Prognostic Stratification Research Articles

Stratification of Lung Adenocarcinoma Patients Based on In Silico and Immunohistochemistry Analyses of Oxidative Stress-Related Genes.

Background: Lung adenocarcinoma (LUAD) remains heterogeneous in the prognosis of patients; oxidative stress (OS) has been widely linked to cancer progression. Therefore, it is necessary to explore the prognostic value of the OS-associated genes in LUAD. Methods: An OS-associated prognostic signature was developed using the Cox regression and random forest model in The Cancer Genome Atlas-LUAD dataset. Kaplan-Meier (K-M) survival curve and time-dependent receiver operating characteristic (tROC) curves were applied to evaluate and validate the predictive accuracy of this signature among the training and testing cohorts. A nomogram was constructed and also verified by the concordance index (C-index), calibration curves, and tROC curves, respectively. ESTIMATE algorithm and CIBERSORT algorithms were conducted to explore the signature's immune characteristics. Core target genes of the prognostic signature were identified in the protein-protein interaction network. Results: A six OS-associated prognostic gene signature (CDC25C, ERO1A, GRIA1, TERT, CAV1, BDNF) was developed. The tROC and K-M survival curves in the training and testing cohorts revealed that the signature had good and robust predictive capability to predict the overall survival of LUAD patients. Meanwhile, the risk score was an independent prognostic factor influencing patients' overall survival. The results of the C-index (0.714), calibration curves, and the 1-, 2-, and 3-year tROC curves (area under the curve = 0.703, 0.737, and 0.723, respectively) suggested that the nomogram had good predictive efficacy and prognostic value for LUAD. Then, the authors found that the high-risk group may be depletion or loss of antitumor function of immune cells. Finally, 10 core genes of the signature were predicted. Conclusion: Their study may provide a novel understanding for the identification of prognostic stratification in LUAD patients, as well as the regulation of OS-associated genes in LUAD progression.

A cross-species transcriptomic analysis reveals a novel 2-dimensional classification system explaining the invasiveness heterogeneity of pancreatic neuroendocrine tumor

Pancreatic neuroendocrine tumors (PanNETs), the second most common type of primary pancreatic tumors, display notable heterogeneity in invasiveness. Current knowledge regarding genomic alterations, including DAXX/ATRX, MEN1 mutations, and copy number variations (CNVs), provides some insights into tumor invasiveness. However, the underlying reasons for the significant variation in invasiveness between insulinoma and other types of PanNETs remain unclear. To construct a comprehensive model for the stratification of prognosis, we employed analysis of both the well-established Rip1-Tag2 (RT2) mouse model of PanNETs and human PanNETs with various functional types. Firstly, by applying single-cell and bulk RNA sequencing in PanNETs from different ages and strains of RT2 mice and human PanNETs, we introduced a 2-dimensional (2D) classification system. Based on the 2-D classification system, human PanNETs were mainly classified as benign insulinomas or non-insulinomas subclusters. Non-insulinomas subtypes mainly included gastrinomas, glucagonomas, VIPomas, and NF-PanNETs, which all exhibited potential invasiveness. In addition, we discovered an enrichment of specific CNV patterns and mutations in corresponding human PanNET subclusters. Then we denoted somatic DAXX/ATRX as the ‘second hit’ and confounding factors for invasiveness. Finally, by combining the 2D system, DAXX/ATRX mutation status, and tumor diameter, a group of indolent PanNETs with minimal recurrence risk was identified. In conclusion, our current work constructed a comprehensive model to elucidate the heterogeneity of invasiveness in PanNETs and improve prognostic stratification.

Predicting complication risks after sleeve lobectomy for non-small cell lung cancer.

Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy. We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method. Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis. Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.

