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OBJECTIVE: The Personalized Advantage Index (PAI) is a method to guide treatment selection by investigating which of two or more treatments is optimal for a given individual. Recently, it was shown that, on average, twice-weekly sessions of psychotherapy for depression lead to better outcomes compared to once-weekly sessions. The present study applied the PAI method to assess if subgroups of patients may have a differential response to psychotherapy frequency.METHOD: Data came from a clinical trial (n = 200) randomizing depressed patients into different session frequencies: weekly sessions versus twice-weekly sessions. Machine-learning techniques were used to select pretreatment variables and develop a multivariable prediction model that calculated each patient's PAI. Differences in observed depression post-treatment scores (Beck Depression Inventory-II [BDI-II]) were tested between patients that received their PAI-indicated versus non-indicated session frequency. Between-group effect sizes (Cohen's d) were reported.RESULTS: We identified prognostic indicators generally associated with lower post-treatment BDI-II regardless of treatment assignment. In addition, we identified specific demographic and psychometric features associated with differential response to weekly- versus twice-weekly therapy sessions. Observed post-treatment BDI-II scores were significantly different between individuals receiving the PAI-indicated versus non-indicated session frequency (d = .37).CONCLUSIONS: Although a higher session frequency is more effective on average, different session frequencies seem beneficial for different patients. Future studies should externally validate these findings before they can be generalized to other settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset (n = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets (n = 442, n = 226 and n = 127). The MRG was constructed based on BIRC5, PLK1, CDKN3, and CYP4B1 genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4+T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents.

Objectives. The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients.Methods and Participants. The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort).Results. The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively).Conclusions. The CADOT index has comparable prognostic power to the BODE and ADO indices.The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices. CMRD research project has been funded by Ministry of Health of the Czech Republic (15/14/NAP, 5/15/NAP, UHHK 00179906, MH CZ-DRO FNBr65269705), and the Charles University Czech Republic (PROGRES Q40, and PROGRES Q42), and a consortium of several pharmaceutical companies (Angelini, AstraZeneca, Boehringer Ingelheim, Cipla, CSL Behring, GSK, Novartis, and Sandoz). All companies supported the CMRD project via unrestricted research grants. The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. The opinions, results, and conclusions reported in this article are independent of the funding sources. The authors would like to thank to physicians and their nursing staff (not mentioned as authors) of all participating centers of the CMRD of COPD, for assistance with data collection, namely: Petra Vogelova, Tomas Dvorak – Pulmonary Department, Hospital Mlada Boleslav, Petr Safranek – Pulmonary Department, University Hospital, Pilsen, Ondrej Sobotik – Pulmonary Department, University Hospital Motol, Prague, Rostislav Simek – Pulmonary Department, Regional Hospital of T. Bata, Zlin, Jaroslav Lnenicka, Blanka Snelerova – Pulmonary Department, Masaryk Hospital, Usti nad Labem, Zuzana Liptakova – Pulmonary Department, Ceske Budejovice Hospital, Libor Nevoranek, Eva Kocova, Michal Kopecky, Sarka Pracharova, and Lukas Varhanik – University Hospital Hradec Kralove, Lucie Heribanova – Pulmonary Department, Thomayer Hospital, Prague, Katerina Neumannova – Palacky University, Olomouc and Milada Sipkova – Pulmonary Department, Liberec Hospital.

Pancreatic cancer (PC) is one of the most fatal malignancies. Pyroptosis, a type of inflammatory cell death, likely plays a critical role in the development and progression of tumors. However, the relationship between pyroptosis-related genes (PRGs) and prognosis and immunity to PC is not entirely clear. This study, aimed at identifying the key PRGs in PC, highlights their prognostic value, immune characteristics, and candidate drugs for therapies. We screened 47 differentially expressed PRGs between PC and normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Afterwards, a pyroptosis-related gene prognostic index (PRGPI) was constructed based on eight PRGs (AIM2, GBP1, HMGB1, IL18, IRF6, NEK7, NLRP1 and PLCG1) selected by univariate and multivariate Cox regression analysis and LASSO regression analysis, and verified in two external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. We found that the PC patients in the PRGPI-defined subgroups not only reflected significantly different levels of infiltration in a variety of immune cells, such as M1 macrophages, but also showed differential expression in genes of the human leukocyte antigen (HLA) family and immune checkpoints. Additionally, molecular characteristics and drug sensitivity also stayed close to the PRGPI risk scores. Therefore, PRGPI may serve as a valuable prognostic biomarker and may potentially provide guidance toward novel therapeutic options for PC patients.

