Predictive Factor For Poor Prognosis Research Articles

Relationship of prognostic factors in stomach cancer with Helicobacter pylori: A retrospective study

Background and study aims: The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. Patients and methods: The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. Results: Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. Conclusion: While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.

Correlation between percentage of fat mass and level of disease activity in rheumatoid arthritis.

Introduction:Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation.Objective:To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis.Materials and methods:This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28).Results:The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson’s correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76).Conclusion:The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.

Vasohibin 2 promotes lymphangiogenesis of lung squamous cell carcinoma through snail-dependent vascular endothelial growth factor-D (VEGF-D) signaling pathway.

BackgroundTumor lymphatic metastasis is mostly dependent on lymphangiogenesis, which was less studied compared to angiogenesis and the molecular mechanisms involved remained unclear.MethodsWe analyzed the mRNA expression profiles of 937 primary lung squamous cell carcinoma (LUSC) samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the genes related to lymphatic metastasis in LUSC. We focused on vasohibin 2 (VASH2) and investigated its biological functions in LUSC proliferation, apoptosis, migration, invasion, as well as lymphangiogenesis capacity by forced over-expressing VASH2 in LUSC cell line H520 in vitro and in vivo. We also evaluated the anti-tumor efficacy of specific anti-VASH2 antibody in LUSC xenograft-bearing mice models.ResultsVasohibin2 (VASH2) was filtered out as a significant predictive factor of poor prognosis and lymphatic metastasis in LUSC patients both in public datasets and an independent Chinese LUSC cohort. VASH2 promoted the proliferation and invasion of LUSC cells in vitro and vivo. Forced over-expression of VASH2 in LUSC cells promoted the amplification and tube formation capacity of human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) via up-regulating vascular endothelial growth factor-D (VEGF-D), which could be reversed via Snail inhibition. Furthermore, blocking VASH2/VEGF-D signaling using specific antibodies dramatically inhibited tumor growth in mice by interfering with the proliferation of cancer cells and lymphangiogenesis in tumor tissues.ConclusionsIn conclusion, VASH2 facilitated lymphangiogenesis and tumor growth in a Snail-dependent manner and might serve as a novel biomarker for early diagnosis and prognosis prediction, as well as a potential therapeutic target in LUSC.

Insights of Worsening Renal Function in Type 1 Cardiorenal Syndrome: From the Pathogenesis, Biomarkers to Treatment

Type-1 cardiorenal syndrome refers to acute kidney injury induced by acute worsening cardiac function. Worsening renal function is a strong and independent predictive factor for poor prognosis. Currently, several problems of the type-1 cardiorenal syndrome have not been fully elucidated. The pathogenesis mechanism of renal dysfunction is unclear. Besides, the diagnostic efficiency, sensitivity, and specificity of the existing biomarkers are doubtful. Furthermore, the renal safety of the therapeutic strategies for acute heart failure (AHF) is still ambiguous. Based on these issues, we systematically summarized and depicted the research actualities and predicaments of the pathogenesis, diagnostic markers, and therapeutic strategies of worsening renal function in type-1 cardiorenal syndrome.

Upregulated Transcription Factor PITX1 Predicts Poor Prognosis in Kidney Renal Clear Cell Carcinoma-Based Bioinformatic Analysis and Experimental Verification.

Paired-like homeodomain transcription factor 1 (PITX1) is involved in numerous biological processes, including cell growth, progression, and invasion in various malignant tumors. Nevertheless, the relationship between PITX1 and kidney renal clear cell carcinoma (KIRC) remains unclear. The clinical role and functions of PITX1 were analyzed by integrating multiple open-access online datasets. Further experimental verification was performed via quantitative real-time PCR (qRT-PCR) to detect the expression of PITX1 in 10 pairs of KIRC tissues. Our results revealed that PITX1 mRNA was overexpressed in tumor tissues compared with normal tissues in the TCGA-KIRC database (p < 0.001) and numerous independent cohorts (p < 0.05). Further, high expression of PITX1 mRNA was detected in KIRC tissues compared with adjacent normal tissues in our center by qRT-PCR (N = 10, p < 0.05). Logistic regression analysis demonstrated that the PITX1 level was positively associated with KIRC patients, T and M stages, histologic grade, and pathologic stage (all p < 0.05). Survival analysis showed that upregulation of PITX1 mRNA was associated with poor overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) (all p < 0.05). Univariate/multivariate Cox hazard regression analysis revealed that PITX1 was an independent risk factor for OS in patients with KIRC (HR = 1.998, p = 0.003). Accordingly, the time-independent receiver operating characteristic (ROC) curve confirmed that PITX1 had good predictive efficacy for OS and DSS. Meanwhile, a prediction model constructed by nomogram was used to predict the OS of KIRC patients, and the calibration plot indicated this model shows high accuracy. We also revealed some downstream target genes of PITX1-related signaling pathways. Our finding suggested that high PITX1 mRNA expression may act as an independent predictive factor of poor prognosis in patients with KIRC. The prognostic model based on the nomogram would be instrumental in evaluating the survival rate in KIRC patients.

