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Aims: Patients with low muscle mass have increased risk of paclitaxel‐induced peripheral neuropathy, which is dependent on systemic paclitaxel exposure. Dose optimization may be feasible through the secondary use of radiologic data for body composition. The objective of this study was to interrogate morphomic parameters as predictors of paclitaxel pharmacokinetics to identify alternative dosing strategies that may improve treatment outcomes. Methods: This was a secondary analysis of female patients with breast cancer scheduled to receive 80 mg/m2 weekly paclitaxel infusions. Paclitaxel was measured at the end of initial infusion to estimate maximum concentration (Cmax). Computed tomography (CT) scans were used to measure 29 body composition features for inclusion in pharmacokinetic modelling. Monte Carlo simulations were performed to identify infusion durations that limit the probability of exceeding Cmax > 2885 ng/mL, which was selected based on prior work linking this to an unacceptable risk of peripheral neuropathy. Results: Thirty‐nine patients were included in the analysis. The optimal model was a two‐compartment pharmacokinetic model with T11 skeletal muscle area as a covariate of paclitaxel volume of distribution (Vd). Simulations suggest that extending infusion of the standard paclitaxel dose from 1 hour to 2 and 3 hours in patients who have skeletal muscle area 4907–7080 mm2 and <4907 mm2, respectively, would limit risk of Cmax > 2885 ng/mL to <50%, consequently reducing neuropathy, while marginally increasing overall systemic paclitaxel exposure. Conclusion: Extending paclitaxel infusion duration in ~25% of patients who have low skeletal muscle area is predicted to reduce peripheral neuropathy while maintaining systemic exposure, suggesting that personalizing paclitaxel dosing based on body composition may improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: High‐dose methotrexate (HD‐MTX) is used to treat primary central nervous system lymphoma (PCNSL), but potential differences in MTX clearance (CL) due to obesity have not been studied. We characterized the relationship between HD‐MTX CL and computed tomography (CT)‐generated body composition (morphomic), body size descriptors, and laboratory measurements in a cohort of obese and non‐obese patients with PCNSL. Methods: Medical records from adult patients with PCNSL treated with HD‐MTX over a 10‐year period were queried. Individuals with CT data within 30 days of the first cycle of treatment were included. Population pharmacokinetic analysis was performed using a 2‐compartment base structural model. We specifically compared body surface area (BSA) to standard body size, morphomic, and renal function estimation methods as covariates of HD‐MTX CL. Results: The final data set consisted of non‐obese (n=45) and obese (n=28) patients with 291 observations (3–7 samples per patient) with a mean (standard deviation) weight of 69.8 (11.6) kg and 104 (14.9) kg, respectively (p=0.0001). Vertebral body height was more informative than BSA of MTX CL. Similarly, a CL model incorporating age, albumin, and serum creatinine was more informative than kidney function equations and body size. The final model of MTX CL was based on age, albumin, serum creatinine, and vertebral body height. Conclusions: Common clinical variables coupled with vertebral body height are more predictive of first cycle MTX CL than BSA, alternate body size descriptors, and commonly used kidney function equations. [ABSTRACT FROM AUTHOR]

Existing clinical approaches and tools to measure burn tissue destruction are limited resulting in misdiagnosis of injury depth in over 40% of cases. Thus, our objective in this study was to characterize the ability of short‐wave infrared (SWIR) imaging to detect moisture levels as a surrogate for tissue viability with resolution to differentiate between burns of various depths. To accomplish our aim, we constructed an imaging system consisting of a broad‐band Tungsten light source; 1,200‐, 1,650‐, 1,940‐, and 2,250‐nm wavelength filters; and a specialized SWIR camera. We initially used agar slabs to provide a baseline spectrum for SWIR light imaging and demonstrated the differential absorbance at the multiple wavelengths, with 1,940 nm being the highest absorbed wavelength. These spectral bands were then demonstrated to detect levels of moisture in inorganic and in vivo mice models. The multiwavelength SWIR imaging approach was used to diagnose depth of burns using an in vivo porcine burn model. Healthy and injured skin regions were imaged 72 hours after short (20 seconds) and long (60 seconds) burn application, and biopsies were extracted from those regions for histologic analysis. Burn depth analysis based on collagen coagulation histology confirmed the formation of superficial and deep burns. SWIR multispectral reflectance imaging showed enhanced intensity levels in long burned regions, which correlated with histology and distinguished between superficial and deep burns. This SWIR imaging method represents a novel, real‐time method to objectively distinguishing superficial from deep burns. [ABSTRACT FROM AUTHOR]

