Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer.

MYC stimulates both metabolism and protein synthesis, but how cells coordinate these complementary programs is unknown. Previous work reported that, in a subset of small-cell lung cancer (SCLC) cell lines, MYC activates guanosine triphosphate (GTP) synthesis and results in sensitivity to inhibitors of the GTP synthesis enzyme inosine monophosphate dehydrogenase (IMPDH). Here, we demonstrated that primary MYChi human SCLC tumors also contained abundant guanosine nucleotides. We also found that elevated MYC in SCLCs with acquired chemoresistance rendered these otherwise recalcitrant tumors dependent on IMPDH. Unexpectedly, our data indicated that IMPDH linked the metabolic and protein synthesis outputs of oncogenic MYC. Coexpression analysis placed IMPDH within the MYC-driven ribosome program, and GTP depletion prevented RNA polymerase I (Pol I) from localizing to ribosomal DNA. Furthermore, the GTPases GPN1 and GPN3 were upregulated by MYC and directed Pol I to ribosomal DNA. Constitutively GTP-bound GPN1/3 mutants mitigated the effect of GTP depletion on Pol I, protecting chemoresistant SCLC cells from IMPDH inhibition. GTP therefore functioned as a metabolic gate tethering MYC-dependent ribosome biogenesis to nucleotide sufficiency through GPN1 and GPN3. IMPDH dependence is a targetable vulnerability in chemoresistant MYChi SCLC.

Late outcomes of strategic arch resection in acute type A aortic dissection.

OBJECTIVE: To compare perioperative and long-term outcomes in patients undergoing hemiarch and aggressive arch replacement for acute type A aortic dissection (ATAAD). METHODS: From 1996 to 2017, we compared outcomes of hemiarch (n = 322) versus aggressive arch replacements (zones 2 and 3 arch replacement with implantation of 2-4 arch branches, n = 150) in ATAAD. Indications for aggressive arch were arch aneurysm >4 cm or intimal tear in the aortic arch that was not resectable by hemiarch replacement, or dissection of arch branches with malperfusion. RESULTS: Patients in the aggressive arch group were significantly younger (mean age: 57 vs 61 years old) and had significantly longer hypothermic circulatory arrest, cardiopulmonary bypass, and aortic crossclamp times. There were no significant differences in perioperative outcomes between hemiarch and aggressive arch groups, including 30-day mortality (5.3% vs 7.3%, P = .38) and postoperative stroke rate (7% vs 7%, P = .96). Over 15 years, Kaplan-Meier survival was similar between hemiarch and aggressive arch groups (log-rank P = .55, 10-year survival 70% vs 72%). Given death as a competing factor, incidence rates of reoperation over 15 years (2.1% vs 2.0% per year, P = 1) and 10-year cumulative incidence of reoperation (14% vs 12%, P = .89) for arch and distal aorta pathology were similar between the 2 groups. CONCLUSIONS: Both hemiarch and aggressive arch replacement are appropriate approaches for select patients with ATAAD. Aggressive arch replacement should be considered for an arch aneurysm >4 cm or an intimal tear at the arch unable to be resected by hemiarch replacement, or dissection of the arch branches with malperfusion.

Medicare's Acute Care Episode Demonstration: Effects of Bundled Payments on Costs and Quality of Surgical Care.