STRATIFICATION OF WELL-DIFFERENTIATED THYROID CANCER BASED ON MOLECULAR GENETIC TESTING: A LITERATURE REVIEW

Relevance: Thyroid cancer (TC) is among the most significant malignant diseases of the head and neck, with a steadily growing number of newly diagnosed cases throughout the world. Despite a relatively modest 17th place of TC in the structure of cancer incidence, its treatment in recent decades has seriously worried scientists and physicians due to a very rapid increase in TC incidence among young and middle-aged people. Iodine deficiency decreases immune function, and the effects of ionizing radiation play a role in the development of thyroid cancer. This leads to the development of a stratification system for well-differentiated thyroid cancer (WDTC) at the molecular genetic level. This system is necessary to select patients at risk of progression and to apply aggressive radionuclide therapy and suppressive hormone therapy only to those patients who need it. The study aimed to systematize data from the current literature to assess the need to develop a prognostic stratification of patients with WDTC based on molecular genetic testing. Methods: A literature review of scientific publications was conducted from the PubMed search database from September 2017 to December 2023. Inclusion criteria: publication date from 2017 to present for the main keywords: ‘High differentiated thyroid cancer”, “ prognostic stratification of WDTC based on molecular tests, ‘WDTC mutation markers.’ Some clinical studies of domestic and foreign specialists were also considered. Results: Based on a meta-review of literature data on prognostic stratification of WDTC patients, the rationale for expanding the panel of genetic markers associated with aggressive forms of WDTC is presented, the importance of gene mutation in the occurrence of disease recurrence, and the choice of adequate treatment is proven. Conclusions: Research efforts are underway to find genetic and pathomorphologic predictors of the prognosis of the disease. Knowledge of molecular and genetic mechanisms of tumorigenesis provides a wide range of opportunities for applying molecular diagnostics in differential diagnosis, prognosis of the course of the disease, and treatment of aggressive forms of tumors.

Prognostic risk stratification using C-reactive protein, albumin, and associated inflammatory biomarkers in patients with advanced cancer in palliative care

PurposeTo evaluate the prognostic value of C-reactive protein (CRP), albumin, CRP/albumin ratio (CAR), and modified Glasgow Prognostic Score (mGPS) at different thresholds in patients with advanced cancer in palliative care. MethodsProspective cohort study with patients evaluated at a palliative care unit in Brazil between July 2016 and March 2020. We included patients ≥ 20 years old, both sexes, able to provide the necessary information or accompanied by someone able to do so, and Karnofsky Performance Status ≥ 30 %. The exclusion criteria were the absence of laboratory data and previous diagnosis of autoimmune and infectious diseases. The thresholds analyzed were: CRP < 5 vs. 5-10 vs. > 10 mg/L, albumin < 2.4 vs. 2.4-2.9 vs. 3.0-3.5 vs. > 3.5 g/dL; CAR <1.2 vs. 1.2–2.0 vs. > 2.0, and mGPS equal to 0 vs. 1 vs. 2. Kaplan-Meier curves and Cox regression models (with hazard ratios [HR] and 95% confidence interval [CI]) were used to evaluate prognostic value, and the concordance statistic (C-statistic) was used to evaluate the predictive accuracy of these thresholds to predict death within 90 days. ResultsA total of 1,877 patients were included. Median overall survival was 51 (19;124) days and decreased in line with the deterioration of the inflammatory biomarkers. According to the Cox regression models, HR increased as the thresholds worsened (CRP: 1.74 [95% CI, 1.50-2.02] to 2.30 [95% CI, 2.00-2.64]; albumin: 1.77 [95% CI, 1.52-2.07] to 2.60 [95% CI, 2.15-3.14]; CAR: 1.47 [95% CI, 1.21-1.77] to 2.35 [95% CI, 2.05-2.69]; mGPS: 1.78 [95% CI, 1.40-2.23] to 1.89 [95% CI, 1.65-2.15]). All the inflammatory biomarkers evaluated showed discriminatory accuracy for predicting death (C-statistic >0.70), with CAR as the best parameter (C-statistic: 0.80). ConclusionOur results suggest that CRP, albumin, CAR, and mGPS can be used as clinically meaningful biomarkers to stratify patients with advanced cancer in palliative care according to the severity of these indicators.