Background: Bladder cancer (BLCA) is one of the most common urinary tract malignant tumors. It is associated with poor outcomes, and its etiology and pathogenesis are not fully understood. There is great hope for immunotherapy in treating many malignant tumors; therefore, it is worthwhile to explore the use of immunotherapy for BLCA.Methods: Gene expression profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal. Differentially-expressed and survival-associated IRGs in patients with BLCA were identified using computational algorithms and Cox regression analysis. We also performed functional enrichment analysis. Based on IRGs, we employed multivariate Cox analysis to develop a new prognostic index.Results: We identified 261 IRGs that were differentially expressed between BLCA tissue and adjacent tissue, 30 of which were significantly associated with the overall survival (all P

Tumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell., Graphical abstract

Abnormal autophagic levels have been implicated in the pathogenesis of multiple cancers, however, its role in tumors is complex and has not yet been explored clearly. Hence, we aimed to explore the prognostic values of autophagy‐related genes (ARGs) for kidney renal clear cell carcinoma (KIRC). Differentially expressed ARGs and transcription factors (TFs) were identified in KIRC patients obtaining from the The Cancer Genome Atlas (TCGA) database. Then, networks between TFs and ARGs, gene ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted. Next, we performed consensus clustering, COX regression analysis and Lasso regression analysis to identify the prognostic ARGs. Finally, an individual prognostic index (PI, riskScore) was established. Based on TCGA cohort and ArrayExpress cohort, Survival analysis, ROC curve, independent prognostic analysis, and clinical correlation analysis were also performed to evaluate this PI. Based on differentially expressed ARGs, KIRC patients were successfully divided into two clusters (P = 5.916e‐04). AS for PI, it was constructed based on 11 ARGs and significantly classified KIRC patients into high‐risk group and low‐risk group in terms of OS (P = 4.885e‐15 for TCGA cohort, P = 6.366e‐03 for ArrayExpress cohort). AUC of its ROC curve reached 0.747 for TCGA cohort and 0.779 for ArrayExpress cohort. What's more, this PI was proven to be a valuable independent prognostic factor in both univariate and multivariate COX regression analysis (P, The strength of this article was that we performed a systematic analysis of the roles of autophagy in kidney renal clear cell carcinoma (KIRC) with a robust statistical approach. A novel prognostic index (PI) was successfully established and carefully evaluated. Moreover, networks between autophagy‐related genes (ARGs) and transcription factors were constructed for future basic research. Tumor clustering based on ARGs was effective, indicating ARGs played a vital role in KIRC. Last but not least, small molecule drugs related to ARGs were also identified for KIRC.

Background Huntington's disease (HD) develops in individuals with extended cytosine-adenine-guanine (CAG) repeats within the huntingtin (HTT) gene, causing neurodegeneration and progressive motor and cognitive symptoms. The inclusion of mutant HTT carriers in whom overt symptoms are not yet fully manifest in therapeutic trials would enable the development of treatments that delay or halt the accumulation of significant disability. Objectives The present analyses assess whether screening prediagnosis (preHD) individuals based on a normalized prognostic index (PIN) score would enable the selection of prodromal preHD subjects in whom longitudinal changes in established outcome measures might provide robust signals. It also compares the relative statistical effect size of longitudinal change for these measures. Methods Individual participant data from 2 studies were used to develop mixed effect linear models to assess longitudinal changes in clinical metrics for participants with preHD and PIN-stratified subcohorts. Relative effect sizes were calculated in 5 preHD studies and internally normalized to evaluate the strength and consistency of each metric across cohorts. Results Longitudinal modeling data demonstrate the amplification of effect sizes when preHD subcohorts were selected by PIN score thresholds of >0.0 and >0.4. These models and relative effect sizes across 5 studies consistently indicate that the Unified Huntington's Disease Rating Scale total motor score exhibits the greatest change in preHD. Conclusions These analyses suggest that the employment of PIN scores to homogenize and stratify preHD cohorts could improve the efficiency of current outcome measures, the most robust of which is the total motor score. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209 ), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years ( P < .001) and 7.1 years ( P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa).Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated.Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients.Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

Background Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass Results and conclusions Univariate and multivariate analyses revealed that platelets9/L, albumin

Purpose Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by chronic infection with human T-lymphotropic virus type 1 with diverse clinical features and prognosis. ATL remains a challenging disease as a result of its diverse clinical features, multidrug resistance of malignant cells, frequent large tumor burden, hypercalcemia, and/or frequent opportunistic infection. In 2009, we published a consensus report to define prognostic factors, clinical subclassifications, treatment strategies, and response criteria. The 2009 consensus report has become the standard reference for clinical trials in ATL and a guide for clinical management. Since the last consensus there has been progress in the understanding of the molecular pathophysiology of ATL and risk-adapted treatment approaches. Methods Reflecting these advances, ATL researchers and clinicians joined together at the 18th International Conference on Human Retrovirology—Human T-Lymphotropic Virus and Related Retroviruses—in Tokyo, Japan, March, 2017, to review evidence for current clinical practice and to update the consensus with a new focus on the subtype classification of cutaneous ATL, CNS lesions in aggressive ATL, management of elderly or transplantation-ineligible patients, and treatment strategies that incorporate up-front allogeneic hematopoietic stem-cell transplantation and novel agents. Results As a result of lower-quality clinical evidence, a best practice approach was adopted and consensus statements agreed on by coauthors (> 90% agreement). Conclusion This expert consensus highlights the need for additional clinical trials to develop novel standard therapies for the treatment of ATL