OBJECTIVE: To evaluate whether participation in Medicare's Acute Care Episode (ACE) Demonstration Program-an early, small, voluntary episode-based payment program-was associated with a change in expenditures or quality of care. DATA SOURCES/STUDY SETTING: Medicare claims for patients who underwent cardiac or orthopedic surgery from 2007 to 2012 at ACE or control hospitals. STUDY DESIGN: We used a difference-in-differences approach, matching on baseline and pre-enrollment volume, risk-adjusted Medicare payments, and clinical outcomes to identify controls. PRINCIPAL FINDINGS: Participation in the ACE Demonstration was not significantly associated with 30-day Medicare payments (for orthopedic surgery: -$358 with 95 percent CI: -$894, +$178; for cardiac surgery: +$514 with 95 percent CI: -$1,517, +$2,545), or 30-day mortality (for orthopedic surgery: -0.10 with 95 percent CI: -0.50, 0.31; for cardiac surgery: -0.27 with 95 percent CI: -1.25, 0.72). Program participation was associated with a decrease in total 30-day post-acute care payments (for cardiac surgery: -$718; 95 percent CI: -$1,431, -$6; and for orthopedic surgery: -$591; 95 percent CI: $-$1,161, -$22). CONCLUSIONS: Participation in Medicare's ACE Demonstration Program was not associated with a change in 30-day episode-based Medicare payments or 30-day mortality for cardiac or orthopedic surgery, but it was associated with lower total 30-day post-acute care payments.

Impact of a National Bariatric Surgery Center of Excellence Program on Medicare Expenditures.

INTRODUCTION: In 2006, the Centers for Medicare and Medicaid Services (CMS) issued a national coverage decision restricting bariatric surgery to designated centers of excellence (COE). Although prior studies show mixed results on complications and reoperations, no prior studies evaluated whether this policy reduced spending for bariatric surgery. We sought to determine whether the coverage restriction to COE-designated hospitals was associated with lower payments from CMS. METHODS: We utilized national Medicare claims data to examine 30-day episode payments for patients who underwent bariatric surgery from 2003 to 2010 (n = 72,117 patients). We performed an interrupted time series analysis, adjusting for patient factors, preexisting temporal trends, and changes in procedure type, to determine whether the 2006 coverage decision was associated with lower Medicare payments above and beyond any existing secular trends. For these analyses, we included payments for the index hospitalization, readmissions, physician services, and post-discharge ancillary care. RESULTS: After accounting for patient factors, preexisting temporal trends, and changes in procedure type, there were no statistically significant improvements in episode payments after (US$14,720) vs before (US$14,283) the coverage decision (+US$437, 95% CI, -US$10 to +US$883). In a direct assessment of payments for COE-designated hospitals (US$14,481) vs. non-COE-designated hospitals (US$14,756), no significant differences in episode payments were found (-US$275, 95% CI, -US$696 to +US$145). CONCLUSIONS: We found no significant reductions in 30-day episode payments after vs before restricting coverage to COE-designated hospitals. Center of excellence status is not a proxy for savings to the healthcare system.

The Society of Thoracic Surgeons Adult Cardiac Surgery Database Version 2.73: More Is Better.

BACKGROUND: With the introduction of version 2.73, several new patient risk factors are now captured in The Society of Thoracic Surgeons' (STS) Adult Cardiac Surgery Database. We sought to evaluate the potential association of these risk factors with mortality. METHODS: We reviewed all patients with an STS predicted risk of mortality in our statewide quality collaborative database from July 2011 to September 2013 (N = 19,743). Univariate analyses were used to determine significant associations between mortality and the new risk factors in version 2.73. We then performed multivariable analysis, incorporating the STS predicted risk of mortality into our regression. RESULTS: In the univariate model, patients with illicit drug use, syncope, unresponsive neurologic state, cancer within the last 5 years, current smoking history, other tobacco use, or sleep apnea had no significant difference in mortality (p > 0.05). Patients with liver disease, elevated Model for End-Stage Liver Disease score, mediastinal radiation, prolonged 5-meter walk test, home oxygen use, inhaled medications or bronchodilator therapy, decreased forced expiratory volume, and history of recent pneumonia had significant increases in operative mortality (p < 0.05). In multivariable analysis incorporating the STS predicted risk models, liver disease, elevated Model for End-Stage Liver Disease score, prolonged 5-meter walk test, home oxygen use, bronchodilator therapy, and abnormal pulmonary function tests were independently predictive of mortality. CONCLUSIONS: Several of the new STS data variables were significantly associated with operative mortality after cardiac surgery. The addition of these patient factors improves our understanding of evolving patient demographics and comorbid conditions and their impact on perioperative risk. This will improve both shared decision making and assessments of provider performance.

