Unfavorable Prognosis Factor Research Articles

Origin of the T790M mutation and its impact on the clinical outcomes of patients with lung adenocarcinoma receiving EGFR-TKIs

ObjectiveRecently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis. Patients and methodsMatched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay. ResultsOf the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P = 0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P < 0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p = 0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p = 0.031, HR 0.310, 95% CI: 0.107-0.900). ConclusionThe ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment.

The Increased Expression of Estrogen-Related Receptor α Correlates with Wnt5a and Poor Prognosis in Patients with Glioma.

Malignant glioma is an often fatal type of cancer. Elevated expression of the orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an unfavorable factor for malignant progression and poor prognosis in several cancers, although the mechanism by which this receptor affects the pathophysiology of cancers remains obscure. However, few studies have been conducted in regard to the role of ERRα in glioma. In the current study, we found that elevated expression of ERRα was observed in 107 glioma cases by means of IHC. Clinically, high expression of ERRα was associated with later stages of disease progression and clinical outcome of patients with glioma. ERRα had the ability to promote cell proliferation and migration in glioma cell lines. Moreover, in a xenograft model, we also found that silencing ERRα had an inhibitory effect on the growth of glioma. Further investigation confirmed that ERRα was involved in the carcinogenesis of glioma via the regulation of the Wnt5a signal pathway in vitro and in vivo Our study was first to show the overexpression of ERRα in glioma tissues and a direct correlation between ERRα expression and clinical prognosis of glioma. Together, these data reveal that ERRα has prognostic significance in glioma, and targeting ERRα may provide a reliable therapeutic strategy for the treatment for human glioma.

Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer.

Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship between these parameters and the main clinical morphological characteristics of the disease was analyzed. Plasma levels of the proteins were measured using standard direct ELISA kits. The level of MMP-7 in patients with gastric cancer was significantly higher than in the control group (medians 2.7 and 1.2 ng/ml, respectively; p<0.01), but only in 51% patients this parameter surpassed the upper threshold normal value (2.35 ng/ml; 95% percentile of control). The level of MMP-9 in gastric cancer patients was lower than in control group by 1.6 times (medians 167 and 267 ng/ml, respectively; p<0.01). Plasma levels of MMP-2 and TIMP-2 in patients with gastric cancer and healthy subjects were similar. No appreciable associations of plasma matrixins and TIMP-2 with the main clinical morphological characteristics of the disease were detected. The patients were followed up for 8 to 85 months (median 70.8 months). Low level of MMP-2 and high level of MMP-7 in the plasma proved to be unfavorable prognostic factors for overall survival. At MMP-2<268 ng/ml, the 5-year overall survival was 32% vs. 60% for patients with the marker level higher than this threshold value (p=0.016). The differences in overall survival in relation to their MMP-7 levels for 5-year observation did not surpass 16% (39% at marker level >2.7 ng/ml and 55% at lower level; p=0.048). Plasma levels of MMP-2 and TIMP-2 were not significantly associated with overall survival. Multivariate analysis showed that only T index (p=0.034) and plasma MMP-7 level (p=0.007) were essential for overall survival. The increase in plasma or serum MMP-7 levels is a universal phenomenon in tumors of different histogenesis, which precluded the use of this parameter as a specific diagnostic marker of gastric cancer. At the same time, it could be useful for monitoring the treatment efficiency and detection of relapses. In addition, high plasma level of MMP-7 remained an independent factor of unfavorable prognosis for overall survival of patients with gastric cancer.

