Brian A. Derstine

The Michigan Surgical Home and Optimization Program is a scalable model to improve care and reduce costs

Background: The Michigan Surgical Home and Optimization Program is a structured, home‐based, preoperative training program targeting physical, nutritional, and psychological guidance. The purpose of this study was to determine if participation in this program was associated with reduced hospital duration of stay and health care costs. Methods: We conducted a retrospective, single center, cohort study evaluating patients who participated in the Michigan Surgical Home and Optimization Program and subsequently underwent major elective general and thoracic operative care between June 2014 and December 2015. Propensity score matching was used to match program participants to a control group who underwent operative care prior to program implementation. Primary outcome measures were hospital duration of stay and payer costs. Multivariate regression was used to determine the covariate‐adjusted effect of program participation. Results: A total of 641 patients participated in the program; 82% were actively engaged in the program, recording physical activity at least 3 times per week for the majority of the program; 182 patients were propensity matched to patients who underwent operative care prior to program implementation. Multivariate analysis demonstrated that participation in the Michigan Surgical Home and Optimization Program was associated with a 31% reduction in hospital duration of stay (P < .001) and 28% lower total costs (P < .001) after adjusting for covariates. Conclusion: A home‐based, preoperative training program decreased hospital duration of stay, lowered costs of care, and was well accepted by patients. Further efforts will focus on broader implementation and linking participation to postoperative complications and rigorous patient‐reported outcomes.

Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients

Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post‐LT mortality. We examined the impact of body composition on post‐LT mortality in patients with HCC. Data on adult LT recipients who received Model for End‐Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty‐two (27%) patients died during the median follow‐up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P < 0.001), BMD (HR = 0.90/Hounsfield units [HU]; P = 0.03), pre‐LT locoregional therapy (HR = 0.14; P < 0.001), and donor age (HR = 1.05; P < 0.001) were the independent predictors of post‐LT mortality. DMG area did not affect post‐LT survival. In conclusion, in addition to number of HCC lesions and pre‐LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post‐LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092–1098 2016 AASLD

Skeletal muscle cutoff values for sarcopenia diagnosis using T10 to L5 measurements in a healthy US population

Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for ‘low’ values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18–40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey’s difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm2, 34.4 cm2/m2, and 34.3 HU in females, and 144.3 cm2, 45.4 cm2/m2, and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.

Body composition predicts survival in patients with hepatocellular carcinoma treated with transarterial chemoembolization

Purpose The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival. Materials and Methods We included patients from a single center (Ann Arbor VA)who had TACE as the primary treatment forHCC and had a pre-treatment computed tomography scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of 1-year survival. Results were validated in an external cohort(University of MichiganHealth System) ofHCC patientswho underwent TACE as their primary treatment. Results In the 75 patients in the derivation cohort, median survival was 439 (interquartile range, 377 to 685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (p < 0.001). Patients with VFD above the 56th percentile had a 1-year survival of 39% versus 78% for those below the 56th percentile. VFD also correlated with 1-year survival in the external validation cohort (44% vs. 72%, p < 0.001). In a secondary analysis, patients with higher VFD were significantly more likely to experience hepatic decompensation after TACE (p < 0.001). Conclusion VFD served as an objective predictor of mortality in patients undergoing TACE, possibly through its ability to predict hepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.

Relationships of Vancomycin Pharmacokinetics to Body Size and Composition Using a Novel Pharmacomorphomic Approach Based on Medical Imaging

ABSTRACT Antibiotics such as vancomycin are empirically dosed on the basis of body weight, which may not be optimal across the expanding adult body size distribution. Our aim was to compare the relationships between morphomic parameters generated from computed tomography images to conventional body size metrics as predictors of vancomycin pharmacokinetics (PK). This single-center retrospective study included 300 patients with 1,622 vancomycin concentration (52% trough) measurements. Bayesian estimation was used to compute individual vancomycin volume of distribution of the central compartment (Vc) and clearance (CL). Approximately 45% of patients were obese with an overall median (5th, 95th percentile) weight and body mass index of 87.2 (54.7, 123) kg and 28.8 (18.9, 43.7) kg/m2, respectively. Morphomic parameters of body size such as body depth, total body area, and torso volume of the twelfth thoracic through fourth lumbar vertebrae (T12 to L4) correlated with Vc. The relationship of vancomycin Vc was poorly predicted by body size but was stronger with T12-to-L4 torso volume (coefficient of determination [R2] = 0.11) than weight (R2 = 0.04). No relationships between vancomycin CL and traditional body size metrics could be discerned; however, relationships with skeletal muscle volume and total psoas area were found. Vancomycin CL independently correlated with total psoas area and inversely correlated with age. Thus, vancomycin CL was significantly related to total psoas area over age (R2 = 0.23, P < 0.0001). This proof-of-concept study suggests a potential role for translation of radiographic information into parameters predictive of drug pharmacokinetics. Prediction of individual antimicrobial pharmacokinetic parameters using analytic morphomics has the potential to improve antimicrobial dose selection and outcomes of obese patients.

