Receiver Operator Characteristic Cutoff Research Articles

Narrow interval dual phase 18F-FDG PET/CT: A practical approach for distinguishing tumor recurrence from radiation necrosis in brain metastasis.

Purpose of our research is to demonstrate efficacy of narrow interval dual phase [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in distinguishing tumor recurrence (TR) from radiation necrosis (RN) in patients treated for brain metastases. 35 consecutive patients (22 female, 13 male) with various cancer subtypes, lesion size > 1.0 cm3, and suspected recurrence on brain magnetic resonance imaging (MRI) underwent narrow interval dual phase FDG-PET/CT (30 and 90 min after tracer injection). Clinical outcome was determined via sequential MRIs or pathology reports. Maximum standard uptake value (SUVmax) of lesion (L), gray matter (GM), and white matter (WM) was measured on early (1) and delayed (2) imaging. Analyzed variables include % change, late phase, and early phase for L uptake, L/GM uptake, and L/WM uptake. Statistical analysis (P < .01), receiver operator characteristic (ROC) curve and area under curve (AUC) cutoff values were obtained. Change in L/GM ratio of > -2% was 95% sensitive, 91% specific, and 93% accurate (P < .001, AUC = 0.99) in distinguishing TR from RN. Change in SUVmax of lesion alone was the second-best indicator (P < .001, AUC = 0.94) with an ROC cutoff > 30.5% yielding 86% sensitivity, 83% specificity, and 84% accuracy. Other variables (L alone or L/GM ratios in early or late phase, all L/WM ratios) were significantly less accurate. Utilizing narrow interval dual phase FDG-PET/CT in patients with brain metastasis treated with radiation therapy provides a practical approach to distinguish TR from RN. Narrow time interval allows for better patient comfort, greater efficiency of PET/CT scanner, and lower disruption of workflow.

The Role of Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) in Appendicitis

Aim: Predictive values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with poor outcomes in several diseases. Furthermore, there has been limited publication of those parameters in appendicitis patients in Indonesia. This study aims to evaluate the role of NLR and PLR in differentiating complicated appendicitis and uncomplicated appendicitis. Methods: The design of this study is a retrospective using medical records of appendicitis patients from January 1, 2016, to December 31, 2020, conducted at PKU Muhammadiyah Bantul Hospital. There are 408 data on appendicitis patients that can be analyzed. Results: The WBC, neutrophils, NLR, and PLR was significantly higher in the complicated appendicitis group than in the uncomplicated group [11,5 (3.79-35.2) vs. 8.42 (3.32-39.30), p&lt;0.0001; 8.63 (2.359-2.647) vs. 5.446 (1.691-35.960), p&lt;0.0001; 5.65 (0.95-23.86) vs.3.82 (0.81-23.86), p&lt;0.0001; 168.57 (37.27-974.03) vs.139.40 (56.84-1274.31), p&lt;0.0001, respectively] followed by a significantly lower lymphocyte count [1.709 (0.154-5.71) vs. 2.094 (0.401-5.812), p&lt;0.0001, respectively]. The area under the receiver operating characteristic (ROC) curve, cutoff point, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of NLR for diagnosis of complicated appendicitis were 0.76, &gt;2.84, 75.21%, 62.65%, 74.6%, 63.4%, 2.01, 0.40, respectively. In contrast, an area under ROC curve, cutoff point, sensitivity, specificity, PPV, NPV, and likelihood ratio of PLR for differentiating complicated and uncomplicated appendicitis were 0.605, &gt;140.6, 65.70%, 51.81%, 66.5%, 50.9%, 1.36, and 0.66 respectively. Conclusion: The cutoff values of NLR (&gt;2.84) and PLR (&gt;140.6) were significant diagnostic parameters for complicated appendicitis (p = 0.0001). Hence, NLR and PLR can assist in diagnosing complicated appendicitis.

