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Background: Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies. Aim: To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC. Methods: We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients' medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients' overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems. Results: Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit. Conclusion: HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases. [ABSTRACT FROM AUTHOR]

Abstract Background Accurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies. Aim To compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC. Methods We conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients’ medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients’ overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems. Results Hepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit. Conclusion HKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases.

To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8–96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8–89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication. • This study examined prognostic performance of the 2023 FIGO endometrial cancer staging schema. • Stage-shifting included: upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %). • 5-year OS rate of stage IA3 was comparable to stage IB-C (88.0 % vs 86.7–89.5 %). • Stage IIC had distinct overall survival compared to stage IA1-IIB (75.4 % vs 85.8–96.1 %). • In IIIC disease, macrometastasis and micrometastasis had discrete survival. [ABSTRACT FROM AUTHOR]

Ya-Ming Xie,1 Wenfeng Lu,2 Jian Cheng,1 Mugen Dai,3 Si-Yu Liu,4 Dong-Dong Wang,1 Tian-Wei Fu,1 Tai-Wei Ye,1 Jun-Wei Liu,1 Cheng-Wu Zhang,1 Dong-Sheng Huang,1 Lei Liang1 1Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 3Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Lei Liang; Dong-Sheng Huang, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email liangl1992@hotmail.com; huangdshz88@hotmail.comBackground: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC.Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems.Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038– 3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358– 5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262– 3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586– 0.712, P < 0.05).Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, Naples prognostic score, nutritional indicator, inflammatory indicator, prognostic performance

Objective: To validate the 7th and 8th editions of the AJCC staging system for patients with invasive carcinomas arising in association with IPMN (IPMN-associated PDAC). Background Data: Although several studies have validated AJCC systems in patients with conventional PDAC, their applicability to IPMN-associated PDAC has not been assessed. Methods: Two hundred seventy-five patients who underwent resection for IPMN-associated PDAC between 1996 and 2015 at 3 tertiary centers and had data on the size of the invasive component and lymph node status were identified. Concordance probability estimates (CPE) were calculated and recursive partitioning analysis was employed to identify optimal prognostic cutoffs for T and N. Results: The CPE for the 7th and 8th editions of the AJCC schema were relatively good (0.64 for both) and similar for colloid and tubular subtypes (0.64 for both). The 8th edition introduced T1a sub-staging and a new distinction between N1 and N2. The utility of the former was confirmed, although the latter did not improve prognostic discrimination. The successful validation of the 8th edition of the AJCC criteria in patients with tubular and colloid subtypes allowed us to compare these patients in early vs late T and N stages which showed that with advanced disease, the prognostic superiority of colloid tumors over their tubular counterparts diminishes. Conclusions: Our findings support the use of the AJCC 8th edition in the IPMN-associated PDAC population, but suggest that certain cutoffs may need to be revisited. In advanced AJCC stages, patients with colloid vs tubular subtypes have comparable prognosis. [ABSTRACT FROM AUTHOR]

(1) Background: Differences in access to biomarker testing and cancer treatment in resource-limited settings may affect the clinical utility of the AJCC8 staging system compared to the anatomical AJCC7 system. (2) Methods: A total of 4151 Malaysian women who were newly diagnosed with breast cancer from 2010 to 2020 were followed-up until December 2021. All patients were staged using the AJCC7 and AJCC8 systems. Overall survival (OS) and relative survival (RS) were determined. Concordance-index was used to compare the discriminatory ability between the two systems. (3) Results: Migration from the AJCC7 to AJCC8 staging system resulted in the downstaging of 1494 (36.0%) patients and the upstaging of 289 (7.0%) patients. Approximately 5% of patients could not be staged using the AJCC8 classification. Five-year OS varied between 97% (Stage IA) and 66% (Stage IIIC) for AJCC7, and 96% (Stage IA) and 60% (Stage IIIC) for AJCC8. Concordance-indexes for predicting OS using the AJCC7 and AJCC8 models were 0.720 (0.694–0.747) and 0.745 (0.716–0.774), and for predicting RS they were 0.692 (0.658–0.728) and 0.710 (0.674–0.748), respectively. (4) Conclusions: Given the comparable discriminatory ability between the two staging systems in predicting the stage-specific survival of women with breast cancer in the current study, the continued use of the AJCC7 staging system in resource-limited settings seems pragmatic and justifiable. [ABSTRACT FROM AUTHOR]

