Univariate Cox Proportional Hazards Analyses Research Articles

A novel autophagy-related lncRNA survival model for lung adenocarcinoma.

Long non‐coding RNA (lncRNA) is an important regulatory factor in the development of lung adenocarcinoma, which is related to the control of autophagy. LncRNA can also be used as a biomarker of prognosis in patients with lung adenocarcinoma. Therefore, it is important to determine the prognostic value of autophagy‐related lncRNA in lung adenocarcinoma. In this study, autophagy‐related mRNAs‐lncRNAs were screened from lung adenocarcinoma and a co‐expression network of autophagy‐related mRNAs‐lncRNAs was constructed by using The Cancer Genome Atlas (TCGA). The univariate and multivariate Cox proportional hazard analyses were used to evaluate the prognostic value of the autophagy‐related lncRNAs and finally obtained a survival model composed of 11 autophagy‐related lncRNAs. Through Kaplan‐Meier analysis, univariate and multivariate Cox regression analysis and time‐dependent receiver operating characteristic (ROC) curve analysis, it was further verified that the survival model was a new independent prognostic factor for patients with lung adenocarcinoma. In addition, based on the survival model, gene set enrichment analysis (GSEA) was used to illustrate the function of genes in low‐risk and high‐risk groups. These 11 lncRNAs were GAS6‐AS1, AC106047.1, AC010980.2, AL034397.3, NKILA, AL606489.1, HLA‐DQB1‐AS1, LINC01116, LINC01806, FAM83A‐AS1 and AC090559.1. The hazard ratio (HR) of the risk score was 1.256 (1.196‐1.320) (P < .001) in univariate Cox regression analysis and 1.215 (1.149‐1.286) (P < .001) in multivariate Cox regression analysis. And the AUC value of the risk score was 0.809. The 11 autophagy‐related lncRNA survival models had important predictive value for the prognosis of lung adenocarcinoma and may become clinical autophagy‐related therapeutic targets.

Timing of surgery in patients with partial response or stable disease after neoadjuvant chemotherapy for advanced ovarian cancer

ObjectiveThe ideal number of neoadjuvant chemotherapy (NACT) cycles prior to interval tumor-reductive surgery (iTRS) for advanced ovarian cancer is poorly defined. We sought to assess survival stratified by number of NACT cycles and residual disease following iTRS in patients with advanced ovarian cancer with partial response (PR) or stable disease (SD) following 3–4 cycles of NACT. MethodsWe retrospectively identified patients with advanced high-grade ovarian cancer (diagnosed 2/1/2013 to 2/1/2018) who received at least 3 cycles of NACT and iTRS and had a PR or SD. The population was divided into four groups based on the number of NACT cycles prior to iTRS and residual disease status after (CGR [complete gross residual] or incomplete resection [any amount of residual disease]): 1) 3–4 NACT cycles/CGR, 2) 3–4 NACT cycles/incomplete resection, 3) > 4 cycles/CGR, and 4) >4 cycles/incomplete resection. Overall survival (OS) and progression-free survival (PFS) were estimated using a Kaplan-Meier product-limit estimator and modeled using univariable and multivariable Cox proportional hazards analysis. ResultsThe cohort consisted of 265 patients with advanced high-grade ovarian cancer with a median age at diagnosis of 65 years. Most were White (87%), had serous histology (89%), and stage IV disease (57%), with an overall CGR rate of 81%. In a multivariable analysis receipt of >4 NACT cycles was not associated with worse PFS or OS (adjusted hazard ratio [aHR] 1.02, 95% CI 0.74–1.42; aHR 1.12, 95% CI, 0.73–1.72 respectively) than was receipt of 3–4 cycles. Any amount of residual disease was associated with worse PFS and OS regardless of the number of NACT cycles (aHR 1.56, 95% CI 1.09–2.22; aHR 2.38, 95% CI 1.52–3.72 respectively). ConclusionsResidual disease was associated with worse survival outcomes regardless of the number of NACT cycles in patients with PR or SD after NACT for advanced high-grade ovarian cancer. These data suggest that the ability to achieve CGR should take precedence in decision-making regarding the timing of surgery.

A characterization and prognosis prediction model for primary squamous cell carcinoma of the thyroid.