Measuring rib cortical bone thickness and cross section from CT

HighlightsImage resolution of clinical CT limits our ability to measure rib cortical bone.Segmentation followed by cross‐cortex image resampling allows for use of cortical bone mapping algorithms.Performance of these measurements from clinical CT is tested against target microCT values.Accurate local thickness and overall cross‐sectional properties can be obtained using clinical CT. Graphical abstract Figure. No caption available. ABSTRACT This study assesses the ability to measure local cortical bone thickness, and to obtain mechanically relevant properties of rib cross‐sections from clinical‐resolution computed tomography (CT) scans of human ribs. The study utilized thirty‐four sections of ribs published by Perz et al. (2015) in three modalities: standard clinical CT (clinCT), high‐resolution clinical CT (HRclinCT), and microCT (&mgr;CT). Clinical‐resolution images were processed using a Cortical Bone Mapping (CBM) algorithm applied to cross‐cortex signals resampled perpendicularly to an initial smooth periosteal border. Geometric constraints were applied to remove outlier signals from consideration, and final predicted periosteal and endosteal borders from HRclinCT and clinCT were developed. Target values for local cortical thickness and for overall cross‐sectional area and inertial properties were obtained from segmentation of the periosteal and endosteal borders on each corresponding &mgr;CT image. Errors in prediction (mean ± SD) of local cortical bone thickness for HRclinCT and clinCT resolutions were Symbol mm and Symbol mm, respectively, with R2 coefficients of determination from linear regression of 0.82 and 0.71 (p < 0.0001 for both). Symbol. No caption available. Symbol. No caption available. Predicted cortical shell measures derived from the periosteal and endosteal borders included total cross‐sectional area (prediction errors of 6 ± 3% and Symbol% respectively for HRclinCT and clinCT with R2 correlations of 0.99 and 0.96), cortical shell area (errors of Symbol% and Symbol% with R2 correlations of 0.91 and 0.87), and principal area moment of inertia (errors of 2 ± 8% and Symbol% with R2 correlations of 0.98 and 0.95). Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Results here show substantial reductions in rib cross‐sectional measurement error compared to past histogram‐based thresholding methods and provide first validation of the CBM method when applied to rib bones. With the ubiquity of clinical CT scans covering the thorax and ribs, this study opens the door for individualized and population‐wide quantification of rib structural properties and their corresponding effects on rib injury.

Quantifying Sarcopenia Reference Values Using Lumbar and Thoracic Muscle Areas in a Healthy Population

BackgroundSarcopenia is defined as the loss of skeletal muscle mass and function associated with aging. Muscle mass can be reliably and accurately quantified using clinical CT scans but reference measurements are lacking, particularly in healthy US populations.MethodsTwo-phase CT scans from healthy kidney donors (age 18-40) at the University of Michigan between 1999-2010 were utilized. Muscle mass was quantified using two thoracic and two lumbar muscle cross-sectional area (CSA) measures. Indexed measurements were computed as area divided by height-squared. Paired analyses of non-contrast and contrast phases and different Hounsfield Unit (HU) ranges for muscle were conducted to determine their effect on CSA muscle measures. We report the means, standard deviations, and 2SD sarcopenia cutoffs from this population.ResultsHealthy population CSA (cm2) cutoffs for N=604 males/females respectively were: 34.7/20.9 (T12 Dorsal Muscle), 91.5/55.9 (T12 Skeletal Muscle), 141.7/91.2 (L3 Skeletal Muscle), 23.5/14.3 (L4 Total Psoas Area), and 23.4/14.3 (L4 Psoas Muscle Area). Height-indexed CSA (cm2/m2) cutoffs for males/females respectively were: 10.9/7.8 (T12 Dorsal Muscle), 28.7/20.6 (T12 Skeletal Muscle), 44.6/34.0 (L3 Skeletal Muscle), 7.5/5.2 (L4 Total Psoas Area), and 7.4/5.2 (L4 Psoas Muscle Area). We confirmed that a mask of -29 to 150 HU is optimal and shows no significant difference between contrast-enhanced and non-contrast CT scan CSA measurements.ConclusionsWe quantified reference values for lumbar and thoracic muscle CSA measures in a healthy US population. We defined the effect of IV contrast and different HU ranges for muscle. Combined, these results facilitate the extraction of clinically valuable data from the large numbers of existing scans performed for medical indications.

