Sven Holcombe

Sarcopenia and Mortality after Liver Transplantation

BACKGROUND Surgeons frequently struggle to determine patient suitability for liver transplantation. Objective and comprehensive measures of overall burden of disease, such as sarcopenia, could inform clinicians and help avoid futile transplantations. STUDY DESIGN The cross-sectional area of the psoas muscle was measured on CT scans of 163 liver transplant recipients. After controlling for donor and recipient characteristics using Cox regression models, we described the relationship between psoas area and post-transplantation mortality. RESULTS Psoas area correlated poorly with Model for End-Stage Liver Disease score and serum albumin. Cox regression revealed a strong association between psoas area and post-transplantation mortality (hazard ratio = 3.7/1,000 mm(2) decrease in psoas area; p < 0.0001). When stratified into quartiles based on psoas area (holding donor and recipient characteristics constant), 1-year survival ranged from 49.7% for the quartile with the smallest psoas area to 87.0% for the quartile with the largest. Survival at 3 years among these groups was 26.4% and 77.2%, respectively. The impact of psoas area on survival exceeded that of all other covariates in these models. CONCLUSIONS Central sarcopenia strongly correlates with mortality after liver transplantation. Such objective measures of patient frailty, such as sarcopenia, can inform clinical decision making and, potentially, allocation policy. Additional work is needed develop valid and clinically relevant measures of sarcopenia and frailty in liver transplantation.

Analytic morphomics, core muscle size, and surgical outcomes.

Objective:Assess the relationship between lean core muscle size, measured on preoperative cross-sectional images, and surgical outcomes. Background:Novel measures of preoperative risk are needed. Analytic morphomic analysis of cross-sectional diagnostic images may elucidate vast amounts of patient-specific data, which are never assessed by clinicians. Methods:The study population included all patients within the Michigan Surgical Quality Collaborative database with a computerized tomography(CT) scan before major, elective general or vascular surgery (N = 1453). The lean core muscle size was calculated using analytic morphomic techniques. The primary outcome measure was survival, whereas secondary outcomes included surgical complications and costs. Covariate adjusted outcomes were assessed using Kaplan-Meier analysis, multivariate cox regression, multivariate logistic regression, and generalized estimating equation methods. Results:The mean follow-up was 2.3 years and 214 patients died during the observation period. The covariate-adjusted hazard ratio for lean core muscle area was 1.45 (P = 0.028), indicating that mortality increased by 45% per 1000 mm2 decrease in lean core muscle area. When stratified into tertiles of core muscle size, the 1-year survival was 87% versus 95% for the smallest versus largest tertile, whereas the 3-year survival was 75% versus 91%, respectively (P < 0.003 for both comparisons). The estimated average risk of complications significantly differed and was 20.9%, 15.0%, and 12.3% in the lower, middle, and upper tertiles of lean core muscle area, respectively. Covariate-adjusted cost increased significantly by an estimated

Surgical Site Infection and Analytic Morphometric Assessment of Body Composition in Patients Undergoing Midline Laparotomy

10,110 per 1000 mm2 decrease in core muscle size (P = 0.003). Conclusions:Core muscle size is an independent and potentially important preoperative risk factor. The techniques used to assess preoperative CT scans, namely analytic morphomics, may represent a novel approach to better understanding patient risk.

Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer

BACKGROUND Obesity is a known risk factor for surgical site infection (SSI). Our hypothesis is that morphometric measures of midline subcutaneous fat will be associated with increased risk of SSI and will predict SSI better than conventional measures of obesity. STUDY DESIGN We identified 655 patients who underwent midline laparotomy (2006 to 2009) using the Michigan Surgical Quality Collaborative database. Using novel, semiautomated analytic morphometric techniques, the thickness of subcutaneous fat along the linea alba was measured between T12 and L4. To adjust for variations in patient size, subcutaneous fat was normalized to the distance between the vertebrae and anterior skin. Logistic regression analyses were used to identify factors independently associated with the incidence of SSI. RESULTS Overall, SSIs were observed in 12.5% (n = 82) of the population. Logistic regression revealed that patients with increased subcutaneous fat had significantly greater odds of developing a superficial incisional SSI (odds ratio [OR] = 1.76 per 10% increase, 95% CI 1.10 to 2.83, p = 0.019). Smoking, steroid use, American Society of Anesthesiologists (ASA) classification, and incision-to-close operative time were also significant independent risk factors for superficial incisional SSI. When comparing subcutaneous fat and body mass index (BMI) as the only model variables, subcutaneous fat significantly improved model predictions of superficial incisional SSI (area under the receiver operating characteristic curve [AUC] 0.60, p = 0.023); BMI did not (AUC 0.52, p = 0.73). CONCLUSIONS Abdominal subcutaneous fat is an independent predictor of superficial incisional SSI after midline laparotomy. Novel morphometric measures may improve risk stratification and help elucidate the pathophysiology of surgical complications.