Revolutionizing Pathology with Artificial Intelligence: Innovations in Immunohistochemistry.

Artificial intelligence (AI) is a reality of our times, and it has been successfully implemented in all fields, including medicine. As a relatively new domain, all efforts are directed towards creating algorithms applicable in most medical specialties. Pathology, as one of the most important areas of interest for precision medicine, has received significant attention in the development and implementation of AI algorithms. This focus is especially important for achieving accurate diagnoses. Moreover, immunohistochemistry (IHC) serves as a complementary diagnostic tool in pathology. It can be further augmented through the application of deep learning (DL) and machine learning (ML) algorithms for assessing and analyzing immunohistochemical markers. Such advancements can aid in delineating targeted therapeutic approaches and prognostic stratification. This article explores the applications and integration of various AI software programs and platforms used in immunohistochemical analysis. It concludes by highlighting the application of these technologies to pathologies such as breast, prostate, lung, melanocytic proliferations, and hematologic conditions. Additionally, it underscores the necessity for further innovative diagnostic algorithms to assist physicians in the diagnostic process.

Identification of immunotherapy-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognostic signature in gastric carcinoma.

Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types, the present study aimed to explore the immunotherapy-related genes (IRGs) and develop a prognostic risk signature in gastric carcinoma (GC) based on these genes. IRGs were identified by comparing immunotherapy responders and non-responders in GC. Then, GC patients were divided into distinct subtypes by unsupervised clustering method based on IRGs, and the differences in immune characteristics and prognostic stratification between these subtypes were analyzed. An immunotherapy-related risk score (IRRS) signature was developed and validated for risk classification and prognosis prediction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Besides, the predictive ability of the IRRS in immunotherapy response was also determined. A total of 63 IRGs were identified, and 371 GC patients were stratified into two molecular subgroups with significantly different prognosis and immune characteristics. Then, an IRRS signature comprised of three IRGs (CENP8, NRP1, and SERPINE1) was constructed to predict the prognosis of GC patients in TCGA cohort. Importantly, external validation in multiple GEO cohorts further confirmed the universal applicability of the IRRS in distinct populations. Furthermore, we found that the IRRS was significantly correlated with patient's responsiveness to immunotherapy, GC patients with low IRRS are more likely to benefit from existing immunotherapy. The risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for immunotherapy and may be helpful for clinical decision making in GC patients.

Assessment of prognostic factors in pediatric adrenocortical tumors: the modified pediatric S-GRAS score in an international multicenter cohort-a work from the ENSAT-PACT working group.

Pediatric adrenocortical carcinoma (pACC) is rare, and prognostic stratification remains challenging. We aimed to confirm the prognostic value of the previously published pediatric scoring system (pS-GRAS) in an international multicenter cohort. Analysis of pS-GRAS items of pACC from 6 countries in collaboration of ENSAT-PACT, GPOH-MET, and IC-PACT. We received patient data of the pS-GRAS items including survival information from 9 centers. PS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index: 0%-9% = 0; 10%-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX/R1/R2 = 1 point), age (<4 years = 0; ≥4 years = 1 point), and hormone production (androgen production = 0; glucocorticoid-/mixed-/no-hormone production = 1 point) generating 8 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-7). Primary endpoint was overall survival (OS). We included 268 patients with median age of 4 years. The analysis of the pS-GRAS score showed a significantly favorable prognosis in patients with a lower scoring compared to higher scoring groups (5-year OS: Group 1 98%; group 2 87% [hazard ratio {HR} of death 3.6, 95% CI of HR 1.6-8.2]; group 3 43% [HR of death 2.8, 95% CI 1.9-4.4]; group 4: OS 18% [HR of death 2.1, 95% CI 1.7-2.7]). In the multivariable analysis, age (HR of death 3.5, 95% CI 1.8-7.0), resection status (HR of death 5.5, 95% CI 2.7-11.1), tumor stage (HR of death 1.9, 95% CI of HR 1.2-3.0), and Ki67 index (HR of death 1.7, 95% CI 1.2-2.4) remained strong independent outcome predictors. Especially infants < 4 years showed more often low-risk constellations with a better OS for all tumor stages. In an international multicenter study, we confirmed that the pS-GRAS score is strongly associated with overall survival among patients with pACC. Age, resection status, stage, and Ki67 index are important parameters for risk stratification.