Primary squamous cell carcinoma of the thyroid (PSCCTh) is a sporadic malignancy arising from the thyroid gland. The factors that affect treatment and survival in patients with PSCCTh remain unclear. Our study aims to characterize PSCCTh and establish a prognosis prediction model for patients with PSCCTh. Clinical data and follow-up information for 277 patients from 1973 to 2016 were collected from the Surveillance, Epidemiology, and End Results Program (SEER) 18-registry database (RRID:SCR_003293). Univariate and multivariate Cox proportional hazards analyses and nomogram modeling of potential prognostic factors were conducted. Among the collected patient cases, 57% were female and 43% were male. The median survival of all cases was 6 months; by gender, median survival was 5 and 8 months in the female and male groups, respectively. Univariate and multivariate Cox proportional hazards analyses revealed that age, extent of disease (EOD), T stage, N stage, and treatment were independent prognostic indicators for overall survival (OS) and disease-specific survival (DSS) in patients with PSCCTh. In addition, it was confirmed that the established nomogram model had good consistency and discrimination for PSCCTh prognosis as measured by the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), and calibration curves. Our study indicates that age, EOD, T stage, N stage, and treatment may correlate with OS and DSS in patients with PSCCTh. Importantly, our nomogram prediction model, constructed using parameters including age, T stage, N stage, and treatment, may assist physicians in evaluating patients' prognoses and providing precise therapy for PSCCTh.

Long-term outcome and axillary recurrence in elderly women (≥70 years) with breast cancer: 10-years follow-up from a matched cohort study

Background and objectivesThe oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. MethodsPatients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan–Meier method and univariate Cox-proportional hazard ratio analysis. ResultsA total of 1.748 patients were identified and stratified by age (70–74, 75–79, 80–84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2–46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6–33.3) and luminal B tumors (16.8%, 95% CI 5.9–35.5). ConclusionsAxillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.

Is Blood Eosinophil Count a Biomarker for Chronic Obstructive Pulmonary Disease in a Real-World Clinical Setting? Predictive Property and Longitudinal Stability in Japanese Patients.

The authors examined predictive properties and the longitudinal stability of blood eosinophil count (BEC) or three strata (<100 cells/mm3, 100–299 cells/mm3 and ≥300 cells/mm3) in patients with chronic obstructive pulmonary disease (COPD) for up to six and a half years as part of a hospital-based cohort study. Of the 135 patients enrolled, 21 (15.6%) were confirmed to have died during the follow-up period. Episodes of acute exacerbation of COPD (AECOPD) were identified in 74 out of 130 available patients (56.9%), and admission due to AECOPD in 35 out of 132 (26.5%). Univariate Cox proportional hazards analyses revealed that almost all the age, forced expiratory volume in 1 s (FEV1) and health status measures using St. George’s Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) Score were significantly related to these types of events, but the relationship between age and AECOPD did not reach statistical significance (p = 0.05). Neither BEC nor the three different groups stratified by BEC were significant predictors of any subsequent events. There were no significant differences in the BEC between Visits 1–3 (p = 0.127, Friedman test). The ICC value was 0.755 using log-transformed data, indicating excellent repeatability. In the case of assigning to strata, Fleiss’ kappa was calculated to be 0.464, indicating moderate agreement. The predictive properties of BEC may be limited in a real-world Japanese clinical setting. Attention must be paid to the fact that the longitudinal stability of the three strata is regarded as moderate.

Clinical features and outcome of dogs and cats with bidirectional and continuous right-to-left shunting patent ductus arteriosus.

