Reduced incidence of diabetes during the COVID-19 pandemic in Alberta: A time-segmented longitudinal study of Alberta's Tomorrow Project.

AIM: To characterize the impact of the COVID-19 pandemic on diabetes diagnosis using data from Alberta's Tomorrow Project (ATP), a population-based cohort study of chronic diseases in Alberta, Canada. MATERIALS AND METHODS: The ATP participants who were free of diabetes on 1 April 2018 were included in the study. A time-segmented regression model was used to compare incidence rates of diabetes before the COVID-19 pandemic, during the first two COVID-19 states of emergency, and in the period when the state of emergency was relaxed, after adjusting for seasonality, sociodemographic factors, socioeconomic status, and lifestyle behaviours. RESULTS: Among 43 705 ATP participants free of diabetes (65.5% females, age 60.4 ± 9.5 years in 2018), the rate of diabetes was 4.75 per 1000 person-year (PY) during the COVID-19 pandemic (up to 31 March 2021), which was 32% lower (95% confidence interval [CI] 21%, 42%; p < 0.001) than pre-pandemic (6.98 per 1000 PY for the period 1 April 2018 to 16 March 2020). In multivariable regression analysis, the first COVID-19 state of emergency (first wave) was associated with an 87.3% (95% CI -98.6%, 13.9%; p = 0.07) reduction in diabetes diagnosis; this decreasing trend was sustained to the second COVID-19 state of emergency and no substantial rebound (increase) was observed when the COVID-19 state of emergency was relaxed. CONCLUSIONS: The COVID-19 public health emergencies had a negative impact on diabetes diagnosis in Alberta. The reduction in diabetes diagnosis was likely due to province-wide health service disruptions during the COVID-19 pandemic. Systematic plans to close the post-COVID-19 diagnostic gap are required in diabetes to avoid substantial downstream sequelae of undiagnosed disease.

Non-fasting lipids and cardiovascular disease in those with and without diabetes in Alberta's Tomorrow Project: A prospective cohort study.

AIMS: Non-fasting remnant cholesterol (RC) is a novel marker of cardiovascular disease (CVD) risk, however, data on this relationship in Canadians with diabetes (at high risk of CVD) is lacking. The objective of this analysis was to determine the relationship of RC with CVD in individuals with and without diabetes in the Alberta's Tomorrow Project (ATP) cohort. METHODS: Non-fasting lipid data collected as part of the ATP was linked to administrative health records (October 2000-March 2015) to ascertain incident CVD and prevalent diabetes. Participants without prevalent CVD or incident diabetes and who had complete, non-negative non-fasting lipid data collected with triglycerides <4.5 mmol/L were included (n = 13,631). The relationship between non-fasting RC and incident CVD diagnoses was assessed by Cox proportional hazards regression, after stratification by diabetes status. RESULTS: Participants were 69.8% women with a mean age of 61.6 ± 9.7 years, and 6.5% had prevalent diabetes. Non-fasting RC was higher in participants with diabetes compared to those without (mean 0.94 ± 0.41 mmol/L vs. 0.77 ± 0.38 mmol/L, p < 0.0001) and was associated with increased risk of incident CVD among those without diabetes (adjusted hazard ratio (aHR) 1.22, 95% CI 1.03-1.43, p = 0.02). Although a similar trend was observed in participants with diabetes it did not reach statistical significance (aHR 1.31, 95% CI 0.84-2.05, p = 0.23). CONCLUSIONS: Elevated non-fasting RC predicted increased CVD risk in middle and older-aged adults without diabetes; similar trends were observed in participants with diabetes and require further testing in a larger sample.

Impact of Comorbidity on Hospitalization and Emergency Room Visits in Adults With Diabetes: A Longitudinal Study of Alberta's Tomorrow Project.

