Prognostic Cut-off Value Research Articles

Serum levels of soluble B and T lymphocyte attenuator predict overall survival in patients undergoing immune checkpoint inhibitor therapy for solid malignancies.

Therapy with immune checkpoint inhibitors (ICIs) can lead to durable tumor control in patients with various advanced stage malignancies. However, this is not the case for all patients, leading to an ongoing search for biomarkers predicting response and outcome to ICI. The B and T lymphocyte attenuator (BTLA) is an immune checkpoint expressed on immune cells that was shown to modulate therapeutic responses. Here, we evaluate circulating levels of its soluble form, soluble B and T lymphocyte attenuator (sBTLA), as a biomarker for the prediction of treatment response and outcome to ICI therapy. Serum levels of sBTLA were analyzed by multiplex immunoassay in n=84 patients receiving ICI therapy for solid malignancies and 32 healthy controls. BTLA expression was evaluated on peripheral blood mononuclear cells in a subset of patients (n=6) using multicolor flow cytometry. Baseline sBTLA serum levels were significantly higher in cancer patients compared to healthy controls. Importantly, circulating sBTLA levels were an independent prognostic factor for overall survival (OS). As such, patients with initial sBTLA levels above the calculated prognostic cutoff value (311.64 pg/mL) had a median OS of only 138 days compared to 526 for patients with sBTLA levels below this value (P= .001). Uni- and multivariate Cox regression analyses confirmed the prognostic role of sBTLA in the context of ICI therapy. Finally, we observed a significant correlation between sBTLA levels and the frequency of CD3 + CD8 + BTLA+ T cells in peripheral blood. Thus, our data suggest that circulating sBTLA could represent a noninvasive biomarker to predict outcome to ICI therapy, helping to select eligible therapy candidates.

The relationship between evolving sarcopenia and efficacy of immune checkpoint inhibitor in non-small cell lung cancer patients.

e21049 Background: Sarcopenia has been receiving attention due to its association with prognoses in patients with cancer. We investigated the association between evolving sarcopenia assessed with computed tomography (CT) and outcome of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Methods: In this retrospective study, 47 NSCLC patients who received ICIs at our Hirosaki University Hospital were enrolled. Skeletal muscle area at the level of the third lumbar vertebra (L3-SMA) was measured from CT images before and 90 days after the ICI treatment. The factor related to the poor efficacy of ICIs was determined by logistic regression analysis. The prognostic cut-off value was estimated by a receiver operating characteristic (ROC) curve. As covariate factors, age, gender, smoking history, histology, performance status (PS), PD-L1 tumor proportion score (TPS), status of driver mutations, body mass index (BMI), serum protein and albumin levels, and lymphocyte count were included. Results: In the univariate analysis, reduction rate of L3-SMA, PS, BMI, serum protein and albumin levels, and lymphocyte count were significantly associated with efficacy. In the multivariate analysis, only reduction rate of L3-SMA was significant. The cut-off value was estimated to be 6%. The study subjects were divided into two groups by the cut-off value. In both of progression free and overall survival analysis, those with more than 6% of reduction had significantly shorter period being free of events than that of the other. Conclusions: Evolving sarcopenia assessed with CT images is promising as a prognostic factor in Japanese NSCLC patients receiving ICIs.

Impact of the preoperative prognostic nutritional index as a predictor for postoperative complications after resection of locally recurrent rectal cancer

BackgroundLocal recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer.MethodsThis retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves.ResultsSevere postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171–8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044–6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications.ConclusionsWe found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy.

BackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation, whose levels are prognostic in various cancers. We evaluated circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors.MethodsA total of n = 87 patients receiving ICI therapy for different solid malignancies as well as 32 healthy controls were included into this study. Serum levels of suPAR were measured by ELISA prior to and sequentially at two time points during ICI therapy.ResultsBaseline suPAR serum levels were significantly higher in solid tumor patients compared to healthy controls. Importantly, patients with low suPAR levels both before or during ICI treatment were more likely to have a favorable response to treatment at three and six months, respectively. This finding was confirmed by multivariate binary logistic regression analysis including several clinicopathological parameters. Moreover, circulating suPAR levels before and during therapy were an independent prognostic factor for overall survival (OS). As such, patients with initial suPAR levels above our ideal prognostic cut-off value (4.86 ng/ml) had a median OS of only 160 days compared to 705 days for patients with suPAR levels below this cut-off value. Finally, low baseline suPAR levels identified a subgroup of patients who experienced ICI-related side effects which in turn were associated with favorable treatment response and outcome.ConclusionOur data suggest that measurements of suPAR serum levels are a previously unknown, easily accessible tool to predict individual treatment response and outcome to ICI therapy. Circulating suPAR might therefore be implemented into stratification algorithms to identify the ideal candidates for ICI treatment.