BackgroundStudies describing the clinical progression of animals with reverse patent ductus arteriosus (PDA) are lacking.ObjectivesTo describe the signalment, presenting signs, echocardiographic features, and survival in a group of dogs and cats with bidirectional and continuous right‐to‐left PDA.AnimalsForty‐six client‐owned animals included, comprising 43 dogs and 3 cats with bidirectional or continuous right‐to‐left PDA.MethodsRetrospective multicenter study. Medical records and echocardiographic findings reviewed from animals diagnosed with bidirectional or continuous right‐to‐left PDA. Impact of ductal morphology, spectral Doppler flow profile, PCV, sildenafil treatment at presentation, sildenafil dose, severity of pulmonary hypertension, general anesthesia with or without surgery and the presence of right‐sided congestive heart failure (R‐CHF) on crude mortality rate were evaluated via Mantel‐Cox log rank comparison of Kaplan‐Meier survival curves. Univariable and multivariable Cox proportional hazards analysis was performed, and hazard ratio (HR) (95% confidence intervals [CI]) was presented.ResultsHindlimb collapse was the most common presenting sign in dogs (n = 16). Clinical signs in cats were variable. Median survival time was 626 days in dogs (range 1‐3628 days). Dogs with R‐CHF had a shorter median survival time (58 days vs 1839 days, P = .03). Dogs treated with sildenafil at initial presentation survived longer (1839 days vs 302 days, P = .03), which was the only independent predictor of survival (HR 0.35, CI 0.15‐0.86, P = 0.021).Conclusions and Clinical ImportanceDogs and cats with reverse PDA have a variable clinical presentation and prognosis. Survival time was longer in animals prescribed sildenafil at diagnosis. Dogs with R‐CHF at presentation have a worse overall outcome.

The adapted Heart Donor Score.

SummaryThe Heart Donor Score (HDS) predicts donor organ discard for medical reasons and survival after heart transplantation (HTX) in the Eurotransplant allocation system. Our aim was to adapt the HDS for application in the United Network for Organ Sharing (UNOS) registry. To adjust for differences between the Eurotransplant and UNOS registries, the “adapted HDS” was created (aHDS) by exclusion of the covariates “valve function,” “left‐ventricular hypertrophy,” and exclusion of “drug abuse” from the variable “compromised history.” Two datasets were analyzed to evaluate associations of the aHDS with donor organ discard (n = 70 948) and survival (n = 19 279). The aHDS was significantly associated with donor organ discard [odds ratio 2.72, 95% confidence interval (CI) 2.68–2.76, P < 0.001; c‐statistic: 0.937). The score performed comparably in donors <60 and ≥60 years of age. The aHDS was a significant predictor of survival as evaluated by univariate Cox proportional hazards analysis (hazard ratio 1.04, 95% CI 1.01–1.07, P = 0.023), although the association lost significance in a multivariable model. The aHDS predicts donor organ discard. Negative effects of most aHDS components on survival are likely eliminated by highly accurate donor selection processes.

KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer.

5‐Fluorouracil (5‐FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5‐FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS‐mutant organoids and cell lines in comparison with KRAS wild‐type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3‐positive patients was significantly worse compared with that of KHDRBS3‐negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3‐positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage‐independent growth by maintaining stem cell‐like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.

A simple-to-use web-based calculator for survival prediction in Parkinson's disease.

Background: To establish and validate a nomogram and corresponding web-based calculator to predict the survival of patients with Parkinson’s disease (PD).Methods: In this cohort study, we retrospectively evaluated patients (n=497) with PD using a two-stage design, from March 2004 to November 2007 and from July 2005 to July 2015. Predictive variables included in the model were identified by univariate and multiple Cox proportional hazard analyses in the training set.Results: Independent prognostic factors including age, PD duration, and Hoehn and Yahr stage were determined and included in the model. The model showed good discrimination power with the area under the curve (AUC) values generated to predict 4-, 6-, and 8-year survival in the training set being 0.716, 0.783, and 0.814, respectively. In the validation set, the AUCs of 4- and 6-year survival predictions were 0.85 and 0.924, respectively. Calibration plots and decision curve analysis showed good model performance both in the training and validation sets. For convenient application, we established a web-based calculator (https://tangyl.shinyapps.io/PDprognosis/).Conclusions: We developed a satisfactory, simple-to-use nomogram and corresponding web-based calculator based on three relevant factors to predict prognosis and survival of patients with PD. This model can aid personalized treatment and clinical decision-making.

Copy Number Alterations are Associated with the Risk of Very Early Relapse in Pediatric B-lineage Acute Lymphoblastic Leukemia: A Nested Case-control MIGICCL Study

Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population. The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL. A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted. The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR=4.94, 95% CI=1.87-13.07 and HR=7.42, 95% CI=2.37-23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant. Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.

Association Between Coffee Intake and Incident Heart Failure Risk: A Machine Learning Analysis of the FHS, the ARIC Study, and the CHS.