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study. Hence, we integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset. We first defined differentially-expressed and survival-associated IRGs in PTC patients with a computational difference algorithm and COX regression analysis. The potential molecular mechanisms and properties of these PTC-specific IRGs were also explored with the help of computational biology. A new prognostic index based on immune-related genes was developed, which proved adept at evaluating the PFIs of PTC patients. Relationships between the prognostic index and several clinical and demographic characteristics were also characterized. Intriguingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. Together, our results screened several IRGs of clinical significance, revealed drivers of the immune repertoire, and demonstrated the importance of a personalized, IRG-based immune signature in the recognition, surveillance, and prognosis of PTC. Funding: This study was supported by grants from Innovation Project of Guangxi Graduate Education (YCSW2018104), Guangxi Medical University Training Program for Distinguished Young Scholars, Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University and Fund of Guangxi Provincial Health Bureau Scientific Research Project (Z2018). Declaration of Interest: The authors have no conflicts of interest.

Alternative splicing (AS) is crucial a mechanism by which the complexity of mammalian and viral proteom increased overwhelmingly. There lacks systematic and comprehensive analysis of the prognostic significance of AS profiling landscape for uteri corpus endometrial carcinoma (UCEC). In this study, univariate and multivariate Cox regression analyses were conducted to identify candidate survival-associated AS events curated from SpliceSeq for the construction of prognostic index (PI) models. A correlation network between splicing factor-related AS events and significant survival-associated AS events were constructed using Cytoscape 3.5. As consequence, 28281 AS events from 8137 genes were detected from 506 UCEC patients, including 2630 survival-associated AS events. Kaplan Meier survival analysis revealed that six of the seven PI models (AD, AP, AT, ME, RI and ALL) exhibited good performance in stratifying the prognosis of low risk and high risk group (P

Prognostic indices are commonly used in the context of brain metastases radiotherapy to guide patient decision-making and clinical trial stratification. This study is to choose an appropriate prognostic index (PI) for non-small cell lung cancer (NSCLC) patients with brain metastases (BM) who underwent radiosurgery. A total of 103 patients with BM from NSCLC receiving radiosurgery were analyzed retrospectively. There are six prognostic factors were analyzed, including age, primary tumor control, extracranial metastasis, KPS score, number of lesions, max lesion volume; and four prognostic indices were compared, include Recursive Partitioning Analysis (RPA),Graded Prognostic Assessment (GPA), Score Index for Radiosurgery (SIR), Basic Score for Brain Metastases (BSBM). Survival curves were estimated with the Kaplan-Meier method and compared with a log-rank test stratified according to the PIs. Univariate and multivariate analysis was performed using the Cox regression analysis. The PI's predictive capacity was compared in terms of Akaike information criterion (AIC), Log-rank × 2, Concordance index (C-index) and calibration curve. The median survival time was 8 months, and the 6-months and 12-months survival rate were 61% and 26% respectively. All four prognostic indices were correlated with prognosis (P

Background Coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) diminishes the value of the CD4+ T-cell count in diagnosing AIDS, and increases the rate of HTLV-1–associated myelopathy. It remains elusive how HIV-1/HTLV-1 coinfection is related to such characteristics. We investigated the mutual effect of HIV-1/HTLV-1 coinfection on their integration sites (ISs) and clonal expansion. Methods We extracted DNA from longitudinal peripheral blood samples from 7 HIV-1/HTLV-1 coinfected, and 12 HIV-1 and 13 HTLV-1 monoinfected individuals. Proviral loads (PVL) were quantified using real-time polymerase chain reaction (PCR). Viral ISs and clonality were quantified by ligation-mediated PCR followed by high-throughput sequencing. Results PVL of both HIV-1 and HTLV-1 in coinfected individuals was significantly higher than that of the respective virus in monoinfected individuals. The degree of oligoclonality of both HIV-1– and HTLV-1–infected cells in coinfected individuals was also greater than in monoinfected subjects. ISs of HIV-1 in cases of coinfection were more frequently located in intergenic regions and transcriptionally silent regions, compared with HIV-1 monoinfected individuals. Conclusions HIV-1/HTLV-1 coinfection makes an impact on the distribution of viral ISs and clonality of virus-infected cells and thus may alter the risks of both HTLV-1– and HIV-1–associated disease.