18F-AlF-NOTA-FAPI-04 PET/CT can Predict Treatment Response and Survival in Patients with Inoperable Pancreatic Adenocarcinoma

We investigated whether uptake of 18F-AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic adenocarcinoma (PAAD). We prospectively evaluated 47 patients with histopathologically confirmed primary PAAD and pretreatment 18F-FAPI PET/CT scans to determine uptake of fibroblast activation protein (FAP) and compare the findings with those from blood tests and immunohistochemically stained tumor specimens. Cox regression and Kaplan-Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cutoff points for distinguishing patients according to good response vs poor response per RECIST v. 1.1. The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean); metabolic tumor volume (MTV); and total lesion FAP expression (TLF) were positively correlated with cancer-associated fibroblast (CAF) markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P<0.05). MTV and Log2TLF were associated with survival in patients with inoperable PAAD (all P<0.05). Analyses controlling for sex, age, cTNM, and performance status showed that MTV and Log2TLF were associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016 and Log2TLF HR = 4.093, P = 0.003). ROC cutoff analysis indicated that elevated MTV and TLF were associated with poorer survival. Greater changes from before to after chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P<0.05). ΔMTV, ΔTLF and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan-Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cutoff values (based on medians) of -4.95 for ΔMTV (HR = 8.09, P = 0.013) and -77.83 for ΔTLF (HR = 4.62, P = 0.012). Higher baseline MTV on 18F-FAPI-04 PET/CT scans was associated with poorer survival in patients with inoperable PAAD. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PAAD who are at high risk of disease progression.

Investigation of ischemia-modified albumin and thiol/disulfide homeostasis for the determination of oxidative stress in sheep with toxoplasmosis

In this study, the aim was to investigate the thiol/disulfide homeostasis (TDH) parameters and ischemia-modified albumin (IMA) (ABSU) levels to determine oxidative stress in sheep with toxoplasmosis. Twenty-four Morkaraman sheep used in this study were allocated into two groups, one control group and one experimental group. Each group included 12 sheep. Blood samples were taken from all sheep only once and blood serum levels of albumin (ALB) (g/L), IMA (ABSU), native thiol (NT) (μmol/L), total thiol (TT) (μmol/L), disulfide (Ds) (μmol/L), Ds/NT, Ds/TT, NT/TT were investigated. Our results showed that the IMA (ABSU) levels of toxoplasma group were significantly higher than control group (p < 0.05). However, NT (μmol/L) and TT (μmol/L) level of toxoplasma group were significantly lower than the control group (p < 0.05). While the oxidant and antioxidant parameters were positively correlated within themselves, a negative correlation was determined between the antioxidant and oxidant parameters. In the Receiver Operating Characteristic (ROC) analysis, the area under the ROC curve (AUC), sensitivity, cut off and specificity values were determined for IMA (ABSU) values. These values were determined as 0.812, 1.24, 91.7% and 75.0%, respectively. For TT (μmol/L), these values were obtained as 0.750, 330.55, 75.0% and 66.7%. It was concluded that oxidative stress is intensely formed in sheep with toxoplasmosis, thiol-disulphide homestasis markers, and IMA (ABSU) are valuable markers in determining oxidative stress in toxoplasmosis.

Performance of spleen stiffness measurement by 2D-shear wave elastography in evaluating the presence of high-risk varices: comparative analysis of idiopathic portal hypertension versus hepatitis B virus

BackgroundNoninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV).MethodsA retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV.ResultsIn patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters.ConclusionSS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.