Coronary heart disease, heart failure (HF), and stroke are complex diseases with multiple phenotypes. While many risk factors for these diseases are well known, investigation of as-yet unidentified risk factors may improve risk assessment and patient adherence to prevention guidelines. We investigated the diet domain in FHS (Framingham Heart Study), CHS (Cardiovascular Heart Study), and the ARIC study (Atherosclerosis Risk in Communities) to identify potential lifestyle and behavioral factors associated with coronary heart disease, HF, and stroke. We used machine learning feature selection based on random forest analysis to identify potential risk factors associated with coronary heart disease, stroke, and HF in FHS. We evaluated the significance of selected variables using univariable and multivariable Cox proportional hazards analysis adjusted for known cardiovascular risks. Findings from FHS were then validated using CHS and ARIC. We identified multiple dietary and behavioral risk factors for cardiovascular disease outcomes including marital status, red meat consumption, whole milk consumption, and coffee consumption. Among these dietary variables, increasing coffee consumption was associated with decreasing long-term risk of HF congruently in FHS, ARIC, and CHS. Higher coffee intake was found to be associated with reduced risk of HF in all three studies. Further study is warranted to better define the role, possible causality, and potential mechanism of coffee consumption as a potential modifiable risk factor for HF.

A Novel Prognostic Model of Early-Stage Lung Adenocarcinoma Integrating Methylation and Immune Biomarkers

Lung adenocarcinoma (LUAD) is caused by multiple biological factors. Therefore, it will be more meaningful to study the prognosis from the perspective of omics integration. Given the significance of epigenetic modification and immunity in tumorigenesis and development, we tried to combine aberrant methylation and tumor infiltration CD8 T cell-related genes to build a prognostic model, to explore the key biomarkers of early-stage LUAD. On the basis of RNA-seq and methylation microarray data downloaded from The Cancer Genome Atlas (TCGA), differentially expressed genes and aberrant methylated genes were calculated with “DEseq2” and “ChAMP” packages, respectively. A Chi-square test was performed to obtain methylation driver genes. Weighted correlation network analysis (WGCNA) was utilized to mine cancer biomarkers related to CD8 T cells. With the consequences of univariate Cox proportional hazards analysis and least absolute shrinkage and selection operator (LASSO) COX regression analysis, the prognostic index based on 17 methylation driver genes (ZNF677, FAM83A, TRIM58, CLDN6, NKD1, NFE2L3, FKBP5, ITGA5, ASCL2, SLC24A4, WNT3A, TMEM171, PTPRH, ITPKB, ITGA2, SLC6A17, and CCDC81) and four CD8 T cell-related genes (SPDL1, E2F7, TK1, and TYMS) was successfully established, which could make valuable predictions for the survival risk of patients with early-stage LUAD.

Lymph Node Ratio Rather Than Positive Lymph Node Counts Has Better Prognostic Value in Patients With Testicular Germ Cell Tumors.

Background:Testicular cancer represents the most common malignancy in young adult men. In the current study, we sought to analyze and compare the prognostic value of lymph node ratio (LNR) as well as positive lymph node counts (LNC) to understand its clinical significance in testicular germ cell tumors.Methods:We employed eligibility criteria to recruit a total of 931 patients, with testicular cancer, from 2010 to 2015 from The Surveillance, Epidemiology, and End Results (SEER) database. We then used the X-Tile program to calculate LNR and LNC cutoff values and discriminate survival. We then calculated the overall and cancer specific survival rates and analyzed the association between LNR/LNC and clinical pathological characteristics using the χ2 test. Finally, we assessed the relationships between clinical pathological factors and patient survival using univariate Cox proportional hazard analysis.Results:Univariate analysis revealed a significant association between prognosis with age (HR, 5.169; 95% CI, 1.758-15.200; P = 0.003), AJCC stage (III vs I: HR, 9.298; 95% CI, 2.691-32.131; P < 0.001), M stage (HR, 7.897; 95% CI, 3.417-18.251; P < 0.001) and LNR (HR, 3.009; 95% CI, 1.275-7.098; P = 0.012). On the other hand, LNC (HR, 1.743; 95% CI, 0.687-4.420; P = 0.242) was not significantly associated with prognosis. Analysis of the association between LNR/LNC and clinical pathological characteristics showed that high LNR patients tended to have significantly larger tumor sizes (χ2 = 7.877, P = 0.005), as well as advanced T (χ2 = 13.195, P = 0.004), N ( χ2 = 86.775, P < 0.001), M (χ2 = 19.948, P < 0.001) and 7th AJCC (χ2 = 103.074, P < 0.001) stages. In addition, high LNC patients were significantly associated with T (χ2 = 8.799, P = 0.032), N (χ2 = 74.390, P < 0.001) and 7th AJCC (χ2 = 111.759, P < 0.001) stages.Conclusion:LNR was a better predictor for long-term prognosis and was closely associated with clinical pathological characteristics than LNC in patients with testicular germ cell tumors.