Social Parameters Are Independent Predictors for Survival in Chronic Myeloid Leukemia

Introduction and data: Social and demographic personal data are important to be included in analysis and interpretation of results of any population studies in oncology. But it looks like social status is underestimated as cofounder for survival of patients with chronic myeloid leukemia (CML). The aim of this study was to check the prognostic value of social parameters like marital status and education level in comparison with standard risk factors. Russian CML Registry include more than 10 thousand patients (pts) data. In the analysis 8326 CML pts in chronic phase (CP) with first line TKI therapy were included: 91% of pts were treated by Imatinib and 9% by other TKIs. Mean age was 49years, 4607 f/ 3705 m. Me of follow-up-4.24years. Overall survival(OS) was estimated starting the diagnosis date, event was death from any reason, date of last contact was censored for alive pts. Survival analysis was performed by SAS procedures. Results:Firstly, we perform one-way survival analysis and estimate OS depending upon the 3 parameters Sokal Score, Marital Status and Education. There are high significant dependences OS on all three factors as shown on picture 1 (OS estimates depending on values of: 1A) Sokal score (low, intermediate, high), 1B) Marital Status (married, single, widowed/divorced), 1C) Education (low/secondary, higher). Marital Status and Education are correlated with Sokal Score (corresponding Pearson's coefficients are 0.19 and 0.12, p<0.0001). This association is caused by age but is not so strong. Than we have estimate OS in each Sokal's risk groups (picture 2. OS estimates depending on Marital Status (single, married - blue line, widowed/divorced - green line) in different Sokal's risk groups: 2A) - low, 2B) - intermediate, 2C) - high). OS estimates depending on Education (picture 3; (low/secondary red line, higher- blue line) in different Sokal's risk groups: 3A) low, 3B) intermediate, 3C) high. And we see that Marital Status and Education are predictive in each risk group but the most influent in high risk group. Marital Status and Education are correlated with other impotent cofounder- age. It should be checked in additional multi factor analysis we plan to do. We also run the proportional risk regression Cox's model on this data. Hazard ratio (HR) and significance (Px2) for included parameters are following: Sokal score - HR=1.59, Px2<0.0001; Education- HR=1.76, Px2<0.0001; Marital Status- HR=1.40, Px2<0.0006. Conclusions: The social and demographic personal data should be included in any analysis of CML population data. Marital Status and Educationare obviously associated with adherence behavior of CML patients and must influent on longitude therapy output. The highly education level is favorable factor, widowed/divorced marital status is unfavorable factor for OS prognosis. [Display omitted] DisclosuresKulikov:Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.

Change of Circulating and Tissue-Based miR-20a in Human Cancers and Associated Prognostic Implication: A Systematic Review and Meta-Analysis.

Background Previous literatures have investigated the change of miR-20a expression level in the progression of multiple cancers and its influence on patients' survival outcome, but results of now-available evidence are inconsistent. Objective To elucidate the prognostic value of circulating and tissue-based miR-20a for patients with various cancers. Methods A systematic search and review of eligible publications were carried out in three electronic databases including the Cochrane Library, PubMed, and Embase, and the methodological quality of included studies was assessed according to Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and progressive-free survival (PFS) of each study were pooled using a random effect model. Results In total, 24 studies involving 4186 samples of multiple cancers published in 20 articles were included in the statistical analysis. As for circulating miR-20a, five kinds of cancers containing gastric cancer, lymphoma, glioblastoma, prostate cancer, and non-small-cell lung cancer reported upregulated level in patients compared with normal healthy control, and overexpressed circulating miR-20a could confer an unfavorable factor for OS (HR = 1.71, 95% CIs: 1.43 -2.04, p < 0.01) and DFS (HR = 1.90, 95% CIs: 1.45-2.49, p < 0.01). As for tissue-based samples, 6 kinds of malignancies including colorectal cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, colon cancer, gastrointestinal cancer, and alveolar rhabdomyosarcoma revealed upregulated miR-20a expression level compared with paired nontumorous tissue, of which high expression of miR-20a was significantly associated with poor OS (HR = 2.74, 95% CIs: 1.38-5.42, p < 0.01) and DFS (HR = 2.68, 95% CIs: 1.32-5.45, p < 0.01); meanwhile, other 5 tumors containing breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and epithelial ovarian cancer demonstrated downregulated miR-20a expression level compared with benign tissue, of which low miR-20a expression was significantly related to shorter OS (HR = 3.48, 95% CIs: 2.00-6.06, p < 0.01) and PFS/RFS (HR = 4.05, 95% CIs: 2.89-5.66, p < 0.01). Conclusion Change of circulating and tissue-based miR-20a expression possesses vital prognostic implication for human cancers. Augmented expression of circulating miR-20a predicts poor survival outcome for patients with cancers. Tissue-based miR-20a level may be upregulated or downregulated depending on cancer types; in the former condition, high expression of tissue miR-20a is a risk factor for unfavorable prognosis and in the latter condition low expression of tissue miR-20a is associated with shorter survival.