Background Device replacement is the ideal time to reassess health care goals regarding continuing implantable cardioverter-defibrillator (ICD) therapy. Only few data are available on the decision making at this time. Objectives The goals of this study were to identify factors associated with poor prognosis at the time of ICD replacement and to develop a prognostic index able to stratify those patients at risk of dying early. Methods DEtect long-term COmplications after implantable cardioverter-DEfibrillator replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating long-term complications in a large population of patients who underwent ICD/cardiac resynchronization therapy – defibrillator replacement. Potential predictors of death were investigated, and all these factors were gathered into a survival score index (SUSCI). Results We included 983 consecutive patients (median age 71 years (63-78)); 750 (76%) were men, 537 (55%) had ischemic cardiomyopathy; 460 (47%) were implanted with cardiac resynchronization therapy – defibrillator. During a median follow-up period of 761 days (interquartile range 628–904 days), 114 patients (12%) died. In multivariate Cox regression analysis, New York Heart Association class III/IV, ischemic cardiomyopathy, body mass index Conclusion A simple score that includes a limited set of variables appears to be predictive of total mortality in an unselected real-world population undergoing ICD replacement. Evaluation of the patient’s profile may assist in predicting vulnerability and should prompt individualized options, especially for high-risk patients.

Background and Aim: The aim of the present study is to evaluate a new index (PECS (PsECogSii)index) influenced by PS ECOG and systemic immune-inflammation index (SII) in unresectable locally advanced or metastatic BTC patients treated with first-line chemotherapy. Methods: This multicenter, international, study was conducted on a training cohort of 130 patients and in three European and Korean validation cohorts The PECS index was calculated as ECOG × SII index (neutrophil count × platelet count/lymphocyte count). Event-time distributions were estimated using the Kaplan–Meier method and survival curves were compared using the log-rank test. Results: In the training cohort, the median overall survival (mOS) was 13.2months, 8.7months, and 3.8months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR=1; PECS-1: HR 1.41; PECS-2: HR 3.23) (p&nbsp

BACKGROUND & AIMS Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA)

Background Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM, STC2, NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.

Background Colorectal cancer (CRC) accounts for the highest fatality rate among all malignant tumors. Immunotherapy has shown great promise in management of many malignant tumors, necessitating the need to explore its role in CRC. Results Our analysis revealed a total of 71 differentially expressed IRGs, that were associated with prognosis of CRC patients. Ten IRGs (FABP4, IGKV1-33, IGKV2D-40, IGLV6-57, NGF, RETNLB, UCN, VIP, NGFR, and OXTR) showed high prognostic performance in predicting CRC outcomes, and were further associated with tumor burden, metastasis, tumor TNM stage, gender, age, and pathological stage. Interestingly, the IRG-based prognostic index (IRGPI) reflected infiltration of multiple immune cell types. Conclusions This model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor prognosis of CRC. Methods We performed a comprehensive analysis of expression profiles for immune-related genes (IRGs) and overall survival time in 437 CRC patients from the TCGA database. We employed computational algorithms and Cox regression analysis to estimate the relationship between differentially expressed IRGs and survival rates in CRC patients. Furthermore, we investigated the mechanisms of action of the IRGs involved in CRC, and established a novel prognostic index based on multivariate Cox models.

Background Growing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD). Methods We retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS). Results The estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS. Conclusion Specific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.

Objective: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. Study design: We reviewed medical records of children 13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. Results: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children 26%. Conclusions: The HUS severity score was able to discriminate between high- and low-risk children

Purpose: Tumour metabolism has become a novel factor targeted by personalised cancer drugs. This research evaluated the prognostic significance of metabolism-related genes (MRGs) in ovarian serous cystadenocarcinoma (OSC). Methods: MRGs in 379 women surviving OSC were obtained using The Cancer Genome Atlas (TCGA) database. Then, several biomedical computational algorithms were employed to identify eight hub prognostic MRGs that were significantly relevant to OSC survival. These eight genes have important clinical significance and prognostic value in OSC. Subsequently, a prognostic index was constructed. Drug sensitivity analysis was used to screen the key genes in eight MRGs. Immunohistochemistry (IHC) staining confirmed the expression levels of key genes and their correlations with clinical parameters and prognosis for patients. Results: A total of 701 differentially expressed MRGs were confirmed in women with OSC by the TCGA database. The random walking with restart (RWR) algorithm and the univariate Cox and lasso regression analyses indicated a prognostic signature based on eight MRGs (i.e., ENPP1, FH, CYP2E1, HPGDS, ADCY9, NDUFA5, ADH1B and PYGB), which performed moderately well in prognostic predictions. Drug sensitivity analysis indicated that PYGB played a key role in the progression of OSC. Also, IHC staining confirmed that PYGB has a close correlation with clinical parameters and poor prognosis in OSC. Conclusion: The results of the present study may help to establish a foundation for future research attempting to predict the prognosis of OSC patients and to characterise OSC metabolism.