A methylomics-correlated nomogram predicts the recurrence free survival risk of kidney renal clear cell carcinoma

&lt;abstract&gt; &lt;sec&gt;&lt;title&gt;Background&lt;/title&gt;&lt;p&gt;Various studies have suggested that the DNA methylation signatures were promising to identify novel hallmarks for predicting prognosis of cancer. However, few studies have explored the capacity of DNA methylation for prognostic prediction in patients with kidney renal clear cell carcinoma (KIRC). It's very promising to develop a methylomics-related signature for predicting prognosis of KIRC.&lt;/p&gt; &lt;/sec&gt; &lt;sec&gt;&lt;title&gt;Methods&lt;/title&gt;&lt;p&gt;The 282 patients with complete DNA methylation data and corresponding clinical information were selected to construct the prognostic model. The 282 patients were grouped into a training set (70%, n = 198 samples) to determine a prognostic predictor by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The internal validation set (30%, n = 84) and an external validation set (E-MTAB-3274) were used to validate the predictive value of the predictor by receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis.&lt;/p&gt; &lt;/sec&gt; &lt;sec&gt;&lt;title&gt;Results&lt;/title&gt;&lt;p&gt;We successfully identified a 9-DNA methylation signature for recurrence free survival (RFS) of KIRC patients. We proved the strong robustness of the 9-DNA methylation signature for predicting RFS through ROC analysis (AUC at 1, 3, 5 years in internal dataset (0.859, 0.840, 0.817, respectively), external validation dataset (0.674, 0.739, 0.793, respectively), entire TCGA dataset (0.834, 0.862, 0.842, respectively)). In addition, a nomogram combining methylation risk score with the conventional clinic-related covariates was constructed to improve the prognostic predicted ability for KIRC patients. The result implied a good performance of the nomogram.&lt;/p&gt; &lt;/sec&gt; &lt;sec&gt;&lt;title&gt;Conclusions&lt;/title&gt;&lt;p&gt;we successfully identified a DNA methylation-associated nomogram, which was helpful in improving the prognostic predictive ability of KIRC patients.&lt;/p&gt; &lt;/sec&gt; &lt;/abstract&gt;

Prognostic role of inflammation index in patients with resected I–II stages of non-small-cell lung cancer

Nowadays, inflammatory cell sin peripheral blood are considered as prognostic factors in different malignan-cies. The aim of this study was to identify the prognostic value of pretreatment blood inflammatory biomarkers for patients undergoing surgery for I–II stages of non-small-cell lung cancer (NSCLC). Methods. A single-center retro-spective review from 2003 to 2017 enrolled 403 patients with early stages of NSCLC who underwent surgical resec-tion in our hospital. Results. Univariate Cox proportional hazards analysis showed that age (&gt;70), high level of the systematic immune-inflammation index (&gt;489.67 • 109/l) and neutrophil to lymphocyte ratio (&gt;2.03 • 109/l) were identified as the independent prognostic factors (OR 1.908 CI: 1.361–2.677; 1.735 CI: 1.018–2.956 and 1.626 CI: 0.994–2.659 respectively р&lt;0.05). Conclusions. Pre-operative level of blood hematological biomarkers may serve as a useful and accessible prognostic indicators for predicting outcomes in patients with I– II stages of NSCLC.

Prognostic factors for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: a multicenter study in China.