Variation in the femoral bow: a novel high-throughput analysis of 3922 femurs on cross-sectional imaging.

Preoperative risk assessment, particularly for patient frailty, remains largely subjective. This study evaluated the relationship between core muscle size and patient outcomes following esophagectomy for malignancy. Using preoperative computed tomography scans in 230 subjects who had undergone transhiatal esophagectomy for cancer between 2001 and 2010, lean psoas area (LPA), measured at the fourth lumbar vertebra, was determined. Cox proportional hazards regression was employed to analyze overall survival (OS) and disease-free survival (DFS) adjusted for age, gender, and stage, and the Akaike information criterion was used to determine each covariate contribution to OS and DFS. Univariate analysis demonstrated that increasing LPA correlated with both OS (P = 0.017) and DFS (P = 0.038). In multivariate analysis controlling for patient and tumor characteristics, LPA correlated with OS and DFS in patients who had not received neoadjuvant treatment (n = 64), with higher LPA associated with improved OS and DFS. Moreover, LPA was of equivalent, or slightly higher importance than pathologic stage. These measures were not predictive among patients (n = 166) receiving neoadjuvant chemoradiation. Core muscle size appears to be an independent predictor of both OS and DFS, as significant as tumor stage, in patients following transhiatal esophagectomy. Changes in muscle mass related to preoperative treatment may confound this effect. Assessment of core muscle size may provide an additional objective measure for risk stratification prior to undergoing esophagectomy.

Abdominal aortic calcification and surgical outcomes in patients with no known cardiovascular risk factors.

Objectives: To evaluate femoral radius of curvature in a large sample of computed tomography scans to definitively determine the relationship between radius of curvature and femoral length, age, gender, ethnicity, body mass index and cortical thickness. Methods: A retrospective review was conducted of the electronic medical records and advanced imaging of 1961 patients who underwent pulmonary embolism protocol computed tomography scans between December 1999 and March 2010. The computed tomography scans were imported from the clinical picture archiving and communication system archive into a research image archive and analysis system. Each scan was processed by an automated system that algorithmically determined bony landmarks, adjusted for body position within the scanner and measured the radius of curvature. Results: The mean medullary radius of curvature of 3922 femurs was 112 cm (SD = 26 cm). The mean anterior radius of curvature of the femurs was 145 cm (SD = 55 cm). There was a moderately strong positive correlation (0.36–0.39) between femoral length and radius of curvature (P < 0.0001) that was not affected by age, body mass index, cortical thickness, gender, or ethnicity. No significant relationship was found between either gender or ethnicity and radius of curvature independent of femoral length. Conclusions: Differences in radius of curvature based on ethnicity and gender exist primarily because of the variation in average height, and therefore femur length, that exists between ethnic groups and genders. These data may prove useful in the design of safer intramedullary implants that accommodate a greater spectrum of anatomic variation.

Transsacral screw safe zone size by sacral segmentation variations

Introduction:In the setting of cardiovascular (CV) risk evaluation before major elective surgery, current risk assessment tools are relatively poor for discriminating among patients. For example, patients with clinical CV risk factors can be clearly identified; but among those without appreciated clinical CV risk, there may be a subset with stigmata of CV disease noted during the preoperative radiographic evaluation. Our study evaluated the relationship between abdominal aortic (AA) calcification measured on preoperative computed tomography (CT) imaging and surgical complications in patients undergoing general elective and vascular surgery. We hypothesized that patients with no known CV risk factors but significant aortic calcification on preoperative imaging will have inferior surgical outcomes. Methods:The study group included 1180 patients from the Michigan Surgical Quality Collaborative (MSQC) database who underwent major general or vascular elective surgery between 2006 and 2009 and who had a CT scan of the abdomen specifically for preoperative planning. AA calcification was measured using novel analytic morphomic techniques and reported as a percentage of the total wall area containing calcification. Patients were divided into cohorts by clinical CV risk and extent of AA calcification. Univariate analysis was used to compare postoperative morbidity between patient cohorts. Multivariate logistic regression analysis was used to compare continuous AA calcification with overall morbidity in patients with no clinical CV risk factors. Results:AA calcification was strongly skewed to the right (53.5% had no AA calcification) and was significantly correlated with age (&rgr; = 0.43, P < 0.001). Unadjusted univariate analysis of morbidity showed no significant differences in complication rates between patients in the clinical CV risk and significant AA calcification (no known CV risk factor) categories. The clinical CV risk (P < 0.001) and significant AA calcification without CV risk factors (P = 0.009) populations both had significantly more infectious and overall complications than patients with no AA calcification and no clinical CV risk. Multivariate logistic regression confirmed that AA calcification was a significant predictor of morbidity in patients with no clinical CV risk factors (odds ratio = 1.35, P = 0.017). Discussion:This study suggests that AA calcification may be related to progression of CV disease and surgical outcomes. A better understanding of the complex interaction of patient physiology with overall ability to recover from major surgery, using novel approaches such as analytic morphomics, has great potential to improve risk stratification and patient selection.