OBJECTIVE: Our aim in this study was to characterize the impact of comorbidities, including number and types, on hospitalization and emergency room (ER) visits in people with diabetes. METHODS: Incident cases of diabetes from Alberta's Tomorrow Project with >24 months of follow-up were included. Comorbidities, classified by Elixhauser conditions, were updated every 12 months after diagnosis. A generalized estimating equation model was used to examine the association (by incidence rate ratio [IRR]) between time-varying comorbidity profile and hospitalization and ER visits per year of follow-up after adjusting for sociodemographic factors, lifestyle behaviours, and historic health-care utilization in the previous 5 years. RESULTS: Among 2,110 incident cases of diabetes (51.0% females; median age at diagnosis: 59.5 years; median follow-up: 7.19 years), the average number of Elixhauser comorbidities was 1.9±1.6 in the first year of diagnosis and 3.3±2.0 in year 15 after diagnosis. The number of comorbidities in the previous year was positively associated with risk of hospitalization (IRR=1.33 [95% confidence interval {CI}: 1.04 to 1.70] and 2.14 [95% CI: 1.67 to 2.74] for 1 or 2 and ≥2 comorbidities, respectively) and ER visits (IRR=1.31 [95% CI: 1.15 to 1.50] and 1.62 [95% CI: 1.41 to 1.87] for 1 or 2 and ≥2 comorbidities, respectively) in the subsequent year. Cardiovascular diseases, peripheral vascular diseases, cancer, liver disease, fluid and electrolyte disorders, and depression were the conditions most typically associated with increased health-care utilization. CONCLUSIONS: The number of comorbidities was a major risk factor of health-care utilization for people with diabetes. Vascular diseases, cancer, and conditions closely related to diabetic frailty (e.g. fluid and electrolyte disorders and depression) were the main drivers of hospital care and ER visits.

Sarcopenia reduces overall survival in unresectable oesophageal cancer: a systematic review and meta-analysis.

Sarcopenia measured through body composition analysis is emerging as an important prognosticator among various malignancies, including oesophageal cancer. Skeletal muscle index (SMI) as determined by the third lumbar vertebrae on cross-sectional CT images has been demonstrated as a predictor of overall survival in oesophageal cancer, using pre-defined cut off values for sarcopenia. However, this is largely within the setting of resectable disease. The primary objective of this systematic review and meta-analysis was to determine the effect of sarcopenia defined by SMI on overall-survival in patients with unresectable oesophageal cancer. On 30 January 2021, a systematic search of the literature was conducted to identify the role of SMI among patients with unresectable oesophageal cancer, with overall survival as the primary outcome. Databases included MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library. Inclusion criteria included age >18, diagnosis of oesophageal cancer, and non-operative management. A meta-analysis was conducted using RevMan 5.4.1 using an inverse variance, random effects model. After the removal of duplicates, 2755 unique search results were obtained. Manual screening of titles and abstracts resulted in 287 full text articles that were reviewed. Of these, five studies met the inclusion criteria with data evaluating the effect of sarcopenia defined by SMI on overall survival. A total of 783 patients, the majority of which were male (n = 638, 81%), with a mean age of 68 ± 2.3 years were included. 641 (82%) patients were diagnosed with squamous cell carcinoma. Sarcopenia, as determined by SMI using pre-defined cut-off values, was reported in 517 patients (66%). Meta-analysis demonstrated decreased overall survival in the sarcopenia group compared with the non-sarcopenia group (HR = 1.51; 95% CI 1.21-1.89; P = 0.0003; I2  = 0%; Figure 1). No significant publication bias was noted on assessment of funnel plot and Egger's test (P = 0.295). Sarcopenia as defined by SMI is predictive of overall survival among patients with nonoperative oesophageal cancer. Further analysis on the effect of sarcopenia on treatment related adverse effects and complications, particularly related to chemotherapy, radiotherapy, and oesophageal stenting, is needed to identify the degree of prognostication offered by body composition analysis. Studies on the modifiability of sarcopenia will help determine the utility of nutritional interventions.

