence over the patient's lifetime; and 21 (10.2%) defined cure as return to baseline population risk for that specific cancer. Over half of surgeons (n = 112, 56.9%) perceived that to "be cured" was among the top 2 priorities of patients presenting for operative treatment., Conclusion: When discussing relative benefits and goals of therapy, surgeon self-reported discussions of cure varied considerably. Despite identifying cure as a top priority for patients, surgeons were not inclined to incorporate cure into discussions of risks, benefits, and goals of therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Comparative data on surgeon payments for operative procedures are not well documented. We sought to assess variations in surgeon payments after common general and orthopedic operations using a nationally representative sample of privately insured patients., Methods: A total of 486,506 patients who underwent a general (appendectomy, cholecystectomy, colectomy) or orthopedic (total knee replacement, total hip replacement) operation between 2010-2012 were identified from the Truven Health MarketScan database., Results: Median age was 54 years (general operation, 44 years vs orthopedic operation, 58 years; P < .001). Patients had an average Charlson Comorbidity Index of 0 (interquartile range [IQR]: 0, 1). Median duration of stay was 3 days (IQR: 2, 4) (general operation, 3 days [IQR: 1, 5] vs orthopedic operation, 3 days [IQR: 2, 3]; P < .001). Total hospital payments averaged $18,209 (IQR: $11,751, $26,598) (general operation: $12,744 [IQR: $8,402, $19,896] vs orthopedic operation: $22,386 [IQR: $16,888, $30,100]; P < .001). Median surgeon reimbursement was $1,923 (IQR: $1,146, $2,676), with orthopedic surgeon payments being on average twice as high as general surgeon payments ($2,349 vs $1,191; P < .001). Median surgeon payment varied among both general (appendectomy: $903 vs cholecystectomy: $1,125 vs colectomy: $2,209; P < .001) and orthopedic operations (total knee replacement: $2,282 vs total hip replacement: $2,392; P < .001). The presence of a postoperative complication resulted in an increase in hospital payments by 25% and surgeon payments by 11%., Conclusions: Hospital and surgeon payments following routine general and orthopedic operations vary greatly. Patients with comorbid conditions and those who experienced a postoperative complication resulted in higher overall payments. Though significant variability existed at the surgeon level, hospital payments were responsible for the highest source of variability., (Copyright © 2016 Elsevier Inc. All rights reserved.)