Here we present detailed regional bone thickness and cross‐sectional measurements from full adult ribs using high resolution CT scans processed with a cortical bone mapping technique. Sixth ribs from 33 subjects ranging from 24 to 99 years of age were used to produce average cortical bone thickness maps and to provide average ± 1SD corridors for expected cross‐section properties (cross‐sectional areas and inertial moments) as a function of rib length. Results obtained from CT data were validated at specific rib locations using direct measurements from cut sections. Individual thickness measurements from CT had an accuracy (mean error) and precision (SD error) of −0.013 ± 0.167 mm (R2 coefficient of determination of 0.84). CT‐based measurement errors for rib cross‐sectional geometry were −0.1 ± 13.1% (cortical bone cross‐sectional area) and 4.7 ± 1.8% (total cross‐sectional area). Rib cortical bone thickness maps show the expected regional variation across a typical rib's surface. The local mid‐rib maxima in cortical thickness along the pleural rib aspect ranged from range 0.9 to 2.6 mm across the study population with an average map maximum of 1.4 mm. Along the cutaneous aspect, rib cortical bone thickness ranged from 0.7 to 1.9 mm with an average map thickness of 0.9 mm. Average cross‐sectional properties show a steady reduction in total cortical bone area from 10% along the rib's length through to the sternal end, whereas overall cross‐sectional area remains relatively constant along the majority of the rib's length before rising steeply towards the sternal end. On average, male ribs contained more cortical bone within a given cross‐section than was seen for female ribs. Importantly, however, this difference was driven by male ribs having larger overall cross‐sectional areas, rather than by sex differences in the bone thickness observed at specific local cortex sites. The cortical bone thickness results here can be used directly to improve the accuracy of current human body and rib models. Furthermore, the measurement corridors obtained from adult subjects across a wide age range can be used to validate future measurements from more widely available image sources such as clinical CT where gold standard reference measures (e.g. such as direct measurements obtained from cut sections) are otherwise unobtainable. [ABSTRACT FROM AUTHOR]

Background: Granular diagnostic criteria for adult malnutrition are lacking.Objective: This study uses analytic morphomics to define the Morphomic Malnutrition Score (MMS), a robust screening tool for severe malnutrition.Methods: The study population (n = 643) consisted of 2 cohorts: 1) 124 emergency department patients diagnosed with severe malnutrition by a registered dietitian (RD) and an available computed tomography (CT) scan within 2 days of RD evaluation, and 2) 519 adult kidney donor candidates to represent a healthy cohort. Body composition markers of muscle area and abdominal adiposity were measured from patient CT scans using analytic morphomic assessment, and then converted to sex- and age-adjusted percentiles using the Reference Analytic Morphomics Population (RAMP). RAMP consists of 6000 patients chosen to be representative of the general population. The combined cohort was then randomly divided into training (n = 453) and validation (n = 190) sets. MMS was derived using logistic regression. The model coefficients were transformed into a score, normalized from 0 to 10 (10 = most severe).Results: Severely malnourished patients had lower amounts of muscle and fat than kidney donors, specifically for dorsal muscle group area at the twelfth thoracic vertebral level (P < 0.001), psoas muscle area at the fourth lumbar vertebral level (P < 0.001), and subcutaneous fat area at the third lumbar vertebral level (P < 0.001)-all parameters in MMS. MMS for severely malnourished patients was higher than kidney donors (7.7 ± 2.2 vs 3.8 ± 2.0, respectively; P-value < 0.001). An MMS > 6.1 was accurate in determining nutrition diagnosis (82.1% sensitivity; 88.3% specificity; 85.2% balanced accuracy).Conclusions: MMS provides an evidence-based, granular assessment to distinguish severely malnourished adults from a healthy population. [ABSTRACT FROM AUTHOR]