Background: We compared the predictive performance of the 7th and 8th editions of the AJCC staging systems in stratifying disease-related survival outcomes in patients with GBC undergoing curative intent surgery., Methods: Patients that underwent curative intent surgery for GBC at our institution (2014 and 2021) were included in the study. Various clinico-pathological data were extracted to perform Kaplan-Meier survival analysis., Results: A total of 240 patients were included in the study. Both, TNM-7, and TNM-8 staging systems can stratify patients into stages with statistically significant differences in disease-free and overall survival. Survival rates drop with stage progression. Using TNM-8, 8/240 (3.33%) patients were upstaged from Stage IIIB (TNM-7) to IVB (TNM-8) and 12/240 (5%) were down-staged from Stage IVB(TNM-7) to IIIB(TNM-8). Survival curves of the re-classified patients matched those of the corresponding TNM-8 stage. Additionally, there was statistically significant difference in their survival (p < 0.001) compared to their corresponding TNM-7 stage. There was no statistically significant difference in survival rates between stages IIA, IIB (TNM-8), and stage II (TNM-7). However, stage IIA had a slightly better survival than stage IIB., Conclusion: Though both TNM-7 and TNM-8 are useful for stratifying patients with GBC, TNM-8 has a better prognostic performance than TNM-7., (© 2024 Wiley Periodicals LLC.)

(1) Background: Differences in access to biomarker testing and cancer treatment in resource-limited settings may affect the clinical utility of the AJCC8 staging system compared to the anatomical AJCC7 system. (2) Methods: A total of 4151 Malaysian women who were newly diagnosed with breast cancer from 2010 to 2020 were followed-up until December 2021. All patients were staged using the AJCC7 and AJCC8 systems. Overall survival (OS) and relative survival (RS) were determined. Concordance-index was used to compare the discriminatory ability between the two systems. (3) Results: Migration from the AJCC7 to AJCC8 staging system resulted in the downstaging of 1494 (36.0%) patients and the upstaging of 289 (7.0%) patients. Approximately 5% of patients could not be staged using the AJCC8 classification. Five-year OS varied between 97% (Stage IA) and 66% (Stage IIIC) for AJCC7, and 96% (Stage IA) and 60% (Stage IIIC) for AJCC8. Concordance-indexes for predicting OS using the AJCC7 and AJCC8 models were 0.720 (0.694–0.747) and 0.745 (0.716–0.774), and for predicting RS they were 0.692 (0.658–0.728) and 0.710 (0.674–0.748), respectively. (4) Conclusions: Given the comparable discriminatory ability between the two staging systems in predicting the stage-specific survival of women with breast cancer in the current study, the continued use of the AJCC7 staging system in resource-limited settings seems pragmatic and justifiable.

Background: CT lung extent has emerged as a potential risk factor of COVID-19 pneumonia severity with mainly semiquantitative assessment, and outcome was not assessed in the specific oncology setting. The main goal was to evaluate the prognostic role of quantitative assessment of the extent of lung damage for early mortality of patients with COVID-19 pneumonia in cancer patients.Methods: We prospectively included consecutive cancer patients with recent onset of COVID-19 pneumonia assessed by chest CT between March 15, 2020, and April 20, 2020, and followed until May 1, 2020. Demographic, clinical, laboratory test data and imaging findings were recorded. Quantitative chest CT assessment of COVID-19 pneumonia was based on the density distribution of lung lesions using a freely available software recently released (Myrian XP-Lung). The association between extent of lung damage and overall survival was studied by univariate and multivariate Cox analysis. The Uno C-index was used to assess the discriminatory value of the quantitative CT extent of lung damage.Results: Seventy cancer patients with chest CT evidence of COVID-19 were included. After a median follow-up of 25 days, 17 patients (24%) had died. The median quantitative chest CT extent of COVID-19 was 20% (IQR = 14–35, range = 3–59) for non-survivors vs. 10% (IQR = 6–15, range = 2–55) for survivors (p = 0.002). The extent of COVID-19 pneumonia was correlated with inpatient management (p = 0.003) and oxygen therapy requirements (p < 0.001). Independent factors associated with death were performance status (PS) ≥2 (HR = 3.9, 95% CI = [1.1–13.8] p = 0.04) and extent of COVID-19 pneumonia ≥30% (HR = 12.0, 95% CI = [2.2–64.4] p = 0.004). No differences were found regarding the histology of cancer, cancer stage, metastases sites, or type of oncologic treatment between the survivor and non-survivor groups. The cross-validated Uno C-index of the model including PS and extent of COVID-19 pneumonia was 0.83, 95% CI = [0.73–0.93].Conclusions: The quantitative chest CT extent of COVID-19 pneumonia was a strong independent prognostic factor of early inpatient mortality in a population of cancer patients.