Oxidative stress and macrophage infiltration in IgA nephropathy.

The aim of this study wasto evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years,with a follow-up period ≥ 1 year or whoshowed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, withC4d and CD68 staining. Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated withthe intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. An increased number of macrophages in the glomerular and tubulointerstitial area may play arole in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Relationship of prognostic factors in stomach cancer with helicobacter pylori: a retrospective study.

The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.

Impact of coexistent preserved ratio impaired spirometry on the survival of patients with lung cancer: Analysis of data from the Korean Association for Lung Cancer Registry.

BackgroundPreserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor.MethodsWe retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1] < 80% predicted and FEV1/forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis.ResultsOf the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel–Cox log‐rank test, p < 0.05). In the risk‐adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC.ConclusionsPRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre‐existing PRISm should be considered a predictive factor of poor prognosis.

Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors.

The introduction of checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC) treatment landscape, resulted in improvements in overall survival (OS) in metastatic patients. Brain metastases (BMs) are a specific metastatic site of interest representing a predictive factor of poor prognosis. Patients with BMs were usually excluded from prospective clinical trials in the past. Despite recent evidence suggest the efficacy and safety of ICIs, the BMs treatment remains a challenge; the immunotherapy responsiveness seems to be multifactorial and dependent on several factors, such as the genetic intratumor heterogeneity and the immunosuppressive role of the brain tumor microenvironment. This review, starting from the immunological background in RCC BMs, provide an overview of the upcoming evidence from clinical trials, address the issues related to the neuroradiological immunotherapy response evaluation and, with a look to the future, describes how the epigenetic modulation of immune evasion could represent a background for new therapeutic strategies.

Neutrophil-to-lymphocyte ratio predicts prognosis of patients with hepatocellular carcinoma: a systematic review and meta-analysis

BackgroundNeutrophil-to-lymphocyte ratio (NLR) is one predictive factor for poor prognosis of patients with hepatocellular carcinoma (HCC). In response to contradictory data concerning the predictive ability of NLR, we performed a meta-analysis for the determination of its prognostic value in patients with HCC.MethodsWe systematically searched several databases including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang databases with the updated date of September 21, 2020. Inclusion criteria: RCT studies reporting the prognostic value of the serum levels of NLR in HCC patients receiving treatment were enrolled. Pooled estimates of odds ratio (OR) and diagnostic odds ratio (DOR) were used to assess the prognostic performance of NLR in HCC patients. Overall survival (OS) was the primary outcome and progression-free survival (PFS) was secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Furthermore, risk of bias assessment of included studies is specified by Cochrane Risk Bias Assessment Tool.ResultsThis analysis included 9 studies containing a total of 3,862 HCC patients. High baseline NLR was significantly correlated with poor prognosis or recurrence. The patient-based analysis of pooled estimates was as follows: sensitivity, 0.68 (95% CI: 0.58–0.77); specificity, 0.73 (95% CI: 0.61–0.82); DOR, 6.347 (95% CI: 5.450–7.391). The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were 2.5 (95% CI: 1.8–3.6) and 0.43 (95% CI: 0.33–0.57). Furthermore, the area under the curve (AUC) of summary receiver operating characteristic (SROC) reflecting the prognostic accuracy was 0.76 (95% CI: 0.72–0.80). Results obtained from subgroup meta-analyses and overall meta-analyses were accordingly consistent with each other.ConclusionsOur findings suggested that NLR is an effective prognostic factor for patients with HCC, especially for those from East Asian populations with high incidence. In the future, trials with larger sample sizes and more high-quality evidence are needed to further improve patient outcomes.