Preoperative Psoas Muscle Size Predicts Postoperative Delirium in Older Adults Undergoing Surgery: A Pilot Cohort Study

To the Editor: Individuals aged 65 and older account for more than 30% of surgical procedures in the United States and undergo operations at a rate twice that of the general population. Postoperative delirium is an increasingly recognized postoperative occurrence in these individuals, resulting in prolonged length of stay (LOS), functional decline, and greater mortality. Given that delirium may be preventable in more than one-third of cases with proper intervention, attention has been focused on identification of frail individuals before surgery who are at greater risk of delirium. Functional status can be used as a surrogate for frailty, although comprehensive geriatric assessment has not become part of standard preoperative protocols. Trunk muscle size, as defined by total psoas area (TPA) on computed tomography (CT), is a novel objective marker of surgical frailty and has been shown to correspond to functional status. The objective of this study was to examine the relationship between TPA and postoperative delirium in older adults planning to undergo elective general surgical procedures, controlling for other delirium risk factors identifiable in a comprehensive geriatric assessment. This was an observational cohort study of a subsample of individuals from the larger Vulnerable Elders Surgical Pathways and outcomes Assessment (VESPA) study at the University of Michigan from 2007 to 2011. Inclusion criteria were aged 70 and older, CTwithin 90 days before elective surgery, and a LOS of longer than 1 day (n = 142). TPA was calculated at the L4 vertebral level using validated analytic morphomic methods. In this study, TPA was defined as the sum of normal(31–100 Hounsfield Units (HU)) and lowdensity muscle (0–30 HU). Individuals with a low TPA were defined as falling within the lowest tertile of the sex-standardized study population. Retrospective medical record review was used to assess for the incidence of delirium or acute confusional state in the postoperative period, modified from a previously described methodology. Multivariate logistic regression was used to estimate the association between TPA and development of any signs or symptoms of postoperative delirium, controlling for extent of surgery and known delirium risk factors. The following factors were adjusted for: age (per 5-year increase), surgical complexity determined according to relative value units, comorbidity using the Charlson Comorbidity Index, degree of preoperative functional impairment (having difficulty in 0–5 activities of daily living (bathing, walking, shopping, light housework, managing finances) modified from a previous study), and cognitive impairment (documented dementia, cognitive impairment, positive preoperative Mini-Cog). A significance level of a = 0.05 was used. As a sensitivity analysis, influential observations were identified using Pregibon influence statistics. All statistical analysis was performed using Stata version 13 (StataCorp LP, College Station, TX). Of the 142 individuals in the analytical sample, 22 (15.5%) developed documented signs or symptoms of postoperative delirium during their hospitalization. Individuals who developed delirium had a median LOS of 12.2 days, vs 8 days for those who did not (P = .001) and were more likely to be discharged to destinations other than home (45.5% vs 21.6%) (P = .02). Postoperative signs and symptoms of delirium were associated with low TPA (vs normal or high TPA, odds ratio (OR) = 3.51, 95% confidence interval (CI) = 1.37–8.95) and older age (OR = 1.12, 95% CI = 1.02–1.21 per year increase). In the multivariate model controlling for age, comorbidity, surgical complexity, cognitive impairment, and preoperative functional status, the effect of low TPA remained substantial, although confidence intervals included 1 (OR = 2.63, 95% CI = 0.94–7.39, P = .07), a loss of statistical significance that was sensitive to a single highly influential and outlying case (dbeta = 2.35) who had a middle-tertile TPA but high functional impairment. After removal of this individuals, low psoas muscle area (OR = 3.12, 95% CI = 1.02–9.56, P = .046) was substantively and statistically independent of age and the other risk factors, with an area under the receiver operating characteristic curve of 0.8077. Individuals with TPA in the lowest tertile of the study population had a 27% risk of delirium during their during hospitalization, compared with a 10% risk for those in the highest tertile (Figure 1).

Dorsal Muscle Attenuation May Predict Failure to Respond to Interleukin-2 Therapy in Metastatic Renal Cell Carcinoma

RATIONALE AND OBJECTIVES To explore whether the sarcopenia body type can help predict response to interleukin-2 (IL-2) therapy in metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective cohort study of 75 subjects with metastatic RCC who underwent pretreatment contrast-enhanced computed tomography within 1 year of initiating IL-2 therapy. Cross-sectional area and attenuation of normal-density (31-100 Hounsfield units [HU]) and low-density (0-30 HU) dorsal muscles were obtained at the T11 vertebral level. The primary outcome was partial or complete response to IL-2 using RECIST 1.1 criteria at 6 weeks. A conditional inference tree was used to determine an optimal HU cutoff for predicting outcome. Bonferroni-adjusted multivariate logistic regression was conducted to investigate the independent associations between imaging features and response after controlling for demographics, doses of IL-2, and RCC prognostic scales (eg, Heng and the Memorial Sloan Kettering Cancer Center [MSKCC]). RESULTS Most subjects had intermediate prognosis by Heng (65% [49 of 75]) and the MSKCC (63% [47 of 75]) criteria; 7% had complete response and 12% had partial response. Mean attenuation of low-density dorsal muscles was a significant univariate predictor of IL-2 response after Bonferroni correction (P = 0.03). The odds of responding to treatment were 5.8 times higher for subjects with higher-attenuation low-density dorsal muscles (optimal cutoff: 18.1 HU). This persisted in multivariate analysis (P = 0.02). Body mass index (P = 0.67) and the Heng (P = 0.22) and MSKCC (P = 0.08) clinical prognostic scales were not significant predictors of response. CONCLUSIONS Mean cross-sectional attenuation of low-density dorsal muscles (ie, sarcopenia) may predict IL-2 response in metastatic RCC. Clinical variables are poor predictors of response.