Background: CT lung extent has emerged as a potential risk factor of COVID-19 pneumonia severity with mainly semiquantitative assessment, and outcome was not assessed in the specific oncology setting. The main goal was to evaluate the prognostic role of quantitative assessment of the extent of lung damage for early mortality of patients with COVID-19 pneumonia in cancer patients. Methods: We prospectively included consecutive cancer patients with recent onset of COVID-19 pneumonia assessed by chest CT between March 15, 2020, and April 20, 2020, and followed until May 1, 2020. Demographic, clinical, laboratory test data and imaging findings were recorded. Quantitative chest CT assessment of COVID-19 pneumonia was based on the density distribution of lung lesions using a freely available software recently released (Myrian XP-Lung). The association between extent of lung damage and overall survival was studied by univariate and multivariate Cox analysis. The Uno C-index was used to assess the discriminatory value of the quantitative CT extent of lung damage. Results: Seventy cancer patients with chest CT evidence of COVID-19 were included. After a median follow-up of 25 days, 17 patients (24%) had died. The median quantitative chest CT extent of COVID-19 was 20% (IQR = 14–35, range = 3–59) for non-survivors vs. 10% (IQR = 6–15, range = 2–55) for survivors (p = 0.002). The extent of COVID-19 pneumonia was correlated with inpatient management (p = 0.003) and oxygen therapy requirements (p < 0.001). Independent factors associated with death were performance status (PS) ≥2 (HR = 3.9, 95% CI = [1.1–13.8] p = 0.04) and extent of COVID-19 pneumonia ≥30% (HR = 12.0, 95% CI = [2.2–64.4] p = 0.004). No differences were found regarding the histology of cancer, cancer stage, metastases sites, or type of oncologic treatment between the survivor and non-survivor groups. The cross-validated Uno C-index of the model including PS and extent of COVID-19 pneumonia was 0.83, 95% CI = [0.73–0.93]. Conclusions: The quantitative chest CT extent of COVID-19 pneumonia was a strong independent prognostic factor of early inpatient mortality in a population of cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Background Disease prevalence is rarely explicitly considered in the early stages of the development of novel prognostic tests. Rather, researchers use the area under the receiver operating characteristic (AUROC) as the key metric to gauge and report predictive performance ability. Because this statistic does not account for disease prevalence, proposed tests may not appropriately address clinical requirements. This ultimately impedes the translation of prognostic tests into clinical practice. Methods A method to express positive- and/or negative predictive value criteria (PPV, NPV) within the ROC space is presented. Equations are derived for so-called equi-PPV (and equi-NPV) lines. Herewith it is possible, for any given prevalence, to plot a series of sensitivity-specificity pairs which meet a specified PPV (or NPV) criterion onto the ROC space. This concept is introduced by firstly reviewing the well-established “mechanics”, strengths and limitations of the ROC analysis in the context of developing prognostic models. Then, the use of PPV (and/or) NPV criteria to augment the ROC analysis is elaborated. Additionally, an interactive web tool was also created to enable people to explore the dynamics of lines of equi-predictive value in function of prevalence. The web tool also allows to gauge what ROC curve shapes best meet specific positive and/or negative predictive value criteria ( http://d4ta.link/ppvnpv/ ). Results To illustrate the merits and implications of this concept, an example on the prediction of pre-eclampsia risk in low-risk nulliparous pregnancies is elaborated. Conclusions In risk stratification, the clinical usefulness of a prognostic test can be expressed in positive- and negative predictive value criteria; the development of novel prognostic tests will be facilitated by the possibility to co-visualise such criteria together with ROC curves. To achieve clinically meaningful risk stratification, the development of separate tests to meet either a pre-specified positive value (rule-in) or a negative predictive value (rule-out) criteria should be considered: the characteristics of successful rule-in and rule-out tests may markedly differ.