New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study

IntroductionThe presence of organ metastases is a major factor for unfavorable prognosis in lung adenocarcinoma (LADC). However, the influence of primary tumor location on metastatic sites and sequence has not been extensively analyzed. MethodsWe performed a multicenter cohort study, evaluating clinicopathological data of 1126 Caucasian LADC patients, focusing on the distinct location of primary tumors and metastatic sites during disease progression. ResultsMetastases to the lung (p < 0.001), pleura (p < 0.001) and adrenal glands (p < 0.001) occurred earlier during disease progression and central primary tumors were associated with early metastases (OR 1.43, p = 0.02). In secondary exploratory analysis we found that bone metastases were more frequent in patients with central tumors (OR 1.86, p = 0.017), whereas lung metastases in those with peripheral tumors (OR 1.35, p = 0.015). Central primary LADCs were associated with decreased median overall survival (vs. peripheral tumors, 10.2 vs. 22 months) both in univariate (HR 2.075, p = 0.001) and in multivariate (HR 1.558, p < 0.001) analyses and independent from stage and T factor. By subsequent analysis, we found that bone metastases tend to appear together with adrenal and liver metastases, and adrenal with skin, and pleural with pericardial metastases more frequently than expected if metastatic events occurred independently. ConclusionThis comprehensive large cohort analysis demonstrates metastatic site- and sequence-specific variations in patients with LADC. Central LADC is associated with early metastatic disease, bone involvement and, consequently, decreased survival.

High expression of mitogen-activated and stress-activated protein kinase 1 indicates poor prognosis in patients with glioma.

Mitogen-activated and stress-activated protein kinase 1 (MSK1), which belongs to the subfamily of MAPK-activated protein kinase, plays an important role in cell proliferation and neoplastic transformation. It has been recently reported that MSK1 overexpression was closely related to the progression of some tumors such as colorectal cancer. However, the clinical significance of MSK1 in glioma has not been addressed. To investigate the potential role of MSK1 in glioma, we first examined the expression pattern of MSK1 in glioma tissues and normal brain tissues using quantitative RT-PCR, and the results showing that MSK1 expression was significantly elevated in glioma tissues compared with normal brain tissues. The clinical relevance of MSK1 expression level was then analyzed, and we found that high expression of MSK1 was closely related to the larger tumor size and advanced WHO grade. Univariate and multivariate analyses revealed that glioma patients with higher expression of MSK1 had poorer overall survival, and MSK1 was identified as an independent unfavorable prognosis factor. In addition, the effects of MSK1 on glioma cells were tested through cellular experiments, and we demonstrated that MSK1 can promote proliferation and invasion capacities of tumor cells. In conclusion, patients with glioma with higher MSK1 expression were more predisposed to poorer clinical outcomes and unfavorable prognosis, indicating the potential role of MSK1 as a novel clinical biomarker and therapeutic target.