Reliability of surgeon-specific reporting of complications after colectomy.

OBJECTIVE: We sought to determine the reliability of surgeon-specific postoperative complication rates after colectomy. BACKGROUND: Conventional measures of surgeon-specific performance fail to acknowledge variation attributed to statistical noise, risking unreliable assessment of quality. METHODS: We examined all patients who underwent segmental colectomy with anastomosis from 2008 through 2010 participating in the Michigan Surgical Quality Collaborative Colectomy Project. Surgeon-specific complication rates were risk-adjusted according to patient characteristics with multiple logistic regression. Hierarchical modeling techniques were used to determine the reliability of surgeon-specific risk-adjusted complication rates. We then adjusted these rates for reliability. To evaluate the extent to which surgeon-level variation was reduced, surgeons were placed into quartiles based on performance and complication rates were compared before and after reliability adjustment. RESULTS: A total of 5033 patients (n = 345 surgeons) undergoing partial colectomy reported a risk-adjusted complication rate of 24.5%. Approximately 86% of the variability of complication rates across surgeons was explained by measurement noise, whereas the remaining 14% represented true signal. Risk-adjusted complication rates varied from 0% to 55.1% across quartiles before adjusting for reliability. Reliability adjustment greatly diminished this variation, generating a 1.2-fold difference (21.4%-25.6%). A caseload of 168 colectomies across 3 years was required to achieve a reliability of more than 0.7, which is considered a proficient level. Only 1 surgeon surpassed this volume threshold. CONCLUSIONS: The vast majority of surgeons do not perform enough colectomies to generate a reliable surgeon-specific complication rate. Risk-adjusted complication rates should be viewed with caution when evaluating surgeons with low operative volume, as statistical noise is a large determinant in estimating their surgeon-specific complication rates.

Medicare's Hospital Readmissions Reduction Program in Surgery May Disproportionately Affect Minority-serving Hospitals.

OBJECTIVE: To project readmission penalties for hospitals performing cardiac surgery and examine how these penalties will affect minority-serving hospitals. BACKGROUND: The Hospital Readmissions Reduction Program will potentially expand penalties for higher-than-predicted readmission rates to cardiac procedures in the near future. The impact of these penalties on minority-serving hospitals is unknown. METHODS: We examined national Medicare beneficiaries undergoing coronary artery bypass grafting in 2008 to 2010 (N = 255,250 patients, 1186 hospitals). Using hierarchical logistic regression, we calculated hospital observed-to-expected readmission ratios. Hospital penalties were projected according to the Hospital Readmissions Reduction Program formula using only coronary artery bypass grafting readmissions with a 3% maximum penalty of total Medicare revenue. Hospitals were classified into quintiles according to proportion of black patients treated. Minority-serving hospitals were defined as hospitals in the top quintile whereas non-minority-serving hospitals were those in the bottom quintile. Projected readmission penalties were compared across quintiles. RESULTS: Forty-seven percent of hospitals (559 of 1186) were projected to be assessed a penalty. Twenty-eight percent of hospitals (330 of 1186) would be penalized less than 1% of total Medicare revenue whereas 5% of hospitals (55 of 1186) would receive the maximum 3% penalty. Minority-serving hospitals were almost twice as likely to be penalized than non-minority-serving hospitals (61% vs 32%) and were projected almost triple the reductions in reimbursement ($112 million vs $41 million). CONCLUSIONS: Minority-serving hospitals would disproportionately bear the burden of readmission penalties if expanded to include cardiac surgery. Given these hospitals' narrow profit margins, readmission penalties may have a profound impact on these hospitals' ability to care for disadvantaged patients.

Using same-hospital readmission rates to estimate all-hospital readmission rates.

BACKGROUND: Since October of 2012, Medicare's Hospital Readmissions Reduction Program has fined 2,200 hospitals a total of $500 million. Although the program penalizes readmission to any hospital, many institutions can only track readmissions to their own hospitals. We sought to determine the extent to which same-hospital readmission rates can be used to estimate all-hospital readmission rates after major surgery. STUDY DESIGN: We evaluated 3,940 hospitals treating 741,656 Medicare fee-for-service beneficiaries undergoing CABG, hip fracture repair, or colectomy between 2006 and 2008. We used hierarchical logistic regression to calculate risk- and reliability-adjusted rates of 30-day readmission to the same hospital and to any hospital. We next evaluated the correlation between same-hospital and all-hospital rates. To analyze the impact on hospital profiling, we compared rankings based on same-hospital rates with those based on all-hospital rates. RESULTS: The mean risk- and reliability-adjusted all-hospital readmission rate was 13.2% (SD 1.5%) and mean same-hospital readmission rate was 8.4% (SD 1.1%). Depending on the operation, between 57% (colectomy) and 63% (CABG) of hospitals were reclassified when profiling was based on same-hospital readmission rates instead of on all-hospital readmission rates. This was particularly pronounced in the middle 3 quintiles, where 66% to 73% of hospitals were reclassified. CONCLUSIONS: In evaluating hospital profiling under Medicare's Hospital Readmissions Reduction Program, same-hospital rates provide unstable estimates of all-hospital readmission rates. To better anticipate penalties, hospitals require novel approaches for accurately tracking the totality of their postoperative readmissions.

Center-level variation in infection rates after coronary artery bypass grafting.

BACKGROUND: Health-care-acquired infections (HAIs) are a leading cause of morbidity and mortality after cardiac surgery. Prior work has identified several patient-related risk factors associated with HAIs. We hypothesized that rates of HAIs would differ across institutions, in part attributed to differences in case mix. METHODS AND RESULTS: We analyzed 20 896 patients undergoing isolated coronary artery bypass grafting surgery at 33 medical centers in Michigan between January 1, 2009, and June 30, 2012. Overall HAIs included pneumonia, sepsis/septicemia, and surgical site infections, including deep sternal wound, thoracotomy, and harvest/cannulation site infections. We excluded patients presenting with endocarditis. Predicted rates of HAIs were estimated using multivariable logistic regression. Overall rate of HAI was 5.1% (1071 of 20 896; isolated pneumonia, 3.1% [n=644]; isolated sepsis/septicemia, 0.5% [n=99]; isolated deep sternal wound infection, 0.5% [n=96]; isolated harvest/cannulation site, 0.5% [n=97]; isolated thoracotomy, 0.02% [n=5]; multiple infections, 0.6% [n=130]). HAI subtypes differed across strata of center-level HAI rates. Although predicted risk of HAI differed in absolute terms by 2.8% across centers (3.9-6.7%; min:max), observed rates varied by 18.2% (0.9-19.1%). CONCLUSIONS: There was a 18.2% difference in observed HAI rates across medical centers among patients undergoing isolated coronary artery bypass grafting surgery. This variability could not be explained by patient case mix. Future work should focus on the impact of other factors (eg, organizational and systems of clinical care) on risk of HAIs.

Development of Team Action Projects in Surgery (TAPS): a multilevel team-based approach to teaching quality improvement.

OBJECTIVES: To meet the Accreditation Council for Graduate Medical Education core competency in Practice-Based Learning and Improvement, educational curricula need to address training in quality improvement (QI). We sought to establish a program to train residents in the principles of QI and to provide practical experiences in developing and implementing improvement projects. DESIGN: We present a novel approach for engaging students, residents, and faculty in QI efforts-Team Action Projects in Surgery (TAPS). SETTING: Large academic medical center and health system. PARTICIPANTS: Multiple teams consisting of undergraduate students, medical students, surgery residents, and surgery faculty were assembled and QI projects developed. Using "managing to learn" Lean principles, these multilevel groups approached each project with robust data collection, development of an A3, and implementation of QI activities. RESULTS: A total of 5 resident led QI projects were developed during the TAPS pilot phase. These included a living kidney donor enhanced recovery protocol, consult improvement process, venous thromboembolism prophylaxis optimization, Clostridium difficile treatment standardization, and understanding variation in operative duration of laparoscopic cholecystectomy. Qualitative and quantitative assessment showed significant value for both the learner and stakeholders of QI related projects. CONCLUSION: Through the development of TAPS, we demonstrate a novel approach to addressing the increasing focus on QI within graduate medical education. Efforts to expand this multilevel team based approach would have value for teachers and learners alike.

Reliability of hospital readmission rates in vascular surgery.

OBJECTIVE: The Center for Medicare and Medicaid Services recently began assessing financial penalties to hospitals with high readmission rates for a narrow set of medical conditions. Because these penalties will be extended to surgical conditions in the near future, we sought to determine whether readmissions are a reliable predictor of hospital performance with vascular surgery. METHODS: We examined 4 years of national Medicare claims data from 1576 hospitals on beneficiaries undergoing three common vascular procedures: open or endovascular abdominal aortic aneurysm repair (n = 81,520) or lower extremity arterial bypass (n = 57,190). First, we divided our population into two groups on the basis of operative date (2005-2006 and 2007-2008) and generated hospital risk- and reliability-adjusted readmission rates for each time period. We evaluated reliability through the use of the "test-retest" method; highly reliable measures will show little variation in rates over time. Specifically, we evaluated the year-to-year reliability of readmissions by calculating Spearman rank correlation and weighted κ tests for readmission rates between the two time periods. RESULTS: The Spearman coefficient between 2005-2006 readmissions rankings and 2007-2008 readmissions rankings was 0.57 (P < .001) and weighted κ was 0.42 (P < .001), indicating a moderate correlation. However, only 32% of the variation in hospital readmission rates in 2007-2008 was explained by readmissions during the 2 prior years. There were major reclassifications of hospital rankings between years, with 63% of hospitals migrating among performance quintiles between 2005-2006 and 2007-2008. CONCLUSIONS: Risk-adjusted readmission rates for vascular surgery vary substantially year to year; this implies that much of the observed variation in readmission rates is either random or caused by unmeasured factors and not caused by changes in hospital quality that may be captured by administrative data.

Racial disparities in readmissions and site of care for major surgery.

BACKGROUND: Racial disparities have been described in many surgical outcomes. We sought to examine whether these disparities extend to postoperative readmission rates and whether the disparities are associated with differences in patient mix and/or hospital-level differences. STUDY DESIGN: National Medicare beneficiaries undergoing operations in 3 different specialties from 2006 to 2008 were examined: colectomy, hip replacement, and coronary artery bypass grafting (CABG) (n = 798,279). Our outcome measure was risk-adjusted 30-day readmission. We first used logistic regression to adjust for patient factors. We then stratified hospitals into quintiles according to the proportion of black patients treated and examined the differences in readmission rates between blacks and whites. Finally, we used fixed effects regression models that further adjust for the hospital to explore whether the disparity was attenuated after accounting for hospital differences. RESULTS: Black patients were readmitted more often after all 3 operations compared with white patients. The unadjusted odds ratio (OR) for readmission for all 3 operations combined was 1.25 (95% CI 1.22 to 1.28) (colectomy OR 1.17, 95% CI 1.13 to 1.22; hip replacement OR 1.20, 95% CI 1.14 to 1.27; CABG OR 1.25, 95% CI 1.19 to 1.30). Adjusting for patient factors explained 36% of the disparity for all 3 operations (35% for colectomy, 0% for hip replacement, and 32% for CABG), but in analysis that adjusts for hospital differences, we found that the hospitals where care was received also explained 28% of the disparity (35% for colectomy, 70% for hip replacement and 20% for CABG). CONCLUSIONS: Black patients are significantly more likely to be readmitted to the hospital after major surgery compared with white patients. This disparity was attenuated after adjusting for patient factors as well as hospital differences.