Neuron-specific enolase concentrations for the prediction of poor prognosis of comatose patients after out-of-hospital cardiac arrest: an observational cohort study.

Neuron-specific enolase (NSE) is a biomarker for neurological outcomes after cardiac arrest with the most evidence collected thus far; however, recommended prognostic cutoff values are lacking owing to the discrepancies in the published data. The aim of the study was to establish NSE cutoff values for prognostication in the environment of a cardiac intensive care unit following out-of-hospital cardiac arrest (OHCA). A consecutive series of 82 patients admitted after OHCA were enrolled. Blood samples for the measurement of NSE levels were collected at admission and after 1 hour, 3, 12, 24, 48, and 72 hours. Neurological outcomes were quantified using the cerebral performance category (CPC) index. Each patient was classified into either the good (CPC ≤2) or poor prognosis (CPC ≥3) group. Median NSE concentrations were higher in the poor prognosis group, and the difference reached statistical significance at 48 and 74 hours (84.4 ng/ml vs 22.9 ng/ml at 48 hours and 152.1 ng/ml vs 18.7 ng/ml at 72 hours; P <0.001, respectively). Moreover, in the poor prognosis group, NSE increased significantly between 24 and 72 hours (P <0.001). NSE cutoffs for the prediction of poor prognosis after OHCA were 39.8 ng/ml, 78.7 ng/ml, and 46.2 ng/ml for 24, 48, and 72 hours, respectively. The areas under the curve were significant at each time point, with the highest values at 48 and 72 hours after admission (0.849 and 0.964, respectively). Elevated NSE concentrations with a rise in levels in serial measurements may be utilized in the prognostication algorithm after OHCA.

Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC.

BackgroundEarly detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC.MethodsThe Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data.ResultsA high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119).ConclusionTumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.

The Prognostic Performance of Log Odds of Positive Lymph Nodes in Patients with Esophageal Squamous Cell Carcinoma: A Population Study of the US SEER Database and a Chinese Single-Institution Cohort

Background: The purpose of this study was to assess the prognostic performance of log odds of positive lymph nodes (LODDS) compared with pN stage and lymph node ratio (LNR), in patients with esophageal squamous cell carcinoma (ESCC). Method: A total of 1,144 patients diagnosed with ESCC from the Surveillance, Epidemiology and End Results (SEER) database and 930 patients from our validation cohort were eligible. Kaplan-Meier plot and multivariate Cox proportional hazards models were conducted to investigate the prognostic value of pN, LNR and LODDS classifications. The homogeneity, discriminatory ability, and monotonicity of these variables were evaluated using the linear trend χ2 test, likelihood ratio χ2 test, Akaike information criterion (AIC) and consistency index (C-index) to determine the potential superiorities. Results: The prognostic cut-off values were determined as -1.49, and -0.55 (P< 0.001). Univariate analyses showed that pN, LNR and LODDS stages significantly influenced the overall survival (OS) of patients (all P < 0.001). Multivariate analyses confirmed that LODDS was an independent prognostic indicator in both the SEER database and our validation cohort. Subgroup analyses identified the LODDS as an important prognostic factor over the ability of distinguish heterogeneous patients within various groups in both two independent databases. Furthermore, the model incorporated LODDS had the highest C-index and the smallest AIC value among the three investigated nodal classifications of both cohorts. Conclusion: The novel LODDS classification showed a better prognostic performance than the traditional N or LNR classifications in patients with ESCC. It can serve as the auxiliary prognostic factor out of the better performance and apply to the evaluation of the lymph node status devoting for precise staging and better survival. Funding Statement: This work was supported by National Natural Science Foundation of China, Clinical Trial Project of Tianjin Medical University, Bethune Charitable Foundation-Excelsior Surgical Fund, and Science and Technology Project of Tianjin Municipal Health Commission. Declaration of Interests: No potential conflicts of interest are disclosed. Ethics Approval Statement: This study obtained approval from the Ethical Committee and institutional review board of Tianjin Medical University Cancer Institute and Hospital.

Prognostic Value of the Leuko-Glycaemic Index in the Postoperative Period of Coronary Artery Bypass Grafting.