Sarcopenia Determined by Skeletal Muscle Index Predicts Overall Survival, Disease-free Survival, and Postoperative Complications in Resectable Esophageal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Sarcopenia has been identified as a prognostic factor among certain types of cancer. In esophageal cancer, patients are at increased risk of malnutrition and sarcopenia, ultimately contributing to poor outcomes. A systematic review was conducted to determine whether sarcopenia, defined by the skeletal muscle index, is predictive of overall survival, disease-free survival, and postoperative complications in resectable esophageal cancer. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up until January 2021. The primary outcome was overall survival; secondary outcomes included disease-free survival, pulmonary complications, and anastomotic leak. RESULTS: Twenty-one studies (4 prospective; 17 retrospective; 3966 patients) were included. Sarcopenia was present in 1940 (48.1%) patients and was associated with lower overall survival [hazard ratio (HR): 1.56; 95% confidence interval (CI): 1.25-1.95; P <0.00001; I2 =71%] and disease-free survival (HR: 1.73; 95% CI: 1.04-2.87; P =0.03; I2 =51%). A decrease in skeletal muscle index, independent of sarcopenia status, was associated with lower overall survival (HR: 1.81; 95% CI: 1.20-2.73; P =0.005; I2 =92%). Sarcopenia was associated with increased odds of pulmonary complications (odds ratio: 1.86; 95% CI: 1.29-2.66; P =0.0008; I2 =41%) and increased odds of anastomotic leak (odds ratio: 1.46; 95% CI: 1.11-1.93; P =0.008; I2 =0%). CONCLUSIONS: Sarcopenia is a predictor of overall survival, disease-free survival, and postoperative complications in patients with resectable esophageal cancer. Studies on the modifiability of sarcopenia in the preoperative period will help determine the utility of nutritional interventions.

Skeletal muscle is prognostic in resected stage III malignant melanoma.

BACKGROUND: Sarcopenia (low skeletal muscle index, SMI) and myosteatosis (low skeletal muscle radiodensity, SMD) have been associated with worse survival in cancer. This study evaluated associations of body composition with survival in patients with resected stage III melanoma. METHODS: A retrospective review was performed of resected stage III melanoma patients in Alberta, Canada from 2007 to 2017. Preoperative CT scans were analyzed to determine SMI and SMD. Cohort-specific SMI and SMD cut-offs that optimally predicted overall survival (OS) were identified through stratification, in addition to testing cut-offs previously established in the literature. Overall (OS), melanoma-specific (MSS), and recurrence-free survival (RFS) were determined from date of surgery and analysed using multivariable Cox regressions with age, sex, BMI, stage subgroup, ECOG PS, and tumor location as covariates. RESULTS: We included 330 patients in the final analysis. Mean age was 56 years and 62.4% of patients were male. At time of censoring 150 patients (45.6%) had died. Sarcopenia based on literature cut-offs was associated with decreased OS (HR 1.55, 95% CI 1.00-2.21, p = 0.016). Using cohort-specific cut-offs, sarcopenic patients also had significantly decreased OS (HR 1.87, 95% CI 1.27-2.76, p = 0.002). Myosteatosis defined using cohort-specific cut-offs predicted worse OS (HR 2.15, 95% CI 1.42-3.25, p < 0.001), MSS (HR 2.29, 95% CI 1.40-3.75, p = 0.001) and RFS (HR 1.52, 95% CI 1.02-2.27, p = 0.041). Increased BMI ( ≥ 25) and visceral fat index were not significantly associated with survival. CONCLUSIONS: Sarcopenia and myosteatosis, defined using two sets of cut-offs, are associated with decreased OS and MSS in resected stage III melanoma.

Validity of functional patient-reported outcomes in head and neck oncology: A systematic review.