Membrane particles from mesenchymal stromal cells reduce the expression of fibrotic markers on pulmonary cells.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options in which the telomere shortening is a strong predictive factor of poor prognosis. Mesenchymal stromal cells (MSC) administration is probed in several experimental induced lung pathologies; however, MSC might stimulate fibrotic processes. A therapy that avoids MSC side effects of transformation would be an alternative to the use of living cells. Membranes particles (MP) are nanovesicles artificially generated from the membranes of MSC containing active enzymes involved in ECM regeneration. We aimed to investigate the anti-fibrotic role of MP derived from MSC in an in vitro model of pulmonary fibrosis. Epithelial cells (A549) and lung fibroblasts, from IPF patients with different telomere length, were co-cultured with MP and TGF-β for 48h and gene expression of major pro-fibrotic markers were analyzed. About 90% of both types of cells effectively took up MP without cytotoxic effects. MP decreased the expression of profibrotic proteins such as Col1A1, Fibronectin and PAI-1, in A549 cells. In fibroblasts culture, there was a different response in the inhibitory effect of MP on some pro-fibrotic markers when comparing fibroblast from normal telomere length patients (FN) versus short telomere length (FS), but both types showed an inhibition of Col1A1, Tenascin-c, PAI-1 and MMP-1 gene expression after MP treatment. MP conserve some of the properties attributed to the living MSC. This study shows that MP target lung cells, via which they may have a broad anti-fibrotic effect.

V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as a prognostic biomarker of poor outcomes in esophageal cancer patients

BackgroundEsophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes.MethodsWe used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan–Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models.ResultsThe results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice.ConclusionBRAF overexpression may serve as an effective predictive factor for poor prognosis.

Investigating the Usefulness of European Society of Cardiology Guidelines for Hospitalization in Acute Pericarditis at a Single Tertiary Center

BackgroundThe European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial diseases identify predictive factors of poor prognosis and advise either in favor or against hospitalization accordingly. We aim to evaluate the adequacy of hospitalization criteria in a cohort of patients presenting to the emergency department (ED) with acute pericarditis.MethodsRetrospective analysis of patients admitted to ED with acute pericarditis, from 2009 to 2019. During ED stay, all patients were evaluated by a cardiologist who decided if the patient was to be discharged or hospitalized. Hospitalized and discharged patients were compared regarding the primary outcome, defined by a composite of: the need for pericardiocentesis and/or cardiac surgery, pericarditis recurrence, and all-cause death. The clinical decision was then counterpoised with ESC guidelines.ResultsA total of 192 patients were included in the analysis (median age 44.5 years old, 83.3% male) of which 87 (45.5%) were hospitalized. A total of 25% registered the primary outcome, mainly due to acute pericarditis recurrence, occurring in 21.9%. Predictors of recurrence were: glucocorticoid therapy (Odds Ratio [OR]=11.93, 95% Confidence Inirtval [CI] 3.13-45.5, p<0.001), fever at admission (OR=2.67, 95% CI 1.29-5.49, p=0.008), immunosuppression (OR=4.03, 95% CI 1.280-12.659, p=0.017) and increased cardiothoracic index (OR 3.85, CI 95% 1.67-8.86, p=0.002). Regarding hospitalisation/discharge decision, the ESC guidelines were respected in 73.4% of the cases. However, no significant difference in the primary outcome was noted whether the ESC guidelines were respected or not (27.5% vs. 24.3%, p=0.707).ConclusionsDiscrepancy between current guidelines and the clinical decision did not translate into a different outcome.

TMEM16A overexpression indicates poor prognosis in colorectal cancer patients

to investigate the relationship between TMEM16A and the clinicopathological features and prognosis of patients with colorectal cancer (CRC). ninety-six patients with CRC confirmed by pathology after undergoing surgery at the First Affiliated Hospital of Dalian Medical University between June 2009 and December 2011 were enrolled and followed up. The expression of the TMEM16A protein in CRC was detected by immunohistochemistry in 96 cases. The relationship between the expression of the TMEM16A protein in CRC and the clinical features and clinical prognosis were analyzed. there was no correlation between the TMEM16A protein expression and gender, age, tumor location, size and degree of differentiation (p > 0.05). However, the expression of the TMEM16A protein was significantly associated with the depth of invasion, lymph node metastasis and Dukes stage (p < 0.05). Kaplan-Meier survival curves showed that CRC patients with high expression of the TMEM16A protein had a poorer overall survival compared with those with low expression levels (68.2 % vs 92.3 %, X2 = 9.892, p = 0.002). Multivariate Cox regression analysis showed that upregulation of the TMEM16A protein expression is an independent predictive factor for poor prognosis in patients with CRC (p < 0.05, RR = 6.467, 95 % CI: 1.777-23.538). the expression of the TMEM16A protein in CRC was associated with tumor invasion, lymph node metastasis and Dukes stage. High expression of the TMEM16A protein in CRC can be used as an independent predictive factor for a poor prognosis of patients with CRC.