IntroductionHigh leuko-glycaemic index (LGI) (> 2000) has been associated with poor prognosis in many critical care settings. However, there is no evidence of LGI’s prognostic value in the postoperative period of coronary artery bypass grafting (CABG). This study aims to analyze the prognostic value of LGI in the postoperative period of CABG.MethodsSingle-center retrospective analysis of prospectively collected data was performed. Consecutive adult patients undergoing CABG between 2007 and 2019 were included. Blood glucose levels and white blood cells count were evaluated in the immediate postoperative period. LGI was calculated by multiplying both values and dividing them by 1,000 and analyzed in quartiles. Receiver operating characteristic curve was used to determine the best cutoff value. The primary combined endpoint was in-hospital mortality, low cardiac output (LCO), or acute kidney injury (AKI). Secondary endpoints included in-hospital death, AKI, atrial fibrillation, and LCO.ResultsThe study evaluated 3,813 patients undergoing CABG (88.5% male, 89.8% off-pump surgery, aged 64.6 years [standard deviation 9.6]). The median of LGI was 2,035. Presence of primary endpoint significantly increased per LGI quartile (9.2%, 9.7%, 11.8%, and 15%; P<0.001). High LGI was associated with increased occurrence of in-hospital mortality, LCO, AKI, and atrial fibrillation. The best prognostic cutoff value for primary endpoint was 2,000. In a multivariate logistic regression model, high LGI was independently associated with in-hospital death, LCO, or AKI.ConclusionHigh LGI was an independent predictor of in-hospital mortality, LCO, or AKI in postoperative period of CABG. It was also associated with higher in-hospital death.

Serum Hepcidin as a Clinical Prognostic Marker to Discriminate the Outcome of Canine Babesiosis

Background: We aimed to identify the prognostic value of hepcidin in discriminating against the survival outcome of canine babesiosis. Methods: Semi-nested polymerase chain reaction was performed to confirm the presence of infection. Existence of oxidative stress and inflammatory response, changes in systemic iron status and hepcidin level were assessed in the study population. Based on the outcome Babesia infected dogs were classified into survivors (n=18) and non-survivors (n=14) of infection. 32 healthy dogs formed the control group. Conclusion: In non-survivors of infection, serum hepcidin was positively associated with C-reactive protein (P less than 0.01), serum iron (P less than 0.01), transferrin iron-binding capacity (P less than 0.05), unsaturated iron-binding capacity (P less than 0.01), thiobarbituric acid reactive substance (P less than 0.05) and negatively associated with catalase (P less than 0.01), zinc (P less than 0.01) and low haemoglobin density (P less than 0.01). The prognostic cut-off value of hepcidin in discriminating the survivability of infected dogs was 32.32 ng/mL with 100.00% specificity and 92.86 % sensitivity. The area under the curve of hepcidin in discriminating survivability was about 0.984 and Youden’s index was 0.928. Hence, hepcidin can predict the survival outcome of the disease enabling intensive care for animals with a cut-off value of hepcidin more than 32.32 ng/mL.

Cardiac Computed Tomography-Derived Left Atrial Volume Index as a Predictor of Long-Term Success of Cryo-Ablation in Patients With Atrial Fibrillation

Patients with symptomatic, drug-refractory atrial fibrillation (AF) are frequently treated with catheter ablation. Cryo-ablation has been established as an alternative to radiofrequency ablation but long-term outcome data are still limited. This study aimed at elucidating the influence of the left atrial volume index (LAVI), derived from cardiac computed tomography (cCT) data, on the long-term outcome of ablation-naïve AF patients, after their first cryo-ablation. 415 patients (n = 290 [69.90%] male, 60.00 [IQR: 53.00 to 68.00] years old) who underwent a cCT and subsequent cryo-ablation index procedure were included in this single centre retrospective data analysis. A composite end point was defined (AF on electrocardiogram and/or electric cardioversion and/or re-do). Patients were closely followed for a year and then contacted for long-term follow-up after a median of 53.00 months (IQR: 34.50 to 73.00). Statistical analyses of the outcome and predictors of AF recurrence were conducted. In 224 patients (53.98%) no evidence of AF recurrence could be found. LAVI differed significantly between the positive and adverse (AF recurrence) outcome group (49.96 vs 56.07 ml/m2, p < 0.001). Cox regression analyses revealed cCT LAVI (HR: 1.022, 95% CI: 1.013 to 1.031, p < 0.001), BMI (HR: 1.044, 95% CI: 1.005 to 1.084, p < 0.05) and the type of AF (HR: 1.838 for nonparoxysmal AF, 95% CI: 1.214 to 2.781, p < 0.01) to be effective predictors of AF recurrence. A prognostic cCT LAVI cut-off value of 51.99 ml/m2 was calculated and must be validated in future prospective studies. In conclusion, LAVI is an accurate, yet underutilized predictor of AF recurrence after pulmonary vein isolation with cryo-energy and scores for calculating AF recurrence or progression risks might underemphasize the importance of CT-derived LAVI as a predictive factor.

Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.

To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

Should the Number of Metastatic Pelvic Lymph Nodes be Integrated into the 2018 Figo Staging Classification of Early Stage Cervical Cancer?

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs. 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC.

Serum uric acid level is associated with the incidence of heterotopic ossification following elbow trauma surgery

Heterotopic ossification (HO) is a common complication after surgery for elbow trauma. Uric acid is the end product of purine metabolism and has several physiological and pathogenic roles. However, the relationship between HO and uric acid has not been explored. This retrospective study aimed to assess the relationship between HO and serum uric acid (SUA). We retrospectively reviewed data from 155 patients undergoing elbow trauma surgery in our hospital between January 2013 and December 2018. One hundred patients were included according to the inclusion criteria. They were divided into 2 groups according to the presence or absence of HO, and the SUA level was compared between groups using the independent samples t test. The optimal prognostic cutoff value was obtained using the maximum value of the Youden index. The SUA level was significantly higher in the HO group than in the non-HO group (362.0 ± 87.4 μmol/L vs. 318.3 ± 87.0 μmol/L; P < .05). Using the maximum value of Youden index, 317.5 μmol/L was determined to be the optimal SUA cutoff value for the prediction of HO, with a sensitivity of 68.75% (95% confidence interval [CI], 54.67%-80.05%) and specificity of 55.77% (95%CI,42.34%-68.40%). Our study was the first to find that the high SUA level is a risk factor for HO of the elbow joint after trauma. Moreover, 317.5 μmol/L is the SUA threshold predicting the occurrence and development of HO of the elbow, with high sensitivity and specificity.

Prognostic Significance of Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios in Epithelial Ovarian Cancer

Objective: This study aims to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in epithelial ovarian cancer. Methods: This is a retrospective analysis of 116 patients who were diagnosed with epithelial ovarian tumors at the study center between January 2012 and December 2018. Results: The patients with stage 1 ovarian cancer had significantly lower NLR and PLR values than the patients with stage 2 disease (p=0.002 and p<0.0001). The patients with stage 2 ovarian cancer had significantly lower PLR values than the patients with stage 3 disease (p<0.0001). The NLR and PLR values were significantly higher in the patients with lymphovascular invasion and patients with omentum involvement (p<0.0001 for all). The patients with lymph node involvement, residual tumor and ascites had significantly higher PLR values (p=0.0004, p=0.04 and p=0.007 respectively). The patients with tumor recurrence had significantly higher NLR and PLR values (p<0.0001 for both). The patients with tumor recurrence after chemotherapy had significantly higher NLR and PLR values (p=0.02 and p=0.03 respectively). However, the patients who survived had significantly lower NLR and PLR values (p=0.04 and p=0.06 respectively). Both NLR and PLR values could be used to predict lymphovascular invasion, omentum involvement, and tumor recurrence (p<0.05 for all). Serum CA-125 levels correlated with NLR and PLR values positively and significantly (r=0.335, p<0.0001 and r=0.218, p<0.0001 respectively). Conclusions: Despite the fact that the actual prognostic cut-off values remain unspecified, NLR and PLR might act as complementary tools for other prognostic factors related to epithelial ovarian tumors. Keywords: blood platelets; lymphocytes; neutrophils; ovarian epithelial cancer; prognosis Special Issue of Health Sciences DOI: 10.7176/JSTR/6-03-13

Circulating levels of soluble urokinase plasminogen activator receptor (suPAR) to predict outcome after resection of biliary tract cancer.

572 Background: Surgical resection is the only curatively intended therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better preoperative stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has recently been associated with cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing resection of BTC. Methods: Tumor expression of uPAR, the membrane bound source of suPAR, was analyzed by IHC in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 BTC patients and 76 healthy controls. Results: A high tumoral uPAR expression was associated with an adverse outcome after BTC resection. In line, circulating levels of suPAR were significantly elevated in BTC patients compared to healthy controls and patients with primary sclerosing cholangitis (PSC). Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72ng/ml for BTC patients. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including clinicopathological parameters such as the tumor stage, markers of systemic inflammation or organ dysfunction and established tumor markers revealed suPAR as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative for acute kidney injury after tumor resection. Conclusions: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might be useful to preoperatively identify the ideal candidates for tumor resection.

