Using a polygenic score to account for genomic risk factors in a model to detect individuals with dilated ascending thoracic aortas.

Background: Ascending thoracic aortic dilation is a complex trait that involves modifiable and non-modifiable risk factors and can lead to thoracic aortic aneurysm and dissection. Clinical risk factors have been shown to predict ascending thoracic aortic diameter. Polygenic scores (PGS) are increasingly used to assess clinical risk for multifactorial diseases. The degree to which a PGS can improve aortic diameter prediction is not known. In this study we tested the extent to which the addition of a PGS to clinical prediction algorithms improves the prediction of aortic diameter. Methods: The patient cohort comprised 6,790 Penn Medicine Biobank (PMBB) participants with available echocardiography and clinical data linked to genome-wide genotype data. Linear regression models were used to integrate PGS weights derived from a large genome wide association study of thoracic aortic diameter in the UK biobank and were compared to the performance of the standard and a reweighted variation of the recently published AORTA Score. Results: Cohort participants were 56% male, had a median age of 61 years (IQR 52-70) with a mean ascending aortic diameter of 3.4 cm (SD 0.5). Compared to the AORTA Score which explained 28.4% (95% CI 28.1% to 29.2%) of the variance in aortic diameter, AORTA Score + PGS explained 28.8%, (95% CI 28.1% to 29.6%), the reweighted AORTA score explained 30.4% (95% CI 29.6% to 31.2%), and the reweighted AORTA Score + PGS explained 31.0% (95% CI 30.2% to 31.8%). The addition of a PGS to either the AORTA Score or the reweighted AORTA Score improved model sensitivity for the identifying individuals with a thoracic aortic diameter ≥ 4 cm. The respective areas under the receiver operator characteristic curve for the AORTA Score + PGS (0.771, 95% CI 0.756 to 0.787) and reweighted AORTA Score + PGS (0.785, 95% CI 0.770 to 0.800) were greater than the standard AORTA Score (0.767, 95% CI 0.751 to 0.783) and reweighted AORTA Score (0.780 95% CI 0.765 to 0.795). Conclusions: We demonstrated that inclusion of a PGS to the AORTA Score results in a small but clinically meaningful performance enhancement. Further investigation is necessary to determine if combining genetic and clinical risk prediction improves outcomes for thoracic aortic disease.

Volume of frail patients predicts outcome in frail patients after cardiac surgery.

OBJECTIVE: Recent data from major noncardiac surgery suggest that outcomes in frail patients are better predicted by a hospital's volume of frail patients specifically, rather than overall surgical volume. We sought to evaluate this "frailty volume-frailty outcome relationship" in patients undergoing cardiac surgery. METHODS: We studied 72,818 frail patients undergoing coronary artery bypass grafting or valve replacement surgery from 2010 to 2014 using the Nationwide Readmissions Database. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Multilevel logistic regression was used to assess the independent effect of frailty volume by quartile on mortality, surgical complications, failure to rescue, nonhome discharge, 30-day readmissions, length of stay, and hospital costs in frail patients. RESULTS: In comparing the highest volume quartiles with the lowest, both overall cardiac surgical volume and volume for frail patients were significantly associated with shorter length of stay and reduced costs. However, frailty volume was also independently associated with significantly reduced in-hospital mortality (odds ratio, 0.79; 95% confidence interval, 0.67-0.94; P = .006) and failure to rescue (odds ratio, 0.83; 95% confidence interval, 0.70-0.98; P = .03), whereas no such association was seen between overall volume and either mortality (odds ratio, 0.94; 95% confidence interval, 0.74-1.10; P = .43) or failure to rescue (odds ratio, 0.98; 95% confidence interval, 0.83-1.17; P = .85). Neither frailty volume nor overall volume showed any significant relationship with the rate of 30-day readmissions. CONCLUSIONS: In frail patients undergoing cardiac surgery, surgical volume of frail patients was a significant independent of predictor of in-hospital mortality and failure to rescue, whereas overall surgical volume was not. Thus, the "frailty volume-outcome relationship" superseded the traditional "volume-outcome relationship" in frail patients with cardiac disease.

Economic implications of the modern treatment paradigm of glioblastoma: an analysis of global cost estimates and their utility for cost assessment.

