Objective Risk Stratification Research Articles

The use of longitudinal hemoglobin A1c values to predict adverse obstetric and neonatal outcomes in pregnancies complicated by pregestational diabetes

Although an elevated early pregnancy hemoglobin A1c has been associated with both spontaneous abortion and congenital anomalies, it is unclear whether A1c assessment is of value beyond the first trimester in pregnancies complicated by pregestational diabetes. We sought to investigate the prognostic ability of longitudinal A1c assessment to predict obstetric and neonatal adverse outcomes based on degree of glycemic control in early and late pregnancy. This was a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016 at The Ohio State University Wexner Medical Center with both an early A1c (<20 weeks' gestation) and late A1c (>26 weeks' gestation) available for analysis. Patients were categorized by good (early and late A1c <6.5%), improved (early A1c >6.5% and late A1c <6.5%) and poor (late A1c >6.5%) glycemic control. A multivariate regression model was used to calculate adjusted odds ratios (aOR) for each identified obstetric and neonatal outcome, controlling for maternal age, body mass index, race/ethnicity, type of diabetes, and gestational age at delivery compared to good control as the referent group. A total of 341 patients met inclusion criteria during the study period. The median A1c values improved from early to late gestation in the good (5.7% [interquartile range [IQR], 5.4-6.1%] versus 5.4%; [IQR 5.2-5.7%]), improved (7.5% [IQR, 6.7-8.5] versus 5.9% [IQR, 5.6-6.1%]) and poor (8.3% [IQR, 7.1-9.6%] versus 7.3% [IQR, 6.8-7.9%]) glycemic control groups. There were no statistically significant differences in the rate of adverse outcomes between the goodand improved groups except for an increased rate of neonatal intensive care unit admissions in the improved group (aOR, 3.7; confidence interval [CI], 1.9-7.3). In contrast, the poor control group hadanincreased rate of shoulder dystocia (aOR, 6.8; CI, 1.4-34.0), preterm delivery (aOR, 3.9; CI, 2.1-7.3), neonatal intensive care unit admission (aOR, 2.8; CI, 1.4-5.3), respiratory distress syndrome (aOR, 3.0; CI, 1.1-8.0), hypoglycemia (aOR, 3.2; CI, 1.5-6.9), large for gestational age weight at birth (aOR, 2.7; CI, 1.5-4.9), neonatal length of stay >4 days (aOR, 3.1; CI, 1.6-6.0) and preeclampsia (aOR, 2.4; CI, 1.2-4.6). There were no differences in rates of cesarean delivery, umbilical artery pH <7.1, or Apgar score <7 at 5 minutes after regression analysis. Antenatal hemoglobin A1c values are useful for objective risk stratification of patients with pregestational diabetes. Strict glycemic control throughout pregnancy with a late pregnancy A1c target of <6.5% leads to reduced rates of obstetric and neonatal adverse outcomes independent of early pregnancy glucose control.

372 An Automated, Quantitative Multiplex Immunofluorescence Assay Accurately Risk Stratifies Barrett’s Esophagus Patients With a Community-Based Diagnosis of Low-Grade Dysplasia at a Rate Comparable to Expert Pathologists

INTRODUCTION: The majority of community-based LGD diagnoses are down-staged to non-dysplastic (ND) BE when reviewed by an expert pathologist, whereas patients with confirmed LGD have a 10% annual risk of progression to high-grade dysplasia (HGD) or cancer (Ca). Although recommended by guidelines, expert review is poorly defined, prone to observer variation, and not widely available. Recent studies suggest that an automated, quantitative multiplex immunofluorescence assay may identify NDBE patients with an increased risk of malignant progression. We investigated if this assay also allows objective risk stratification for cases with a community-based diagnosis of LGD at a rate comparable to expert pathologists. METHODS: A blinded nested case-control cohort was derived from the screening cohort of a randomized controlled trial of SUrveillance vs. RadioFrequency ablation (SURF) for BE patients with LGD. 60 patients with a community-based diagnosis of LGD of whom 30 progressed to HGD/Ca and 30 patients who did not progress were matched for age, sex and maximal BE length. All random biopsy levels of the baseline endoscopy were independently reviewed by 3 expert pathologists with an international reputation. All levels were additionally tested by a multiplex biomarker assay. The assay classifies patients into low-risk (LR), intermediate-risk (IR) and high-risk (HR) for progression to HGD/Ca within 5 years. A histological revision diagnosis of NDBE was considered as low- (LR), while indefinite for dysplasia (IND) and LGD were considered as high-risk (HR) for progression. RESULTS: 60 BE patients (52 male), mean age 63 ± 9 years, were studied. Median time between baseline endoscopy and progression was 2.5 years (1.3-5.4). Accuracy, sensitivity and specificity of the biomarker assay vs. the 3 expert pathologists were 73% vs 72-77%, 66% vs 77-80% and 80% vs 63-77%, respectively. 20/26 (78%) patients classified as IR/HR by the biomarker panel and 69-77% classified as HR (IND/LGD) by the 3 expert pathologists progressed to HGD/Ca. CONCLUSION: A quantitative multiplex immunofluorescence assay risk stratified BE patients with a community-based diagnosis of LGD with an accuracy comparable to three renowned expert pathologists. The assay allows for automated, objective risk stratification which may be a practical and effective solution to the lack of standardization of expert pathology review of LGD as advocated by all guidelines.