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer.

Background & AimsSurgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection.MethodsTumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls.ResultsHigh tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection.ConclusionCirculating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery.Lay summarySurgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

Prognosis of colorectal cancer patients is associated with the novel log odds of positive lymph nodes scheme: derivation and external validation.

Background and aim: To construct proper and externally validate cut-off points for log odds of positive lymph nodes scheme (LODDS) staging scheme in colorectal cancer (CRC).Patients and methods: The X-tile approach was used to find the cut-off points for the novel LODDS staging scheme in 240,898 patients from the Surveillance, Epidemiology and End Results (SEER) database and externally validated in 1,878 from the international multicenter cohort. Kaplan-Meier plot and multivariate Cox proportional hazard models were performed to investigate the role of the novel LODDS classification.Results: The prognostic cut-off values were determined as -2.18, and -0.23 (P< 0.001). Patients had 5-year cancer-specific survival rates of 83.8%, 57.4% and 24.4% with increasing LODDS (P< 0.001) in the SEER database. Five-year overall survival rates were 77.2%, 55.0% and 26.7% with increasing LODDS (P< 0.001) in the external international multicenter cohort. Multivariate survival analysis identified both the LODDS classification, the patient's age, the T category, the M status, and the tumor grade as independent prognostic factors in both two independent databases. The analyses of the subgroup of patients stratified by tumor location (colon or rectum), number of retrieved lymph node (< 12 or ≥ 12), TNM stage III, lymph node-negative also confirmed the LODDS as independent prognostic factors (P< 0.001) in both two independent databases.Conclusions: The novel LODDS classification was an independent prognostic factor for patients with CRCs and should be calculated for additional risk group stratification with pN scheme.

Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men. The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.

P1502Age- and gender-specific prognostic cutoff values of coronary flow velocity reserve in vasodilator stress echocardiography

Abstract Background Coronary flow velocity reserve (CFVR) of left anterior descending artery is useful for risk stratification during stress echocardiography (SE) as an add-on to regional wall motion abnormalities (RWMA), but the age-and sex-dependence of prognostic cutoff values remains unclear. Purpose To provide sex and age-specific prognostic cut-off values which may be needed to account for the physiologic decline of CFVR with age, and sex-related differences in resting flow. Methods In an observational, prospective, multicenter, registry study design, we enrolled from August 2003 to August 2017 in 4 Italian cardiology referral centers with accredited, quality-controlled stress echo laboratory a consecutive sample of 5,577 patients (of them, 2,284 women and 110 aged ≥85 years) referred to the SE lab for known or suspected coronary artery disease, after exclusion of patients with inadequate acoustic window (n=295), premature test interruption (n=105), and lost to follow-up (n=173).All underwent dual imaging (RWMA and CFVR) dipyridamole SE (0.84 mg/kg over 6') and were followed-up. All-cause death and non-fatal myocardial infarction were the main outcome measures. Median follow-up of 20 months (1st quartile 8, 3rd quartile 43 months), Results There were 649 hard events (236 deaths and 413 non-fatal myocardial infarctions), 288 of which occurred in women and 38 in patients ≥85 years. With a ROC analysis, the best prognostic cut-off value for CFVR was almost the same for men (2.03) and women (2.02) and consistent across all age strata (&lt;45 years: 2.03; 45–54 years: 2.04; 45–64 years: 2.03; 65–74 and 75–84 years: 2.0) except for the very elderly (&gt;85 years) who showed an optimal value of 1.90. Independent prognostic indicators were RWMA (HR=5.42, 95% CI=2.42–12.15; p&lt;0.0001) and reduced CFVR (HR=3.26, 95% CI 2.27–3.90; p&lt;0.0001) in patients aged &lt;85 years, and RWMA (HR=5.42, 95% CI=2.42–12.15; p&lt;0.0001) in patients aged &gt;85 years. Best prognostic cut-off value of CFVR Conclusion A sex-independent cut-off value of CFVR ≤2.0 provides the optimal risk stratification across all age groups, except those &gt;85 years in whom a lower cut-off &lt;1.90 is needed. Risk stratification is more effective for all age groups when CFVR is combined with RWMA.