Abstract Background Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases. Methods We performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index. Results The original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status. Conclusions The Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.

Objective: Post-stroke depressive symptoms have a vast individual and societal impact. However, research into interventions for such symptoms show contradictory results; it is unclear what works for which patients. In addition, clinical prediction tools are lacking. This study aimed to develop a prognostic index model for treatment outcome in patients with post-stroke depressive symptoms.Methods: Data from a randomized controlled trial (n = 61) evaluating 2 interventions for post-stroke depressive symptoms were used to predict post-treatment post-stroke depressive symptoms and participation. From 18 pre-treatment variables of patients and caregivers, predictors were selected using elastic net regression. Based on this selection, prognostic index scores (i.e. predictions) for both out comes were computed for each individual patient.Results: The depression model included all pre-treatment variables, explaining 44% of the variance. The strongest predictors were: lesion location, employment, participation, comorbidities, mobility, sex, and pre-treatment depression. Six predictors of post-treatment participation were identified, explaining 51% of the variance: mobility, pre-treatment participation, age, satisfaction with participation, caregiver strain, and psychological distress of the spouse. The cross-validated prognostic index scores correlated highly with the actual outcome scores (depression: correlation = 0.672; participation: correlation = 0.718).Conclusion: Post-stroke depressive symptoms form a complex and multifactorial problem. Treatment outcome is influenced by the characteristics of the stroke, the patients, and their spouses. The results show that psychological distress is probably no obstacle to attempting to improve participation. The personalized predictions (prognostic index scores) of treatment outcome show promising results, which, after further replication and validation, could aid clinicians with treatment selection.

Mantle cell lymphoma (MCL) is still considered incurable and the course of the disease is highly variable. Established risk factors include the Mantle Cell Lymphoma International Prognostic Index (MIPI) and the quantification of the proliferation rate of the tumour cells, e.g. by Ki-67 immunohistochemistry. In this study, we aimed to validate the prognostic value of the gene expression-based MCL35 proliferation assay in patient cohorts from randomized trials of the European Mantle Cell Lymphoma Network. Using this assay, we analysed the gene expression proliferation signature in routine diagnostic lymph node specimens from MCL Younger and MCL Elderly trial patients, and the calculated MCL35 score was used to assign MCL patients to low (61%), standard (27%) or high (12%) risk groups with significantly different outcomes. We confirm here in our prospective clinical trial cohort of MCL patients, that the MCL35 assay is strongly prognostic, providing additional information to the Ki-67 index and the MIPI. Thus, this robust assay may assist in making treatment decisions or in devising risk-adapted prospective clinical trials in the future.

Summary Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL‐NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL‐NOS were retained for study. At a median follow‐up of 46 months, the median overall survival (OS) and progression‐free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1–2), and high risk (HiR, 74 patients, 24%, score 3–4), having a 3‐year OS of 76% [95% confidence interval 61–88], 43% [35–51], and 11% [4–21], respectively (P

Background Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. Methods A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. Results Median OS was 15.4 months. Tumour size > 7 cm (p 7 cm, ITN and AEN identified patients with poor prognosis (p

Background: The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI). Methods: Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT. Results: The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001). Conclusions: This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.

Author(s): Tate, Janet P; Sterne, Jonathan AC; Justice, Amy C; Veterans Aging Cohort Study (VACS) and the Antiretroviral Therapy Cohort Collaboration (ART-CC) | Abstract: ObjectiveDespite viral suppression and immune response on antiretroviral therapy, people with HIV infection experience excess mortality compared with uninfected individuals. The Veterans Aging Cohort Study (VACS) Index incorporates clinical biomarkers of general health with age, CD4 cell count, and HIV-1 RNA to discriminate mortality risk in a variety of HIV-positive populations. We asked whether additional biomarkers further enhance discrimination.Design and methodsUsing patients from VACS for development and from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for validation, we obtained laboratory values from a randomly selected visit from 2000 to 2014, at least 1 year after antiretroviral therapy initiation. Patients were followed for 5-year, all-cause mortality through September 2016. We fitted Cox models with established predictors and added new predictors based on model fit and Harrell's c-statistic. We converted all variables to continuous functional forms and selected the best model (VACS Index 2.0) for validation in ART-CC patients. We compared discrimination using c-statistics and Kaplan-Meier plots.ResultsAmong 28 390 VACS patients and 12 109 ART-CC patients, 7293 and 722 died, respectively. Nadir CD4, CD8, and CD4 : CD8 ratio did not improve discrimination. Addition of albumin, white blood count, and BMI, improved c-statistics in VACS from 0.776 to 0.805 and in ART-CC from 0.800 to 0.831. Results were robust in all nine ART-CC cohorts, all lengths of follow-up and all subgroups.ConclusionVACS Index 2.0, adding albumin, white blood count, and BMI to version 1.0 and using continuous variables, provides improved discrimination and is highly transportable to external settings.