Background: Although the current nodal staging system for gallbladder cancer (GBC) was changed based on the number of positive lymph nodes (PLN), it needs to be evaluated in various situations. Methods: We reviewed the clinical data for 398 patients with resected GBC and compared nodal staging systems based on the number of PLNs, the positive/retrieved LN ratio (LNR), and the log odds of positive LN (LODDS). Prognostic performance was evaluated using the C-index. Results: Subgroups were formed on the basis of an restricted cubic spline plot as follows: PLN 3 (PLN = 0, 1–2, ≥ 3); PLN 4 (PLN = 0, 1–3, ≥ 4); LNR (LNR = 0, 0–0.269, ≥ 0.27); and LODDS (LODDS < − 0.8, − 0.8–0, ≥ 0). The oncological outcome differed significantly between subgroups in each system. In all patients with GBC, PLN 4 (C-index 0.730) and PLN 3 (C-index 0.734) were the best prognostic discriminators of survival and recurrence, respectively. However, for retrieved LN (RLN) ≥ 6, LODDS was the best discriminator for survival (C-index 0.852). Conclusion: The nodal staging system based on PLN was the optimal prognostic discriminator in patients with RLN < 6, whereas the LODDS system is adequate for RLN ≥ 6. The following nodal staging system considers applying different systems according to the RLN. [ABSTRACT FROM AUTHOR]

Background: The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases. Methods: Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease‐specific and overall survival (OS) using the proportion of variation explained and Harrell's C‐index. Results: In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease‐specific survival for both N and TNM stages, and OS by TNM stage. Conclusions: The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance. [ABSTRACT FROM AUTHOR]

Background: Peguero electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria are newly developed criteria that have shown better diagnostic performance than the traditional Cornell-voltage and Sokolow-Lyon criteria. However, prediction of poor outcomes rather than detection of increased left ventricular mass is becoming the primary use for ECG-LVH criteria which requires investigating any new ECG-LVH criteria in terms of prediction.Aims: To examine the prognostic significance of the newly developed Peguero ECG-LVH criteria.Methods: We compared the prognostic significance of Peguero ECG-LVH with Cornell-voltage and Sokolow-Lyon ECG-LVH criteria in 7,825 participants (age 59.8 ± 13.4 years; 52.7% women) from the third National Health and Nutrition Examination Survey who were free of major intraventricular conduction defects. ECG-LVH criteria were derived from digital ECG tracings processed at a central core laboratory.Results: At baseline, ECG-LVH was detected in 11.8% by Peguero; in 4.3% by Cornell voltage and in 6.4% by Sokolow-Lyon. During a median follow up of 13.8 years, 2,796 all-cause mortality events occurred. In multivariable models adjusted for demographics and cardiovascular risk factors, presence of Peguero ECG-LVH was associated with increased risk of all-cause mortality [HR (95% CI): 1.29 (1.16, 1.44)]. This association was not significantly different from the associations of Cornell voltage-LVH or Sokolow-Lyon LVH with all-cause mortality [HR (95%CI): 1.32 (1.12, 1.55) and 1.24 (1.07, 1.43), respectively; p-values for comparisons of these HRs with the HR of Peguero ECG-LVH 0.817 and 0.667, respectively]. Similar patterns of associations were observed with cardiovascular, ischemic heart disease and heart failure mortalities.Conclusion: Peguero ECG-LVH is predictive of increased risk of death similar to the traditional ECG-LVH criteria.