Background As patients with chronic kidney disease become older, there is greater need to identify who will most benefit from kidney transplantation. Analytic morphomics has emerged as an objective risk assessment tool distinct from chronologic age. We hypothesize that morphometric age is a significant predictor of survival following transplantation. Methods A retrospective cohort of 158 kidney transplant patients from 2005 to 2014 with 1-year preoperative imaging was identified. Based on a control population comprising of trauma patients and kidney donors, morphometric age was calculated using the validated characteristics of psoas area, psoas density, and abdominal aortic calcification. The primary outcome was post-transplant survival. Results Cox regression showed morphometric age was a significant predictor of survival (hazard ratio, 1.06 per morphometric year [95% confidence interval, 1.03-1.08]; P < .001). Chronological age was not significant (hazard ratio, 1.03 per year [0.98-1.07]; P = .22). Among the chronologically oldest patients, those with younger morphometric age had greater survival rates compared to those with older morphometric age. Conclusions Morphometric age predicts survival following kidney transplantation. Particularly for older patients, it offers improved risk stratification compared to chronologic age. Morphomics may improve the transplant selection process and provide a greater assessment of prospective survival benefits. [ABSTRACT FROM AUTHOR]

Background Better risk assessment tools are needed to predict post-transplantation diabetes mellitus ( PTDM). Using analytic morphomic measurements from computed tomography ( CT) scans, we aimed to identify specific measures of body composition associated with PTDM. Methods We retrospectively reviewed 99 non-diabetic kidney transplant recipients who received pre-transplant CT scans at a single institution between 1/2005 and 5/2014. Analytic morphomic techniques were used to measure abdominal adiposity, abdominal size, and psoas muscle area and density, standardized by gender. We measured the associations of these morphomic factors with PTDM. Results One-year incidence of PTDM was 18%. The morphomic factors significantly associated with PTDM included visceral fat area ( OR=1.84 per standard deviation increase, P=.020), body depth ( OR=1.79, P=.035), and total body area ( OR=1.67, P=.049). Clinical factors significantly associated with PTDM included African American race ( OR=3.01, P=.044), hypertension ( OR=2.97, P=.041), and dialysis vintage ( OR=1.24 per year on dialysis, P=.048). Body mass index was not associated with PTDM ( OR=1.05, P=.188). On multivariate modeling, visceral fat area was an independent predictor of PTDM ( OR=1.91, P=.035). Conclusions Analytic morphomics can identify pre-transplant measurements of body composition that are predictive of PTDM in kidney transplant recipients. Pre-transplant imaging contains a wealth of underutilized data that may inform PTDM prevention strategies. [ABSTRACT FROM AUTHOR]

Elderly populations have a higher risk of rib fractures and other associated thoracic injuries than younger adults, and the changes in body morphology that occur with age are a potential cause of this increased risk. Rib centroidal path geometry for 20 627 ribs was extracted from computed tomography ( CT) scans of 1042 live adult subjects, then fitted to a six-parameter mathematical model that accurately characterizes rib size and shape, and a three-parameter model of rib orientation within the body. Multivariable regression characterized the independent effect of age, height, weight, and sex on the rib shape and orientation across the adult population, and statistically significant effects were seen from all demographic factors ( P < 0.0001). This study reports a novel aging effect whereby both the rib end-to-end separation and rib aspect ratio are seen to increase with age, producing elongated and flatter overall rib shapes in elderly populations, with age alone explaining up to 20% of population variability in the aspect ratio of mid-level ribs. Age was not strongly associated with overall rib arc length, indicating that age effects were related to shape change rather than overall bone length. The rib shape effect was found to be more strongly and directly associated with age than previously documented age-related changes in rib angulation. Other demographic results showed height and sex being most strongly associated with rib size, and weight most strongly associated with rib pump-handle angle. Results from the study provide a statistical model for building rib shapes typical of any given demographic by age, height, weight, and sex, and can be used to help build population-specific computational models of the thoracic rib cage. Furthermore, results also quantify normal population ranges for rib shape parameters which can be used to improve the assessment and treatment of rib skeletal deformity and disease. [ABSTRACT FROM AUTHOR]