BackgroundIn China, one of the major causes of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of herbals containing pyrrolizidine alkaloid (PA). However, prognostic factors for PA-induced HSOS are poorly understood. The aim of this study was to identify the independent prognostic factors for PA-induced HSOS using a multi-center study.MethodsA total of 117 PA-induced HSOS patients were enrolled for data collection in three university hospitals from November 2003 to September 2018. Univariate and multivariate Cox proportional hazards analysis were used to determine prognostic factors for PA-induced HSOS.ResultsThe median age of the PA-induced HSOS patients was 61 years (range, 21–88 years), and 64% of them were male. The survival rates at 1, 3, and 36 months were 89.71%, 72.60%, and 69.19%, respectively. Significant differences in prothrombin time (PT), international normalized ratio, total bilirubin, severity grading [new criteria for severity grading of hematopoietic stem cell transplantation (HSCT)-related HSOS in adults] were found between patients who survived and those who died. Univariate and multivariate survival analysis using Cox’s regression model demonstrated low serum albumin (<35 g/L), elevated serum urea (>8.2 mmol/L) and severe or very severe HSOS (European Society for Blood and Marrow Transplantation 2016 criteria) were independent prognostic factors of survival.ConclusionsSerum albumin, serum urea, and severity grading were independent prognostic factors for patients with PA-induced HSOS, and can contribute to identifying potentially high-risk patients for early effective intervention.Trial registrationChiCTR-DRD-17010709 (www.chictr.org.cn).

Prognostic values of geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) in elderly patients with Diffuse Large B-Cell Lymphoma.

Background: Geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) are associated with prognosis of various malignancies. Although GNRI and PNI indicates prognosis in some clinical settings, the values of GNRI and PNI on the prognosis of geriatric patients with Diffuse Large B‐Cell Lymphoma (DLBCL) is unclear. This retrospective analysis aimed to explore the prognostic values of GNRI and PNI in elderly DLBCL patients.Methods: A total of 133 geriatric patients with DLBCL were recruited from Affiliated Hospital of Xuzhou Medical University, and clinicopathological variables were analyzed. X-Tile program, restricted cubic spline (RCS) and time-dependent receiver operating characteristic (ROC) analysis were used to determine optimal cut-off points of GNRI, PNI and other continuous variables; univariate and multivariate Cox proportional hazards analyses were used for variables selection; Kaplan‐Meier curve was utilized to analyze the influence of variables on prognosis; log-rank test was performed for difference evaluation between groups.Results: The optimal cut-off points for GNRI and PNI were 106.26 and 47 by using RCS. Multivariate analysis showed that PNI, age, hemoglobin, liver invasion and central nervous system invasion were independent prognostic factors for elderly patients with DLBCL, and PNI was (P = 0.001, HR = 0.413, 95% CI (0.240-0.710) a stronger predictor. Low PNI could predict worse prognosis independently of elderly patients of DLBCL and could re-stratify patients in GCB group, CD5 positive group BCL-2 positive group, and BCL-6 positive group.Conclusions: PNI was an independent adverse factor for elderly DLBCL and patients with low PNI in GCB group, CD5 positive group and BCL-6 positive group were with poor survival.

The obesity paradox for mid- and long-term mortality in older cancer patients: a prospective multicenter cohort study

Overweight and obesity are associated with adverse health outcomes. However, substantial literature suggests that they are associated with longer survival among older people. This "obesity paradox" remains controversial. In the context of cancer, the association between overweight/obesity and mortality is complicated by concomitant weight loss (WL). Sex differences in the relation between BMI (in kg/m2) and survival have also been observed. We studied whether a high BMI was associated with better survival, and whether the association differed by sex, in older patients with cancer. We studied patients aged ≥70 y from the ELCAPA (Elderly Cancer Patients) prospective open cohort (2007-2016; 10 geriatric oncology clinics, Greater Paris urban area). The endpoints were 12- and 60-mo mortality. We created a variable combining BMI at cancer diagnosis and WL in the previous 6 mo, and considered 4 BMI categories-underweight (BMI<22.5), normal weight (BMI=22.5-24.9), overweight (BMI=25-29.9), and obesity (BMI≥30)-and 3 WL categories-<5% (minimal), 5% to <10% (moderate), and ≥10% (severe). Univariate and multivariate Cox proportional hazards analyses were conducted in men and women. A total of 2071 patients were included (mean age: 81 y; women: 48%; underweight: 30%; normal weight: 23%; overweight: 33%; obesity: 14%; predominant cancer sites: colorectal (18%) and breast (16%); patients with metastases: 49%). By multivariate analysis, obese women with WL<5% had a lower 60-mo mortality risk than normal-weight women with WL<5% (adjusted HR: 0.56; 95% CI: 0.37, 0.86; P=0.012). Overweight/obese women with WL≥5% did not have a lower mortality risk than normal-weight women with WL<5%. Overweight and obese men did not have a lower mortality risk, irrespective of WL. By taking account of prediagnosis WL, only older obese women with cancer with minimal WL had a lower mortality risk than their counterparts with normal weight.This trial was registered at clinicaltrials.gov as NCT02884375.