BACKGROUND: The key regulator of tumor metabolome is the glycolytic isoenzyme M2-PK which favors the generation of nucleic acid via glutaminolysis as hypoxic adaptive mechanism in the tumor cells. AIM: The study aimed to evaluate the prognostic role of M2-PK, CRP, and CA 15-3 in preoperative and metastatic breast carcinomas. PATIENTS AND METHODS: The study included 70 females; 15 controls, 33 preoperative primary breast carcinomas clinically metastasis free, and 22 clinically diagnosed metastatic breast carcinomas. M2-PK and CA 15-3 were detected by ELISA. CRP was quantified using the CRP LATEX kit. RESULTS: TuM2-PK significantly increased in metastatic and preoperative groups when compared to controls (p = 0.049, p = 0.001); respectively. Both CRP and CA 15-3 were significantly increased in metastatic than the preoperative group (p = 0.002). CA 15-3 was significantly increased in both groups when compared to controls (p = 0.016; p < 0.001; respectively). TuM2-PK level significantly related to tumor size in metastatic group (p = 0.006) and with menstruation status (p = 0.039), and liver metastasis (p = 0.036) in preoperative group. TuM2-PK significantly correlated with CRP (r = 0.793, p = 0.004), and CA 15-3 (r = 0.568, p = 0.006) in the metastatic group. Metastatic group with TuM2-PK ⩽ 15 U/ml had significantly higher survival rate than those with > 15 U/ml (x2 = 13.841, p < 0.001) within 3.3-4.2 but not after 10-20 years follow up period. Metastasis to bone and lymph nodes significantly increased in the metastatic than the preoperative group (p = 0.002, p = 0.013; respectively). Within 3.3-4.2 years, CA15.3 has the highest prognostic performance in metastatic group while both TuM2-PK and CRP have same specificity. On the other hand, TuM2-PK has the highest prognostic performance in preoperative group. After 20 years follow up period, there was neither significant difference in the performance of the three markers in predicting mortality in metastatic and preoperative groups nor in predicting metastasis in preoperative group. CONCLUSION: Current results document for the first time, a cross-talk between TuM2-PK and each of CRP and CA 15-3 in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was "spin-echo planar imaging". A median of 10.5 b-values (range, 3-17) were used. All but three studies included at least 4 b-values below b=200s/mm2. By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85-87% and specificity of 80-100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations. [ABSTRACT FROM AUTHOR]

Background: Preoperative hyponatremia is prevalent in patients undergoing surgical procedures, but it is uncertain if hyponatremia will lead to increased risk of surgical mortality and morbidity. Methods: A systematic search of Medline (PubMed), Embase, and Cochrane Library from inception through July 2, 2021, was performed. Fulllength articles that reported on the association between surgical outcomes among adults aged ≥18 years with documented preoperative hyponatremia were included. Findings: We identified 32 observational studies comprising 1 301 346 participants. All studies had low risk of bias. When adjusted for covariates, patients with hyponatremia had significantly higher odds of developing major complications (defined as a composite measure of 9 major complications) compared with patients with normal sodium concentrations (adjusted odds ratio=12711.37; 95% CI, 1.23-1.53; I²=78%; N =10). Additionally, patients with preoperative hyponatremia also significantly higher hazards of early mortality (<90 days) compared with patients with normonatremia (adjusted hazard ratio=1.27; 95% CI, 1.13-1.43; I²=97%; N =10) after adjustment for covariates. Preoperative hyponatremia also had significant associations with respiratory, renal, and septic complications. In terms of prognostic performance, preoperative hyponatremia performed adequately in predicting major complications in surgical patients (area under the curve=0.70; negative likelihood ratio, 0.90) with a specificity of 88% and a sensitivity of 25%. Interpretation: Our meta-analysis suggests that preoperative hyponatremia is associated with poorer early mortality and major morbidity outcomes in surgical patients. Hyponatremia is also a specific prognosticator for major complications in surgical patients, reiterating its potential use as a clinical indicator of poor outcomes. [ABSTRACT FROM AUTHOR]

Prognostic performance evaluation has gained significant attention in the past few years.Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