Background Current measures of obesity do not accurately describe body composition. Using cross-sectional imaging, objective measures of musculature and adiposity are possible and may inform efforts to optimize liver transplantation outcomes. Methods Abdominal visceral fat area and psoas muscle cross-sectional area were measured on CT scans for 348 liver transplant recipients. After controlling for donor and recipient characteristics, survival analysis was performed using Cox regression. Results Visceral fat area was significantly associated with post-transplant mortality (p < 0.001; HR = 1.06 per 10 cm2, 95% CI: 1.04-1.09), as were positive hepatitis C status (p = 0.004; HR = 1.78, 95% CI: 1.21-2.61) and total psoas area ( TPA) (p < 0.001; HR = 0.91 per cm2, 95% CI: 0.88-0.94). Among patients with smaller TPA, the patients with high visceral fat area had 71.8% one-yr survival compared to 81.8% for those with low visceral fat area (p = 0.15). At five yr, the smaller muscle patients with high visceral fat area had 36.9% survival compared to 58.2% for those with low visceral fat area (p = 0.023). Conclusions Abdominal adiposity is associated with survival after liver transplantation, especially in patients with small trunk muscle size. When coupled with trunk musculature, abdominal adiposity offers direct characterization of body composition that can aid preoperative risk evaluation and inform transplant decision-making. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenic liver transplant recipients have higher rates of mortality, but mechanisms underlying these rates remain unclear. Failure to rescue (FTR) has been shown to be a primary driver of mortality following major general and vascular surgery. We hypothesized that FTR is common in sarcopenic liver transplant recipients. Methods: We retrospectively reviewed 348 liver transplant recipients with perioperative CT scans. Analytic morphomic techniques were used to assess trunk muscle size via total psoas area (TPA). One-yr major complication and FTR rates were calculated across TPA tertiles. Results: The one-yr complication rate was 77% and the FTR rate was 19%. Multivariate regression showed TPA as a significant predictor of FTR (OR = 0.27 per 1000 mm² increase in TPA, p < 0.001). Compared to patients in the largest muscle tertile, patients in the smallest tertile had 1.4-fold higher adjusted complication rates (91% vs. 66%) and 2.8-fold higher adjusted FTR rates (22% vs. 8%). Discussion: These results suggest that mortality in sarcopenic liver transplant recipients may be strongly related to FTR. Efforts aimed at early recognition and management of complications may decrease postoperative mortality. Additionally, this work highlights the need for expanded multicenter collaborations aimed at collection and analysis of postoperative complications in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Among liver transplant recipients, development of post-transplant complications such as new-onset diabetes after transplantation ( NODAT) is common and highly morbid. Current methods of predicting patient risk are inaccurate in the pre-transplant period, making implementation of targeted therapies difficult. We sought to determine whether analytic morphomics (using computed tomography scans) could be used to predict the incidence of NODAT. We analyzed peri-transplant scans from 216 patients with varying indications for liver transplantation, among whom 61 (28%) developed NODAT. Combinations of visceral fat, subcutaneous fat, and psoas area were considered in addition to traditional risk factors. On multivariate analysis adjusting for usual risk factors such as type of immunosuppression, subcutaneous fat thickness remained significantly associated with NODAT ( OR = 1.43, 95% CI 1.00-1.88, p = 0.047). Subgroup analysis showed that patients with later-onset of NODAT had higher visceral fat, whereas subcutaneous fat thickness was more correlated with earlier-onset of NODAT (using 10 months post-transplant as the cut-off). Conclusion Analytic morphomics may be used to help assess NODAT risk in patients undergoing liver transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:277-282, 2015. [ABSTRACT FROM AUTHOR]