Case – Control study: Evaluation of plasma procalcitonin concentration as an indicator of inflammation in healthy and sick cows

This case – control study aims to evaluate Procalcitonin (PCT) plasma concentrations in healthy and hospitalized cows with a conclusive diagnosis of inflammation due to bacterial infection. Thirty-four healthy and 131 sick cows were included. Procalcitonin concentrations were assessed using an ELISA kit for cattle. Depending on whether sick cows received antimicrobial treatments prior to admission or not, they were divided in treated (TP) or not treated (NTP) subgroups. Mann-Whitney U tests were performed to determine differences between healthy vs sick cows, while Kruskal-Wallis with Dunn's multiple comparison test were applied for healthy vs sick subgroups. Receiver operating characteristic (ROC) analysis was performed to assess the optimal cut-off value. Kaplan-Meier survival curves were determined for cows belonging to the groups with PCT values below and above ROC cut-offs.Plasma PCT concentration was 200.1 (147.8–324.1) pg/mL and 361.6 (239.7–947.1) pg/mL in the healthy control and in the sick group, respectively (P < 0.001). The optimal cut-off value of plasma PCT concentration was 244.4 pg/mL (sensitivity 73.6%, specificity 60.0%). The plasma PCT concentration was 267.5 (210.3–771.2) pg/mL in the TP subgroup and 425.6 (253.1–1242) pg/mL in the NTP subgroup (P = 0.03). Cows with PCT above the ROC cut-off value had a reduced survival percentage and a higher mortality risk (P < 0.05). Procalcitonin showed the ability of differentiate healthy cows from hospitalized cows with a conclusive diagnosis of inflammation due to bacterial infection. Moreover, PCT was a good predictor of negative prognostic outcome.

Minimal Clinically Important Differences for Patient-Reported Outcomes After TKA Depend on Central Sensitization.

To our knowledge, it is still unknown if central sensitization (CS) influences the magnitude of the minimal clinically important difference (MCID) for patient-reported outcome measures after total knee arthroplasty (TKA). The purpose of this study was to determine the influence of CS on the MCID for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score in patients who underwent TKA for knee osteoarthritis. A total of 422 patients who underwent unilateral TKA and completed a 2-year follow-up were enrolled in this study. CS was measured using the Central Sensitization Inventory (CSI). The WOMAC score was used to evaluate preoperative and postoperative patient-reported outcomes. The measurement of the MCID was performed separately for patients with and without CS using both the anchor-based method and the distribution method. The change difference method defined the MCID as the difference in preoperative-to-postoperative change between the minimal-improvement group and the no-change group. In addition, the MCID was calculated using receiver operating characteristic (ROC) curve analysis. The percentage of MCID achievement in each group was also compared. According to the change difference method, the MCID for the WOMAC total score was 23.4 points for patients with CS and 14.7 points for patients without CS. The MCID using the ROC cutoff value for the WOMAC total score was 29.5 points for the patients with CS and 26.5 points for the patients without CS. MCID achievement rates in WOMAC pain, function, and total scores were all found to be significantly higher in the patients without CS through the change difference method and the ROC method (all p < 0.05). The MCID for the WOMAC score of patients with CS after TKA was greater than that for patients without CS. Furthermore, by applying the calculated MCID to the group to which the patients belonged (with or without CS), we determined that patients with CS showed a lower MCID achievement rate than patients without CS. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

New evidence on the minimal important change (MIC) for the Hand Eczema Severity Index (HECSI).

How changes in hand eczema (HE) severity correlate with the single scores on the Hand Eczema Severity Index (HECSI) is sparsely investigated and particularly needed in clinical trials. To find the minimal important change (MIC) for HECSI based on patient's and physician's assessments using different methods. In this prospective follow-up study, three different anchors were used: two anchor questions for patients and physician, respectively, and the Physician Global Assessment (PGA) with a photographic guide. MIC was estimated by mean change in patients with a one-step increase to anchor-questions, receiver-operating characteristic (ROC) plot, and smallest detectable change (SDC). One hundred fifty-two patients with HE (63.8% female) were included at baseline (89% completed follow-up). The mean change, ROC cutoff, and SDC values were 7.1, 4.5, 21.4 (patient-rating), 8.2, 4.5, 8.3 (physician-rating), and 16.6, 6.5, 27.1 points (PGA), respectively. SDC stratified by baseline severity was 2.9 and 11 points for mild and moderate-severe HE (physician-rating), respectively. Identification of the MIC for the HECSI is important in relation to evaluation of treatment, intervention, and sample-size calculations. An improvement of 8.3 points on the HECSI is recommended as the MIC. MIC values may differ according to baseline severity, and this variation should be clarified in future studies.

RISK FACTORS FOR PATELLAR INSTABILITY USING A QUANTITATIVE ANALYSIS OF TROCHLEAR DYSPLASIA

Objectives:Multiple studies have described several anatomic and demographic risk factors of patellar instability (PI). Trochlear dysplasia (TD) has been shown to be a dominant risk factor for patellar instability but most prediction models have used the qualitative Dejour system to evaluate the influence of TD on PI. The lateral trochlear inclincation (LTI) angle is a described quantitative method to evaluate TD and a recent measurement technique has near perfect inter and intra rater reliability. Our hypothesis is that, in combination with other known radiographic and demographic risk factors of PI, that using a quantitative and numeric evaluation for TD, a highly reliable prediction model for PI can be created.Methods:98 patients in a pediatric and adolescent sports medicine practice were identified with documented PI that had magnetic resonance imaging (MRI) studies available for review. A matched cohort of 100 patients with no history of PI but with MRI’s were identified as a control group. Anatomic risk factors evaluated included the LTI, sulcus angle, lateral condyle index (LCI), lateral patellar inclination angle (LPI), proximal and distal tibial tubercle-trochlear groove distance (pTTTG and dTTTG), Caton-Deschamps ratio (CD ratio), and patellotrochlear index (PTI). Demographic data included age and sex. Receiver operator characteristic (ROC) curves were constructed for each variable to identify which variables were the best predictors of PI (ROC value >0.7). Using the ROC curves with a Youden’s J statistic and setting specificity at 0.9, cutoff values for each variable were created. Each radiographic and demographic variable was analyzed for significance and those that were found to be significant were analyzed. Area under the curve (AUC) was determined for each variable. Two predictive models were created. One was developed from the ROC curve results while the other evaluated all measured variables. The models were designed to produce the best possible fit while trying to limit the total number of predictors. These models were tested on a second cohort of 45 patients with PI and 42 control patients.Results:ROC curve data is in Table 1. Of the two models, the superior model was the model that evaluated all variables, regardless of ROC cutoff value. The model takes on the form of a general logistic regression (Eq 1, Eq 2). Model accuracy on the validation set showed 84% accuracy with 78% sensitivity and 88% specificity. These values are based on a probability of >90%. Patellar height measures had significant AUC’s but were not prime drivers of the final model. Age was not significant in the ROC analysis.Conclusion:This study establishes a highly reliable and predictive model for PI that is driven by various direct (LTI, sulcus angle, LCI) or indirect (dTT-TG, LPI) quantitative measurements of TD. Patellar height did correlate with PI but was not a prime driver of the model which suggests that patella alta is a less common risk factor for PI.

Acute-Phase Stroke Outcome and Lipids.

Objectives:The aim of the study is to investigate the relationship of lipid subgroups with short-term mortality in acute stroke (AS).Methods:This retrospective study included 698 patients with AS who presented within 24 h of symptom onset. A hemogram from peripheral venous blood samples was taken at admission. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TC/HDL-C rate, and TG/HDL-C rate were recorded. Duration of follow-up was defined as 30 days.Results:64 out of 698 patients died during the follow-up period. The mean TG, TG/HDL-C, and TC/HDL-C levels were significantly lower in the mortality group than the survival group. In the receiver operating characteristic (ROC) analysis, the cutoff values and area under the curve of the TG, TG/HDL-C, TC, and TC/HDL-C levels for short-term stroke mortality are as follows ([100.2 mg/dL, 0.648]; [2.52, 0.650]; [170.50 mg/dL, 0.598]; and [4.32, 0.640], respectively). In the Cox regression model, only TG and TG/HDL-C, according to their ROC cutoff values, were independent variables as short-term mortality predictors (TG ≤100.2 mg/dL, HR:2.413 , 95% CI: 1.345–4.327, P:0.004); (TG/HDL ≤2.56, HR: 2.720, 95% CI: 1.389–5.359, P:0.003, respectively).Conclusion:Dyslipidemia is a well-known as a risk factor of stroke. However, this study focused on the estimation that lower TG and TG/HDL-C levels at the time of hospital admission might be predictors of short-term mortality within a month of AS attack, which is a different subject from long term risk factors of stroke. Serum TG level may be a better indicator for mortality in the acute hypercatabolic trauma such as stroke.

Survival prediction model for postoperative hepatocellular carcinoma patients.

This study is to establish a predictive index (PI) model of 5-year survival rate for patients with hepatocellular carcinoma (HCC) after radical resection and to evaluate its prediction sensitivity, specificity, and accuracy.Patients underwent HCC surgical resection were enrolled and randomly divided into prediction model group (101 patients) and model evaluation group (100 patients). Cox regression model was used for univariate and multivariate survival analysis. A PI model was established based on multivariate analysis and receiver operating characteristic (ROC) curve was drawn accordingly. The area under ROC (AUROC) and PI cutoff value was identified.Multiple Cox regression analysis of prediction model group showed that neutrophil to lymphocyte ratio, histological grade, microvascular invasion, positive resection margin, number of tumor, and postoperative transcatheter arterial chemoembolization treatment were the independent predictors for the 5-year survival rate for HCC patients. The model was PI = 0.377 × NLR + 0.554 × HG + 0.927 × PRM + 0.778 × MVI + 0.740 × NT – 0.831 × transcatheter arterial chemoembolization (TACE). In the prediction model group, AUROC was 0.832 and the PI cutoff value was 3.38. The sensitivity, specificity, and accuracy were 78.0%, 80%, and 79.2%, respectively. In model evaluation group, AUROC was 0.822, and the PI cutoff value was well corresponded to the prediction model group with sensitivity, specificity, and accuracy of 85.0%, 83.3%, and 84.0%, respectively.The PI model can quantify the mortality risk of hepatitis B related HCC with high sensitivity, specificity, and accuracy.

Appropriate extent of lymphadenectomy for squamous cell carcinoma of the esophagogastric junction

AimTo investigate the appropriate extent of lymphadenectomy for squamous cell carcinoma (SCC) of the esophagogastric junction (ECJ). MethodsWe retrospectively reviewed the cases of 52 patients with SCC of the ECJ who underwent extended mediastinal lymphadenectomy. We assessed potential risk factors for lymph node metastasis (LNM) in the upper/middle mediastinum by conducting univariate and multivariate analyses, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value. Survival rates were calculated using the Kaplan-Meier method, and the therapeutic value index of each nodal basin dissection was calculated by multiplying the frequency of metastasis at the basin and the 5-year overall survival rate of patients with metastasis at that basin. ResultsTwenty patients (38%) had mediastinal LNM; 13 (25%) had metastasis in the upper/middle mediastinum, and 13 (25%) had metastasis in the lower mediastinum. Tumor length (P = 0.03) and pathological nodal status (P = 0.01) were independent risk factors for upper/middle mediastinal LNM. The optimal ROC cutoff value of tumor length was 54 mm. The 5-year overall survival rate of the patients with LNM in the upper/middle mediastinum was 46%. The therapeutic value index of upper/middle mediastinal lymphadenectomy was 11.6, which was inferior to that of perigastric lymphadenectomy at 17.3, but superior to that of lower mediastinal lymphadenectomy at 5.8. ConclusionAn upper/middle mediastinal lymphadenectomy may be required for patients with tumors that are ≥54 mm long, and in those with suspected LNM.

Serum Ferritin Level At Referral Provides Independent Prognostic Information For Overall Survival In Primary Myelofibrosis

BackgroundRecent studies have suggested that increased circulating free light chains, inflammatory cytokines, hepcidin, ferritin, and ASXL1 mutated status have independent prognostic value for survival in primary myelofibrosis (PMF). In the current retrospective study, we studied all the aforementioned variables in the context of DIPSS-plus to examine their relative prognostic contributions for overall and leukemia-free survival. MethodsThe diagnosis of PMF was according to WHO criteria. The study population included all consecutive referrals to the Mayo Clinic, Rochester, MN where complete information on clinical and laboratory parameters and bone marrow karyotype was available. Inclusion to the study required availability of a research blood sample collected at referral. Levels of circulating free light chains (FLC) (J Clin Oncol. 2012 Apr 1;30(10):1087), inflammatory cytokines (J Clin Oncol. 2011 Apr 1;29(10):1356), hepcidin and ferritin (Am J Hematol. 2013 Apr;88(4):312) were determined as previously described. Disease-relevant mutations (ASXL1, SRSF2, EZH2, IDH-1/2, SF3B1, JAK2V617F and MPLW515) were identified as previously described (Leukemia. 2013 Apr 26. doi: 10.1038/leu.2013.119). ResultsA total of 224 PMF patients were studied (66% male; median age 63 years, range 18-83 years). The DIPSS-plus distribution was: Low 23 (10%), Int-1 26 (12%), Int-2 98 (44%), and High 77 (34%). Clinical characteristics were: unfavorable karyotype 13%, hemoglobin <10 g/dL 58%, leukocyte count >25 x 109/L 13%, platelet count <100 x 109/L 20%, peripheral blasts ≥1% 62%, red blood cell transfusion-dependent 38%, and constitutional symptoms 36%. Mutation frequencies were: JAK2V617F 61% (n=220), MPLW515 6% (n=204), ASXL1 34% (n=154), SRSF2 16% (n=189), IDH-1/2 3% (n=209), EZH2 1.5% (n=134), SF3B1 5% (n=91) and SETBP1 4% (n=114). Distribution of circulating biomarkers was: FLC >receiver operating characteristic (ROC) cutoff of 3.78 mg/dL 37% (n=222), interleukin (IL)-2R and/or IL-8 >3 standard deviations above normal mean (SD) 75% (n=197), ferritin ≥1000 mcg/L 18% (n=146), ferritin ≥500 30% (n=146), and hepcidin >3SD 72% (n=203).Median follow up from the time of referral was 45 months (range 1-317 months); during this period, 139 deaths (62%) and 27 (12%) leukemic transformations have been documented.The median overall survival of the entire cohort was 61 months. The following variables had DIPSS-plus independent predictive value for inferior survival: ferritin ≥1000 mcg/L (HR 1.9), ASXL1 mutated status (HR 1.7) and FLC >ROC cutoff (HR 2.0) and IL-2R and/or IL-8 >3SD (HR 1.6) (all p<0.05). When the aforementioned variables were added to the multivariate model (sequentially or altogether), only serum ferritin >1000 mcg/L retained its significance for overall survival independent of DIPSS-plus (HR 2.1; p=0.03). The predictive significance for increased ferritin level was maintained in RBC transfusion-dependent (ferritin ≥1000 mcg/L; n=26/54; median survival 21 versus 59 months; p=0.03) and -independent (ferritin >500 mcg/L; n=5/92; median survival 20 versus 80 months; p=0.0002) patients.Multivariable analysis identified the following predictors for inferior leukemia-free survival: SRSF2 mutated status (HR 4.8), unfavorable karyotype (HR 4.0), and circulating blasts ≥1% (HR 3.0) (p<0.05). ConclusionsWhen considering composite risk-assessment in PMF where input variables were disease-relevant mutations and circulating biomarkers in addition to traditional clinical parameters, only increased serum ferritin levels at time-of-referral retained adverse predictive value for overall survival independent of DIPSS-plus. The prognostic value of serum ferritin was independent of anemia and RBC transfusion need. It appears to more fully capture the severity of the underlying erythropoietic defect in PMF by also likely reflecting (as an acute-phase reactant) the marrow-suppressive effect of disease-related inflammation. The shortened survival in patients with increased ferritin levels was unrelated to iron overload since none of the deaths, where information was available, were caused by cardiac siderosis. Serum ferritin levels were not associated with leukemic transformation risk. In the latter analysis, only SRSF2 mutations, unfavorable karyotype and presence of circulating blasts were independently associated with inferior leukemia-free survival. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Validity and Reliability of the 45-15 Test for Aerobic Fitness in Young Soccer Players

The aim of this study was to examine the reliability and validity of a popular field test for aerobic fitness used in soccer (45-15) in Italy. Alternating progressive 45-s runs with 15 s passive recovery until exhaustion, the test considers peak speed (PS) as a reflection of maximal aerobic speed (MAS). The validity and reliability of the 45-15 was assessed in 18 young male soccer players (age 16.7 ± 1.8 y, body mass 70 ± 7.45 kg, height 177 ± 0.5 cm, 55.62 ± 5.56 mL · kg-1 ·min-1) submitted to laboratory testing for aerobic fitness and repeatedly to the 45-15. Results showed that 45-15 PS was significantly related to VO2max (r = .80, P < .001, 95%CI .47-.93) and MAS (r = .78, P = .001, 95%CI .43-.93). No significant bias between MAS 45-15 PS (P = .11) was found during the measurement-consistency study. Receiver-operating-characteristic (ROC) analysis showed that 45-15 PS was sensitive in detecting VO2max changes in subjects as revealed by area under the curve (.97; 95%CI .73-1). Players with peak 45-15 speed equal to or above 16.5 km/h (ie, ROC cutoff) may be considered to have good aerobic fitness. In light of this study's findings, the 45-15 test may be considered a reliable and valid test to evaluate meaningful information to direct generic aerobic training in soccer.

Potential of 1H MR spectroscopic imaging to segregate patients who are likely to show malignancy of the peripheral zone of the prostate on biopsy

To evaluate the potential of MR spectroscopic imaging (MRSI) to segregate patients who, upon prostate biopsy, are more likely to show a malignancy in the peripheral zone (PZ) of the prostate gland. Before biopsy, MRSI was carried in 123 men with elevated prostate specific antigen level or an abnormal digital rectal examination. After the MRSI investigation, all patients underwent systematic transrectal ultrasound guided biopsy and were categorized using standard random number tables into the following two groups: (i) Group I, a 62 member training set; and (ii) Group II, a 61-member test set. The cutoff value for the [citrate/(choline+creatine)] ratio for patients in the training set was obtained using the receiver operating characteristic (ROC) curve method. This value was then applied to the test set of patients as well. The ROC method gave a cutoff value of 1.2 for the [Citrate/(Choline+Creatine)] ratio. When applied as a malignancy-predictor to the test group of patients (Group II), the ROC method generated the following results: sensitivity, 77%; specificity, 83%; negative predictive value, 93%; positive predictive value, 55% and accuracy, 82%. The results indicate that patients who are deemed as malignancy-positive in the PZ by MRSI using the ROC cutoff may be subjected to prostate biopsy to confirm the diagnosis of cancer.

Cardiac troponins I and T in hemodialysis patients without acute coronary syndrome

BackgroundThere is a reluctance to use cardiac troponins (cTn) for the monitoring of acute coronary syndrome (ACS) in hemodialysis (HD) patients because renal failure per se is thought to lead to increased cTn levels. The aim of this study was to analyse the proportion of patients with increased cTn levels in HD patients without ACS. MethodscTnI was measured with the AccuTnI™ from Beckman (cTnI-B) and Troponin I Stat™ from Dade Behring (cTnI-DB) assays; cTnT was measured with the third generation assay from Roche. The study included 105 HD patients. The clinical outcomes were determined after 2.5 years. ResultsConsidering the receiver operator characteristic (ROC) cutoff, the proportion of patients with elevated cTnI-B, cTnI-DB and cTnT levels was respectively 2%, 3% and 27%. The proportion of patients with abnormal cTn values increased when a lower cutoff value was considered, based on the 99th percentile of a reference population with a coefficient of variation of less than 10% (99th percentile–10% CV cutoff). The proportion of patients with elevated values did not differ before and after the HD session. The 2.5 years mortality was associated with increased levels of cTnT but not with increased levels of cTnI. ConclusionsWhen the ROC cutoff is applied, cTnI assays are suitable for the monitoring of ACS in HD patients. cTnT could lead to false positive diagnosis of myocardial infarction, however it is predictive of long-term mortality. The 99th percentile–10% CV cutoff does not seem appropriate in HD patients.

Improving the analysis of esophageal acid exposure by a new parameter: area under H+.

We aimed to compare the data provided by 24-h continuous esophageal pH monitoring in a group of patients with gastroesophageal reflux disease (GERD) to those from a group of healthy volunteers using both conventional parameters and calculated area under the curve of hydrogen ion activity (AUH+), a new value that describes the true acid exposure, through both duration and depth of acidity changes. Thirty healthy controls and 60 patients with GERD (30 symptomatic patients without endoscopic esophagitis or nonerosive GERD and 30 symptomatic patients with Savary I-IV endoscopic esophagitis or erosive GERD) were enrolled in a study based on 24-h pH monitoring to compare reference values by means of receiver operating characteristic (ROC) discriminant analysis. The best ROC cutoff value for nonerosive GERD patients was AUH+ = 103.7 (mmol/L) x min with sensitivity of 76.7% and specificity of 93.3%. The best ROC cutoff value for erosive GERD patients was AUH+ = 114.1 (mmol/L) x min with sensitivity of 100% and specificity of 96.7%. These cutoff values increase the sensitivity by 16.7% for nonerosive GERD patients and 10% for erosive GERD patients when compared to a common parameter such as the percentage of total time pH is <4 with a limit of 4.2%. AUH+ is a valid quantitative parameter to measure 24-h esophageal acid exposure. It may be a reliable and significant clinical aid because it is a more sensitive test in discriminating negative or positive adult patients with or without esophagitis who are submitted to 24-h esophageal pH monitoring.

Improving the analysis of esophageal acid exposure by a new parameter: area under H+

OBJECTIVES: We aimed to compare the data provided by 24-h continuous esophageal pH monitoring in a group of patients with gastroesophageal reflux disease (GERD) to those from a group of healthy volunteers using both conventional parameters and calculated area under the curve of hydrogen ion activity (AUH+), a new value that describes the true acid exposure, through both duration and depth of acidity changes. METHODS: Thirty healthy controls and 60 patients with GERD (30 symptomatic patients without endoscopic esophagitis or nonerosive GERD and 30 symptomatic patients with Savary I–IV endoscopic esophagitis or erosive GERD) were enrolled in a study based on 24-h pH monitoring to compare reference values by means of receiver operating characteristic (ROC) discriminant analysis. RESULTS: The best ROC cutoff value for nonerosive GERD patients was AUH+ = 103.7 (mmol/L) × min with sensitivity of 76.7% and specificity of 93.3%. The best ROC cutoff value for erosive GERD patients was AUH+ = 114.1 (mmol/L) × min with sensitivity of 100% and specificity of 96.7%. These cutoff values increase the sensitivity by 16.7% for nonerosive GERD patients and 10% for erosive GERD patients when compared to a common parameter such as the percentage of total time pH is <4 with a limit of 4.2%. CONCLUSIONS: AUH+ is a valid quantitative parameter to measure 24-h esophageal acid exposure. It may be a reliable and significant clinical aid because it is a more sensitive test in discriminating negative or positive adult patients with or without esophagitis who are submitted to 24-h esophageal pH monitoring.