Background: Preoperative hyponatremia is prevalent in patients undergoing surgical procedures, but it is uncertain if hyponatremia will lead to increased risk of surgical mortality and morbidity., Methods: A systematic search of Medline (PubMed), Embase, and Cochrane Library from inception through July 2, 2021, was performed. Full-length articles that reported on the association between surgical outcomes among adults aged ≥18 years with documented preoperative hyponatremia were included., Findings: We identified 32 observational studies comprising 1 301 346 participants. All studies had low risk of bias. When adjusted for covariates, patients with hyponatremia had significantly higher odds of developing major complications (defined as a composite measure of 9 major complications) compared with patients with normal sodium concentrations (adjusted odds ratio = 1.37; 95% CI, 1.23-1.53; I2 = 78%; N = 10). Additionally, patients with preoperative hyponatremia also significantly higher hazards of early mortality (<90 days) compared with patients with normonatremia (adjusted hazard ratio = 1.27; 95% CI, 1.13-1.43; I2 = 97%; N = 10) after adjustment for covariates. Preoperative hyponatremia also had significant associations with respiratory, renal, and septic complications. In terms of prognostic performance, preoperative hyponatremia performed adequately in predicting major complications in surgical patients (area under the curve = 0.70; negative likelihood ratio, 0.90) with a specificity of 88% and a sensitivity of 25%., Interpretation: Our meta-analysis suggests that preoperative hyponatremia is associated with poorer early mortality and major morbidity outcomes in surgical patients. Hyponatremia is also a specific prognosticator for major complications in surgical patients, reiterating its potential use as a clinical indicator of poor outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Whether body composition is associated with the N-terminal pro-B-type natriuretic peptide (NTproBNP) level and its prognostic performance in acute coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of body composition on the NT-proBNP level and its prognostic performance among ACS patients. Methods: In total, 1623 ACS patients with NT-proBNP data were enrolled. Percent body fat and lean mass index were estimated using the Clínica Universidad de Navarra--Body Adiposity Estimator equation. Patients were divided into three groups according to the tertiles of sex-specific body mass index, percent body fat, or lean mass index. The endpoints were death from any cause and cardiovascular death. Results: Body mass index was inversely correlated with NT-proBNP levels (β = -0.036, P = 0.003). Lean mass index, but not percent body fat, was inversely associated with NT-proBNP levels (β of lean mass index = -0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes. Multivariate Cox analysis showed that the NT-proBNP level independently predicted all-cause mortality or cardiovascular death in the lower body mass index, lean mass index, and percent body fat groups. However, the prognostic performance of NT-proBNP was attenuated in patients with high body mass index, lean mass index, and percent body fat. In the subgroup of patients with diabetes, inverse associations between NT-proBNP levels and body mass index or body composition were not observed. In addition, the negative influence of high body mass index and body composition on the prognostic performance of the NT-proBNP level appeared to be attenuated. Conclusions: Body mass index and lean mass index, but not percent body fat, are inversely associated with NTproBNP levels. The prognostic performance of this biomarker may be compromised in patients with high body mass index, percent body fat, or lean mass index. Additionally, the influence of body composition on the NT-proBNP level and its prognostic performance might be attenuated in diabetic patients with ACS. [ABSTRACT FROM AUTHOR]

In clinical applications, the prediction error of survival models has to be taken into consideration to assess the practical suitability of conclusions drawn from these models. Different approaches to evaluate the predictive performance of survival models have been suggested in the literature. In this article, we analyze the properties of the estimator of prediction error developed by , Biometrics 56, 249-255), which quantifies the absolute distance between predicted and observed survival functions. We provide a formal proof that the estimator proposed by Schemper and Henderson is not robust against misspecification of the survival model, that is, the estimator will only be meaningful if the model family used for deriving predictions has been specified correctly. To remedy this problem, we construct a new estimator of the absolute distance between predicted and observed survival functions. We show that this modified Schemper-Henderson estimator is robust against model misspecification, allowing its practical application to a wide class of survival models. The properties of the Schemper-Henderson estimator and its new modification are illustrated by means of a simulation study and the analysis of two clinical data sets. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the prognostic performance of clinical T staging based on axial, multiplanar, and 3-dimensional measurement on CT with that of pathological T staging in patients with non-small cell lung cancer.Method: Patients with surgically resected lung cancer without pathological node metastasis between June 2010 and December 2017 were retrospectively included. Clinical T stages were determined based on the maximal tumor size on axial, multiplanar (axial, coronal, and sagittal) images and 3-dimensional tumor mask. The prognostic performances of clinical and pathological T staging for disease-free survival (DFS) were compared using the concordance indices (C-indices).Results: A total of 544 patients (64.7 ± 9.7 years, 352 men) were included; 160 patients (29.4%) experienced events including 29 (5.3%) who expired. The median DFS was 44.1 months. The mean tumor size on axial, multiplanar images, 3-dimensional tumor mask, and pathology was 30.8 ± 17.3, 33.9 ± 19.4, 39.2 ± 21.4, and 33.4 ± 18.0 mm, respectively. Clinical staging based on multiplanar measurement showed a higher agreement (67.5% [367/544]) with pathological staging than axial (60.5% [329/544]) and 3-dimensional measurement (50.9% [277/544]) based staging did (p = .0005 and <.0001, respectively). The adjusted C-indices of axial, multiplanar, 3-dimensional, and pathological tumor stages were 0.66 (95% confidence interval [CI]: 0.66-0.67), 0.66 (95% CI: 0.66-0.66), 0.67 (95% CI: 0.67-0.67), and 0.67 (95% CI: 0.66-0.67), respectively (p > .05).Conclusions: The prognostic performances of tumor staging according to size measurement methods were not significantly different. Multiplanar measurement may be preferable for clinical staging considering its highest agreement with pathological staging. [ABSTRACT FROM AUTHOR]

Simple Summary: This review proposes a comprehensive overview of the main prognostic systems for HCC classified as prognostic scores, staging systems, or combined systems. Prognostic systems for HCC are usually compared in terms of homogeneity, monotonicity of gradients, and discrimination ability. However, despite the great number of published studies comparing HCC prognostic systems, it is rather difficult to identify a system that could be universally accepted as the best prognostic scheme for all HCC patients encountered in clinical practice. In order to give a contribute in this topic, we conducted a study aimed at externally validate the MESH score and the CNLC classification using the ITA.LI.CA database. Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described. [ABSTRACT FROM AUTHOR]

Background: Peguero electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria are newly developed criteria that have shown better diagnostic performance than the traditional Cornell-voltage and Sokolow-Lyon criteria. However, prediction of poor outcomes rather than detection of increased left ventricular mass is becoming the primary use for ECG-LVH criteria which requires investigating any new ECG-LVH criteria in terms of prediction. Aims: To examine the prognostic significance of the newly developed Peguero ECG-LVH criteria. Methods: We compared the prognostic significance of Peguero ECG-LVH with Cornell-voltage and Sokolow-Lyon ECG-LVH criteria in 7,825 participants (age 59.8 ± 13.4 years; 52.7% women) from the third National Health and Nutrition Examination Survey who were free of major intraventricular conduction defects. ECG-LVH criteria were derived from digital ECG tracings processed at a central core laboratory. Results: At baseline, ECG-LVH was detected in 11.8% by Peguero; in 4.3% by Cornell voltage and in 6.4% by Sokolow-Lyon. During a median follow up of 13.8 years, 2,796 all-cause mortality events occurred. In multivariable models adjusted for demographics and cardiovascular risk factors, presence of Peguero ECG-LVH was associated with increased risk of all-cause mortality [HR (95% CI): 1.29 (1.16, 1.44)]. This association was not significantly different from the associations of Cornell voltage-LVH or Sokolow-Lyon LVH with all-cause mortality [HR (95%CI): 1.32 (1.12, 1.55) and 1.24 (1.07, 1.43), respectively; p -values for comparisons of these HRs with the HR of Peguero ECG-LVH 0.817 and 0.667, respectively]. Similar patterns of associations were observed with cardiovascular, ischemic heart disease and heart failure mortalities. Conclusion: Peguero ECG-LVH is predictive of increased risk of death similar to the traditional ECG-LVH criteria.

Objectives: The objective of this study was to evaluate a revised nodal category based on the value of the lymph node (LN) station ratio (SR, metastatic LN stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC) patients., Methods: Data were obtained from 857 ESCC patients who underwent primary radical esophagectomy. Prognostic performance was evaluated using the Harrell concordance index (C-index), Akaike information criterion (AIC), and likelihood ratio χ 2 test (LR χ 2 test)., Results: Each subgroup among the SR categories demonstrated discriminatory results, whereas no significant survival difference was observed between the N2 versus N3 classifications under the AJCC pN system. Using the AJCC TNM staging system, the survival curves separated between stages IIIA-IIIB and IIIB-IVA. However, when the T-SR-M scheme category was applied, the survival curves between stages IIA-IIB, IIIA-IIIB, and IIIB-IVA were significantly different. Furthermore, both the SR category and the T-SR-M staging system showed superior performance with higher C-index and LR χ 2 test values and lower AIC values compared with the pN category and TNM staging system, respectively., Conclusions: Following radical esophagectomy, the SR category demonstrated superior prognostic ability relative to the AJCC pN category in ESCC patients., (© 2017 Wiley Periodicals, Inc.)

