Cut-off Value For Risk Stratification Research Articles

Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p<0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p<0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Incorporation of a machine learning pathological diagnosis algorithm into the thyroid ultrasound imaging data improves the diagnosis risk of malignant thyroid nodules.

This study aimed at establishing a new model to predict malignant thyroid nodules using machine learning algorithms. A retrospective study was performed on 274 patients with thyroid nodules who underwent fine-needle aspiration (FNA) cytology or surgery from October 2018 to 2020 in Xianyang Central Hospital. The least absolute shrinkage and selection operator (lasso) regression analysis and logistic analysis were applied to screen and identified variables. Six machine learning algorithms, including Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Naive Bayes Classifier (NBC), Random Forest (RF), and Logistic Regression (LR), were employed and compared in constructing the predictive model, coupled with preoperative clinical characteristics and ultrasound features. Internal validation was performed by using 10-fold cross-validation. The performance of the model was measured by the area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, F1 score, Shapley additive explanations (SHAP) plot, feature importance, and correlation of features. The best cutoff value for risk stratification was identified by probability density function (PDF) and clinical utility curve (CUC). The malignant rate of thyroid nodules in the study cohort was 53.2%. The predictive models are constructed by age, margin, shape, echogenic foci, echogenicity, and lymph nodes. The XGBoost model was significantly superior to any one of the machine learning models, with an AUC value of 0.829. According to the PDF and CUC, we recommended that 51% probability be used as a threshold for determining the risk stratification of malignant nodules, where about 85.6% of patients with malignant nodules could be detected. Meanwhile, approximately 89.8% of unnecessary biopsy procedures would be saved. Finally, an online web risk calculator has been built to estimate the personal likelihood of malignant thyroid nodules based on the best-performing ML-ed model of XGBoost. Combining clinical characteristics and features of ultrasound images, ML algorithms can achieve reliable prediction of malignant thyroid nodules. The online web risk calculator based on the XGBoost model can easily identify in real-time the probability of malignant thyroid nodules, which can assist clinicians to formulate individualized management strategies for patients.

Validating and Comparing C-TIRADS, K-TIRADS and ACR-TIRADS in Stratifying the Malignancy Risk of Thyroid Nodules.

The thyroid imaging reporting and data system (TIRADS) was proposed by experts for optimal ultrasound evaluation of malignancy risk of thyroid focal lesions. There are several versions of TIRADS, some of them have been validated sufficiently, and the others have not been well assessed. In this study, a recently launched Chinese version of TIRADS (C-TIRADS) for malignancy risk stratification of thyroid nodules was validated, and the performance was compared to that of the Korean TIRADS (K-TIRADS) and American College of Radiology(ACR) TIRADS (ACR-TIRADS). Archives of 2177 patients who had undergone thyroid ultrasound examination, coarse needle tissue biopsy and/or surgery were reviewed, and 1978 patients with 1982 thyroid nodules were assessed according to the three TIRADSs. The histopathology was taken as the golden standard. The results showed the 1982 thyroid nodules were consisted of 1306 benign nodules and 676 malignant nodules. The malignancy risk accounted for 1.09%, 2.14%, 10.34%, 49.28%, 88.19% and 85.29% of the total nodules that were categorised as C-TIRADS 2, 3, 4A, 4B, 4C and 5, respectively; 0.00%, 1.64%, 2.87%,18.71% and 82.22% of the total nodules that were categorised as ACR-TIRADS 1, 2, 3, 4 and 5, respectively; 0.85%, 3.27%, 24.27% and 80.96% of the total nodules that were categorised as K-TIRADS 2, 3, 4 and 5, respectively. The correlation between the category of TIRADS and percentile of malignancy was 0.94 in the C-TIRADS, 1.00 in the ACR-TIRADS, and 1.00 in the K-TIRADS, respectively. The highest values of accuracy(AUC) of ROC curves of C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 were taken as the cut-off values for risk stratification, respectively. The sensitivity, specificity, positive and negative predictive values and AUC by C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 for malignancy risk stratification of thyroid nodules were 90.83%, 84.23%, 74.88% and 94.66% and 0.88, respectively; 83.58%, 89.82%, 80.95%, 91.36% and 0.87, respectively; and 85.50%, 90.35%, 82.10%, 92.33% and 0.88, respectively (P>0.05 for all). We concluded that the C-TIRADS has excellent performance in the malignancy risk stratification of thyroid nodules by the optimized cut-off value, which is comparable to that in K-TIRADS and ACR-TIRADS.