ABSTRACT Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non-invasive near-infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium-chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi-weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near-infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416-1423, 2014. [ABSTRACT FROM AUTHOR]

Introduction Better measures of liver transplant risk stratification are needed. Our previous work noted a strong relationship between psoas muscle area and survival following liver transplantation. The dorsal muscle group is easier to measure, but it is unclear if they are also correlated with surgical outcomes. Methods Our study population included liver transplant recipients with a preoperative CT scan. Cross-sectional areas of the dorsal muscle group at the T12 vertebral level were measured. The primary outcomes for this study were one- and five-yr mortality and one-yr complications. The relationship between dorsal muscle group area and post-transplantation outcome was assessed using univariate and multivariate techniques. Results Dorsal muscle group area measurements were strongly associated with psoas area ( r = 0.72; p < 0.001). Postoperative outcome was observed from 325 patients. Multivariate logistic regression revealed dorsal muscle group area to be a significant predictor of one-yr mortality (odds ratio [ OR] = 0.53, p = 0.001), five-yr mortality ( OR = 0.53, p < 0.001), and one-yr complications ( OR = 0.67, p = 0.007). Conclusion Larger dorsal muscle group muscle size is associated with improved post-transplantation outcomes. The muscle is easier to measure and may represent a clinically relevant postoperative risk factor. [ABSTRACT FROM AUTHOR]

ACADEMIC EMERGENCY MEDICINE 2012; 19:280-286 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: A mass casualty incident (MCI) may strain a health care system beyond surge capacity, affecting patterns of care for casualties and other patients. Prior studies of MCIs have assessed clinical care for casualty patients, but have not examined outcomes or expenditures for noncasualty inpatients in the same time period. Methods: This was a retrospective analysis of administrative hospital claims in a state where an MCI with over 200 casualties occurred; two hospitals that admitted casualties of >5% of their inpatient capacity were studied. The 'surge period' was defined as 7 days after the MCI. Using diagnostic codes, patients admitted on the MCI day with diagnoses of burns or inhalation injury were included in the 'MCI surge cohort.' Patients admitted within a time frame of 7 days prior to 7 days after the MCI who were inpatients during the surge period were included in the 'non-MCI surge cohort.' The authors compared the MCI and non-MCI surge cohorts to a mutually exclusive reference cohort (all inpatients during 6 weeks prior to the MCI), regarding key outcomes of hospital length of stay (LOS) and hospital charges adjusted for age, sex, race/ethnicity, and severity of illness. Results: Fifty-five patients met criteria for the MCI surge cohort, 1,369 for the non-MCI surge cohort, and 5,980 for the reference group. Compared with the reference group and adjusted for covariates, the mean (±SD) hospital LOS was 4.90 (±1.85) days longer for the MCI surge cohort (95% confidence interval [CI] = 1.67 to 8.84) and 1.34 (±0.16) days longer for the non-MCI surge cohort (95% CI = 1.00 to 1.65). The MCI cohort also had significantly longer mean hospital LOS than the non-MCI surge cohort (difference = 3.56 days; 95% CI = 0.36 to 7.36). Also adjusted for covariates, mean (±SD) total hospital charges for the MCI surge cohort were $22,349 (±$8,342) greater than for the reference group (95% CI = $8,182 to $39,485). Mean (±SD) charges for the non-MCI surge cohort were $4,028 (±$633) greater than for the reference group (95% CI = $2,792 to $5,196). The MCI cohort also had higher mean total charges than the non-MCI surge cohort (difference = $18,321; 95% CI = $4,488 to $34,980). Conclusions: When adjusted for severity of illness, casualty patients and noncasualty patients receiving concurrent hospital care have significantly longer LOS and higher charges than typical hospital patients at times unaffected by MCIs. Spillover effects from MCIs for noncasualty patients have not been previously described and have implications for clinical and hospital management in MCI and other high-surge circumstances. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a observational cohort study on the relationship between total psoas area (TPA) and postoperative delirium in older adults planning to undergo elective general surgical procedures.