Malignancy and treatment effects in head and neck oncology can be devastating to functional aspects of patient life such as swallowing, blinking, speech, salivation, and facial expression. Historically, the subjective nature of patient experience has resulted in difficulty with quantification and measurement of functional outcomes. Patient-Reported Outcomes (PROs) are questionnaires developed with patient input, forming the new gold standard for clinician assessment of subjective functional outcomes. The current review aims to identify and characterize the validation of PROs pertaining to four critical functional outcomes in head and neck oncology: swallowing, speech, dry mouth, and chewing. A literature search was conducted using MEDLINE, EMBASE, and the Cochrane databases for published, English language, peer-reviewed abstracts involving patients ≥ 18 years of age. Of 708 results, 705 were excluded at abstract or full text screening for not meeting inclusion criteria, exclusion of head and neck SCC patients in development, or absence of a functional domain measurement. The three reviewed studies-Xerostomia Questionnaire, Swallowing Outcomes After Laryngectomy, and Edmonton 33-exhibited strong reliability and construct and content validity, though two applied only to individual functional outcomes within specific patient populations receiving radiation or laryngectomy. While many PROs have been developed in head and neck oncology, very few properly employed extensive patient input in the development process. Further work must be committed to increasing head and neck cancer patient input in PRO development, particularly in the functional domains of speech and chewing.

Cost-utility analysis of normothermic machine perfusion compared to static cold storage in liver transplantation in the Canadian setting.

To estimate the incremental cost-effectiveness of a liver transplant program that utilizes normothermic machine perfusion (NMP) alongside static cold storage (SCS) compared to SCS alone (control). A Markov model compared strategies (NMP vs. control) using 1-year cycle lengths over a 5-year time horizon from the public healthcare payer perspective. Primary micro-costing data from a single center retrospective trial were applied along with utility values from literature sources. Transition probabilities were deduced using the retrospective trial cohort, local transplant data, and supplemented with literature values. Scenario and probabilistic sensitivity analysis (PSA) were conducted. The NMP strategy was cost-effective in comparison to the control strategy, which was dominated. The mean cost for NMP was $456 455 (2021 US$) and the control was $519 222. The NMP strategy had greater incremental quality-adjusted life years (QALYs) gains over 5 years compared to the control, with 3.48 versus 3.17, respectively. The overarching results remained unchanged in scenario analysis. In PSA, NMP was cost-effective in 63% of iterations at a willingness-to-pay threshold of $40 941. The addition of NMP to a liver transplant program results in greater QALY gains and is cost-effective from the public healthcare payer perspective.

Chronic disease surveillance in Alberta's tomorrow project using administrative health data.

INTRODUCTION: Alberta's Tomorrow Project (ATP) is the largest population-based prospective cohort study of cancer and chronic diseases in Alberta, Canada. The ATP cohort data were primarily self-reported by participants on lifestyle behaviors and disease risk factors at the enrollment, which lacks sufficient and accurate data on chronic disease diagnosis for longer-term follow-up. OBJECTIVES: To characterize the occurrence rate and trend of chronic diseases in the ATP cohort by linking with administrative healthcare data. METHODS: A set of validated algorithms using ICD codes were applied to Alberta Health (AH) administrative data (October 2000-March 2018) linked to the ATP cohort to determine the prevalence and incidence of common chronic diseases. RESULTS: There were 52,770 ATP participants (51.2±9.4 years old at enrollment and 63.7% females) linked to the AH data with average follow-up of 10.1±4.4 years. In the ATP cohort, hypertension (18.5%), depression (18.1%), chronic pain (12.8%), osteoarthritis (10.1%) and cardiovascular diseases (8.7%) were the most prevalent chronic conditions. The incidence rates varied across diseases, with the highest rates for hypertension (22.1 per 1000 person-year), osteoarthritis (16.2 per 1000 person-year) and ischemic heart diseases (13.0 per 1000 person-year). All chronic conditions had increased prevalence over time (p < for trend tests), while incidence rates were relatively stable. The proportion of participants with two or more of these conditions (multi-morbidity) increased from 3.9% in 2001 to 40.3% in 2017. CONCLUSIONS: This study shows an increasing trend of chronic diseases in the ATP cohort, particularly related to cardiovascular diseases and multi-morbidity. Using administrative health data to monitor chronic diseases for large population-based prospective cohort studies is feasible in Alberta, and our approach could be further applied in a broader research area, including health services research, to enhance research capacity of these population-based studies in Canada.