Influence of Pretransplant Factors on Posttransplant Anemia Recovery Rate in Primary Deceased Donor Kidney Transplant Recipients.

Our objective was to evaluate the influence of pretransplant risk factors on posttransplant anemia recovery. This single-center observational retrospective study included 80 deceased donor kidney transplant recipients who had been followed up to 16 months after kidney transplant. Time point of posttransplant anemia recovery was considered the time when hemoglobin of 11.0 g/dL was achieved and maintained for 3 consecutive monthly visits. We collected donor/transplant characteristics (age, sex, hypertension history, cause of death, donor kidney function, expanded criteria donor status, deceased donor score, HLA mismatch, and cold ischemia time) and recipient data (pretransplant hemoglobin, parathyroid hormone, kidney graft function, delayed graft function, acute rejection, infections, surgical bleeding, posttransplant parathyroid hormone, iron stores, and C-reactive protein and tacrolimus levels). We used univariate and multivariate Cox proportional hazards analyses and Kaplan-Meier plots to determine associations between variables and posttransplant anemia recovery rate. P < .05 was considered significant. We identified 62 deceased donors (33 male; mean age 50 ± 15.1 years) and 80 kidney transplant recipients (52 male; mean age 47.0 ± 10.6 years). Mean pretransplant hemoglobin was 11.4 ± 1.5 g/dL. Donor age, deceased donor score, pretransplant parathyroid hormone, posttransplant transferrin saturation (all P < .05), and tacrolimus level (P < .01) were significantly related to posttransplant anemia recovery. Kaplan-Meier curve identified that recipients of deceased donors below 60 years old achieved hemoglobin of 11.0 g/dL more frequently and earlier than recipients of deceased donors above 60 years old (P < .05). Deceased donor age, deceased donor score, pretransplant serum parathyroid hormone, posttransplant transferrin saturation, and tacrolimus level were significantly associated with posttransplant anemia recovery rate in deceased donor kidney transplant recipients. Anemia recovery was more frequent and earlier in recipients of deceased donors below 60 years than in recipients of donors 60 years old and above.

Radiation-Induced Sarcoma: A Retrospective Population-Based Study Over 34 Years in a Single Institution

AimsAbout a half of all cancer patients receive radiotherapy as part of their oncological treatment. Because of the carcinogenic effect of ionising radiation, there is a rare, but definite, risk of developing secondary malignancies, including sarcomas. The aim of this retrospective study was to describe the prevalence, patient and tumour characteristics, as well as prognosis and outcome, of patients with radiation-induced sarcomas (RIS) in a cohort of patients treated in the Sarcoma Centre at Aarhus University Hospital over a period of 34 years. Materials and methodsAll patients who fulfilled the criteria for RIS and were treated for RIS in the period 1979–2013 were included. Patient data were retrieved from the Aarhus Sarcoma Registry and the National Danish Sarcoma Database, crosschecked with the National Register of Pathology and validated using the patients' medical records. The primary end point was the effect of surgery and treatment intent on overall survival. Overall survival is reported using the Kaplan–Meier estimates and compared using the Log-rank test. Descriptive statistics are presented for patients, tumours and treatment characteristics. ResultsOf 2845 patients diagnosed with sarcoma between 1979 and 2013, 64 (2%) were diagnosed with RIS. The median interval from the original malignancy was 11 years. The most common histological type was undifferentiated pleomorphic sarcoma (33%). Curative treatment was intended for 45 patients. Fifty patients underwent surgery, of whom 80% had microscopically radical resection (R0). The 5-year overall survival for the whole cohort was 32%. Patients who underwent surgery had a significantly better overall survival compared with patients who were not treated with surgery. In the univariate Cox proportional hazard analyses, no metastases at diagnosis, surgery and R0 resection were favourable prognostics factors of survival. ConclusionThis study showed that RIS patients are unique in their epidemiology and tumour characteristics. They have a poor prognosis and need special research investigating new intensive treatment strategies to improve the outcome.