Background Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. Methods We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). Results Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P

BackgroundCurrent ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders.MethodBaseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14–35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses.ResultsAt 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56–7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21–6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14–6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01–1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00–1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class.ConclusionsPredicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.

目的 比较IPI、美国国家综合癌症网络IPI（NCCN-IPI）及年龄调整的IPI（aa-IPI）三种预后分层模型在弥漫大B细胞淋巴瘤（DLBCL）患者中的预后分层能力。 方法 回顾性分析2003年1月至2012年12月311例初治DLBCL患者资料，根据治疗方案将患者分为CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松）方案及利妥昔单抗（R）-CHOP方案组，分别采用IPI、NCCN-IPI及aa-IPI对DLBCL患者进行危险度分层。采用Harrell's C统计评价不同模型的预后分层能力。 结果 ①311例患者中接受CHOP方案治疗者128例，接受R-CHOP方案治疗者183例。②CHOP方案组患者的5年总生存（OS）率结果显示，aa-IPI（71.0%对25.0%，P

Prostate adenocarcinoma (PRAD) is one of the most common types of malignancy in males and at present, effective prognostic indicators are limited. The development of PRAD has been associated with abnormalities in alternative splicing (AS), a requisite biological process of gene expression in eukaryotic cells; however, the prognostic value of AS products and splicing events remains to be elucidated. In the present study, the data of splicing events and the clinical information of PRAD patients were obtained from The Cancer Genome Atlas (TCGA)SpliceSeq and TCGA databases, respectively. A prognostic index (PI) was generated from disease-free survival-associated splicing events (DFS-SEs), which were identified by univariate/multivariate Cox regression analysis. A total of 6,909 DFS-SEs were identified in PRAD. The corresponding genes for the DFS-SEs were significantly enriched in mitochondria and their associated pathways according to Gene Ontology annotation and in the pathways of fatty acid metabolism, oxidative phosphorylation and Huntington's disease according to a Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PI for mutually exclusive exons had the greatest ability to predict the probability of five-year disease-free survival of patients with PRAD, with an area under the time-dependent receiver-operating characteristic curve of 0.7606. Patients with PRAD, when divided into a 'low' and a 'high' group based on their median PI for exon skip values, exhibited a marked difference in disease-free survival (low vs. high, 3,588.45±250.51 vs. 1,531.08±136.50 days; P=7.43×10−9). A correlation network between DFS-SEs of splicing factors and non-splicing factors was constructed to determine the potential mechanisms in PRAD, which included the potential regulatory interaction between the splicing event of splicing factor RNA binding motif protein 5-alternate terminator (AT)-64957 and the splicing event of non-splicing factor heterochromatin protein 1 binding protein 3-AT-939. In conclusion, the PIs derived from DFS-SEs are valuable prognostic factors for patients with PRAD, and the function of splicing events in PRAD deserves further exploration.

Primary cancer of the parotid gland (PG) is a rare disease characterized by a wide variety of histologies and subtypes. The aim of the study was to identify factors influencing survival and validate the prognostic scores (PS1 and PS2) by Vander Poorten et al. STUDY DESIGN: Retrospective cohort study.All patients with previously untreated PG epithelial malignancies who underwent surgery with curative intent from 2002 to 2015 at a single center were retrospectively reviewed.104 patients were included. Mean age was 60.2 years (range 14-88). Definitive pT staging was: 26 (25%) pT1, 19 (18.3%) pT2, 15 (14.4%) pT3, 41 (39.4%) pT4a, and 3 (2.9%) pT4b. Lateral neck nodal metastases were diagnosed in 27 (26%) patients. Five- and 10-year overall survival was 74.7% and 69.4%, respectively. Disease-specific survival at 5 and 10 years was 80.4% and 76.5%, respectively. Recurrence-free survival at 5 and 10 years was 66.9%. PS-1 and PS-2 scores correlated with prognosis. The most critical prognostic variables were grading, nodal metastases, perineural infiltration, lympho-vascular invasion, and skin infiltration.Major risk factors in primary PG carcinomas can effectively identify high-risk patients. The prognostic score by Vander Poorten et al. is a highly reliable tool to predict the prognostic profile.