Risk stratification in patients with anaplastic thyroid carcinoma: role of age.

Thyroid carcinoma is the only cancer that regards age as an important predictor of thyroid cancer-specific survival (CSS). While the 8th American Joint Committee on Cancer (AJCC) staging system raised the age cutoff from 45 to 55 years for differentiated thyroid carcinoma (DTC) to more accurately predict the prognosis, there is no new information regarding the role of age in the prognosis of anaplastic thyroid carcinoma (ATC). The aim of this study was to determine the optimal age cutoff values for mortality risk stratification in ATC patients. Furthermore, a nomogram to predict ATC CSS was developed in each age group. Patients diagnosed with ATC between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. After applying inclusion and exclusion criteria, a total of 1140 patients were enrolled as cohort 1 to describe the characteristics of ATC, while a total of 556 patients were included as cohort 2 to determine age cutoff values for risk stratification by X-tile program. Training set and testing set were randomly generated to develop and validate a predictive nomogram of CSS in each age group. The 6-month, 1-year, and 2-year survival was 27.6%, 15.1%, and 6.2%, respectively, in cohort 1. X-tile program results showed that the optimal age cutoff values for mortality risk stratification were 65 and 85 years old (p < 0.001). Distant metastasis was independently associated with CSS in patients younger than 85 years old, and these patients benefited more from complete resection of the tumor and radiotherapy/chemotherapy. However, no predictors of CSS were identified in patients over 85 years old, and interventions (surgery, radiotherapy, and chemotherapy) targeting ATC had little role in disease control in these patients. The nomogram was developed and validated based on the independent CSS predictors in each age group. The C-index values of the training set and testing set were 0.735 [95% CI, 0.696-0.774] and 0.733 [95% CI, 0.663-0.804] for CSS in patients of ≤64 years old, while the values were 0.767 [95% CI, 0.730-0.804] and 0.783 [95% CI, 0.718-0.848] in patients of 65-84 years old. All of the C-index values were larger than 0.7, which showed acceptable prediction performance of the nomograms. Age can be used as an auxiliary stratification factor of prognosis in ATC patients. The survival may be improved in patients younger than 85 years old if combination therapy (surgery, radiotherapy, and chemotherapy) was indicated and applicable, while no optimal therapeutic strategy was determined in patients older than 85 years old. The established nomograms can provide good prediction of CSS according to age group.

Integrated Immunologic Monitoring in Solid Organ Transplantation: The Road Toward Torque Teno Virus-guided Immunosuppression.

Potent immunosuppressive drugs have been introduced into clinical care for solid organ transplant recipients. It is now time to guide these drugs on an individual level to optimize their efficacy. An ideal tool simultaneously detects overimmunosuppression and underimmunosuppression, is highly standardized, and is straightforward to implement into routine. Randomized controlled interventional trials are crucial to demonstrate clinical value. To date, proposed assays have mainly focused on the prediction of rejection and were based on the assessment of few immune compartments. Recently, novel tools have been introduced based on a more integrated approach to characterize the immune function and cover a broader spectrum of the immune system. In this respect, the quantification of the plasma load of a highly prevalent and apathogenic virus that might reflect the immune function of its host has been proposed: the torque teno virus (TTV). Although TTV control is driven by T cells, other major immune compartments might contribute to the hosts’ response. A standardized in-house polymerase chain reaction and a conformité européenne-certified commercially available polymerase chain reaction are available for TTV quantification. TTV load is associated with rejection and infection in solid organ transplant recipients, and cutoff values for risk stratification of such events have been proposed for lung and kidney transplantation. Test performance of TTV load does not allow for the diagnosis of rejection and infection but is able to define at-risk patients. Hitherto TTV load has not been used in interventional settings, but two interventional randomized controlled trials are currently testing the safety and efficacy of TTV-guided immunosuppression.

NT-proBNP Cut-off Values for Risk Stratification in Acute MI and Comparison with Other Risk Assessment Scores

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) provides prognostic information regarding the risk of death, acute heart failure and the development of AF in patients with acute coronary syndrome. While there are established cut-off values for the association between clinical risk assessment scores and in-hospital mortality, there is no clear cut-off value for NT-proBNP to guide risk stratification in patients with acute MI (AMI). Our study sought to evaluate the cut-off values of NT-proBNP in all-cause mortality post AMI and to compare with other available risk assessment scores. Methods: We conducted a multi-centre, prospective, observational study involving 411 patients admitted for AMI. Plasma NT-proBNP was assessed within 24 hours of admission. Results: One-year all-cause mortality occurred in 31 (7.6%) of 411 patients. NT-proBNP ≥404 pg/ml had an area under the curve of 0.66 (95% CI [0.54–0.77]; p=0.004) to predict all-cause mortality at 1 year (sensitivity: 80.6%; specificity: 36.9%; positive predictive value: 9.47%; negative predictive value: 95.89%). Using the Youden index, an NT-proBNP level ≥1,995 pg/ml was an independent predictor of all-cause mortality at 1 year (adjusted HR 2.6; 95% CI [1.3–5.5]; p=0.010), regardless of cardiovascular disease risk factors or revascularisation status. There were no significant differences among the predictive values of NT-proBNP, Thrombolysis in MI risk score, Global Registry of Acute Coronary Events risk score and left ventricular ejection fraction in predicting all-cause mortality at 1 year (p&gt;0.05). Conclusion: NT-proBNP level ≥1,995 pg/ml measured within 24 hours of admission for AMI was associated with higher all-cause mortality at 1 year. Randomised controlled trials are needed to further validate the usefulness of NT-proBNP for risk stratification in patients with AMI.

Red Cell Distribution Width Is Independently Associated with Mortality in Sepsis

Background: Mortality in sepsis remains high. Studies on small cohorts have shown that red cell distribution width (RDW) is associated with mortality. The aim of this study was to validate these findings in a large multicenter cohort. Methods: We conducted this retrospective analysis of the multicenter eICU Collaborative Research Database in 16,423 septic patients. We split the cohort in patients with low (≤15%; n = 7,129) and high (>15%; n = 9,294) RDW. Univariable and multivariable multilevel logistic regressions were used to fit regression models for the binary primary outcome of hospital mortality and the secondary outcome intensive care unit (ICU) mortality with hospital unit as random effect. Optimal cutoffs were calculated using the Youden index. Results: Patients with high RDW were more often older than 65 years (57% vs. 50%; p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) IV scores (69 vs. 60 pts.; p < 0.001). Both hospital (adjusted odds ratios [aOR] 1.18; 95% CI: 1.16–1.20; p < 0.001) and ICU mortality (aOR 1.16; 95% CI: 1.14–1.18; p < 0.001) were associated with RDW as a continuous variable. Patients with high RDW had a higher hospital mortality (20 vs. 9%; aOR 2.63; 95% CI: 2.38–2.90; p < 0.001). This finding persisted after multivariable adjustment (aOR 2.14; 95% CI: 1.93–2.37; p < 0.001) in a multilevel logistic regression analysis. The optimal RDW cutoff for the prediction of hospital mortality was 16%. Conclusion: We found an association of RDW with mortality in septic patients and propose an optimal cutoff value for risk stratification. In a combined model with lactate, RDW shows equivalent diagnostic performance to Sequential Organ Failure Assessment (SOFA) score and APACHE IV score.

Web-based calculator for biliary atresia screening in neonates and infants with cholestasis.

BackgroundDistinguishing biliary atresia from non-biliary atresia in patients with cholestasis is challenging, as these conditions have a similar clinical presentation. We developed and externally validated a screening model for biliary atresia and devised a web-based calculator for use in clinical settings.MethodsA screening model was developed based on data from 227 cholestatic infants (82 and 145 with and without biliary atresia, respectively) and validated in 234 infants (90 and 144 with and without biliary atresia, respectively) admitted to three hospitals. Variables were selected from routine examination results using the least absolute shrinkage and selection operator method and entered into a logistic regression model to construct a biliary-atresia-risk–predicting equation. Cutoff values for risk stratification were estimated using model sensitivity, derived from the receiver-operating characteristic curves.ResultsThe final screening model included seven variables (i.e., weight at admission, clay-colored stools, γ-glutamyl transpeptidase and albumin levels at admission, abnormal gallbladder, triangular cord sign, and change in total bilirubin levels). The model generated an area under the curve of 0.94 with a sensitivity of 91.46 and specificity of 86.62 in the derivation cohort. This was confirmed in the validation cohort, as we found an area under the curve of 0.93 with a sensitivity of 93.1 and specificity of 80.15. Patients were stratified into three risk groups (low-, moderate-, and high-risk groups). Biliary atresia was excluded in the low-risk group. The high-risk group showed a higher detection rate of biliary atresia compared to the stool color screening method alone. This model was integrated into a user-friendly web-based system.ConclusionsThe screening tool had a high predictive value and may help in decision-making by physicians at tertiary and community hospitals.

Identification of the optimal hsTnI cut-off value for risk stratification of normotensive patients with pulmonary embolism

Abstract Background/Introduction While numerous studies confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), the prognostic relevance of high-sensitivity troponin I (hsTnI) is inappropriately studied and disease specific cut-off values remain undefined. Purpose To investigate the prognostic relevance of hsTnI in normotensive PE patients, establish the optimal cut-off value for risk stratification and compare the prognostic performances of hsTnI and hsTnT. Methods Consecutive PE patients enrolled in a prospective single-centre registry between 09/2008 and 04/2018 were studied. Using receiver operating curve analysis, an optimised hsTnI cut-off concentration was identified and the prognostic value for the prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment) and all-cause mortality analysed. Results We analysed data from 459 PE patients (age 69 [interquartile range (IQR) 57–77] years, 52% female). Patients who suffered an in-hospital adverse outcome (4.8%) had higher median hsTnI concentrations compared to those with a favorable clinical course (57 [IQR 22–197] vs. 15 [IQR 10–86] pg/ml, p=0.03). A hsTnI cut-off value of 16 ng/ml provided the best prognostic performance and predicted an in-hospital adverse outcome (Odds ratio [OR] 6.5, 95% confidence interval [CI] 1.9–22.4) and all-cause mortality (OR 3.7, 95% CI 1.0–13.3). Between female and male patients, no relevant differences in hsTnI concentrations (17 [IQR 10–97] vs. 17 [IQR 10–92] pg/ml, p=0.79) or optimized cut-off values (17 pg/ml and 19 pg/ml, respectively) were observed. Stratification of patients to risk classes according to the 2019 European Society of Cardiology (ESC) algorithm revealed no differences if calculated based on either hsTnI or hsTnT (Table). Conclusions Our findings confirm the prognostic relevance of hsTnI in normotensive PE. An optimal hsTnI cut-off value of 16 pg/ml predicted in-hospital adverse outcome and all-cause mortality. The use of sex specific cut-off values does not appear necessary. Importantly, our results suggest that hsTnI and hsTnT can be used interchangeably for risk stratification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503). BRAHMS GmbH, part of Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany provided financial support for biomarker measurements. The sponsor was neither involved in biomarker measurements, statistical analyses, writing of the abstract nor had any influence on the scientific contents.

High-sensitivity troponin I for risk stratification in normotensive pulmonary embolism.

While numerous studies have confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), high-sensitivity troponin I (hsTnI) is inappropriately studied. This study aimed to investigate the prognostic relevance of hsTnI in normotensive PE, establish the optimal cut-off value for risk stratification and to compare the prognostic performances of hsTnI and hsTnT.Based on data from 459 consecutive PE patients enrolled in a single-centre registry, receiver operating characteristic analysis was used to identify an optimal hsTnI cut-off value for prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment) and all-cause mortality.Patients who suffered an in-hospital adverse outcome (4.8%) had higher hsTnI concentrations compared with those with a favourable clinical course (57 (interquartile range (IQR) 22–197) versus 15 (IQR 10–86) pg·mL−1, p=0.03). A hsTnI cut-off value of 16 ng·mL−1 provided optimal prognostic performance and predicted in-hospital adverse outcomes (OR 6.5, 95% CI 1.9–22.4) and all-cause mortality (OR 3.7, 95% CI 1.0–13.3). Between female and male patients, no relevant differences in hsTnI concentrations (17 (IQR 10–97) versus 17 (IQR 10–92) pg·mL−1, p=0.79) or optimised cut-off values were observed. Risk stratification according to the 2019 European Society of Cardiology algorithm revealed no differences if calculated based on either hsTnI or hsTnT (p=0.68).Our findings confirm the prognostic role of hsTnI in normotensive PE. HsTnI concentrations >16 pg·mL−1 predicted in-hospital adverse outcome and all-cause mortality; sex-specific cut-off values do not seem necessary. Importantly, our results suggest that hsTnI and hsTnT can be used interchangeably for risk stratification.

The Performance of a Calcaneal Quantitative Ultrasound Device, CM-200, in Stratifying Osteoporosis Risk among Malaysian Population Aged 40 Years and Above.

Background: Calcaneal quantitative ultrasound (QUS) is widely used in osteoporosis screening, but the cut-off values for risk stratification remain unclear. This study validates the performance of a calcaneal QUS device (CM-200) using dual-energy X-ray absorptiometry (DXA) as the reference and establishes a new set of cut-off values for CM-200 in identifying subjects with osteoporosis. Methods: The bone health status of Malaysians aged ≥40 years was assessed using CM-200 and DXA. Sensitivity, specificity, area under the curve (AUC) and the optimal cut-off values for risk stratification of CM-200 were determined using receiver operating characteristic (ROC) curves and Youden’s index (J). Results: From the data of 786 subjects, CM-200 (QUS T-score <−1) showed a sensitivity of 82.1% (95% CI: 77.9–85.7%), specificity of 51.5% (95% CI: 46.5–56.6%) and AUC of 0.668 (95% CI: 0.630–0.706) in identifying subjects with suboptimal bone health (DXA T-score <−1) (p < 0.001). At QUS T-score ≤−2.5, CM-200 was ineffective in identifying subjects with osteoporosis (DXA T-score ≤−2.5) (sensitivity 14.4% (95% CI: 8.1–23.0%); specificity 96.1% (95% CI: 94.4–97.4%); AUC 0.553 (95% CI: 0.488–0.617); p > 0.05). Modified cut-off values for the QUS T-score improved the performance of CM-200 in identifying subjects with osteopenia (sensitivity 67.7% (95% CI: 62.8–72.3%); specificity 72.8% (95% CI: 68.1–77.2%); J = 0.405; AUC 0.702 (95% CI: 0.666–0.739); p < 0.001) and osteoporosis (sensitivity 79.4% (95% CI: 70.0–86.9%); specificity 61.8% (95% CI: 58.1–65.5%); J = 0.412; AUC 0.706 (95% CI: 0.654–0.758); p < 0.001). Conclusion: The modified cut-off values significantly improved the performance of CM-200 in identifying individuals with osteoporosis. Since these values are device-specific, optimization is necessary for accurate detection of individuals at risk for osteoporosis using QUS.

Prognostic significance of semi-quantitative FDG-PET parameters in stage I non-small cell lung cancer treated with carbon-ion radiotherapy

PurposePrognostic significance of volumetric 18F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cut-off values for risk stratification were assessed.MethodsThirty-nine patients (29 men and 10 women, 71.9 ± 8.3 years) who underwent FDG PET/CT examinations before C-ion RT were retrospectively evaluated. FDG-PET parameters: standardized uptake values (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinicopathological variables were assessed for prognosis using Cox proportional hazards regression analysis. Mann-Whitney test compared medians of significant parameters between adenocarcinoma (AC) and squamous cell carcinoma (SCC), and Kaplan-Meier curves were plotted for median-based low- and high-risk groups.ResultsMedian follow-up period was 44.8 months. 1/2/3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 94.9/84.3/70.8, 82.1/69.2/58.4 and 97.3/85.7/82.3%. Multivariate analysis revealed age (hazard ratio, HR: 1.09; 95% confidence interval, CI: 1.0–1.19, p < 0.05) and MTV (HR 4.83, 95% CI 1.21–19.27, p < 0.03) predicted OS, and only MTV predicted PFS (HR 5.3, CI 1.32–21.35, p < 0.02) independently. Compared with AC, SCC had higher MTV (median, 6.625cm3 vs 0.2 cm3, p < 0.01). Single MTV cut-off based on overall cohort was insignificant in SCC for PFS (p > 0.02); separate cut-offs of MTV, 0.2 cm3 for AC (p < 0.03) and 6.625 cm3 for SCC (p < 0.05) were relevant.ConclusionAmong all FDG PET/CT parameters, only MTV beared prognostic ability for stage I NSCLC treated with C-ion RT, and its histological variation may need consideration for risk-adapted therapeutic management.

Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer.

To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer

PurposeTo investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40–50–60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival –OS; disease free survival – DFS) was evaluated. ResultsThe categorized TLG40–50–60 were the only parameters related to FIGO stage I versus II-III-IV (p=0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p=0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40–50–60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50–60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p=0.0486). TLG50>77.58cm3 was the only variable associated with a higher risk of relapse (p=0.0472). ConclusionTLG40–50–60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

The clinical utility of shock index to predict the need for blood transfusion and outcomes in trauma

BackgroundWe aimed to evaluate the clinical utility of shock index (SI) to assess the need for blood transfusion and predict the outcomes in trauma. Materials and methodsWe conducted a retrospective analysis for trauma patients between 2012 and 2016 in a level-1 trauma center. Data included patient demographics, vital signs, mechanism of injury, Injury Severity Score (ISS), New Injury Severity Score (NISS), Trauma and Injury Severity Score (TRISS), blood transfusion, hospital length of stay (HLOS), and mortality. Patients were classified into group I (SI < 0.8) and group II (SI ≥ 0.8). ResultsOut of 8710 admitted patients, 1535 (22%) had SI ≥ 0.8 and 976 (12.5%) received blood transfusion (89 received massive transfusion, following massive blood transfusion protocol [MTP]). In comparison to lower SI, patients with SI ≥ 0.8 were mostly female patients, 8 y younger (43 ± 22 versus 51 ± 23), had greater ISS (15 ± 12 versus 10.5 ± 8), higher NISS (19 ± 15 versus 14 ± 11), lower pulse pressure (43 ± 14 versus 62 ± 18), lower TRISS (0.892 ± 0.20 versus 0.953 ± 0.11), and received more blood transfusion (28.6% versus 9.0%) or MTP (17.7% versus 3%), P = 0.001. Also, they had mostly exploratory laparotomy (13.3% versus 6.6%, P = 0.001), longer HLOS (11.3 versus 7.0 d, P = 0.001), and higher mortality (7.0% versus 3.1%, P = 0.001). SI was correlated with age (r = −0.188), pulse pressure (r = −0.51), HLOS (r = 0.168), ISS (r = 0.251), NISS (r = 0.211), amount of blood transfused (r = 0.27), Glasgow Coma Scale (r = −0.96), and TRISS (r = −0.230). After adjusting for age and sex, ISS, and Glasgow Coma Scale in two multivariable analyses, high SI was found to be an independent predictor for mortality (odd ratio, 2.553; 95% confidence intervals: 1.604-4.062) and blood transfusion (odd ratio, 3.57; 95% confidence intervals: 3.012-4.239). The cutoff point of SI for predicting MTP is 0.81 (sensitivity, 85%; specificity, 64%; positive predictive value, 16%; and negative predictive value, 98%). ConclusionsThe SI after injury can be used early to predict the need for MTP and laparotomy and mortality. It correlates with other physiological and anatomical variables. However, its cutoff values for risk stratification and prognostication need further evaluation.

Evaluation of Quantra Hologic Volumetric Computerized Breast Density Software in Comparison With Manual Interpretation in a Diverse Population.

Objective:Increased mammographic breast density is a well-established risk factor for breast cancer development, regardless of age or ethnic background. The current gold standard for categorizing breast density consists of a radiologist estimation of percent density according to the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) criteria. This study compares paired qualitative interpretations of breast density on digital mammograms with quantitative measurement of density using Hologic’s Food and Drug Administration–approved R2 Quantra volumetric breast density assessment tool. Our goal was to find the best cutoff value of Quantra-calculated breast density for stratifying patients accurately into high-risk and low-risk breast density categories.Methods:Screening digital mammograms from 385 subjects, aged 18 to 64 years, were evaluated. These mammograms were interpreted by a radiologist using the ACR’s BI-RADS density method, and had quantitative density measured using the R2 Quantra breast density assessment tool. The appropriate cutoff for breast density–based risk stratification using Quantra software was calculated using manually determined BI-RADS scores as a gold standard, in which scores of D3/D4 denoted high-risk densities and D1/D2 denoted low-risk densities.Results:The best cutoff value for risk stratification using Quantra-calculated breast density was found to be 14.0%, yielding a sensitivity of 65%, specificity of 77%, and positive and negative predictive values of 75% and 69%, respectively. Under bootstrap analysis, the best cutoff value had a mean ± SD of 13.70% ± 0.89%.Conclusions:Our study is the first to publish on a North American population that assesses the accuracy of the R2 Quantra system at breast density stratification. Quantitative breast density measures will improve accuracy and reliability of density determination, assisting future researchers to accurately calculate breast cancer risks associated with density increase.

Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of pulmonary embolism.

High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk of an adverse outcome. In 682 normotensive pulmonary embolism patients we investigate whether an optimised hsTnT cut-off value and adjustment for age improve the identification of patients at elevated risk. Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT cut-off value of 14 pg·mL(-1) retained its high prognostic value (OR (95% CI) 16.64 (2.24-123.74); p=0.006) compared with the cut-off value of 33 pg·mL(-1) calculated by receiver operating characteristic analysis (7.14 (2.64-19.26); p<0.001). In elderly (aged ≥75 years) patients, an age-optimised hsTnT cut-off value of 45 pg·mL(-1) but not the established cut-off value of 14 pg·mL(-1) predicted an adverse outcome. An age-adjusted hsTnT cut-off value (≥14 pg·mL(-1) for patients aged <75 years and ≥45 pg·mL(-1) for patients aged ≥75 years) provided additive and independent prognostic information on top of the simplified pulmonary embolism severity index (sPESI) and echocardiography (OR 4.56 (1.30-16.01); p=0.018, C-index=0.77). A three-step approach based on the sPESI, hsTnT and echocardiography identified 16.6% of all patients as being at higher risk (12.4% adverse outcome). Risk assessment of normotensive pulmonary embolism patients was improved by the introduction of an age-adjusted hsTnT cut-off value. A three-step approach helped identify patients at higher risk of an adverse outcome who might benefit from advanced therapy.

Ki67 as a Biomarker of Prognosis and Prediction: Is it Ready for Use in Routine Pathology Practice?

Breast cancer is the most common cancer in women, and the search for effective markers to design therapeutic strategies and patient management algorithms is still a work in progress. Ki67, a proliferative marker, has gained attention as a prognostic and predictive factor in early breast cancer and/or to decide response to chemotherapy. Individual studies and meta-analyses have provided evidence of its usefulness in this regard. Immunohistochemical staining Ki67 has emerged as an easy and cheap tool to assess proliferation in laboratory setting. However, debate continues over its meaningful clinical use, given the lack of standardization of staining techniques and firm recommendations about pre-analytical tissue handling, interpretation of the stain, and methods to estimate Ki67, resulting in high interlaboratory and interobserver variability. Importantly, no consensus has been reached on the cut-off values for risk stratification. The Breast Cancer Working Group proposed guidelines for immunohistochemical evaluation of Ki67 in 2011. However, the follow-up study showed poor reproducibility even among experts, and the use of Ki67 in daily practice is still in question.

Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism

The optimal N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off value for risk stratification of pulmonary embolism remains controversial. In this study we validated and compared different proposed NT-proBNP cut-off values in 688 normotensive patients with pulmonary embolism. During the first 30 days, 28 (4.1%) patients reached the primary outcome (pulmonary embolism-related death or complications) and 29 (4.2%) patients died. Receiver operating characteristic analysis yielded an area under the curve of 0.70 (0.60-0.80) for NT-proBNP. A cut-off value of 600 pg·mL(-1) was associated with the best prognostic performance (sensitivity 86% and specificity 50%) and the highest odds ratio (6.04 (95% CI 2.07-17.59), p=0.001) compared to the cut-off values of 1000, 500 or 300 pg·mL(-1). Using multivariable logistic regression analysis, NT-proBNP ≥ 600 pg·mL(-1) had a prognostic impact on top of that of the simplified Pulmonary Embolism Severity Index and right ventricular dysfunction on echocardiography (OR 4.27 (95% CI 1.22-15.01); p=0.024, c-index 0.741). The use of a stepwise approach based on the simplified Pulmonary Embolism Severity Index, NT-proBNP ≥ 600 pg·mL(-1) and echocardiography helped optimise risk assessment. Our findings confirm the prognostic value of NT-proBNP and suggest that a cut-off value of 600 pg·mL(-1) is most appropriate for risk stratification of normotensive patients with pulmonary embolism. NT-proBNP should be used in combination with a clinical score and an imaging procedure for detecting right ventricular dysfunction.

Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment

Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on beta-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26-75 months). Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879-0.975; chi(2): 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P=0.02, for patients not on BBL and 4.3 versus 16.2%, P<0.001, for patients on BBL. This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.