CT-based assessment of body composition and skeletal muscle in melanoma: A systematic review.

BACKGROUND/OBJECTIVES: Sarcopenia (low skeletal muscle index) and myosteatosis (low skeletal radiodensity) have been associated with poor outcomes in melanoma. This systematic review was performed to summarize and critically evaluate current literature surrounding body composition in melanoma. METHODS: MEDLINE and Embase databases were searched for studies of melanoma patients with computed tomography (CT) based body composition analysis from 2000 to 2020. Outcomes of interest were survival, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS), as well as treatment-related adverse events (AEs). RESULTS: Nine studies of 914 patients were included in the final review. The majority of studies were of metastatic melanoma patients treated with immunotherapy. Studies demonstrated a variety of CT analysis techniques and cut-offs to define sarcopenia and myosteatosis. Associations of sarcopenia or myosteatosis with survival (OS, PFS, DFS) or risk of treatment-related AEs were conflicting. Multiple studies had low quality of evidence due to small sample sizes, use of non-validated CT measures, and lack of multivariable analyses. CONCLUSIONS: Due to methodologic heterogeneity and low quality of evidence, impacts of CT-derived body composition parameters on outcomes in melanoma are unclear. Further research should be conducted to elucidate impacts of body composition in melanoma.

An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel.

BACKGROUND: Body composition is increasingly being studied as a method of predicting chemotherapy toxicity. Our study aimed to evaluate associations of body composition with treatment toxicity in a group of pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel. METHODS: A retrospective review was performed for all patients who received first-line gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer at a northern Alberta cancer institute (Canada) from 2014 to 2017. Total lean body mass (LBM) was derived from measurements of muscle surface area at L3 on baseline computed tomography (CT) scans. Optimal stratification, or minimal p-value analysis, was used to assess for a threshold of nab-paclitaxel dose per LBM (mg/kg) associated with a higher risk of dose-limiting toxicity (DLT). RESULTS: 152 patients were included in the study, of whom 62 (40.8%) experienced DLT. nab-Paclitaxel dose/LBM ranged from 0.98 to 8.76 mg/kg. A threshold for nab-paclitaxel dose/LBM that optimally predicted risk of DLT was identified at 5.83 mg/kg. Above this cut-off, 18/31 (58.1%) patients experienced DLT, compared to 44/121 (36.4%) patients below (p = 0.028). Patients above this cut-off had a higher incidence of peripheral neuropathy compared to those below, though this was not statistically significant based on an adjusted p-value threshold (48.4 vs. 29.8% respectively, p = 0.050). Body mass index, body surface area, and absolute initial doses of nab-paclitaxel or gemcitabine did not significantly impact likelihood of DLT. CONCLUSIONS: nab-Paclitaxel dose normalized to LBM, based on CT-derived measures of skeletal muscle, has potential to predict risk of chemotherapy toxicity. Chemotherapy dosing based on body composition, rather than conventional anthropometric measures, may be effective in reducing treatment toxicity.

Gaps in evidence for the use of medically authorized cannabis: Ontario and Alberta, Canada.

BACKGROUND: With legal access to medical cannabis in Canada since 2001, there is a need to fully characterize its use at both the individual and population levels. We draw on data from Canada's largest cohort study of medical cannabis to identify the primary reasons for medical cannabis authorization in Canada from 2014 to 2019 in two major provinces: Alberta (AB) and Ontario (ON), and review the extent that evidence supports each indication. METHODS: Self-reported baseline assessments were collected from adult patients in ON (n = 61,835) and AB (n = 3410) who were authorized medical cannabis. At baseline, sociodemographic, primary medical information, and validated clinical questionnaires were completed by patients as part of an individual assessment. Patients' reasons for seeking medical cannabis were compared to published reviews and guidelines to assess the level of evidence supporting medical cannabis use for each condition. RESULTS: Medical cannabis use in both AB and ON was similar in both demographic and reason for authorization. The most common reasons for medical cannabis authorization were: (1) pain (AB = 77%, ON = 76%) primarily due to chronic musculoskeletal, arthritic, and neuropathic pain, (2) mental health concerns (AB = 32.9%, ON = 38.7%) due to anxiety and depression, and (3) sleep problems (AB = 28%, ON = 25%). More than 50 other conditions were identified as reasons for obtaining authorization. CONCLUSION: In both AB and ON, the majority of reasons for medical cannabis authorization are not substantiated by clinical evidence to fully support its efficacy for long-term use. Ongoing epidemiological studies on medical cannabis on these treatments are warranted to fully outline its treatment benefits or risks.

Safe opioid prescribing: a prognostic machine learning approach to predicting 30-day risk after an opioid dispensation in Alberta, Canada.

OBJECTIVE: To develop machine learning models employing administrative health data that can estimate risk of adverse outcomes within 30 days of an opioid dispensation for use by health departments or prescription monitoring programmes. DESIGN, SETTING AND PARTICIPANTS: This prognostic study was conducted in Alberta, Canada between 2017 and 2018. Participants included all patients 18 years of age and older who received at least one opioid dispensation. Pregnant and cancer patients were excluded. EXPOSURE: Each opioid dispensation served as an exposure. MAIN OUTCOMES/MEASURES: Opioid-related adverse outcomes were identified from linked administrative health data. Machine learning algorithms were trained using 2017 data to predict risk of hospitalisation, emergency department visit and mortality within 30 days of an opioid dispensation. Two validation sets, using 2017 and 2018 data, were used to evaluate model performance. Model discrimination and calibration performance were assessed for all patients and those at higher risk. Machine learning discrimination was compared with current opioid guidelines. RESULTS: Participants in the 2017 training set (n=275 150) and validation set (n=117 829) had similar baseline characteristics. In the 2017 validation set, c-statistics for the XGBoost, logistic regression and neural network classifiers were 0.87, 0.87 and 0.80, respectively. In the 2018 validation set (n=393 023), the corresponding c-statistics were 0.88, 0.88 and 0.82. C-statistics from the Canadian guidelines ranged from 0.54 to 0.69 while the US guidelines ranged from 0.50 to 0.62. The top five percentile of predicted risk for the XGBoost and logistic regression classifiers captured 42% of all events and translated into post-test probabilities of 13.38% and 13.45%, respectively, up from the pretest probability of 1.6%. CONCLUSION: Machine learning classifiers, especially incorporating hospitalisation/physician claims data, have better predictive performance compared with guideline or prescription history only approaches when predicting 30-day risk of adverse outcomes. Prescription monitoring programmes and health departments with access to administrative data can use machine learning classifiers to effectively identify those at higher risk compared with current guideline-based approaches.

Myosteatosis is prognostic in metastatic melanoma treated with nivolumab.

BACKGROUND: While immunotherapy agents have improved outcomes in metastatic melanoma (MM), predictive biomarkers in these patients are lacking. Parameters identified from body composition analysis, such as low SMD (also termed myosteatosis), may prognosticate MM patients on immunotherapy. METHODS: In this retrospective study, 44 MM patients received nivolumab, either as monotherapy or in combination with ipilimumab. Pre-treatment computed tomography (CT) scans were analyzed to determine skeletal muscle density (SMD) in Hounsfield units (HU) and muscle surface area (MSA) in cm2 at L3. MSA was used to determine nivolumab dosing in mg/cm2. RESULTS: Low SMD was associated with worse overall survival (OS) by log rank test (median 12.03 vs. 34.96 months, p = 0.001) and in multivariate analysis when accounting for age, sex, performance status, and number of prior lines of therapy (HR 4.40, 95% CI 1.44-13.42, p = 0.009). Lower nivolumab dosing by MSA was significantly associated with improved OS (median 42.9 vs. 12.3 months, p < 0.001). This association remained significant in multivariate analysis with age, sex, performance status, and number of prior lines of therapy (HR 0.05, 95% CI 0.01-0.30, p = 0.001). Neither SMD nor higher nivolumab dose per MSA were associated with increased incidence of treatment toxicity. CONCLUSIONS: Low SMD is prognostic in MM treated with nivolumab immunotherapy. Presence of myosteatosis or higher nivolumab dose based on body composition did not predict treatment toxicity.