The Problem of Early Surgical Revisions After Abdominal Surgery, Study About 83 Cases Recorded in Bangui, Central African Republic

Objectives: To describe the characteristic of reoperated patients, the predictive factors of morbidity and mortality as well as the evolution after early reoperations. Materials and method: The study included a retrospective and prospective series. The files of patients reoperated after abdominal surgery from January 2014 to December 2019 at the general surgery department of Sino-Central African Friendship University Hospital in Bangui were analyzed. Results: Out of 1249 patients operated on and hospitalized in the surgical department and, 83 (6.6%) patients were reoperated. They were 53% male subjects. The average age was 38.4 years old. An initial intervention was carried out urgently by unqualified operators (71.1%). Postoperative peritonitis (42.2%) was the main reasons for reoperation. Time to reoperation was 8.4 days on average. The founding during reoperation was anastomotic disunity (39.8%). A bypass stoma (33.7%) associated with washing and drainage of the peritoneal cavity was performed. In 19.2% of cases, patients underwent iterative reoperation. The rate of death was 24%. Predictive factors of poor prognosis were, initial surgery for acute peritonitis, dirty surgery, patient with ASA score II and III, NISS 2 and 3, unqualified operators, iterative reoperations and digestive fistula. Conclusion: Early re-operations occurred after emergency surgery performed by an unqualified surgeon. They dependent on high mortality. To reduce rate of early reoperations and improve the prognosis, qualified surgical personnel are needed. Unqualified surgeons must be regularly retrained in essential surgical care with particular emphasis on respecting the basic principles of emergency surgery.

High expression of RRM2 as an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.

Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues (p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs. T1: OR = 1.88, p = 0.001; N2 vs. N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 (p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of RRM2. RRM2 over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.

The complement C7 variant rs3792646 is associated with amyotrophic lateral sclerosis in a Han Chinese population

The complement system has been shown to have a critical pathogenetic role in amyotrophic lateral sclerosis (ALS). Recently a C7 variant in rs3792646 was linked to neurodegenerative diseases in a Chinese population. We used whole exome sequencing to evaluate the role of C7 (rs3792646) in ALS in a Chinese cohort with 1970 individuals. The minor allele frequency in cases was 0.032 while 0.016 in controls, suggesting this variant was associated with ALS. Further analyses showed the prevalence of the variant was significantly higher in Chinese than Caucasian, suggesting its importance in Han individuals. rs3792646-C was significantly associated with a lower onset age in both genders, and a survival analysis revealed a significant relationship between the variant and decreased survival. There was no significant association between the variant and other common ALS-related variants. Our study further elucidated the relationship between the complement system and ALS from a genetic perspective. In addition, the results suggested C7 (rs3792646) could be a potential predictive factor for poor prognosis in ALS.

Acute pericarditis: who should stay and who should go?

Abstract Background The European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial diseases identify predictive factors of poor prognosis and advise either in favour or against hospitalisation accordingly. Our aim is to evaluate the adequacy of hospitalisation criteria in a cohort of patients presenting to the emergency department (ED) with acute pericarditis. Methods Retrospective analysis of patients admitted in ED with acute pericarditis, from 2009 to 2019. All patients were evaluated by a cardiologist during ED stay who decided if the patient was to be discharged or hospitalized. Hospitalized and discharged patients were compared regarding primary outcome, defined by a composite of: need for pericardiocentesis and/or cardiac surgery, pericarditis recurrence and all-cause death. Clinical decision was then counterpoised with ESC guidelines. Results A total of 192 patients were included in the analysis (aged 46±18.5 years-old, 83.3% male) of which 87 (45.5%) were hospitalized. A total of 25% registered the primary outcome, mainly due to acute pericarditis recurrence, occurring in 21.9%. Predictors of recurrence were: glucocorticoid therapy (OR=11.93, 95% CI 3.13–45.5, p&amp;lt;0.001), fever at admission (OR=2.67, 95% CI 1.29–5.49, p=0.008), immunosuppression (OR=4.03, 95% CI 1.280–12.659, p=0.017) and increased cardiothoracic index (OR 3.85, CI 95% 1.67–8.86, p=0.002). Regarding hospitalisation/discharge decision, the ESC guidelines were respected in 72.9% of the cases. However, no significant difference in primary outcome was noted whether the ESC guidelines were respected or not (27.5% vs. 24.3%, p=0.707). Conclusions Discrepancy between current guidelines and clinical decision did not translate into a different outcome. Funding Acknowledgement Type of funding source: None

The predictive value of coexisting BRAFV600E and TERT promoter mutations on poor outcomes and high tumour aggressiveness in papillary thyroid carcinoma: A systematic review and meta-analysis.