INTRODUCTION: Glioblastoma is the most common primary brain tumor in adults. Standard of care includes maximal surgical resection of the tumor followed by concurrent chemotherapy and radiation. The treatment of glioblastoma must account for an increased disease severity and treatment intensity compared to other cancers which place a significant cost burden on the patient and health system. Cost assessments of glioblastoma treatment have been sparse in comparison to other solid cancer subtypes. This study evaluates all currently available cost literature with an emphasis on the modern treatment paradigm to properly assess the economic implications of this disease. METHODS: A critical review of 21 studies from 13 different countries measuring direct costs related to glioblastoma management was performed. Evaluated data included itemized costs, total costs of treatment regimens from diagnosis until death, the cost of second-line care after recurrence, and the incremental costs and cost-effectiveness of emerging therapies. RESULTS: The average cost of a craniotomy was $10,042 across studies. Imaging for the duration of glioblastoma care had a mean cost of $2,788 ± 3,719. Studies examined different combinations of treatment modalities. Utilization of the modern treatment paradigm led to survival of 16.3 months across studies and had a mean cost of $62,602. Surgery for the recurrent disease had an average cost of $27,442 ± 18,992. LIMITATIONS AND CONCLUSIONS: Direct cost estimates for glioblastoma varied substantially between institutions and countries and often failed to uniformly describe direct cost estimates associated with care for glioblastoma. The limitations of these studies make a true economic assessment of standards of care, costs of recurrence, and incremental costs associated with adjunctive therapy uncertain.

An additive score optimized by a genetic learning algorithm predicts readmission risk after glioblastoma resection.

Thirty-day readmission following glioblastoma (GBM) resection is not only correlated with decreased overall survival but also increasingly tied to quality metrics and reimbursement. This study aimed to determine factors linked with 30-day readmission to develop a simple risk stratification score. From 2005 to 2016, 666 unique resections (467 patients) of primary/recurrent tissue-confirmed glioblastoma were retrospectively identified. We recorded patient demographics and medical history, tumor characteristics, post-operative complications and 30-day readmission. Univariate and multivariate logistic regression, optimized using a genetic learning algorithm, were used to determine factors associated with readmission. The multivariate model was converted to a simple additive score. The 30-day readmission rate was 20.3% in our cohort of 666 unique resections (60.7% first resection). Lower pre/post-operative KPS, recurrent resection, surgical-site infection, post-operative VTE, post-operative VPS, and discharge to a rehabilitation facility were significantly associated with an increased readmission risk (p < 0.05). MGMT methylation and chemoradiation were associated with decreased readmission risk (p < 0.05). Medical co-morbidities and past medical history, location of tumor in eloquent areas of the brain, and length of ICU/hospital stay did not predict readmission. The Glioblastoma Readmission Risk Score, developed from the multivariate model, accounts for increased BMI, decreased pre-operative KPS, current smoking, post-operative complications, MGMT methylation, and post-operative radiation. This risk score can be routinely used to stratify risk and assist in clinical decision making and outcome analyses.

Predictors of 30-day readmission and resource utilization after thoracic endovascular aortic repair.

OBJECTIVES: The introduction and expansion of thoracic endovascular aortic repair (TEVAR) have revolutionized the treatment of a variety of thoracic aortic diseases. We sought to evaluate the incidence, causes, predictors and costs associated with 30-day readmission after TEVAR in a nationally representative cohort. METHODS: Adult patients undergoing isolated TEVAR were identified in the National Readmissions Database from 2010 to 2014. Hospital costs were estimated by converting individual hospital charge data adjusted to 2014 consumer price indices. Multivariable logistic regression was utilized to determine hospital- and patient-level factors associated with readmissions. RESULTS: A total of 24 983 TEVARs were noted during the study period; the average age of the patients was 65 ± 16 years; 40% were women. The most common indication was an intact thoracic aneurysm (43.5%), followed by aortic dissection (30.5%). The average cost of the index admission was $63 644 ± $52 312; the average hospital stay was 11 ± 14 days; the index mortality rate was 6.7%. Readmissions within 30 days occurred in 17.4% of patients. Indications for readmission were varied; the most common aetiologies were cardiac (17.8%), infectious (16.0%) and pulmonary (12.1%). On multivariable analysis, the strongest predictor of readmission was the diagnosis, with a ruptured thoraco-abdominal aneurysm having the highest readmission burden (adjusted odds ratio 2.23, 1.17-4.24; P = 0.015). Notably, hospital volume did not predict index hospital length of stay, costs or 30-day readmissions (all P > 0.10). CONCLUSIONS: Annual TEVAR volume was not associated with any of the outcomes assessed. Rather, indication for TEVAR was the strongest predictor for many outcomes. As TEVAR becomes increasingly utilized, a focus on cardiac and vascular diseases may reduce readmissions and improve quality of care.

Nationwide Analysis of 30-Day Readmissions After Esophagectomy: Causes, Costs, and Risk Factors.

BACKGROUND: Postsurgical readmissions are an increasingly scrutinized marker of health care quality. We sought to estimate the rate, risk factors, causes, and costs associated with readmissions after esophagectomy in a large, nationally representative cohort. METHODS: We studied patients from the Nationwide Readmissions Database undergoing esophagectomy from 2010 to 2014. Data were collected on the prevalence and indications for readmission within 30 days as well as the hospital-, procedure-, and patient-level risk factors as determined by multivariable logistic regression. RESULTS: Among 13,282 cases, the rate of 30-day readmission was 19.4%, with the most common indications for readmission being pulmonary (20.6%) and gastrointestinal complications (20%). Median cost of readmission was $9660 (interquartile range, $5392 to $20,447), and pulmonary complications accounted for the greatest total cost burden at 25.8% of all readmission-related costs. Independent risk factors for readmission on multivariable analysis included perioperative blood transfusion (adjusted odds ratio [AOR] 1.33; 95% confidence interval [CI], 1.08 to 1.65; P = .008), discharge to a nursing facility (AOR 1.83; 95% CI, 1.41 to 2.39; P < .001), high illness severity based on All Patients Refined Diagnosis-Related Groups scoring (AOR 1.49; 95% CI, 1.21 to 1.84; P < .001), chronic renal failure (AOR 1.61; 95% CI, 1.13 to 2.29; P = .009), and comorbid drug abuse (AOR 2.19; 95% CI, 1.08 to 4.41; P = .029). CONCLUSIONS: Nearly 1 in 5 patients undergoing esophagectomy are readmitted within 30 days of discharge, at a median cost of $9660 per readmission. Pulmonary complications account for the greatest number of readmissions and the greatest total cost burden. Targeting the causes of readmission, especially pulmonary causes, may help significantly reduce the total morbidity and health care costs associated with esophagectomy.

Causes, Risk Factors, and Costs of 30-Day Readmissions After Mitral Valve Repair and Replacement.

BACKGROUND: Postsurgical readmissions are an increasingly scrutinized marker of health care quality. We sought to estimate the risk factors and costs associated with readmissions after mitral valve (MV) surgery in a large, nationally representative cohort. METHODS: Adult patients undergoing MV repair or replacement were queried from the National Readmissions Database from 2010 to 2014. Data were collected on the prevalence and indications for readmission within 30 days as well as the hospital-, procedure, and patient-level risk factors as determined by multivariable logistic regression. RESULTS: Among 76,342 patients undergoing MV surgery, the rate of 30-day readmission was 17.0%. Those undergoing replacement procedures had significantly higher readmission rates (20.7% vs 13.1%; P < .001) compared with repair. Significant independent predictors of readmission after both MV repair and replacement included length of stay ≥8 days, chronic lung disease, chronic renal disease, and low hospital procedural volume for MV surgery. Readmissions to nonindex hospitals accounted for 26.6% of all readmissions. The most common indications for readmission were heart failure (21.4%), arrhythmia (17.0%) and respiratory diagnoses (15.0%), and infections (10.2%). The mean cost per readmission was $15,397, and among readmitted patients, the cost of readmission accounted for 17.8% of the total cost of the episode of care. CONCLUSIONS: Nearly 1 in 5 patients undergoing MV surgery are readmitted within 30 days. Treatment at a low-volume center was strongly associated with readmission, and much of the readmission burden falls on nonindex hospitals. Further characterization of readmissions may improve the quality of care associated with MV surgery.

Liver disease is an independent predictor of poor 30-day outcomes following surgery for degenerative disease of the cervical spine.

BACKGROUND AND CONTEXT: The impact of underlying liver disease on surgical outcomes has been recognized in a wide variety of surgical disciplines. However, less empiric data are available about the importance of liver disease in spinal surgery. PURPOSE: To measure the independent impact of underlying liver disease on 30-day outcomes following surgery for the degenerative cervical spine. STUDY DESIGN: Retrospective comparative study. PATIENT SAMPLE: A cohort of 21,207 patients undergoing elective surgery for degenerative disease of the cervical spine from the American College of Surgeons National Surgical Quality Improvement Program. OUTCOME MEASURES: Outcome measures included mortality, hospital length of stay, and postoperative complications within 30 days of surgery. METHODS: The NSQIP dataset was queried for patients undergoing surgery for degenerative disease of the cervical spine from 2006 to 2015. Assessment of underlying liver disease was based on aspartate aminotransferase-to-platelet ratio index and Model of End-Stage Liver Disease-Sodium scores, computed from preoperative laboratory data. The effect of liver disease on outcomes was assessed by bivariate and multivariate analyses, in comparison with 16 other preoperative and operative factors. RESULTS: Liver disease could be assessed in 21,207 patients based on preoperative laboratory values. Mild liver disease was identified in 2.2% of patients, and advanced liver disease was identified in 1.6% of patients. The 30-day mortality rates were 1.7% and 5.1% in mild and advanced liver diseases, respectively, compared with 0.6% in patients with healthy livers. The 30-day complication rates were 11.8% and 31.5% in these patients, respectively, compared with 8.8% in patients with healthy livers. In multivariate analysis, the presence of any liver disease (mild or advanced) was independently associated with an increased risk of mortality (OR=2.00, 95% CI=1.12-3.55, p=.019), morbidity (OR=1.35, 95% CI=1.07-1.70, p=.012), and length of hospital stay longer than 7 days (OR=1.73, 95% CI=1.40-2.13, p<.001), when compared with 18 other preoperative and operative factors. Liver disease was also independently associated with perioperative respiratory failure (OR=1.80, 95% CI=1.21-2.68, p=.004), bleeding requiring transfusion (OR=1.43, 95% CI=1.01-2.02, p=.044), wound disruption (OR=2.82, 95% CI=1.04-7.66, p=.042), and unplanned reoperation (OR=1.49, 95% CI=1.05-2.11, p=.025). CONCLUSIONS: Liver disease independently predicts poor perioperative outcome following surgery for degenerative disease of the cervical spine. Based on these findings, careful consideration of a patient's underlying liver function before surgery may prove valuable in surgical decision-making, preoperative patient counseling, and postoperative patient care.

Complications Predicting Perioperative Mortality in Patients Undergoing Elective Craniotomy: A Population-Based Study.

OBJECTIVE: The objective of this study was to assess the independent effect of complications on 30-day mortality in 32,695 patients undergoing elective craniotomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried for patients undergoing elective craniotomy from 2006 to 2015. Multivariate logistic regression was used to examine the effect of complications on mortality independent of preoperative risk and other postoperative complications. This effect was further assessed in risk-stratified patient subgroups using the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator. RESULTS: Of 13 complications analyzed, the 5 most strongly associated with mortality independent of preoperative risk factors were unplanned intubation (odds ratio [OR], 12.1; 95% confidence interval [CI], 9.5-15.4; P < 0.001), stroke (OR, 11.1; 95% CI, 8.3-14.9; P < 0.001), ventilator requirement >48 hours after surgery (OR, 9.9; 95% CI, 7.9-12.6; P < 0.001), and renal failure (OR, 8.5; 95% CI, 4.4-16.2; P < 0.001). These same complications were also the 5 most associated with mortality independent of other postoperative complications. They were also associated with mortality across all risk-stratified patient subgroups. On the contrary, venous thromboembolism (OR, 1.3; 95% CI, 0.98-1.7; P = 0.06), urinary tract infection (OR, 1.1; 95% CI, 0.76-1.6; P = 0.61), unplanned reoperation (OR, 1.1; 95% CI, 0.83-1.4; P = 0.55), and surgical site infection (OR, 0.35; 95% CI, 0.18-0.71; P = 0.004) showed no significant link with increased mortality independent of other complications. CONCLUSIONS: Of 13 complications analyzed, myocardial infarction, unplanned intubation, prolonged ventilator requirement, stroke, and renal failure showed the strongest association with mortality independent of preoperative risk, independent of other complications, and across all risk-stratified subgroups. These findings help identify causes of perioperative mortality after elective craniotomy. Dedicating additional resources toward preventing and treating these complications postoperatively may help reduce rates of failure-to-rescue in the neurosurgical population.

The Effect of Underlying Liver Disease on Perioperative Outcomes Following Craniotomy for Tumor: An American College of Surgeons National Quality Improvement Program Analysis.

BACKGROUND: The association between underlying liver disease and poor surgical outcomes has been well documented across a wide variety of surgical disciplines. However, little is known about the importance of liver disease in neurosurgery. In this report, we assess the independent effect of liver disease on perioperative outcomes in patients undergoing craniotomy for tumor. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for patients undergoing craniotomy for tumor from 2006 to 2015. Presence and severity of underlying liver disease was assessed with the aspartate aminotransferase-to-platelet ratio index and the Model for End-Stage Liver Disease-Sodium scores, computed from preoperative laboratory values. RESULTS: Among 11,897 patients, mild and advanced disease was identified in 2.4% and 1.9% of patients, respectively. Rates of 30-day mortality were 4.5% and 15.8% in these patients, compared with 3.1% in patients with healthy livers. The 30-day complication rate was 40.3%, 28.0%, and 19.8% in patients with advanced, mild, and no liver disease, respectively. In multivariate analysis, the presence of any liver disease (mild or advanced) was independently associated with mortality (OR = 2.46; 95% confidence interval [CI], 1.68-3.59; P < 0.001), morbidity (OR, 1.49; 95% CI, 1.18-1.87; P = 0.001), and length of hospital stay over 10 days (OR, 1.35; 95% CI, 1.07-1.70; P = 0.012), when compared with 13 covariates. Liver disease showed the strongest independent association with mortality of all risk factors analyzed. CONCLUSIONS: Liver disease is an independent predictor of poor 30-day outcomes following craniotomy for tumor. Consideration of underlying liver function can have a role in surgical decision making and postoperative care for these patients.

Pseudohypoparathyroidism type 1B in a patient conceived by in vitro fertilization: another imprinting disorder reported with assisted reproductive technology.

Pseudohypoparathyroidism type 1B (PHP1B) is characterized by renal tubular resistance to parathyroid hormone (PTH) leading to hyperphosphatemia, hypocalcemia, elevated PTH, and hyperparathyroid bone changes. PHP1B is an imprinting disorder that results from loss of methylation at the maternal GNAS gene, which suppresses transcription of the alpha subunit of the stimulatory G protein of the PTH receptor. Emerging evidence supports an association between assisted reproductive technologies (ART) and imprinting disorders; however, there is currently little evidence linking PHP1B and ART. We present a twin boy conceived by ART to parents with no history of subfertility who presented at age 12 with bilateral slipped capital femoral epiphysis and bilateral genu valgum deformity. Clinical and laboratory investigation revealed markedly elevated PTH, low ionized calcium, elevated phosphorus, TSH resistance, and skeletal evidence of hyperparathyroidism, leading to the diagnosis of PHP1B. A partial loss of methylation at the GNAS exon A/B locus was observed. The patient's dizygotic twin sibling was asymptomatic and had normal laboratory evaluation. This is the second reported case of a child with PHP1B conceived by ART, further supporting the possibility that ART may lead to an increased risk for imprinting defects.

Outcomes and Prognostic Factors in Pediatric Oligodendroglioma: A Population-Based Study.

BACKGROUND/AIMS: Pediatric oligodendroglioma (pODG) is a rare primary brain tumor that remains poorly understood. Demographics, outcomes, and prognostic factors were analyzed in 346 pODG cases from the Surveillance, Epidemiology, and End Results database. METHODS: Gender, race, age, tumor location, tumor size, tumor grade, extent of resection, and use of radiotherapy were evaluated with respect to overall survival (OS) by univariate and multivariate analysis. These factors were assessed in the pediatric cohort and 5,753 adult oligodendroglioma cases for comparison. RESULTS: The mean OS in pODG was 199.6 months. Five- and 10-year survival rates were 85 and 81%. pODG arose less frequently in the frontal lobe than adult tumors (53 vs. 22%) but was more common in the temporal lobe (32 vs. 18%) and extracortical regions (19 vs. 5%, p < 0.0001). pODG presented with smaller size (55 vs. 24%, p < 0.0001) and lower grade (72 vs. 54%, p < 0.0001) than adult tumors. Tumor location, size, grade, use of radiotherapy, and extent of resection were significant prognostic factors. Size and grade were much stronger prognostic factors in children than adults. While children with oligodendroglioma survive much longer than adults on the whole, there was no difference in outcome between children with high-grade tumors and adults with high-grade tumors. CONCLUSION: pODG differs significantly from adult oligodendroglioma along a number of demographic and tumor factors at a population level, and key prognostic factors influence survival differently in pODG than in adult disease.