Use of morphometric assessment of body composition to quantify risk of surgical-site infection in patients undergoing component separation ventral hernia repair.

Variations in sacral segmentation may preclude safe placement of transsacral screws for posterior pelvis fixation. We developed a novel automated 3D technique to determine the safe zone size for transsacral screws in the upper two sacral segments in 526 adult pelvis computed tomography scans. Safe zone sizes were then compared by gender and sacral segmentation variations (number of neuroforamen and the presence/absence of lumbosacral transitional vertebrae, ±LSTV). Ten millimeters was used as the safety threshold for a large screw. 3 (0.6%), 366 (70%), and 157 (30%) sacra had 3, 4, or 5 neuroforamen, respectively. Eighty‐eight (17%) were +LSTV. Safe zone size depended on gender, number of neuroforamen in −LSTV sacra and presence of LSTV (p < 0.001) but not on the uni‐ or bilateral nature of the LSTV. 17% of −LSTV sacra were below the safety threshold in S1, 27% in S2, whereas 3% of +LSTV sacra were below in S1, 74% in S2. Of −LSTV sacra that cannot take an S1 screw safely, 77% can do so in S2, leaving only 4% of sacra that cannot accommodate a screw safely in either upper segment. The results demonstrate a predictable pattern of safe zone size based on gender and sacral segmentation variations.

Development of a quantitative method for the diagnosis of cirrhosis

Background: Body mass index does not allow accurate risk stratification for individuals undergoing component separation repair of ventral hernias. The authors hypothesized that tissue morphology measurements (morphomics) of preoperative computed tomography scans stratify the risk of surgical site infection in patients undergoing ventral hernia repair with a component separation technique. Methods: The authors identified 93 patients who underwent component release ventral hernia repair (2004 to 2012). The surgical technique involved release of the external oblique muscle lateral to the linea semilunaris. Using analytic morphomic techniques, the authors measured patients’ morphology using routine preoperative computed tomography scans. Two-sample t test was used to evaluate the effect of morphomic and demographic factors on surgical-site infection. Separate logistic regression analyses were performed on these morphomic factors to evaluate their predictive value in assessing the risk of surgical site infection, controlling for demographic covariates. Results: Surgical site infections were observed in 31 percent (n = 29) of the population. Subcutaneous fat area, total body area, and total body circumference had increased odds ratios for surgical site infection (p = 0.004, 0.014, and 0.012, respectively), indicating that these measures are better associated with surgical site infection than body mass index. These calculations control for demographic covariates, confirming that these morphomic parameters are predictive of surgical site infection. Conclusion: Specific morphomic values serve as superior predictors of surgical site infection in patients undergoing component separation technique hernia repair than currently used values such as body mass index. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Can Anatomical Morphomic Variables Help Predict Abdominal Injury Rates in Frontal Vehicle Crashes

Abstract Objective. To develop a novel non-invasive, quantitative approach utilizing computed tomography scans to predict cirrhosis. Materials and methods. A total of 105 patients (54 cirrhosis and 51 normal) who had CT scans within 6 months of a liver biopsy or were identified through a Trauma registry were included in this study. Patients were randomly divided into the training set (n = 81) and the validation set (n = 24). Each liver was segmented in a semi-automated fashion from a computed tomography scan using Mimics software. The resulting liver surfaces were saved as a stereo lithography mesh into an Oracle database, and analyzed in MATLAB® for morphological markers of cirrhosis. Results. The best predictive model for diagnosing cirrhosis consisted of liver slice-bounding box slice ratio, the dimensions of the liver bounding box, liver slice area, slice perimeter, surface volume and adjusted surface area. With this model, we calculated an area under the receiver operating characteristic curve of 0.90 for the training set, and 0.91 for the validation set. For comparison, we calculated an area under the receiver operating characteristic curve of 0.70 for our dataset when we used the lab value based aspartate aminotransferase-platelet ratio index, another reported model for predicting cirrhosis. Last, by combining the aspartate aminotransferase-platelet ratio index and our model, we obtained an area under the receiving operating characteristic of 0.95. Conclusion. This study shows “proof of concept” that quantitative image analysis of livers on computed tomography scans may be utilized to predict cirrhosis in the absence of a liver biopsy.