BRAFV600E mutation is highly prevalent in patients with papillary thyroid carcinoma (PTC), and TERT promoter (TERTp) mutation is strongly associated with cancer-related mortality. However, predictive power of the two mutations remains inconclusive. We aimed to verify the prognostic effects of both mutations to assess the value of mutation detection for risk stratification in terms of PTC prognosis and tumour invasion, to guide PTC diagnosis and treatment. We conducted a literature search in the MEDLINE (PubMed), EMBASE, Web of Science and CENTRAL (Cochrane library) databases, from inception to February 2020. Basic characteristics, prognoses and clinicopathological features were collected from the included studies for further analysis. Twelve studies involving 4184 PTC patients were enrolled in our analysis. In total, 2412 (57.6%) of the patients carried either BRAFV600E or TERTp mutation, and 290 (6.9%) patients had both mutations. TERTp mutation was more common in patients with BRAFV600E mutation (RR=1.75 [95% CI 1.44-2.13]). Patients with both mutations had a worse prognosis compared with those with a single mutation (vs BRAFV600E only: RR=5.34 [4.20-6.78] vs TERTp only: RR=2.12 [1.41-3.19]). TERTp mutation alone independently increased the risk of a poor prognosis (RR=2.90 [1.93-4.35]) in terms of mortality (RR=15.09 [7.75-29.37]), disease persistence (RR=4.00 [2.03-7.90]), recurrence (RR=4.34 [4.20-6.78]), lymph node metastasis (RR=1.57 [1.24-1.99]) and distant metastasis (RR=2.94 [1.13-7.65]). We found that PTC patients with BRAFV600E mutation were more likely to have TERTp mutation. TERTp mutation was an independent predictive factor for poor prognosis of PTC patients, but the predictive value of BRAFV600E mutation remains inconclusive. Patients with both mutations have remarkably higher risks of adverse outcomes compared with those with a single mutation. PTC patients could benefit from mutation detection for aiding risk stratification (BRAF+TERT+>BRAF-TERT+>BRAF+TERT-).

Predictive factors of poor prognosis in children with acute kidney injury treated with renal replacement therapy

Objective: To investigate the predictive factors of poor prognosis in children with acute kidney injury (AKI) treated with renal replacement therapy (RRT). Methods: In this retrospective case-control study, the clinical data were collected from 134 pediatric patients (82 male, 52 female) with AKI treated with RRT in six tertiary hospitals from May 2015 to June 2018. According to the serum creatinine level at discharge, the patients were divided into the favorable outcome group and unfavorable outcome group. The data of sex, age, primary diseases, AKI stage, time from diagnosis of AKI to start of RRT (h) and whether to start RRT within 24 hours, urine volume and complications between the two groups were compared. Continuous variables were compared by t test and Mann-Whitney U test, and percentage or proportions were compared by Chi square test. The predictive factors of adverse prognosis were analyzed by using univariate and unconditional binary logistic regression analysis. Results: The average age of the 134 AKI patients was (6±4) years. There were 114 patients (85.0%) in the favorable outcome group and 20 patients (15.0%) in the unfavorable outcome group. No statistically significant differences were found between the two groups in terms of sex (χ(2)=2.596, P=0.107), age (t=0.718, P=0.474), primary disease (χ(2)=2.076, P=0.722), AKI stage (χ(2)=0.004, P=0.998), time from diagnosis of AKI to start RRT (h) (P=0.745), whether to start RRT within 24 hours (χ(2)=0.016, P=0.899), urine volume (χ(2)=3.118, P=0.374), fluid overload (χ(2)=0.014, P=0.905), multiple organ dysfunction syndrome (MODS) (χ(2)=2.972, P=0.085), acidosis (χ(2)=3.204, P=0.073), hyperkalemia (χ(2)=2.829, P=0.093), the level of blood urea nitrogen (t=1.351, P=0.179) and serum creatinine (P=0.901) at the beginning of RRT. In the unfavorable outcome group, the proportion of patients with mechanical ventilation (45.0% (9/20) vs. 12.3% (14/114), χ(2)=12.811, P<0.01) and the incidence of extra organ injury (≥3) (30.0% (6/20) vs. 10.5% (12/114), χ(2)=6.365, P=0.041) were higher than those in the favorable outcome group. Logistic regression analysis showed that mechanical ventilation (OR=12.540, 95%CI: 3.376-46.577, P<0.01) and hyperkalemia (OR=4.611, 95%CI: 1.265-16.805, P=0.021) were the predictive factors of poor prognosis in patients with AKI treated with RRT. Conclusion: Mechanical ventilation and hyperkalemia may predict a poor prognosis in AKI patients treated with RRT.