Measurement of Skeletal Muscle Area Improves Estimation of Aminoglycoside Clearance across Body Size.

A consistent approach to the dosing of aminoglycosides across the modern body size distribution has been elusive. We evaluated whether radiologically derived measures of body composition could explain more of the interpatient variability in aminoglycoside pharmacokinetics (PK) than standard body size metrics. This retrospective study included adult patients treated with gentamicin or tobramycin with at least three drug concentrations and computed tomography (CT) imaging available. Aminoglycoside volume and clearance (CL) estimates were computed using a two-compartment model by Bayesian analysis. Morphomic data were extracted from CT images using a custom algorithm. Bivariable and multivariable linear regression were used to assess relationships between PK parameters and covariates. A total of 335 patients were included with a median (minimum, maximum) of 4 (3, 16) aminoglycoside concentrations per patient. The median (minimum, maximum) age, height, and weight of included patients were 57 (21, 93) years, 170 (145, 203) centimeters, and 81 (42, 187) kilograms. Both standard and morphomic measures poorly explained variability in volume (R2 < 0.06). Skeletal muscle area and volume explained more of the interpatient variability in CL than weight or sex. Higher precision was observed using a modified Cockcroft-Gault equation with skeletal muscle area at L3 (R2= 0.38) or L4 (R2= 0.37) than the standard Cockcroft-Gault equation using lean (R2= 0.23), adjusted (R2= 0.23), or total (R2= 0.22) body weights. These results highlight that skeletal muscle measurements from CT images obtained in the course of care can improve the precision of aminoglycoside CL estimation over current body size scalars.

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

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.

Perioperative changes in trunk musculature and postoperative outcomes.

BACKGROUND: Surgeons often face difficult decisions in selecting which patients can tolerate major surgical procedures. Although recent studies suggest the potential for trunk muscle size, as measured on preoperative imaging, to inform surgical risk, these measures are static and do not account for the effect of the surgery itself. We hypothesize that trunk muscle size will show dynamic changes over the perioperative period, and this change correlates with postoperative mortality risk. METHODS: A total of 425 patients who underwent inpatient general surgery were identified to have both a 90-d preoperative and a 90-d postoperative abdominal computed tomography scan. The change in trunk muscle size was calculated using analytic morphomic techniques. The primary outcome was 1-y survival. Covariate-adjusted outcomes were assessed using multivariable logistic regression. RESULTS: A total of 82.6% patients (n = 351) experienced a decrease in trunk muscle size in the time between their scans (average 62.1 d). When stratifying patients into tertiles of rate of change in trunk muscle size and adjusting for other covariates, patients in the tertile of the greatest rate loss had significantly increased risk of 1-y mortality than those in the tertile of the least rate loss (P = 0.002; odds ratio = 3.40 95% confidence interval, 1.55-7.47). The adjusted mortality rate for the tertile of the greatest rate loss was 24.0% compared with 13.3% for the tertile of the least decrease. CONCLUSIONS: Trunk muscle size changes rapidly in the perioperative period and correlates with mortality. Trunk muscle size may be a critical target for interventional programs focusing on perioperative optimization of the surgical patient.

Analytic morphomics corresponds to functional status in older patients.

BACKGROUND: Older patients account for nearly half of the United States surgical volume, and age alone is insufficient to predict surgical fitness. Various metrics exist for risk stratification, but little work has been done to describe the association between measures. We aimed to determine whether analytic morphomics, a novel objective risk assessment tool, correlates with functional measures currently recommended in the preoperative evaluation of older patients. MATERIALS AND METHODS: We retrospectively identified 184 elective general surgery patients aged >70 y with both a preoperative computed tomography scan and Vulnerable Elderly Surgical Pathways and outcomes Assessment within 90 d of surgery. We used analytic morphomics to calculate trunk muscle size (or total psoas area [TPA]) and univariate logistic regression to assess the relationship between TPA and domains of geriatric function mobility, basic and instrumental activities of daily living (ADLs), and cognitive ability. RESULTS: Greater TPA was inversely correlated with impaired mobility (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.25-0.85, P = 0.013). Greater TPA was associated with decreased odds of deficit in any basic ADLs (OR = 0.36 per standard deviation unit increase in TPA, 95% CI 0.15-0.87, P <0.03) and any instrumental ADLs (OR = 0.53, 95% CI 0.34-0.81; P <0.005). Finally, patients with larger TPA were less likely to have cognitive difficulty assessed by Mini-Cog scale (OR = 0.55, 95% CI 0.35-0.86, P <0.01). Controlling for age did not change results. CONCLUSIONS: Older surgical candidates with greater trunk muscle size, or greater TPA, are less likely to have physical impairment, cognitive difficulty, or decreased ability to perform daily self-care. Further research linking these assessments to clinical outcomes is needed.

A correction score to compare aortic calcification in contrast enhanced and non-contrast measurements from computed tomography scans.

BACKGROUND: Aortic wall calcification shows strong promise as a cardiovascular risk factor. While useful for visual enhancement of vascular tissue, enhancement creates heterogeneity between scans with and without contrast. We evaluated the relationship between aortic calcification in routine abdominal computed tomography scans (CT) with and without contrast. METHODS: Inclusion was limited to those with abdominal CT-scans with and without contrast enhancement within 120 days. Analytic Morphomics, a semi-automated computational image processing system, was used to provide standardized, granular, anatomically indexed measurements of aortic wall calcification from abdominal CT-scans. Aortic calcification area (ACA) and aortic wall calcification percent (ACP) and were the outcomes of interest. Multiple linear regression was used to evaluate the relationship of aortic measurements. Models were further controlled for age and sex. Stratification of measurements by vertebral level was also performed. RESULTS: A positive association was observed for non-contrast calcification in ACP ß 0.74 (95% CI 0.72, 0.76) and ACA ß 0.44 (95% 0.43, 0.45). Stratified results demonstrated the highest coefficient of determination at L2 for percent and L3 for area models [R2 0.91 (ACP) 0.74 (ACA)]. Adjusted lumber-level associations between non-contrast and contrast measurements ranged from (ß 0.69-0.82) in ACP and (ß 0.37-0.54) in ACA. CONCLUSION: A straightforward correction score for comparison of abdominal aortic calcification measurements in contrast-enhanced and non-contrast scans is discussed. Correction of aortic calcification from CT scans can reduce scan heterogeneity and will be instrumental in creating larger cardiovascular cohorts as well as cardiovascular risk surveillance programs.

Morphomic calcification score from clinical CT scans: A proxy for coronary artery calcium.

BACKGROUND: Screening of cardiovascular risk is essential in preventing cardiac events and quantifying asymptomatic risk. Coronary artery calcium (CAC) scores are a well-established in predicting cardiovascular risk, but require specialized computed tomography (CT) scans. Given the relationship of aortic calcification with cardiovascular risk, we sought to determine whether aortic calcification measures from incidental CT scans may approximate CAC. STUDY DESIGN: Retrospective CT scans and corresponding volumetric CAC scores were obtained from patients at the University of Michigan. Aortic calcifications were measured in 166 scans. Correlations between a novel morphomic calcium (MC) percent score and CAC score were evaluated using Kendall's correlation coefficients. Comparison of receiver operating characteristic (ROC) curves based on MC at different vertebral levels showed the highest predictive values for measures taken at L4. RESULTS: MC at L4 shows promise in predicting CAC (AUC 0.90 in non-contrast scans, 0.70 in post-contrast scans). Proposed MC threshold are (4.21% for best sensitivity, B 12.93% for balance, C = 19.26% for specificity) in scans without contrast enhancement and (D = 7.31 for sensitivity, E 8.06 for specificity) in scans with contrast enhancement. CONCLUSION: The MC score demonstrates promising potential in approximating CAC, particularly at the L4 level. The utilization of MC from incidental CT scans may be useful for assessment of cardiovascular risk. The ability to extract MC from contrast scans makes it especially valuable to patients receiving additional medical or surgical care. Recognition of high-risk patients would allow the use of indicated preventative strategies to avoid hard cardiovascular events in at risk patients.

Statewide Prehabilitation Program and Episode Payment in Medicare Beneficiaries.

BACKGROUND: Prehabilitation has been shown to improve postoperative outcomes in a variety of patient populations undergoing major operations. The feasibility, generalizability, and value of broad implementation of prehabilitation outside the research environment are unknown. METHODS: Medicare claims data from 2014 to 2017 were used to conduct a multicenter (21 Michigan hospitals) pragmatic cohort study. Patients and controls were followed for the duration of their index surgical hospitalization and for 90 days postoperatively. Medicare beneficiaries older than 18 years who underwent inpatient surgical procedures at a participating hospital during the study time period were eligible for inclusion. The prehabilitation program involved a home-based walking program with supplementary education on nutrition, smoking cessation, and psychological preparation for surgical procedure. Data were analyzed with an intention-to-treat approach using t-tests and Wilcoxon rank sum tests. Propensity score matching used comorbidities and demographic factors to match controls to patients in a 2:1 manner with an exact match required for operation type. RESULTS: Patients (n = 523) and controls (n = 1,046) had no significant differences in demographic factors or comorbidities. Patients had significantly shorter median hospital length of stay (6 vs 7 days; p < 0.01) than controls and were more likely to be discharged to home (65.6% vs 57.0%, p < 0.01). Total episode payments were significantly lower for patients compared with controls ($31,641 vs $34,837; p = 0.04). Patients had significantly lower post-acute care payments for skilled nursing facility ($941 vs $1,566; p = 0.02) and home health ($829 vs $960; p = 0.03) services. CONCLUSIONS: Participation in a prehabilitation program in Michigan was associated with shorter length of stay and lower total episode payments after operation. Payers and hospitals should invest in the implementation of simple home-based prehabilitation programs.

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.

Investigating the clinical significance of body composition changes in patients undergoing chemoradiation for oropharyngeal cancer using analytic morphomics.

BACKGROUND: The purpose is to investigate the clinical significance of body morphomics changes in stage III-IV oropharyngeal cancer patients during concurrent chemoradiotherapy (CRT). METHODS: Fifty patients who underwent CRT were selected for body composition analyses by either availability of pre/post treatment DEXA scans or a novel CT-based approach of body morphomics analysis (BMA). BMA changes (lean psoas and total psoas area) were compared to total lean body mass changes by DEXA scans using two-sample t tests. Pearson correlation was used to compare the BMA measures to head and neck specific quality of life outcomes. Cox hazards model was used to predict mortality and tumor recurrence. RESULTS: Clinically significant declines in total psoas area and lean body mass of similar magnitude were observed in both BMA and DEXA cohorts after CRT. Loss of psoas area (P < 0.05) was associated with greater frailty and mobility issues (3 out of 15 UWQOL domains). Total psoas area is more sensitive for local recurrence than weight changes and T-stage on multivariate analyses. CONCLUSIONS: BMA specifically evaluating psoas area appears to correlate with head and neck cancer quality of life physical domains. Pre- and post-treatment total psoas area at L4 appears prognostic for tumor recurrence.