Диагностические ошибки и диализные осложнения – факторы неблагоприятного прогноза в 4–5-й стадиях хронической болезни почек

Диагностические ошибки и диализные осложнения – факторы неблагоприятного прогноза в 4–5-й стадиях хронической болезни почек

Successful sequential immune epigenetic therapy of erythrodermic mycosis fungoidesessful sequential immune epigenetic therapy with the resistant course of erythrodermic mycosis fungoides

Mucosis fungoidea (МF) belongs to the class of epidermotropic T-cell lymphomas. MF is represented by over 10 sub-types only in terms of its clinical manifestations, with one of them being erythrodermic MF (EMF). This disease is characterized by diverse symptomatology in the form of erythroderma and intense skin itch, aggressive сlinical course and unfavorable prognosis. The disease prognosis also correlates with age, previous history of long-term systemic gluco-corticosteroid treatment (GCS), increased activity of lactate dehydrogenase (LDH) and hypereosinophilia. The choice of MF treatment is determined by the disease stage and somatic status of the patient. In EMF, a therapy combining various effective preparations and taking into account the specifics of the given case is required. Extracorporeal photopheresis (ECP) is frequently an approach of choice; however, it has demonstrated the highest efficacy in Sezary disease or in EFM associated with leucemization. Application of new pharmaceuticals (monoclonal antibodies, epigenetic agents) in combination or in sequence with immune therapy is a promising direction, particularly for treating patients older than 75 years. In this paper, we describe the clinical case of an elderly patient suffering from EMF without peripheral blood leukemia with multimodal factors of unfavorable prognosis, such as age, increased lactate dehy drogenase activity, history of prolonged inefficient treatment with gluco-cortecosteroid preparations and eosinophilia. A long-term positive response to the treatment using sequential immune epigenetic therapy has not been achieved, although the treatment tolerability and the patient's life quality were satisfactory.

INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001).

High ubiquitin-conjugating enzyme E2s expression is an independent factor of unfavorable prognosis in patients with gallbladder cancer

Objective To investigate the expression of ubiquitin-conjugating enzyme E2s (UBE2S) in gallbladder cancer (GBC) tissues and its clinical significance. Methods The expression of UBE2S was examined in 85 GBC, 28 pre-malignant lesion and 15 benign lesion tissues of the gallbladder by immunohistochemistry, and was verified by western blotting. The relationship between UBE2S expression and clinicopathological characteristics and prognostic factors of GBC patients was analyzed. Results Immunohistochemistry showed that UBE2S was highly expressed in GBC tissues compared to pre-malignant lesion tissues [stain index (SI): 4.082±3.413 vs. 2.607±2.025, P=0.021)] and benign lesion tissues (SI: 4.082±3.413 vs. 2.067±1.335, P=0.001), and western blotting showed that UBE2S protein was highly expressed in GBC tissues compared to benign lesion tissues (grey-scale value: 0.734±0.181 vs. 0.197±0.099, P=0.002). UBE2S was positively correlated with tumor differentiation degree (χ2=6.978, P=0.031) and liver metastasis (χ2=8.155, P=0.004). Cox model showed that UBE2S expression (P=0.024) as well as tumor differentiation degree (P=0.000), Nevin stage (P=0.040) and R0 resection (P=0.011) were prognostic factors of GBC patients. High UBE2S expression patients with GBC have a shorter survival time (P=0.011). Conclusion High UBE2S expression is an independent factor of unfavorable prognosis in GBC patients. Key words: Ubiquitin-conjugating enzyme E2s; Gallbladder neoplasm; Prognosis

Abstract 2751: Regorafenib attenuates IFN-γ-induced PD-L1 expression and enhances antitumor immunity

Abstract Immune checkpoint blocked therapy (ICB) targeting the PD-1/PD-L1 axis induce durable tumor regressions in a sizeable minority of cancer patients. To enhance the efficacy of existing immunotherapies, we implemented a screen of kinase inhibitors capable of increasing the activity of T cells suppressed by PD-L1. Here, we identified regorafenib, which was approved to treat patients with advanced gastrointestinal stromal tumors and metastatic colorectal cancer, as a potent agent significantly attenuating IFN-γ-induced PD-L1 expression without affecting MHC-I expression, contributing to enhanced anti-tumor effects with ICB in vitro and in vivo, due in part to inhibit JAK1/2-STAT1 signaling and the activation of ERK by suppressing the tyrosine kinase receptor RET-Src axis. Additionally, our analysis of GEO database and TCGA database revealed that RET and Src co-high expression was an independent unfavorable prognosis factor in both melanoma patients with or without ICB via inhibiting anti-tumor immune response. Further, gene set enrichment analysis (GSEA) demonstrated, compared to RET and Src co-high expression group, anti-tumor immune response related gene signatures as prominent modules in other group. Collectively, our data unveiled a new mechanism of reducing IFN-γ-induced PD-L1 expression and provided a rationale to explore a new combination of immunotherapies and regorafenib in melanoma treatment. Citation Format: Xiao-Feng Zhu. Regorafenib attenuates IFN-γ-induced PD-L1 expression and enhances antitumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2751.

DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway.

DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry. The percentage of DKC1 expression in ccRCC (61.3%) was markedly higher than that in paracancerous tissues (34.7%) (P=0.001). Positive DKC1 expression tends to significantly be associated with unfavorable clinicopathological characteristics such as tumor diameter >7cm (P=0.002) and tumor‑node‑metastasis (TNM) stage III or IV (P<0.001). Multivariate COX analysis revealed that positive DKC1 expression was an independent unfavorable factor for prognosis of ccRCC patients [hazard ratio (HR)=1.932, 95% CI, 1.290‑2.893, P=0.001 for 5‑year overall survival; HR=1.778, 95% CI,1.150‑2.748, P=0.010 for disease‑free survival]. In the PROGgeneV2 platform, we also found that ccRCC patients with high DKC1 mRNA expression had a poorer prognosis than patients with low DKC1 expression in The Cancer Genome Atlas (TCGA). Furthermore, we found that knockdown of DKC1 inhibited proliferation, migration and invasion of ccRCC through regulation of the NF‑κB/MMP‑2 signaling pathway invitro. We also demonstrated that DKC1 regulated ccRCC proliferation and the expression of NF‑κB‑p65 and MMP‑2 invivo. In summary, the expression of DKC1 was upregulated in ccRCC, which was associated with unfavorable clinicopathological characteristics and DKC1 may act as an independent prognostic indicator of ccRCC patients.

943 - Latent viral infection as a factor of unfavorable prognosis of bladder cancer

943 - Latent viral infection as a factor of unfavorable prognosis of bladder cancer

COMBINATION OF INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma. Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis. Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %. Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009).

Targeting microthrombosis and neuroinflammation with vepoloxamer for therapeutic neuroprotection after traumatic brain injury.

Targeting microthrombosis and neuroinflammation with vepoloxamer for therapeutic neuroprotection after traumatic brain injury.

Cвязь степени поражения коронарного русла и особенностей стентирования с краткосрочными и отдаленными исходами у пациентов с острым коронарным синдромом (данные регистра РЕКОРД-3)

It was shown in this retrospective analysis of data from the Russian registry of acute coronary syndromes (ACS) RECORD-3 that compared with patients in whom coronary angiography revealed no hemodynamically significant (>50 %) stenosis, patients with such stenosis in one vessel (with single vessel disease - SVD) and especially in multiple vessels (with multi-vessel disease - MVD) had much more anamnestic and clinical factors of unfavorable prognosis. Rates of all cause death as well as composite of death and new myocardial infarction (MI) during hospitalization in patients without significant stenosis and those with SVD were not significantly different but rates of these outcomes among patients with MVD were significantly higher than among patients with SVD or without significant stenosis. Presence of MVD was associated with worse remote outcomes developed after discharge from hospital compared with absence of significant stenosis (rate of death, MI, and urgent revascularization was significantly higher for 6 and 12 months after ACS), and compared with SVD (rate of death, MI, and urgent revascularization was significantly higher for 12 months after ACS). During percutaneous coronary interventions bare metal stents were used 2 times more often than drug eluting stents. Implantation of 2 or more stents compared with implantation of 1 stent was associated with higher rate of unfavorable outcomes (composite of death, MI, and urgent revascularization) developed after hospital discharge during 12 months after onset of ACS.