371 Evaluation of Additional Spatial and Temporal Information Increases the Overall Accuracy of an Objective Risk Prediction Assay in Patients With Non-Dysplastic Barrett’s Esophagus

INTRODUCTION: An automated, quantitative multiplex immunofluorescence assay has previously been shown to objectively identify non-dysplastic Barrett’s esophagus (NDBE) patients with an increased risk of malignant progression, independently of current clinical variables. These studies evaluated esophageal biopsies from a single level from one endoscopy. We investigated the results produced by this risk prediction assay at multiple endoscopic levels and multiple endoscopies in NDBE patients to determine whether assessment of additional spatial and temporal information can increase the accuracy of the assayin predicting progression from NDBE to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: A blinded, nested case-control cohort was derived from a community based BE cohort with and without progression. 76 patients with a diagnosis of NDBE of whom 38 progressed to HGD/EAC (progressors) and 38 patients did not progress (non-progressors) were matched for age, sex and maximal BE length. Baseline was defined as the endoscopy 2-5 years prior to the endpoint for progressors or last follow up for non-progressors. All random biopsy levels from the baseline endoscopy and all available prior endoscopies were retrieved and tested by the risk predictionassay in a blinded manner. The assay classifies patients into low-risk (LR), intermediate-risk (IR) and high-risk (HR) for progression to HGD/EAC within 5 years. RESULTS: 76 BE patients (58 male), mean age 63 ± 1 years, were studied. Median time between baseline endoscopy and progression was 3 years, and median surveillance time in non-progressors was 6 years. Sensitivity of the risk prediction assay (HR and IR combined vs. LR) at the baseline endoscopy was 39.5 % when a single biopsy level was selected for risk assessment (biopsy closest to the gastroesophageal junction (GEJ)). Sensitivity increased to 65.8% when all available baseline biopsy levels were assessed, and further increased to 73.7% when all available baseline and pre-baseline biopsies were assessed by the risk prediction assay (Table 1). CONCLUSION: Evaluation of spatial and temporal information increases the sensitivity and overall accuracy of an automated, quantitative risk prediction assay in patients with NDBE. The assay allows for objective risk stratification which may be a practical and effective solution to aid decision-making on surveillance intervals and therapeutic interventions in the management of NDBE patients.

Objective risk stratification of prostate cancer using machine learning and radiomics applied to multiparametric magnetic resonance images

Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), but its interpretation is generally variable due to its relatively subjective nature. Radiomics and classification methods have shown potential for improving the accuracy and objectivity of mpMRI-based PCa assessment. However, these studies are limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and classification methods. This paper presents a systematic and rigorous framework comprised of classification, cross-validation and statistical analyses that was developed to identify the best performing classifier for PCa risk stratification based on mpMRI-derived radiomic features derived from a sizeable cohort. This classifier performed well in an independent validation set, including performing better than PI-RADS v2 in some aspects, indicating the value of objectively interpreting mpMRI images using radiomics and classification methods for PCa risk assessment.

Objective risk stratification of prostate cancer using machine learning and radiomics applied to multiparametric magnetic resonance images

Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), but its interpretation is generally variable due to its relatively subjective nature. Radiomics and classification methods have shown potential for improving the accuracy and objectivity of mpMRI-based PCa assessment. However, these studies are limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and classification methods. This paper presents a systematic and rigorous framework comprised of classification, cross-validation and statistical analyses that was developed to identify the best performing classifier for PCa risk stratification based on mpMRI-derived radiomic features derived from a sizeable cohort. This classifier performed well in an independent validation set, including performing better than PI-RADS v2 in some aspects, indicating the value of objectively interpreting mpMRI images using radiomics and classification methods for PCa risk assessment.

Risk assessment and survival of patients with pulmonary hypertension: Multicenter experience in Turkey.

Objective:Risk stratification continues to evolve in pulmonary arterial hypertension (PAH). Our aim was to further confirm the risk assessment strategy in our cohort and to determine the most reliable model.Methods:We enrolled incident patients with idiopathic PAH (IPAH), heritable, drug-induced, congenital heart disease (CHD), connective tissue diseases (CTD) subsets, and chronic thromboembolic pulmonary hypertension (CTEPH) from January 2008 to February 2018. Data from the baseline and subsequent follow-ups within 1 year of diagnosis were included. An abbreviated risk assessment strategy was applied using the following variables: functional class (FC), 6-minute walk distance (6 MWD), N-terminal pro–brain natriuretic peptide (NT-proBNP) or BNP, right atrial (RA) area, pericardial effusion, the mean RA pressure, cardiac index, and mixed venous oxygen saturation. Three different methods were applied to categorize patients.Results:A total of 189 subjects (46±17 years, 23% male) were included. Sixty-one patients had died. The survival differed significantly between the risk groups both at diagnosis and during the follow-up. Patients with a low-risk profile had a better survival rate. An abbreviated risk assessment tool predicted mortality at early follow-up in the entire group and CHD, CTD subsets, and CTEPH, separately. An overall mortality among risk categories was significantly different according to each categorization method. The most reliable model comprised FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up.Conclusion:The abbreviated risk assessment tool may be valid for the PAH subsets and CTEPH. Echocardiographic variables do matter. A model comprising FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up could be useful for better prognostication.

Use of Venous Thromboembolism Prophylaxis in Hospitalized Patients

National guidelines1 recommend objective risk stratification for venous thromboembolism (VTE) in hospitalized medical patients. The Padua Prediction Score risk assessment model2 is recommended to categorize patients as high or low risk. The Michigan Hospital Medicine Safety Consortium (HMS), a statewide quality collaborative aimed at preventing adverse events in hospitalized medical patients, collects detailed data on VTE risk factors, prophylactic treatment, and outcomes. Using data from the HMS,3 we sought to determine whether patients in this cohort were receiving appropriate VTE prophylaxis.

Recursive partitioning analysis is predictive of overall survival for patients undergoing spine stereotactic radiosurgery

Spine stereotactic radiosurgery (SRS) offers excellent radiographic and pain control for patients with spine metastases. We created a prognostic index using recursive partitioning analysis (RPA) to allow better patient selection for spine SRS. Patients who underwent single-fraction spine SRS for spine metastases were included. Primary histologies were divided into favorable (breast/prostate), radioresistant (renal cell/sarcoma/melanoma) and other. Cox proportional hazards regression was done to identify factors associated with overall survival (OS). RPA was performed to identify factors to classify patients into distinct risk groups with respect to OS. A total of 444 patients were eligible. Median dose was 16Gy (range 8-18) in 1 fraction and median follow-up was 11.7months. At time of analysis, 103 (23.1%) patients were alive. Median OS was 12.9months. RPA identified three distinct classes. Class 1 was defined as KPS > 70 with controlled systemic disease (n = 142); class 3 was defined as KPS ≤ 70 and age < 54years or KPS ≤ 70 age ≥ 54years and presence of visceral metastases (n = 95); all remaining patients comprise class 2 (n = 207). Median overall survival was 26.7months for class 1, 13.4months for class 2, and 4.5months for class 3 (p < 0.01). Our analysis demonstrates that there is considerably variability in survival among patients undergoing spine SRS. We created an objective risk stratification via RPA for spine SRS. Given the safety and efficacy of spine SRS and good survival in class 1 and 2 patients, this RPA can help clinicians identify patients who may benefit from upfront spine SRS.

Multimodal Prehabilitation Programs as a Bundle of Care in Gastrointestinal Cancer Surgery: A Systematic Review.

Prehabilitation reflects a proactive process of preoperative optimization undertaken between cancer diagnosis and definitive surgical treatment, with the intent of improving physiological capacity to withstand the major insult of surgery. Prehabilitation before GI cancer surgery is currently not widely adopted, and most research has focused on unimodal interventions such as exercise therapy, nutritional supplementation, and hematinic optimization. A review of the existing literature was undertaken to investigate the impact of multimodal prehabilitation programs as a "bundle of care." A systematic literature search was performed utilizing Medline, PubMed, Embase, Cinahl, Cochrane, and Google Scholar databases. The quality of studies was assessed by using the Cochrane tool for assessing risk of bias (randomized trials) and the Newcastle-Ottawa Quality Assessment scale (cohort studies). Studies were chosen that involved pre-operative optimization of patients before GI cancer surgery. The primary outcome measured was the impact of prehabilitation programs on preoperative fitness and postoperative outcomes. Of the 544 studies identified, 20 were included in the qualitative analysis. Two trials investigated the impact of multimodal prehabilitation (exercise, nutritional supplementation, anxiety management). Trials exploring prehabilitation with unimodal interventions included impact of exercise therapy (7 trials), impact of preoperative iron replacement (5 trials), nutritional optimization (5 trials), and impact of preoperative smoking cessation (2 trials). Compliance within the identified studies was variable (range: 16%-100%). There is a lack of adequately powered trials that utilize objective risk stratification and uniform end points. As such, a meta-analysis was not performed because of the heterogeneity in study design. Although small studies are supportive of multimodal interventions, there are insufficient data to make a conclusion about the integration of prehabilitation in GI cancer surgery as a bundle of care. Larger, prospective trials, utilizing uniform objective risk stratification and structured interventions, with predefined clinical and health economic end points, are required before definitive value can be assigned to prehabilitation programs.

Combined Measurement of Soluble ST2 and Amino-Terminal Pro-B-Type Natriuretic Peptide Provides Early Assessment of Severity in Cardiogenic Shock Complicating Acute Coronary Syndrome.

Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock. CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality. Nine tertiary care university hospitals. Patients with cardiogenic shock caused by acute coronary syndrome (n=145). In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement. The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients. The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

Strategy to achieve biomarker-driven immunosuppression after solid organ transplantation by an academic-industry partnership within the European BIO-DrIM consortium

Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost unchanged and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high allo-responsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppress- ion to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.

Strategy to achieve biomarker-driven immunosuppression after solid organ transplantation by an academic-industry partnership within the European BIO-DrIM consortium

Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost un-changed and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high alloresponsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppression to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.

Evaluation of the new simple and objective clinical decision rule “I-DVT” in patients with clinically suspected acute deep vein thrombosis

IntroductionThe Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DVT). However, it is often incorrectly used leading to an excessive number of diagnostic tests used in daily practice and diagnostic failures. A simpler objective risk stratification tool may improve adherence to the guidelines. We evaluated the diagnostic performance of the I-DVT score, which consists of four easy assessable variables: Immobilization, >3cm Difference in calve circumferences, prior Venous thromboembolism (VTE) and active malignant Tumor. MethodsWe performed an observational study in 617 consecutive patients with suspected DVT. All patients were managed according to the recommended algorithm starting with the Wells rule followed by D-dimer test and/or compression ultrasonography (CUS). The I-DVT score was prospectively calculated at baseline and evaluated post-hoc. ResultsThe DVT prevalence was 36%. DVT could be excluded in 13% of patients without CUS by the Wells rule and a normal D-dimer test, with a 3-month VTE incidence of 1.2% (95%CI 0.03–6.5%). Using the I-DVT score, DVT would have been excluded in 9.1% of patients without additional CUS, with a 3-month VTE incidence of 0% (95%CI 0.0–6.4%). The area under the ROC curve (AUC) was 0.70 (95%CI 0.66–0.74) and 0.65 (95%CI 0.61–0.70) for the Wells rule and I-DVT score respectively (difference 0.049, 95%CI −0.01–0.11; p=0.13). ConclusionsThe simple I-DVT score and Wells rule have comparable diagnostic accuracy. It's safety, efficiency and associated potential improvement of guideline adherence in clinical practice has to be further evaluated in a prospective management study.

Implementing the Surgical Apgar Score in patients with trauma hip fracture

Trauma hip fractures in elderly patients are associated with high postoperative long-term morbidity and mortality and premature death. The high mortality in these patients can be explained by various factors, including the fracture itself; the preoperative poor condition and comorbidities of these patients; the influence of stressors, such as surgery and type of anaesthesia, on the patient's condition; and the postoperative development of major complications, such as cardiac failure, pulmonary embolism, pneumonia, deep venous thrombosis and acute renal failure. Thus, the Surgical Apgar Score (SAS) could be a valuable tool for objective risk stratification of patients immediately after surgery, and to enable patients with higher risk to receive postoperative ICU care and good management both during and after the hospital stay. The SAS was calculated retrospectively from the handwritten anaesthesia records of 43 trauma hip fracture patients treated operatively in the University Hospital Centre Zagreb over a 1-year period. The primary endpoints were the 30-days major postoperative complications and mortality, length of the ICU and hospital stay, and 6-months major complications development. Statistical analysis was applied to compare SAS with the patients' perioperative variables. A SAS≤4 in the trauma hip fracture patients was a significant predictor for the 30-days major postoperative complications with 80% specificity (95% CI: 0.587-0.864, p=0.0111). However, the SAS was not significant in the prediction of 30-days mortality (95% CI: 0.468-0.771, p=0.2238) and 6-months mortality (95% CI: 0.497-0.795, p=0.3997) as primary endpoints in the hip fracture surgery patients. The SAS shows how intraoperative events affect postoperative outcomes. Calculating the SAS in the operating theatre provides immediate, reliable, real-time feedback information about patient postoperative risk. The results of this study indicate that all trauma hip fracture patients with SAS≤4 should go to the ICU postoperatively and should be under intensive surveillance both during the hospital stay and after hospital discharge.

A cluster randomized trial of objective risk assessment versus standard care for acute coronary syndromes: Rationale and design of the Australian GRACE Risk score Intervention Study (AGRIS)

Assessing risk and weighing the potential benefits from evidence-based therapies are essential in the clinical decision making process of optimizing care and outcomes for patients presenting with acute coronary syndromes (ACS). Such practices are advocated in international clinical guidelines of ACS care. While the GRACE risk score (GRS) is a guideline advocated, well-validated risk stratification tool, its utility in improving care and outcomes remains unproven, and its application has been limited in routine clinical practice. This study will assess the effectiveness using the GRS tool and treatment recommendations during patient assessment on improving the application of guideline-recommended therapies in ACS care. This study employs a PROBE (prospective cluster [hospital-level] randomized open-label, blinded endpoint) design to evaluate objective measures of hospital performance, with clinical events adjudicated by a blinded event committee. This randomized study is nested within the established CONCORDANCE registry of ACS patients, with existing methods for data collection and monitoring of care and clinical outcomes. The hospital-level intervention is the integration of the GRS into routine ACS patient assessment process. The study will assess the use of early invasive management, prescription of guideline recommended pharmacology and referral to cardiac rehabilitation by hospital discharge; with the key composite clinical endpoint of cardiovascular death, new or recurrent myocardial infarction, in-hospital heart failure or cardiovascular readmission at 12 months. Health economic impacts of risk stratification implementation will also be evaluated. The study will recruit 3000 patients from 30 hospitals. The AGRIS trial will establish the effect of routine objective risk stratification using the GRACE risk score on ACS care and clinical outcomes.

Simple and Objective Prediction of Survival in Patients with Lung Cancer: Staging the Host Systemic Inflammatory Response.

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer.

Prognostic significance of a multimarker strategy of biomarkers in acute heart failure.

Heart failure (HF) is a growing public health problem. Patients often present to emergency department (ED) with acute onset dyspnea where a rapid triage is required to avoid misdiagnosis and to institute appropriate therapy. An objective risk-stratification in the ED is warranted to identify patients at high risk of adverse outcomes, so that more intensive therapy and vigilant follow-up after discharge are instituted. Fifty two consecutive acute HF (AHF) patients in NYHA class III/IV were enrolled for the present study. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hsTropT), high-sensitivity C-reactive protein (hsCRP) and Uric acid (UA) were evaluated at admission; a second sample for NT-proBNP and hsTropT was obtained 48h later. The end-point of the study, a composite of cardiovascular death, rehospitalisation for worsening HF symptoms and refractory HF was reached in 32.7% of patients during a median follow-up of 4.8mnth. Although, hsTropT (>0.014ng/ml), hsCRP (>0.5mg/dl) and UA (>5.6mg/dl for females and >7 mg/dl for males) were elevated in the vast majority of patients (92.3%, 75% and 63.5% respectively), baseline and changing patterns of NT-proBNP following treatment were the only predictors of adverse outcomes on follow-up. A significant correlation between hsTropT, hsCRP and UA was observed suggesting a link between inflammation, myocyte injury and oxidative stress in AHF. Baseline and changing patterns of NT-proBNP predicted adverse outcomes on follow-up suggesting that a strategy of serial measurement of NT-proBNP could prove invaluable in early risk stratification. Further research is needed to understand the link between inflammation, myocyte injury and oxidative stress in AHF which could provide potential therapeutic targets.

Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndromes

Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain. The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%-35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772-0.851] versus physician, 0.652 [95% confidence interval, 0.596-0.708]; P<0.0001). The GRACE score added to clinician intuition improved discrimination (integrated discrimination improvement, 0.0632 [SE, 0.012]; P<0.0001). Invasive management correlated with physician-estimated risk but not with GRACE risk. Among patients not at high risk by physician estimation, increased risk by GRACE score was associated with higher mortality (3.7% versus 0.8%; P<0.001). Objective risk assessment provides superior risk discrimination when compared with physician-estimated risk. Whether systematic use of objective risk stratification improves clinical outcomes should be studied in appropriately designed clinical trials.

Risk stratifi cation models in elderly patients: recalibrating or remodeling?

Objective Risk stratifi cation models perform poorly regarding elderly patients. This study aims to evaluate the performance of the Italian Coronary Artery Bypass Graft Outcome Project (ItCABG) model and the logistic European System for Cardiac Operative Risk Evaluation (LogEuroSCORE) model by age group to build a model specifi cally for elderly patients.Methods and results Data from the ItCABG and Mattone Outcome-BYPASS study (MO-BYPASS) have been used. ItCABG and LogEuroSCORE models were applied to the ItCABG population (n = 34,310) stratifi ed by four age classes: < 60, 60-69, 70-79, ≥ 80 years. Each model’s ability to predict 30-day mortality was assessed for accuracy (Brier score and pseudo-R2), calibration (Hosmer-Lemeshow test, χH-L) and discrimination (area under the receiver operating characteristic curve, AUC) in age classes. To estimate the elderly risk function a logistic regression was performed on 2,255 octogenarian patients from ItCABG and MO-BYPASS. Elderly model’s performance was tested. Model accuracy is fair in all age classes although the explained variance is poor. ItCABG and LogEuroSCORE models revealed good discrimination power in patients aged < 60, 60-69, and 70-79 years, but not in patients aged ≥ 80 years (AUCs: 0.82, 0.77, 0.76, 0.64, and 0.78, 0.75, 0.74, 0.65, respectively). Calibration of both models is poor in patients ≥ 80 years (ItCABG: χMH-L= 18.1, P= 0.05; LogEuroSCORE: χH-L= 129.7, P< 0.001). When a new model specifi c to octogenarian patients was built, discrimination power remained poor (AUC = 0.66), although calibration power improved (χH-L= 3.93, P= 0.86).Conclusions ItCABG and LogEuroSCORE models were poor predictors of mortality in octogenarian patients. Elderly-specifi c risk factors must be assessed to improve risk stratifi cation in patients aged 80 years and older.

P16INK4a- und Ki-67-Immunzytochemie als Zusatzmethode für die Gruppe IIID der gynäkologischen Zytologie

Especially the cytological diagnoses of mild and moderate dysplasia are often followed by unnecessary stigmatization of patients and uncertainty in further clinical follow-up and therapy. Data from 222patients including additional investigations by high-risk human papillomavirus (HPV) testing and combined immunocytochemistry for p16(INK4a) and Ki-67 were documented, including cytological and histological follow-up. Overall for cytology, high risk HPV testing and dual staining the following characteristics concerning the presence of cervical intraepithelial neoplasia (CIN)2+ were calculated (in %): sensitivity 100, 95.8 and 92.4, specificity -, 23.3 and 72.8, positive predictive value 53.6, 59.1 and 79.7, negative predictive value -, 82.8 and 89.3, respectively.There was a statistically significant advantage for higher specificity and positive predictive value for dual staining, especially for cytological diagnosis of low grade dysplasia. An objective individual risk stratification of patients with cytology of mild or moderate dysplasia is not available but the uncertainty in the management of these patients will be clearly reduced.