Change in Skeletal Muscle Following Resection of Stage I-III Colorectal Cancer is Predictive of Poor Survival: A Cohort Study.

BACKGROUND: Sarcopenia at time of diagnosis predicts worse survival outcomes. It is currently unknown how changes in muscle mass over time interact with sarcopenia in colorectal patients treated with curative intent. Objectives of this study were to quantify sarcopenia and skeletal muscle loss from time of diagnosis to end of surveillance and determine its effect on survival outcomes after completion of 2 years of surveillance. METHODS: Retrospective cohort study of stage I-III colorectal cancer patients from 2007-2009, who underwent resection and had preoperative and 2-year surveillance computed tomography scans, without recurrence during that time. Body composition analysis was done at both time points to determine lumbar skeletal muscle index, radiodensity and adiposity. Change over time was standardized as a percentage per year. Cox proportional hazard regression modeling was used for survival analysis. RESULTS: Of 667 patients included, median survival from surgery was 7.96 years, with 75 recurrences occurring after 2 years. On average patients lost muscle mass (-0.415%/year; CI -0.789, -0.042) and radiodensity (-5.76 HU/year; CI -6.74, -4.80), but gained total adipose tissue (7.06%/year; CI 4.34, 9.79). Patients with sarcopenia at diagnosis (HR 1.80; CI 1.13, 2.85) or muscle loss over time (HR 1.55; CI 1.01, 2.37) had worse overall survival, with significantly worse joint effect (HR 2.73; CI 1.32, 5.65). CONCLUSIONS: Sarcopenia at diagnosis combined with ongoing skeletal muscle loss over time resulted in significantly worse survival. Patients with these features who are recurrence-free at 2 years are more likely to have a non-colorectal cancer cause of death.

CMV-specific T-cells and CD27-CD28-CD4+ T-cells for assignment of cytomegalovirus (CMV) status in adults awaiting organ transplant.

BACKGROUND/OBJECTIVES: Determination of Cytomegalovirus (CMV) status in solid organ transplant (SOT) candidates is essential to stratify risk of post-transplant CMV disease. Passive transfusion-acquired antibodies can make serologic determination of CMV status unreliable. We evaluated 3 assays, not affected by passive antibodies (PA), in assignment of CMV status: quantification of CMV-specific CD4 + T-cells (CMV-TC) and exhausted CD27-CD28- CD4 + T-cells, and detection of CMV DNA with Nucleic Acid Amplification Testing (NAAT). STUDY DESIGN: We enrolled 50 adults awaiting SOT and 50 immunocompetent age-matched controls, and collected a throat swab, urine, saliva and blood sample on each. Using flow cytometry CD4 + T-cells were phenotypically analyzed for expression of CD27 and CD28 and CMV-specific CD4 + T-cells were identified by CD69 expression and intracellular IFN-γ quantification after stimulation with CMV-antigen lysate. CMV NAAT was performed on all specimens using real-time PCR. CMV serology (CMV IgG) was determined by enzyme immunoassay. Subjects were considered to have potential PA if they received blood products within 2 months of collection. RESULTS: The CMV-TC assay discriminated between CMV-seropositive and seronegative SOT candidates without PA well (sensitivity 79%, specificity 93%) while the CD27-CD28-CD4 + T-cell assay had good sensitivity (86%) but specificity of 74%. Detection of CMV DNA was uncommon in CMV-seropositive SOT candidates (2/21). CONCLUSIONS: Given its high specificity, the CMV-TC assay is valuable in confirming true-positive CMV status in seropositive SOT candidates with PA, while use of CD27-CD28-CD4 + T-cell analysis is limited by moderate specificity. Detection of CMV DNA is of limited value in assignment of CMV status in adults.