Prognostic scoring system based on indicators reflecting the tumor glandular differentiation and microenvironment for patients with colorectal cancer

Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as < 5.0 ng/mL (0 point) and ≧5.0 (1 point). Considering these factors, the following D&M (tumor differentiation and microenvironment) scoring system was applied: I (0–2 points), II (3–4 points), III (5–6 points), and IV (7–9 points). Kaplan–Meier curves showed significant differences in disease-specific survival and recurrence-free survival among the assigned scores, highlighting their enhanced utility compared with the American Joint Committee on Cancer 8th edition staging system. The D&M scoring system was valuable as the initial prognostic nomogram, including DR.

18F]FDG-PET/CT atypical response patterns to immunotherapy in non-small cell lung cancer patients: long term prognosis assessment and clinical management proposal.

To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). 109 patients were prospectively included and underwent [18F]FDG-PET/CT at baseline, after 7 weeks (PETinterim1), and 3 months (PETinterim2) of treatment. On PETinterim1, tumor response was assessed using standard PERCIST criteria. In the event of PERCIST progression at this time-point, the study design provided for continued immunotherapy for 6 more weeks. Additional response patterns were then considered on PETinterim2: pseudo-progression (PsPD, subsequent metabolic response); dissociated response (DR, coexistence of responding and non-responding lesions), and confirmed progressive metabolic disease (cPMD, subsequent homogeneous progression of lesions). Patients were followed up for at least 12 months. Median follow-up was 21 months. At PETinterim1, PERCIST progression was observed in 60% (66/109) of patients and ICPI was continued in 59/66. At the subsequent PETinterim2, 14% of patients showed PsPD, 11% DR, 35% cPMD, and 28% had a sustained metabolic response. Median overall survival (OS) and progression-free-survival (PFS) did not differ between PsPD and DR (27 vs 29 months, p = 1.0; 17 vs 12 months, p = 0.2, respectively). The OS and PFS of PsPD/DR patients were significantly better than those with cPMD (29 vs 9 months, p < 0.02; 16 vs 2 months, p < 0.001), but worse than those with sustained metabolic response (p < 0.001). This 3-group prognostic stratification enabled better identification of true progressors, outperforming the prognostic value of standard PERCIST criteria (p = 0.03). [18F]FDG-PET/CT enables early assessment of response to immunotherapy. The new wsPERCIST ("wait and see") PET criteria proposed, comprising immune-related atypical response patterns, can refine conventional prognostic stratification based on PERCIST criteria. HDH F20230309081206. Registered 20 April 2023. Retrospectively registered.

Complete detection of FR1 to FR3 primer-based PCR patterns of immunoglobulin heavy chain rearrangement in the BIOMED-2 protocol is associated with poor prognosis in patients with diffuse large B-cell lymphoma.

Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B-cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED-2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1-JH, VHFR2-JH, and VHFR3-JH) in the BIOMED-2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline-based immunochemotherapy. Complete detection of the FR1 to FR3 primer-based IgH VH PCR patterns in the BIOMED-2 protocol was associated with low frequency of VH SHMs (p<0.001). Patients who were positive for all these three PCRs (n=79) were significantly associated with shorter 5-year overall survival (OS; 54.2% vs. 73.2%; p=0.002) and progression-free survival (PFS; 34.3% vs. 59.3%; p<0.001) compared to patients with other PCR patterns (n=202). Specifically, the successful FR3-JH detection was associated with significantly worse OS (p<0.001) and PFS (p<0.001). PCR patterns of complete IgH rearrangement using the BIOMED-2 protocol are clinically meaningful indicators for prognostic stratification of DLBCL patients.

Identifying high-risk multiple myeloma patients: A novel approach using a clonal gene signature.

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS demonstrated higher performance in identifying high-risk patients compared to the GEP70 and SKY92 signatures recommended for prognostic stratification of MM. CGS can further stratify patients into subgroups with significantly differential prognoses when applied to the high- and low-risk groups identified by GEP70 and SKY92. Additionally, CGS scores are significantly associated with patient response to dexamethasone, a commonly used treatment for MM. In summary, we proposed a computational framework that requires only gene expression data to identify CGSs for prognosis prediction. CGS provides a useful biomarker for improving prognostic stratification in MM, especially for identifying the highest-risk patients.

The Prognostic Value of Histopathological Features in Early-Stage Mycosis Fungoides: Insights from a Retrospective-Prospective Cohort Study.

Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective-prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte "keepers" significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.

Prognostic risk stratification value of MACC1 expression in patients with gastric cancer.

The prognostic significance of metastasis-associated in colon cancer-1 (MACC1) has been explored in a variety of malignancies. However, its clinical relevance in patients with gastric cancer (GC) is limited, also remains controversial. In this study, we retrospectively evaluated the prognostic value of lesion MACC1 expression in 347 GC patients. Lesion MACC1 expression was analyzed with immunohistochemistry and grouped as MACC1low (n = 172) and MACC1high (n = 175) cases. Data revealed that the degree of MACC1 expression is not related to patient sex, age and disease stage (all p > 0.05). Survival analysis showed that only post-operation advanced pT (p = 0.018), pN (p < 0.001), pM (p = 0.001) and AJCC stages (p < 0.001) are significantly associated with shorter survival, while no obvious difference was observed between MACC1low and MACC1high cases (p = 0.158). However, we found that survival for female (p = 0.032), older (p = 0.028), and early disease stage (pT stage I + II, p = 0.033) patients with MACC1high are remarkably worse than those with MACC1low. In summary, our findings revealed that, though MACC1 expression is not associated with the survival of the whole cohort, the prognostic risk stratification value of lesion MACC1 expression in subgroups of patients with gastric cancer should be noted.

Comparative Validity of the ALBI Grade and CTP Score in Predicting Overall Survival in Patients Receiving TACE Plus Sorafenib Therapy for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) significantly impacts global health, with liver function being a critical factor in patient prognosis. The ALBI grade and Child-Turcotte Pugh (CTP) score are both used to evaluate liver function in HCC patients, but their effectiveness in predicting survival outcomes varies. Objective: This study aimed to evaluate and compare the effectiveness of the ALBI grade and CTP score in predicting overall survival (OS) in HCC patients undergoing combined therapy with sorafenib and transarterial chemoembolization (TACE). Methods: Conducted at Jinnah Hospital Lahore and Hijaz Hospital between January 2019 and June 2023, this study included 103 HCC patients with CTP scores of 5 and 6. We analyzed the predictive values of the ALBI grade and CTP score for OS using multivariate analyses and time-dependent ROC curves. Results: Multivariate analysis indicated significant differences in OS among patients categorized by both scoring systems, with hazard ratios of 2.16 (P&lt;0.001) for the CTP score and 1.49 (P=0.035) for the ALBI grade. Time-dependent ROC analysis showed that the ALBI grade was more effective in discriminating long-term survival. It also remained a significant predictor of OS in a larger number of patient subgroups compared to the CTP score. Conclusion: The ALBI grade demonstrates superior prognostic stratification compared to the CTP score in HCC patients treated with TACE and sorafenib who have stable liver function.