BACKGROUND Rapid effective triage is integral to emergency care in patients hospitalized for heart failure, to guide the type and intensity of therapy. Several indexes and scores have been proposed to predict outcome; most of the them are complex and unfit to use at the bedside. METHODS We propose a new prognostic index for in hospital mortality in acute heart failure. The index is calculated using the following formula: 220 - age - heart rate + systolic blood pressure - (creatinine ×10). The index was tested in 1628 patients admitted for acute heart failure and enrolled, from November 2007 to December 2009, in the Italian Registry on Heart Failure Outcome (IN-HF); a prospective, multicenter, observational study. RESULTS The prognostic index was an independent predictor for in hospital mortality risk (AUC=0.74, P

SummaryBackground Intermediate-stage hepatocellular carcinoma (HCC), for which trans-arterial chemoembolization (TACE) constitutes the standard of care, is a patient subgroup with significant heterogeneity in clinical outcome. Sources of variation relate to differences in tumour burden, hepatic reserve, ethnicity and treatment modalities. Increasing research efforts have been dedicated to minimise the clinical diversity of this patient population and enhance optimal provision of treatment. Aim To comprehensively review the diverse prognostic models that have been proposed to refine the prognostic prediction of patients with HCC undergoing TACE. Results A number of prognostic algorithms (HAP, ART, ABCR score and many others) have shown potential to address the clinical heterogeneity characterising patients with intermediate-stage HCC and facilitate early identification of patients with poor prognostic features in whom alternative treatments or best supportive care might be more appropriate than TACE. Conclusions While an improved characterisation of intermediate-stage HCC is a highly important clinical aim, current evidence suggests that novel prognostic algorithms in this patient population may offer potential benefits but non-negligible challenges in the provision of TACE. This review summarises the currently available evidence to facilitate the development of precision oncology in intermediate-stage HCC.

Background: The randomised phase III TURANDOT trial compared first-line bevacizumab–paclitaxel (BEV–PAC) vs bevacizumab–capecitabine (BEV–CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV–PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. Methods: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV–PAC (bevacizumab 10 mg kg−1 days 1 and 15 plus paclitaxel 90 mg m−2 days 1, 8 and 15 q4w) or BEV–CAP (bevacizumab 15 mg kg−1 day 1 plus capecitabine 1000 mg m−2 bid days 1–14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. Results: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV–PAC in the TNBC cohort and BEV–CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV–PAC. Grade ⩾3 adverse events were consistently less common with BEV–CAP. Conclusions: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).

Background: Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods.\ud \ud Methods: In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes.\ud \ud Results: Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI.\ud \ud Conclusion: This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rearrangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P .0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P .0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.

Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc.

Breast cancer prognosis has improved greatly in recent years. Consequently, a thorough search for sensitive prognostic factors, able to help clinicians offer appropriate therapy, has become a priority in this area. In this study, we considered all new cases of invasive breast cancer diagnosed in the Province of Modena, Italy, between 1997 and 2007, registered by the Modena Cancer Registry. The principal endpoint of this study was relapse-free survival (RFS). A set of 11 clinic and pathological parameters was investigated. After a median follow-up of 73 months, 494 relapses were recorded. Tumor size, node status, grading, HER2 and estrogen receptor status were retained as independent factors in a multivariate analysis. Using these variables, a prognostic model was devised to identify three groups at different risk. In the training sample, the 5-year RFS rates resulted 96.0%, 82.9% and 63.7% in patients at low, intermediate and high risk, respectively (p < 0.0001). In the validation sample, the 5-year RFS was 96.2%, 85.4% and 66.9%, respectively. To conclude our study demonstrates that a very simple prognostic index based on easily available clinical data may represent a useful tool for the identification of patients at different risk of relapse and may be a notable device to predict who truly benefits from medical treatment.

We performed a retrospective review of 281 hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) treated with radiation therapy (RT) between 1998 and 2008 to develop a prognostic model for those patients. Of the 281 patients, PVTT and intrahepatic main masses completely disappeared in 10 patients (3.6%), and shown a partial response in 141 patients (50.2%). The median survival was 11.6 months. Patients who had more than PR have shown significantly longer survival than the others (22.0 months vs 5.0 months, P < 0.001). On the multivariate analysis, pre-treatment poor prognosticators for overall survival were ECOG performance status, Child-Pugh class, multiple tumors, main PVTT, complete portal vein occlusion, lymph node metastasis, and primary tumor size. Prognostic index of RT for PVTT of HCC (PITH) scores were defined as the number of pre-treatment poor prognostic factors. PITH scores correlated well with overall survival. In the analysis of 1 and 2 yr overall survival rate, patients who had PITH scores of 3 or greater showed a significantly lower rate of overall survival than the others (33.0%, 17.3% vs 70.1%, 40.8%, respectively, P < 0.001). The PITH scoring model, proposed in the current study in HCC patients with PVTT, reliably predict overall survival.

Despite significant improvements in treatment modalities over the 10 years, the clinical course of patients with follicular lymphoma (FL) remains heterogeneous. Thus, prognostic indexes are still required to direct treatment choices and for the design of clinical trials. Investigators have conducted a variety of studies aimed at integrated assessment of biological and clinical features in order to identify novel prognostic factors and scoring systems. Genetic studies focused on tumor cells and the tumor microenvironment represent a step forward in understanding the biology of FL and are likely to provide new prognostic tools for future clinical use. Several prognostic factors have been identified and are currently used in combination to establish prognostic scores and to support therapeutic decisions. The FL International Prognostic Index (FLIPI) is currently used for defining individual risk of death. More recently, FLIPI2 was developed by the same group that built FLIPI as a new model for prognostic definition of patients with FL. The model was defined using prospectively collected data from patients who also received the monoclonal therapeutic antibody rituximab and stratifies patients into three risk categories for disease progression. Since many biological factors are not yet clinically validated or easily assessable, clinical data still represent the major source of prognostic information. The progressive development of new and more effective therapies for the treatment of FL makes the study of prognosis a dynamic and evolving area of clinical research.

Objective To determine the reliability of a generic index such as Simplified Acute Physiology Score II (SAPSII), compared with a specific one Intra Cerebral Haemorrhage score (ICH score), as an intensive care unit (ICU) outcome predictor when evaluating a general facility that frequently treats a specific type of patients – those with spontaneous cerebral haemorrhage. Methods The study cohort consisted of a random sample of patients (81) admitted to Modena's Policlinico Teaching Hospital's ICU with spontaneous ICH over a 24-month period. Main outcome measure SAPSII, ICH score, overall mortality. Results The mean ICH score for the 32 surviving patients was 3.41 ± 1.012 while for the 49 deceased patients was of 4.24 ± 0.855 (P = 0.000). The mean SAPSII value for the 32 surviving patients was 49.09 ± 16.58 while for the 49 deceased patients was 49.51 ± 15.93. SAPSII, ICH scores were analysed for mortality, by receiver operating characteristic curves: the area under the curve was significant for ICH, not-significant for SAPSII. Conclusions Regional quality controls use generic prognostic indexes (SAPSII) in relation to mortality and outcome to assess ICUs, which is appropriate when dealing with a general facility when there is not a predominant type of patient, but it may bias the evaluation if the population with specific pathologies (ICH), not included in the general index, is statistically considerable, leading to an incorrect criticality assessment, an inappropriate strategic plan and the subsequent inefficient resource allocation.

Background Reliable estimates of the effectiveness of influenza vaccine among persons 65 years of age and older are important for informed vaccination policies and programs. Short-term studies may provide misleading pictures of long-term benefits, and residual confounding may have biased past results. This study examined the effectiveness of influenza vaccine in seniors over the long term while addressing potential bias and residual confounding in the results. Methods Data were pooled from 18 cohorts of community-dwelling elderly members of one U.S. health maintenance organization (HMO) for 1990-1991 through 1999-2000 and of two other HMOs for 1996-1997 through 1999-2000. Logistic regression was used to estimate the effectiveness of the vaccine for the prevention of hospitalization for pneumonia or influenza and death after adjustment for important covariates. Additional analyses explored for evidence of bias and the potential effect of residual confounding. Results There were 713,872 person-seasons of observation. Most high-risk medical conditions that were measured were more prevalent among vaccinated than among unvaccinated persons. Vaccination was associated with a 27% reduction in the risk of hospitalization for pneumonia or influenza (adjusted odds ratio, 0.73; 95% confidence interval [CI], 0.68 to 0.77) and a 48% reduction in the risk of death (adjusted odds ratio, 0.52; 95% CI, 0.50 to 0.55). Estimates were generally stable across age and risk subgroups. In the sensitivity analyses, we modeled the effect of a hypothetical unmeasured confounder that would have caused overestimation of vaccine effectiveness in the main analysis; vaccination was still associated with statistically significant - though lower - reductions in the risks of both hospitalization and death. Conclusions During 10 seasons, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling elderly persons. Vaccine delivery to this high-priority group should be improved.

Background: The red cell distribution width is a biomarker of early mortality across various disease states. Aim: To verify whether it may refine estimates of survival in hepatocellular carcinoma. Methods: The red cell distribution width measured at diagnosis was analyzed in relationship to mortality by any cause both in a retrospective training cohort (N = 208), and in an independent prospectively collected validation cohort (N = 106) of patients with hepatocellular carcinoma. Based on Cox proportional hazards modelling, a prognostic index was validated. Results: In the training and the validation cohort, median survival time was respectively 1026 and 868 days in patients with red cell distribution width ≤14.6%, vs. 282 and 340 days in patients with red cell distribution width >14.6%; the corresponding hazard ratios were 0.43 (95% CI: 0.31–0.60), p < 0.0001 and 0.28 (95% CI: 0.17–0.47), p < 0.0001. At multivariate analysis, the red cell distribution width remained an independent predictor of survival (p < 0.001) in a Cox model including other widely accepted prognostic factors. Applying to the validation dataset the prognostic index derived from the training dataset, the ability of the model to discriminate the survival probabilities of patients was confirmed (Harrell’s C = 0.769). Conclusions: The red cell distribution width is a novel, reproducible, prospectively validated predictor of survival in patients with hepatocellular carcinoma.