Background: Disease prevalence is rarely explicitly considered in the early stages of the development of novel prognostic tests. Rather, researchers use the area under the receiver operating characteristic (AUROC) as the key metric to gauge and report predictive performance ability. Because this statistic does not account for disease prevalence, proposed tests may not appropriately address clinical requirements. This ultimately impedes the translation of prognostic tests into clinical practice., Methods: A method to express positive- and/or negative predictive value criteria (PPV, NPV) within the ROC space is presented. Equations are derived for so-called equi-PPV (and equi-NPV) lines. Herewith it is possible, for any given prevalence, to plot a series of sensitivity-specificity pairs which meet a specified PPV (or NPV) criterion onto the ROC space.This concept is introduced by firstly reviewing the well-established "mechanics", strengths and limitations of the ROC analysis in the context of developing prognostic models. Then, the use of PPV (and/or) NPV criteria to augment the ROC analysis is elaborated.Additionally, an interactive web tool was also created to enable people to explore the dynamics of lines of equi-predictive value in function of prevalence. The web tool also allows to gauge what ROC curve shapes best meet specific positive and/or negative predictive value criteria (http://d4ta.link/ppvnpv/)., Results: To illustrate the merits and implications of this concept, an example on the prediction of pre-eclampsia risk in low-risk nulliparous pregnancies is elaborated., Conclusions: In risk stratification, the clinical usefulness of a prognostic test can be expressed in positive- and negative predictive value criteria; the development of novel prognostic tests will be facilitated by the possibility to co-visualise such criteria together with ROC curves. To achieve clinically meaningful risk stratification, the development of separate tests to meet either a pre-specified positive value (rule-in) or a negative predictive value (rule-out) criteria should be considered: the characteristics of successful rule-in and rule-out tests may markedly differ., Competing Interests: In addition of being practising clinicians, PNB and LCK have a long-standing record in both basic and translational preeclampsia research. PNB and LCK are well-recognised pioneers in the use of “omics” for the discovery of novel biomarkers to predict pre-eclampsia. RT and GT have been involved in “omics” biomarker discovery and biomarker translational research for over a decade.Not applicable.Not applicable.GT is the owner of SQU4RE, an independent Statistics and Data mining provider. LCK is a minority shareholder in Metabolomic Diagnostics, a company that has licenced technology concerning the use of metabolomics biomarkers in the prediction of pre-eclampsia. LCK has also received consultancy fees and honoraria payments from Alere relating to the Triage PlGF test for the prediction of complications in women with suspected pre-eclampsia. LCK is also Director of INFANT which is funded in part by a range of industry partnerships. Full details can be found at www.infantcentre.ie. PNB is a minority shareholder in Metabolomic Diagnostics, a company that has licenced technology concerning the use of metabolomics biomarkers in the prediction of pre-eclampsia. RT is employed by Metabolomic Diagnostics, which is developing metabolomics-based prognostic tests for adverse pregnancy outcomes.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Whether body composition is associated with the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and its prognostic performance in acute coronary syndrome (ACS) remains unknown. We aimed to investigate the influence of body composition on the NT-proBNP level and its prognostic performance among ACS patients., Methods: In total, 1623 ACS patients with NT-proBNP data were enrolled. Percent body fat and lean mass index were estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator equation. Patients were divided into three groups according to the tertiles of sex-specific body mass index, percent body fat, or lean mass index. The endpoints were death from any cause and cardiovascular death., Results: Body mass index was inversely correlated with NT-proBNP levels (β = -0.036, P = 0.003). Lean mass index, but not percent body fat, was inversely associated with NT-proBNP levels (β of lean mass index = -0.692, P = 0.002). During a median follow-up of 23 months, 161 all-cause deaths occurred, and of these, 93 (57.8 %) were attributed to cardiovascular causes. Multivariate Cox analysis showed that the NT-proBNP level independently predicted all-cause mortality or cardiovascular death in the lower body mass index, lean mass index, and percent body fat groups. However, the prognostic performance of NT-proBNP was attenuated in patients with high body mass index, lean mass index, and percent body fat. In the subgroup of patients with diabetes, inverse associations between NT-proBNP levels and body mass index or body composition were not observed. In addition, the negative influence of high body mass index and body composition on the prognostic performance of the NT-proBNP level appeared to be attenuated., Conclusions: Body mass index and lean mass index, but not percent body fat, are inversely associated with NT-proBNP levels. The prognostic performance of this biomarker may be compromised in patients with high body mass index, percent body fat, or lean mass index. Additionally, the influence of body composition on the NT-proBNP level and its prognostic performance might be attenuated in diabetic patients with ACS.