Myocardial Work Indices Predict Hospitalization in Patients with Advanced Heart Failure.

An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW's feasibility in the prognostic stratification of AdHF. We retrospectively screened patients with AdHF who accessed our hospital in 2018-2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50-62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323-868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan-Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Prognostic Assessment of HLM Score in Heart Failure Due to Ischemic Heart Disease: A Pilot Study.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

A Comparison of Preoperative Predictive Scoring Systems for Postoperative Pancreatic Fistula after Pancreaticoduodenectomy Based on a Single-Center Analysis.

Background: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is associated with major postoperative morbidity and mortality. Several scoring systems have been described to stratify patients into risk groups according to the risk of POPF. The aim of this study was to compare scoring systems in patients who underwent a PD. Methods: A total of 196 patients undergoing PD from July 2019 to June 2022 were identified from a prospectively maintained database of the University Hospital Ghent. After performing a literature search, four validated, solely preoperative risk scores and the intraoperative Fistula Risk Score (FRS) were included in our analysis. Furthermore, we eliminated the variable blood loss (BL) from the FRS and created an additional score. Univariate and multivariate analyses were performed for all risk factors, followed by a ROC analysis for the six scoring systems. Results: All scores showed strong prognostic stratification for developing POPF (p < 0.001). FRS showed the best predictive accuracy in general (AUC 0.862). FRS without BL presented the best prognostic value of the scores that included solely preoperative variables (AUC 0.783). Soft pancreatic texture, male gender, and diameter of the Wirsung duct were independent prognostic factors on multivariate analysis. Conclusions: Although all predictive scoring systems stratify patients accurately by risk of POPF, preoperative risk stratification could improve clinical decision-making and implement preventive strategies for high-risk patients. Therefore, the preoperative use of the FRS without BL is a potential alternative.

Unveiling a cuproptosis-related risk model and the role of FARSB in hepatocellular carcinoma

BackgroundCuproptosis, a type of regulated cell death that was recently identified, has been linked to the development of a variety of diseases, among them being cancers. Nevertheless, the prognostic significance and therapeutic implications of the cuproptosis potential index in hepatocellular carcinoma (HCC) remain uncertain. MethodsSingle-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) methodology was conducted to ascertain the identification of modular genes that are closely linked to cuproptosis. In addition, the gene signature indicative of prognosis was formulated by employing univariate Cox regression analysis in conjunction with a random forest algorithm. The efficacy of this gene signature in predicting outcomes was confirmed through validation in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Furthermore, a study was undertaken to evaluate the association between the risk score and various clinical-pathological characteristics, explore the biological processes linked to the gene signature, and analyze tumor mutational burden and somatic mutations. Lastly, potential drugs targeting the identified gene signature were identified through screening. ResultsThe results of our comprehensive analysis across multiple cancer types demonstrated a positive correlation between an elevated cuproptosis potential index (CPI) and an accelerated rate of tumor progression. Furthermore, employing the WGCNA technique, we successfully identified 640 genes associated with cuproptosis. Among these genes, we meticulously screened and validated a seven-gene signature (TCOF1, NOP58, TMEM69, FARSB, DHX37, SLC16A3, and CBX2) that exhibited substantial prognostic significance. Using the median risk score, the division of HCC patients into cohorts with high- and low-risk highlighted significant disparities in survival results, wherein the group with higher risk exhibited a less favorable overall survival. The risk score exhibited commendable predictive efficacy. Moreover, the in vitro knockdown of FARSB significantly hindered cell viability, induced G1 phase arrest, increased apoptosis, and impaired migration in HepG2 and Huh7 cells. ConclusionOur research has successfully identified a strong seven-gene signature linked to cuproptosis, which could be utilized for prognostic evaluation and risk stratification in patients with HCC. Furthermore, the discovered gene signature, coupled with the functional analysis of FARSB, presents promising prospects as potential targets for therapeutic interventions in HCC.