Predictors of adverse events in the mid-term postoperative period in patients who underwent carotid endarterectomy

Aim. Emphasis in the study was placed on the identification of unfavorable prognosis factors associated with carotid endarterectomy (CEE) during mid-term follow-up.Methods. Over a period from 2015 to 2016, 222 CEE operations were performed. Most patients (n = 190; 85.5%) underwent CEE using a patch of xenopericardium, 14.4% (n = 32) received eversion CEE, and a temporary shunt was used in 14.4% (n = 32). Hybrid revascularization in the volume of percutaneous coronary intervention (PCI) + CEE was performed in 9.9% (n = 22) patients. The groups under study were compared by using a chi-square test followed by subsequent analysis of the shares, or if ordinal characters or quantitative traits with a distribution different from the normal one occurred—by using a Mann – Whitney U-test. Correction of multiple comparisons was done by calculating an average fraction of false discoveries of the hypotheses (false discovery rate). The analysis of prognostic factors was done using the odds ratio (OR) by means of the 2 × 2 tables.Results. Among the complications detected in the mid-term follow-up, the most common adverse event was the development of MI in 3.6% (n = 8) of patients. According to color duplex scanning of brachiocephalic arteries, restenosis of the operated ICA was observed in 4.5% of patients. The following risk factors significantly increased the risk of adverse events: angina pectoris II–III functional class (OR = 3.84%, CI = 1.24–11.9), SYNTAX Score &gt;22 (OR = 2.83, CI = 1.137–7.086).Conclusion. Based on the results of a single-center prospective retrospective study, significant risk factors for adverse outcome in the mid-term postoperative period were identified.Received 10 May 2017. Revised 27 September 2017. Accepted 5 October 2017.Funding: The research was done with support of the grant (No. 12090ГУ/2017) awarded by the Fund for Facilitation of Innovations within the framework of the “Umnik-2016” project (Kemerovo).Conflict of interest: The authors declare no conflict of interest.Author contributionsConception and study design: R.S. Tarasov, A.I. Anufriyev Data collection and analysis: A.R. ShabaevDrafting the article: A.N. Kazantsev, N.N. Burkov Critical revision of the article: A.V. MironovFinal approval of the version to be published: L.S. Barbarash

Overexpression of p53R2 is associated with poor prognosis in lung sarcomatoid carcinoma

BackgroundThis study aimmed to evaluate the expression of p53-inducible RR small subunit 2 homologue (p53R2) in Lung sarcomatoid carcinoma (LSC) and its association with clinicopathological parameters and prognosis.MethodsIn this study, clinicopathological factors and prognostic significance of the expression of p53R2 was investigated by immunohistochemistry (IHC) in 100 cases of LSC.ResultsThe results showed that the expression of p53R2 was significantly correlated with clinical stage (P<0.05). But there was no statistically correlation with gender, age, smoking, tumor size, pT stage, pN stage, pM stage, therapy and relapse. Kaplan-Meier analysis revealed that the expression of p53R2, clinical stage, pT stage, pN stage, pM stage and tumor size were closely related to patients’ survival, and the analysis also revealed that patients with low expression of p53R2 had a longer overall survival than that with high expression (Mean overall survival: 84.8 months vs. 34.7 months, P<0.05). Further multivariate analysis indicated that the expression of p53R2 was identified as an independent prognostic factor in the prediction of the overall survival for patients with LSC (HR = 3.217, P<0.05).ConclusionsThe expression of p53R2 was inversely associated with the proliferation and progression of LSC, and the results indicated that the high expression of p53R2 was an independent factor for unfavorable prognosis of patients with LSC.

Identification of P4HA1 as a prognostic biomarker for high-grade gliomas

BackgroundProlyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined. MethodsThe expression of P4HA1 in 290 gliomas (WHO grade II–IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated. ResultsCytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade (p<0.01) and old age (p=0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas (p<0.01) but not for low-grade gliomas. ConclusionsP4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas.