Calcification circumference, area, and location are associated with carotid stent expansion rate: high-resolution magnetic resonance vessel wall imaging study.

Background: The plaque imaging findings associated with the stent expansion rate (SER) of the carotid artery are not well known. The purpose of this study was to investigate the imaging findings associated with SER. Methods: It was a retrospective investigation. Based on the kind of carotid stents used, retrospective data from 89 patients who had carotid artery stenting (CAS) for atherosclerotic carotid stenosis were gathered and divided into two groups: open-cell stents and closed-cell stents. Patients underwent preoperative carotid high-resolution magnetic resonance vessel wall imaging (HR-VWI). Use HR-VWI to quantitatively evaluate carotid wall thickness and plaque components. Calculate SER using digital subtraction angiography (DSA). All patients' baseline and HR-VWI imaging features were retrospectively analyzed. Simple and multivariable linear regression analysis was used to determine the imaging findings associated with SER of open-cell and closed-cell stents. Results: A total of 89 patients (mean age, 70±8 years; 69 men) were included in the final analysis. Among 89 patients, 35 patients were treated with open-cell stents. Fifty-four patients were treated with closed-cell stents. In the open-cell stents group, the Maximum single-slice calcification circumference score, maximum wall thickness (WTmax), and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that only the Maximum single-slice calcification circumference score (ß=-9.35; 95% CI: -18.15 to -0.56; P=0.03) was associated with SER of open-cell stents. In the closed-cell stents group, the Maximum single-slice calcification circumference score, WTmax, maximum area percentage of calcification, calcification volume, and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that the Maximum area percentage of calcification (ß=-0.67; 95% CI: -1.29 to -0.05; P=0.03), Maximum single-slice calcification circumference score (ß=-8.43; 95% CI: -13.36 to -3.49; P=0.001) and total calcification location score (ß=-0.37; 95% CI: -1.08 to 0.09; P=0.02) were associated with SER of closed-cell stents. Conclusions: Calcified plaques are associated with SER of the carotid artery. Calcification circumference correlates with SER of open-cell stents. Calcification circumference, calcification area, and calcification location are related to SER of closed-cell stents, which may provide a new consideration for clinicians when choosing carotid artery stents.

Paediatric Ulcerative Colitis Is a Fibrotic Disease and Is Linked with Chronicity of Inflammation.

BACKGROUND AND AIMS: Intestinal fibrosis has recently been characterised in adult ulcerative colitis and may affect motility, diarrhoea, and the symptom of urgency. We aimed to charactersze the presence of fibrosis in paediatric patients with ulcerative colitis, and its link to severity and chronicity of mucosal inflammation, as well as clinical factors of severity. METHODS: We performed a single-centre cross-sectional study in children ages 1-18 years with ulcerative colitis, undergoing colectomy or proctocolectomy. Tissue cross-sections were derived from proximal, mid, and distal colon and rectum, and inflammation and fibrosis were graded based on previously developed scores. Clinical data were collected prospectively. RESULTS: From 62 patients, 205 intestinal sections were evaluated. Median age at diagnosis was 13 years, 100% had extensive colitis, and all resections were done for refractory disease. The presence, chronicity, and degree of inflammation were linked with the presence of fibrosis. Thickness of the muscularis mucosa was also linked with presence and chronicity of inflammation. The overall submucosal fibrosis burden was associated with prior anti-tumour necrosis factor use. CONCLUSIONS: Paediatric patients with ulcerative colitis exhibit colorectal submucosal fibrosis and muscularis mucosa thickening, which correlate with the presence, chronicity, and degree of mucosal inflammation. Fibrosis should be recognised as a complication of paediatric ulcerative colitis, and ulcerative colitis should be considered a progressive disease.

Systematic review with meta-analysis: efficacy of balloon-assisted enteroscopy for dilation of small bowel Crohn's disease strictures.

BACKGROUND: Evidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon-assisted enteroscopy is scarce. AIM: To evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon-assisted enteroscopy. METHODS: Citations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta-analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome-relevant risk factors. RESULTS: In the pooled per-study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short-term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow-up, 48.3% of patients reported symptom recurrence, 38.8% were re-dilated and 27.4% proceeded to surgery. On the per-patient-based multivariable analysis, that patients with disease activity in the small intestine had lower short-term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14-0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09-3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34-2.34, P < 0.001). CONCLUSIONS: Balloon-assisted enteroscopy for dilatation of CD-associated small intestinal strictures has high short-term technical and clinical efficacy and low complication rates. However, up to two-thirds of patients need re-dilation or surgery.

Efficacy of digital single-operator cholangioscopy and factors affecting its accuracy in the evaluation of indeterminate biliary stricture.

BACKGROUND AND AIMS: Indeterminate biliary stricture remains a significant diagnostic challenge. The current method of ERCP with bile duct brush cytology has substantial room for improvement. We aimed to determine the efficacy of a digital single-operator cholangioscopy (DSOC) in evaluation of indeterminate biliary stricture. METHODS: An observational cohort study was conducted among the patients who underwent DSOC for the indication of indeterminate biliary stricture at a tertiary academic medical center. The outcomes of interests were the accuracy of DSOC in visual interpretation and bile duct sample and identification of any factor(s) that could influence its effectiveness. RESULTS: One hundred five patients were included. The overall accuracy of DSOC in visual interpretation was 89.5%, whereas the accuracy of bile duct sample was 83.2%. The sensitivities of visual impression and bile duct sample were 89.1% and 69.8% and their specificities were 90% and 97.9%, respectively. The degree of endoscopists' experience with fewer than 25 cases and the severity of hyperbilirubinemia negatively impacted the accuracy of DSOC. Among 55 patients with definitive diagnosis of malignant stricture, the sensitivity of combined intraductal forceps biopsy sampling and brush cytology was 80.6%, whereas the sensitivity of brush cytology alone was 47.1%. CONCLUSIONS: DSOC augments ERCP in evaluating indeterminate biliary stricture. The acquisition of intraductal forceps biopsy samples should be a requisite in evaluation of indeterminate biliary stricture with DSOC. Discovery of modifiable factors such as the degree of endoscopists' expertise and the severity of hyperbilirubinemia, which can influence the accuracy of DSOC, warrants further studies on patient preprocedure optimization and an endoscopic training program that will cultivate procedural competency.

Derivation and Validation of a Model to Predict 30-Day Readmission in Surgical Patients Discharged to Skilled Nursing Facility.

OBJECTIVES: To identify factors associated with 30-day all-cause readmission rates in surgical patients discharged to skilled nursing facilities (SNFs), and derive and validate a risk score. DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: Patients admitted to 1 tertiary hospital's surgical services between January 1, 2011, and December 31, 2014 and subsequently discharged to 110 SNFs within a 25-mile radius of the hospital. The first 2 years were used for the derivation set and the last 2 for validation. METHODS: Data were collected on 30-day all cause readmissions, patient demographics, procedure and surgical service, comorbidities, laboratory tests, and prior health care utilization. Multivariate regression was used to identify risk factors for readmission. RESULTS: During the study period, 2405 surgical patients were discharged to 110 SNFs, and 519 (21.6%) of these patients experienced readmission within 30 days. In a multivariable regression model, hospital length of stay [odds ratio (OR) per day: 1.03, 95% confidence interval (CI) 1.02-1.04], number of hospitalizations in past year (OR 1.24 per hospitalization, 95% CI 1.18-1.31), nonelective surgery (OR 1.33, 95% CI 1.18-1.65), low-risk service (orthopedic/spine service) (OR 0.32, 95% CI 0.25-0.42), and intermediate-risk service (cardiothoracic surgery/urology/gynecology/ear, nose, throat) (OR 0.69, 95% CI 0.53-0.88) were associated with all-cause readmissions. The model had a C index of 0.71 in the validation set. Using the following risk score [0.8 × (hospital length of stay) + 7 × (number of hospitalizations in past year) +10 for nonelective surgery, +36 for high-risk surgery, and +20 for intermediate-risk surgery], a score of >40 identified patients at high risk of 30-day readmission (35.8% vs 12.6%, P < .001). CONCLUSIONS/IMPLICATIONS: Among surgical patients discharged to an SNF, a simple risk score with 4 parameters can accurately predict the risk of 30-day readmission.

Development of a Risk Prediction Model to Estimate the Probability of Malignancy in Pulmonary Nodules Being Considered for Biopsy.

BACKGROUND: Malignancy probability models for pulmonary nodules (PN) are most accurate when used within populations similar to those in which they were developed. Our goal was to develop a malignancy probability model that estimates the probability of malignancy for PNs considered high enough risk to recommend biopsy. METHODS: This retrospective analysis included training and validation datasets of patients with PNs who had a histopathologic diagnosis of malignant or benign. Radiographic and clinical characteristics associated with lung cancer were collected. Univariate logistic regression was used to identify potential predictors. Stepdown selection and multivariate logistic regression were used to build several models, each differing according to available data. RESULTS: Two hundred malignant nodules and 101 benign nodules were used to generate and internally validate eight models. Predictors of lung cancer used in the final models included age, smoking history, upper lobe location, solid and irregular/spiculated nodule edges, emphysema, fluorodeoxyglucose-PET avidity, and history of cancer other than lung. The concordance index (C-index) of the models ranged from 0.75 to 0.81. They were more accurate than the Mayo Clinic model (P < .05 for four of the models), and each had fair to excellent calibration. In an independent sample used for validation, the C-index for our model was 0.67 compared with 0.63 for the Mayo Clinic model. The ratio of malignant to benign nodules within each probability decile showed a greater potential to influence clinical decisions than the Mayo Clinic model. CONCLUSIONS: We developed eight models to help characterize PNs considered high enough risk by a clinician to recommend biopsy. These models may help to guide clinicians' decision-making and be used as a resource for patient communication.

T cell and monocyte/macrophage activation markers associate with adverse outcome, but give limited prognostic value in anemic patients with heart failure: results from RED-HF.

BACKGROUND: Activated leukocytes may contribute to the development and progression of heart failure (HF). We investigated the predictive value of circulating levels of stable and readily detectable markers reflecting both monocyte/macrophage and T-cell activity, on clinical outcomes in HF patients with reduced ejection fraction (HFrEF). METHODS: The association between baseline plasma levels of soluble CD163 (sCD163), macrophage migration inhibitory factor (MIF), granulysin, soluble interleukin-2 receptor (sIL-2R), and activated leukocyte cell adhesion molecule (ALCAM) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anemia, enrolled in the Reduction of Events by darbepoetin alfa in Heart Failure (RED-HF) trial. Modifying effects and interaction with darbepoetin alfa treatment were also assessed. RESULTS: All leukocyte markers, except granulysin, were associated with the primary outcome and all-cause death in univariate analysis (all p < 0.01) and remained significantly associated in multivariable analysis adjusting for conventional clinical variables (e.g. age, gender, BMI, NYHA class, creatinine, LVEF, etiology) and CRP. However, after final adjustment for TnT and NT-proBNP no associations were found with outcomes. No interaction with darbepoetin alpha treatment was observed for any marker. CONCLUSIONS: Leukocyte activation markers sCD163, MIF, sIL-2R, and ALCAM were associated with adverse outcome in patients with HFrEF, but add little as prognostic markers on top of established biochemical risk markers. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00358215 .

Pro-gastrin-releasing peptide and outcome in patients with heart failure and anaemia: results from the RED-HF study.

AIMS: Neuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin-releasing peptide (GRP), derived from the precursor proGRP1-125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction. METHODS AND RESULTS: The association between plasma proGRP (time-resolved immunofluorometric assay) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anaemia, enrolled in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED-HF) trial. Median proGRP levels in the RED-HF cohort were markedly increased [95 ng/L (25th, 75th percentile, 69-129 ng/L)] with 64% patients above the 80 ng/L reference limit. Baseline proGRP correlated with estimated glomerular filtration rate (r = 0.52), N terminal pro brain natriuretic peptide (r = 0.33), troponin T (r = 0.34), and haemoglobin (r = 0.16) (all P < 0.001). The incidence outcome increased with increasing tertiles of baseline proGRP (primary endpoint third tertile vs. the lowest tertile; hazard ratio 1.91; 95% confidence interval 1.60-2.28, P < 0.001). However, these associations were markedly attenuated and non-significant in adjusted models. No interaction between baseline proGRP and the effect of darbepoetin alfa treatment was detected. Moreover, no significant association between changes in proGRP during 6 month follow-up and outcome was observed. CONCLUSIONS: Pro-gastrin-releasing peptide is increased in patients with HF with reduced ejection fraction and anaemia, in particular in patients with poor renal function. However, proGRP adds little as a prognostic marker on top of conventional HF risk factors.

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.

AIMS: To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. METHODS AND RESULTS: Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16-4.98), hsTnT 3.09 (95% CI 2.47-3.88), MR-proADM 2.28 (95% CI 1.83-2.84), copeptin 1.66 (95% CI 1.35-2.04), cystatin C 1.92 (95% CI 1.55-2.37), and hsCRP 1.51 (95% CI 1.27-1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. CONCLUSION: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.

Validation of a Postoperative Nomogram Predicting Recurrence in Patients with Conventional Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (RCC) continues to be the most commonly diagnosed subtype and is associated with more aggressive behavior than papillary and chromophobe RCC. Predicting disease recurrence after surgical extirpation is important for counseling and targeting those at high risk for adjuvant therapy clinical trials. OBJECTIVE: To validate a postoperative nomogram predicting 5-yr recurrence-free probability (RFP) for clinically localized clear cell RCC. DESIGN, SETTING, AND PARTICIPANTS: We identified all patients who underwent nephrectomy for clinically localized clear cell RCC from 1990 to 2009 at Memorial Sloan Kettering Cancer Center. After excluding patients with bilateral renal masses, familial RCC syndromes, and T3c or T4 tumors due to the limited number, 1642 participants were available for analysis. INTERVENTIONS: Partial or radical nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disease recurrence was defined as any new tumor after nephrectomy or kidney cancer-specific mortality, whichever occurred first. A postoperative nomogram was used to calculate the predicted 5-yr RFP, and these values were compared with the actual 5-yr RFP. Nomogram performance was evaluated by concordance index and calibration plot. RESULTS AND LIMITATIONS: Median follow-up was 39 mo (interquartile range: 14-79 mo), and disease recurrence was observed in 50 patients. The nomogram concordance index was 0.81. The calibration curve showed that the nomogram underestimated the actual 5-yr RFP. We updated the nomogram by including the entire patient population, which maintained performance and significantly improved calibration. CONCLUSIONS: The updated clear cell RCC postoperative nomogram performed well in the combined cohort. Underestimation of actual 5-yr RFP by the original nomogram may be due to increased surgeon experience and other unknown variables. PATIENT SUMMARY: We updated a valuable prediction tool used for assessing the disease recurrence probability after nephrectomy for clear cell renal cell carcinoma.

Determining the optimal screening interval for type 2 diabetes mellitus using a risk prediction model.

BACKGROUND: Progression to diabetes mellitus (DM) is variable and the screening time interval not well defined. The American Diabetes Association and US Preventive Services Task Force suggest screening every 3 years, but evidence is limited. The objective of the study was to develop a model to predict the probability of developing DM and suggest a risk-based screening interval. METHODS: We included non-diabetic adult patients screened for DM in the Cleveland Clinic Health System if they had at least two measurements of glycated hemoglobin (HbA1c), an initial one less than 6.5% (48 mmol/mol) in 2008, and another between January, 2009 and December, 2013. Cox proportional hazards models were created. The primary outcome was DM defined as HbA1C greater than 6.4% (46 mmol/mol). The optimal rescreening interval was chosen based on the predicted probability of developing DM. RESULTS: Of 5084 participants, 100 (4.4%) of the 2281 patients with normal HbA1c and 772 (27.5%) of the 2803 patients with prediabetes developed DM within 5 years. Factors associated with developing DM included HbA1c (HR per 0.1 units increase 1.20; 95%CI, 1.13-1.27), family history (HR 1.31; 95%CI, 1.13-1.51), smoking (HR 1.18; 95%CI, 1.03-1.35), triglycerides (HR 1.01; 95%CI, 1.00-1.03), alanine aminotransferase (HR 1.07; 95%CI, 1.03-1.11), body mass index (HR 1.06; 95%CI, 1.01-1.11), age (HR 0.95; 95%CI, 0.91-0.99) and high-density lipoproteins (HR 0.93; 95% CI, 0.90-0.95). Five percent of patients in the highest risk tertile developed DM within 8 months, while it took 35 months for 5% of the middle tertile to develop DM. Only 2.4% percent of the patients in the lowest tertile developed DM within 5 years. CONCLUSION: A risk prediction model employing commonly available data can be used to guide screening intervals. Based on equal intervals for equal risk, patients in the highest risk category could be rescreened after 8 months, while those in the intermediate and lowest risk categories could be rescreened after 3 and 5 years respectively.

A Nomogram Derived by Combination of Demographic and Biomarker Data Improves the Noninvasive Evaluation of Patients at Risk for Bladder Cancer.

BACKGROUND: Improvements in the noninvasive clinical evaluation of patients at risk for bladder cancer would be of benefit both to individuals and to health care systems. We investigated the potential utility of a hybrid nomogram that combined key demographic features with the results of a multiplex urinary biomarker assay in hopes of identifying patients at risk of harboring bladder cancer. METHODS: Logistic regression analysis was used to model the probability of bladder cancer burden in a cohort of 686 subjects (394 with bladder cancer) using key demographic features alone, biomarker data alone, and the combination of demographic features and key biomarker data. We examined discrimination, calibration, and decision curve analysis techniques to evaluate prediction model performance. RESULTS: Area under the receiver operating characteristic curve (AUC) analyses revealed that demographic features alone predicted tumor burden with an accuracy of 0.806 [95% confidence interval (CI), 0.76-0.85], while biomarker data had an accuracy of 0.835 (95% CI, 0.80-0.87). The addition of molecular data into the nomogram improved the predictive performance to 0.891 (95% CI, 0.86-0.92). Decision curve analyses showed that the hybrid nomogram performed better than demographic or biomarker data alone. CONCLUSION: A nomogram construction strategy that combines key demographic features with biomarker data may facilitate the accurate, noninvasive evaluation of patients at risk of harboring bladder cancer. Further research is needed to evaluate the bladder cancer risk nomogram for potential clinical utility. IMPACT: The application of such a nomogram may better inform the decision to perform invasive diagnostic procedures. Cancer Epidemiol Biomarkers Prev; 25(9); 1361-6. ©2016 AACR.

Renal cell carcinoma: A nomogram for the CT imaging-inclusive prediction of indolent, non-clear cell renal cortical tumours.

AIM: To develop a nomogram from clinical and computed tomography (CT) data for pre-treatment identification of indolent renal cortical tumours. PATIENTS AND METHODS: A total of 1201 consecutive patients underwent dedicated contrast-enhanced CT prior to nephrectomy for a renal cortical tumour between January 2000 and July 2011. Two radiologists evaluated all tumours on CT for size, necrosis, calcification, contour, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, nodular enhancement, and the degree of nephrographic phase enhancement. CT and clinical predictors (gender, body mass index [BMI], age) were incorporated into the nomogram. We employed multivariable logistic regression analysis to predict tumour type and internally validated the final model using the data from reader 1. External validation was performed by using all data from reader 2. We applied Wilcoxon rank sum test and Fisher's exact test to investigate for differences in tumour size, BMI, age, and differences in CT imaging features between patients with aggressive and those with indolent tumours. RESULTS: 63.6% (764/1201) of patients had clear-cell or other aggressive non-clear-cell RCC (i.e. papillary RCC type 2, unclassified RCC) and 36.4% (437/1201) had indolent renal cortical tumours (i.e. papillary RCC type 1, chromophobe RCC, angiomyolipoma, or oncocytoma). On CT, indolent tumours were significantly smaller (p < 0.001) than aggressive tumours and significantly associated with well-defined tumour contours (p < 0.001). Aggressive RCC were significantly associated with necrosis, calcification, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, and nodular enhancement (all, p < 0.001). The nomogram's concordance index (C-index) was 0.823 after internal and 0.829 after external validation. CONCLUDING STATEMENT: We present a nomogram based on 1201 patients combining CT features with clinical data for the prediction of indolent renal cortical tumours. When externally validated, this nomogram resulted in a C-index of 0.829.

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METHODS: ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. FINDINGS: Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. INTERPRETATION: Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. FUNDING: None.

Individualized Risk Estimation for Postoperative Complications After Surgery for Oral Cavity Cancer.

IMPORTANCE: Postoperative complications after head and neck surgery carry the potential for significant morbidity. Estimating the risk of complications in an individual patient is challenging. OBJECTIVE: To develop a statistical tool capable of predicting an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series derived from an institutional clinical oncologic database, augmented by medical record abstraction, at an academic tertiary care cancer center. Participants were 506 previously untreated adult patients with biopsy-proven oral cavity squamous cell carcinoma who underwent surgery between January 1, 2007, and December 31, 2012. MAIN OUTCOMES AND MEASURES: The primary end point was a major postoperative complication requiring invasive intervention (Clavien-Dindo classification grades III-V). Patients treated between January 1, 2007, and December 31, 2008 (354 of 506 [70.0%]) comprised the modeling cohort and were used to develop a nomogram to predict the risk of developing the primary end point. Univariable analysis and correlation analysis were used to prescreen 36 potential predictors for incorporation in the subsequent multivariable logistic regression analysis. The variables with the highest predictive value were identified with the step-down model reduction method and included in the nomogram. Patients treated between January 1, 2007, and December 31, 2008 (152 of 506 [30.0%]) were used to validate the nomogram. RESULTS: Clinical characteristics were similar between the 2 cohorts for most comparisons. Thirty-six patients in the modeling cohort (10.2%) and 16 patients in the validation cohort (10.5%) developed a major postoperative complication. The 6 preoperative variables with the highest individual predictive value were incorporated within the nomogram, including body mass index, comorbidity status, preoperative white blood cell count, preoperative hematocrit, planned neck dissection, and planned tracheotomy. The nomogram predicted a major complication with a validated concordance index of 0.79. Inclusion of surgical operative variables in the nomogram maintained predictive accuracy (concordance index, 0.77). CONCLUSIONS AND RELEVANCE: A statistical tool was developed that accurately estimates an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma.

Incorporation of postoperative CT data into clinical models to predict 5-year overall and recurrence free survival after primary cytoreductive surgery for advanced ovarian cancer.

PURPOSE: The use of multivariable clinical models to assess postoperative prognosis in ovarian cancer increased. All published models incorporate surgical debulking. However, postoperative CT can detect residual disease (CT-RD) in 40% of optimally resected patients. The aim of our study was to investigate the added value of incorporating CT-RD evaluation into clinical models for assessment of overall survival (OS) and progression free survival (PFS) in patients after primary cytoreductive surgery (PCS). METHODS: 212 women with PCS for advanced ovarian cancer between 01/1997 and 12/2011, and a contrast enhanced abdominal CT 1-7 weeks after surgery were included in this IRB approved retrospective study. Two radiologists blinded to clinical data, evaluated all CT for the presence of CT-RD, and Cohen's kappa assessed agreement. Cox proportional hazards regression with stepwise selection was used to develop OS and PFS models, with CT-RD incorporated afterwards. Model fit was assessed with bootstrapped Concordance Probability Estimates (CPE), accounting for over-fitting bias by correcting the initial estimate after repeated subsampling. RESULTS: Readers agreed on the majority of cases (179/212, k=0.68). For OS and PFS, CT-RD was significant after adjusting for clinical factors with a CPE 0.663 (p=0.0264) and 0.649 (p=0.0008). CT-RD was detected in 37% of patients assessed as optimally debulked (RD<1cm) and increased the risk of death (HR: 1.58, 95% CI: 1.06-2.37%). CONCLUSION: CT-RD is a significant predictor after adjusting for clinical factors for both OS and PFS. Incorporating CT-RD into the clinical model improved the prediction of OS and PFS in patients after PCS for advanced ovarian cancer.

Therapeutic efficacy of Bifidobacterium longum-mediated human interleukin-2 with endostatin or TRAIL in transplanted tumors in mice.

Interleukin-2 (IL-2), as an important cytokine in immune response, has been demonstrated to have therapeutic activity in several cancer models. In our previous study, we showed that the pBV22210 vector containing a chloramphenicol resistance gene and the cryptic plasmid, pMB1, from the Bifidobacterium longum (B. longum) strain could stably replicate and did not significantly affect the biological characteristics of B. longum. In this study, B. longum was transfected by electroporation with pBV22210 containing IL-2 (B. longum-pBV22210-IL-2), its growth curve was determined, and its inhibitory effect on tumor xenografts in mice was examined. The results showed that B. longum-pBV22210-IL-2 reduced the tumor size and prolonged the survival time of H22 tumor-bearing mice. In addition, when cyclophosphamide (CTX), B. longum-pBV22210-endostatin, or B. longum-pBV22210-TRAIL was combined with B. longum-pBV22210-IL-2, the antitumor effect was significantly enhanced. The survival times of the mice in the combination groups of B. longum-pBV22210-endostatin or B. longum-pBV22210-TRAIL were longer than those of the mice in the B. longum-pBV22210-IL-2 alone group. However, when CTX was added, the survival times of the mice showed no statistically significant difference compared with those of the mice in the dextrose-saline solution group. These results suggest that B. longum-pBV22210-IL-2 has potent antitumor effects that could be enhanced when combined with chemotherapeutic drugs or other antitumor genes.

Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TA) is an autoimmune disease with an unclear etiology and pathophysiology. An antibody-mediated inflammatory response is a known feature of this disease, however, the role of circulating B-lymphocyte production of such antibodies is not known. The objective of this study is to characterize in vitro production of autoimmune antibodies by B-lymphocytes from patients with TA and to examine differences related to disease activity. METHODS: Peripheral blood samples were taken from 72 patients with TA and 50 age-matched controls. Among the patients with TA, 42 had active disease while 31 had inactive disease. The Sharma modified criteria were used for diagnosis, and the National Institutes of Health criteria were used for TA activity assessment. Levels of autoantibodies in culture supernatant of circulating B-lymphocytes, including anti-endothelial cell antibody (AECA), anti-cardiolipin antibody (ACA), anti-beta(2) glycoprotein-I antibody (aß2GPI), and anti-annexin V antibody (AAVA), were assayed by enzyme-linked immunosorbent assay (ELISA) in each participant. RESULTS: In vitro levels of AECA, ACA, aß2GPI, and AAVA from circulating B-lymphocytes were significantly increased in TA patients compared with controls (AECA: 0.6 ± 0.36 vs 0.18 ± 0.09, P < .001; ACA: 0.69 ± 0.22 vs 0.54 ± 0.13, P < .001; aß2GPI: 0.99 ± 0.19 vs 0.83 ± 0.07, P< .001; AAVA: 0.62 ± 0.26 vs 0.41 ± 0.44, P < .001). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in active TA were higher than those in inactive TA (AECA: 0.85 ± 0.29 vs 0.28 ± 0.10, P < .001; ACA: 0.79 ± 0.21 vs 0.56 ± 0.15, P < .001; AAVA: 0.82 ± 0.16 vs 0.36 ± 0.06, P < .001). No difference was found in the in vitro level of aß2GPI between active TA and inactive TA (1.01 ± 0.17 vs 0.96 ± 0.22, P = .115). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in inactive TA showed no statistic difference with those in controls (AECA: 0.28 ± 0.10 vs 0.18 ± 0.09, P = .096; ACA: 0.56 ± 0.15 vs 0.54 ± 0.13, P = .699; AAVA: 0.36 ± 0.06 vs 0.41 ± 0.44, P = .200). In vitro levels of aß2GPI in inactive TA were higher than those in controls (0.96 ± 0.22 vs 0.83 ± 0.07, P < .001). CONCLUSIONS: This study characterizes in vitro production of autoantibodies by circulating B-lymphocytes from patients with TA. Differences in production from those with active versus inactive disease suggest that phenotypic alterations in this cell type may play an important role in pathogenesis.

[Comparison of open and endovascular repair for abdominal aortic aneurysm mid-term outcomes: a single center randomized controlled trial].

OBJECTIVE: To compare the effects of open and endovascular repair for abdominal aortic aneurysm. METHODS: Between January 2009 and January 2011, 84 patients were randomized to endovascular aneurysm repair (EVAR) or open repair. There were 48 patients in EVAR group, 42 cases were male (87.5%), 6 cases were female (12.5%), aged from 50 to 83 years with a mean of 70.8 years. There were 36 patients in open repair group, 31 cases were male (86.1%), 5 cases were female (13.9%), aged from 50 to 80 years with a meal of 67.4 years. The results of perioperative period and follow-up were analyzed. RESULTS: Between the two groups, there was significant difference on operative time (t = 9.863, P = 0.000), blood loss (t = 4.647, P = 0.000), blood transfusion (t = 3.334, P = 0.002), hospital stay (t = 2.327, P = 0.022), and medical expense (t = 2.314, P = 0.023). There was no significant difference for perioperative complications (χ(2) = 0.480, P = 0.488). There was no significant difference for complications (χ(2) = 0.664, P = 0.415) and mortality (P = 0.429) during 3 months follow-up. There was no significant difference for complications during 6 months follow-up (χ(2) = 0.128, P = 0.720). CONCLUSIONS: Operative time, blood loss and transfusion, hospital stay in EVAR group are less than which in open repair group, the medical expense of EVAR was higher than open repair. There is no significant difference for complications during 6 months follow-up between 2 groups. Long-term follow-up and more patents are needed to analyze survival rate and long-term complications.

Circulation levels of acute phase proteins in patients with Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TA) is an immune-mediated disease with an unknown etiology. Assessment of disease activity in patients with TA is challenging owing to the absence of reliable serologic markers. Because circulation levels of acute-phase proteins fluctuate with the severity and extent of the inflammatory reaction, they may be potential biomarkers for the identification of TA activity. To test this hypothesis, certain acute-phase proteins were examined in TA patients and controls. METHODS: The study included 43 prospectively selected TA patients, with 18 in active phase and 25 in inactive phase. The Sharma modified criteria were used for disease diagnosis, and the National Institutes of Health criteria were used for TA activity assessment. Circulation levels of acute-phase proteins, including serum amyloid A (SAA), fibrinogen, complement C4-binding protein (C4BP), C-reactive protein, serum amyloid P, haptoglobin, alpha-acid glycoprotein, transthyretin, alpha1-microglobin, and complement fraction C3c and C4a were investigated by enzyme-linked immunosorbent assay in each participant. RESULTS: Circulating levels of SAA and C4BP were significantly increased in active TA patients compared with inactive TA patients and in controls, with (SAA: 95.9 [interquartile range, 51.9] vs 49.2 [82.0], P = .009; and 23.9 [50.1] mg/L, P = .001, respectively; C4BP: 88.5 [72.6] vs 61.7 [57.7], P = .023; and 32.6 [32.1] mg/L, P < .001, respectively). The levels of both proteins in inactive TA patients were still higher than those in controls (SAA: 49.2 [82.0] vs 23.9 [50.1] mg/L, P = .021; C4BP: 61.7 [57.7] vs 32.6 [32.1] mg/L, P = .025). No difference was found in the levels of the other acute-phase proteins studied. CONCLUSIONS: SAA and C4BP may be useful biomarkers in determining the disease activity of TA. More work should be done to test these results in a large cohort of patients in a longitudinal manner.