The Impact of Muscle and Adipose Tissue on Long-term Survival in Patients With Stage I to III Colorectal Cancer.

BACKGROUND: Computed tomography-derived body composition parameters are emerging prognostic factors in colorectal cancer. OBJECTIVE: This study aimed to determine the roles of sarcopenia, myosteatosis, and obesity as independent and overlapping parameters in stage I to III colorectal cancer. DESIGN: This is a retrospective cohort study from a prospectively collected database. Multivariate Cox proportional hazards models were performed to assess the associations between body composition parameters and survival. SETTINGS: All patients were seen in a tertiary care cancer center. PATIENTS: Adult patients with stage I to III colorectal cancer, undergoing curative resection from 2007 to 2009, were included. INTERVENTION: Computed tomography-derived quantification of skeletal muscle and adipose tissues was used to determine population-specific cutoffs for sarcopenia, myosteatosis, and total adiposity. MAIN OUTCOME MEASURES: Primary outcome measures were overall, recurrence-free, and cancer-specific survival. RESULTS: In the 968 patients included, there were a total of 254 disease recurrences and 350 deaths. Body mass index and CT-derived measures of adiposity did not result in worse survival outcomes. Sarcopenia was independently predictive of worse overall (HR, 1.45; 95% CI, 1.16-1.84), recurrence-free (HR, 1.32; 95% CI, 1.00-1.75), and cancer-specific survival (HR, 1.46; 95% CI, 1.09-1.94) in a multivariate model. Myosteatosis was also independently predictive of overall survival (HR, 1.53; 95% CI, 1.19-1.97). In a model considering joint effects of sarcopenia and myosteatosis, the presence of both predicted the worst overall (HR, 2.23; 95% CI, 1.62-3.06), recurrence-free (HR, 1.53; 95% CI, 1.06-2.21), and cancer-specific survival (HR, 2.40; 95% CI, 1.69-3.42) in a multivariate model. LIMITATIONS: The limitations of this study are inherent in retrospective observational studies. CONCLUSIONS: Sarcopenia and myosteatosis are independent predictors of worse survival in stage I to III colorectal cancer, and their joint effect is highly predictive of reduced overall, recurrence-free, and cancer-specific survival. See Video Abstract at http://links.lww.com/DCR/A923.

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+ T cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28-CD4+ T cells are not likely useful in CMV risk stratification in children.

Barriers to the Interpretation of Body Composition in Colorectal Cancer: A Review of the Methodological Inconsistency and Complexity of the CT-Defined Body Habitus.

BACKGROUND: Measurement of body composition by computed tomography (CT) is an advancing field. Sarcopenia, myosteatosis, and visceral obesity (VO) have been identified as predictive of survival in colorectal cancer (CRC). We performed a systematic review of contemporary studies to characterize this association and highlight methodological inconsistencies. METHODS: MEDLINE and PubMed were queried for articles published from January 2000 on, with populations of resectable CRC and with CT-measured body composition and survival data. The study quality was assessed by two independent reviewers using the Newcastle-Ottawa Scale. RESULTS: Twenty studies met inclusion criteria, with a total of 8895 patients. Only two of the studies scored as high quality and nine as moderate quality. The remaining nine studies scored as low quality. Ten studies considered sarcopenia and 12 considered visceral obesity (VO). Cutoff points to define sarcopenia, myosteatosis, and VO were identified by optimal stratification, quartiles, or median values. The prevalence of sarcopenia varied from 15 to 60%, which based on study population and cutoff value used. Sarcopenia was associated with worse overall and disease-free survival in eight of the included studies. Myosteatosis was considered in three studies with a prevalence of 19-78%. It was significantly predictive of worse overall and disease-free survival in all three studies. VO had a prevalence of 14-70% and was inconsistently predictive of survival outcomes. CONCLUSIONS: There is a lack of methodological consistency within the currently published literature. Despite this, sarcopenia and myosteatosis, but not VO, are consistently associated with worse survival outcomes, when population and cancer-specific cutoffs are utilized.