Kaplan-Meier Survival Curves Of Patients Research Articles

Development of a Cancer-associated Fibroblast Signature for Evaluating Immunotherapy Response and Prognosis of Hepatocellular Carcinoma.

Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and hepatitis B and C are the main pathogenic factors of hepatocellular carcinoma (HCC). Though the current understanding of risk factors for HCC has been improved, patients with this type of cancer are normally diagnosed at advanced stages, posing significant challenges to effective treatment. This study analyzed the HCC datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database (GSE14520 and GSE116174). Stromal and immune cell infiltration in the tumor microenvironment (TME) was quantified by the ESTIMATE algorithm. To identify gene modules associated with cancer-associated fibroblasts (CAFs), weighted gene co-expression network analysis (WGCNA) was performed to develop gene co-expression networks. A CAF prognosis score (CAFPS) model was established based on the prognostic CAF genes screened by univariate and multivariate Cox regression analyses. To determine the role of the genes in the vital module in HCC, we conducted Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, the relationship between CAFPS and drug sensitivity was analyzed using Genomic Data for Cancer Drug Sensitivity (GDSC). In this study, we found significant differences in immune scores, stromal scores, CAFs scores, and CD4/8 T-cell scores between normal samples and samples with different TNM staging. In particular, the proportion of CAFs was higher than all other cells in normal samples. Gene modules related to CAFs were identified by developing a gene co-expression network using WGCNA analysis. The lightyellow and greenyellow modules showed the highest correlation with CAF scores. Univariate COX analysis identified 12 genes related to HCC prognosis from a total of 191 genes in the two modules. The Kaplan-Meier (KM) survival analysis revealed that a high expression of these genes was associated with a lower survival chance. Based on the 12 genes obtained by univariate COX analysis, multivariate COX analysis was performed to construct a risk score model for the characteristics of CAFs (CAFPS). The KM survival curves of patients in the high CAFPS and low CAFPS groups showed that patients in the low CAFPS group had better survival. CAFs played a crucial role in the pathogenesis and treatment response of HCC. Targeting the CAFs milieu may provide therapeutic benefits, highlighting the importance of CAFS in developing a personalized treatment for HCC patients. Further studies are required to verify the current findings and explore their implications in clinical settings.

How to predict the death risk after an in-hospital cardiac arrest (IHCA) in intensive care unit? A retrospective double-centre cohort study from a tertiary hospital in China

ObjectivesOur objective is to develop a prediction tool to predict the death after in-hospital cardiac arrest (IHCA).DesignWe conducted a retrospective double-centre observational study of IHCA patients from January 2015 to...

785. Distribution and Associated Mortality in Carbapenem-Resistant Gram-Negative Bacilli in Japan: A Multicenter Study From Multi-Drug Resistant Organisms Clinical Research Network (MDRnet)

BackgroundCarbapenem-resistant gram-negative bacilli (CRGNB) are increasingly reported around the world as a cause of serious infections. However, the epidemiology and clinical course of patients with CRGNB in Japan is not well understood.MethodsWe prospectively collected CR cases from 4/2019 to 9/2020 in Multi-Drug Resistant organisms clinical research network (MDRnet) consisting of 5 tertiary care facilities in Japan. We looked for all CRGNB, and all unique patients with CR Enterobacterales, CR nonfermenting gram-negative bacilli (NFGNB) and CR Aeromonas sp. isolation were included. Carbapenem resistance was tested by agar dilution method and defined based on the CLSI criteria for each species. Infections were determined by NHSN protocols.ResultsIn total, 156 patients (30 Enterobacterales, 119 NFGNB, 7 Aeromonas spp.) were included (11 Enterobacter spp., 11 Klebsiella spp., 86 Pseudomonas aeruginosa, 29 Stenotrophomonas maltophilia, 7 Aeromonas spp.). Acinetobacter sp. was not detected. Isolation sites were sputum (n = 12) and urine (n = 7) in Enterobacterales, sputum (n = 62) and blood (n = 18) in NFGNB, and blood (n = 6) in Aeromonas spp. The median age and male ratio of the patients were 68 years [IQR: 53-74] and 19 (63.3%) in Enterobacterales, 72 years [IQR: 60-79] and 70 (58.8%) in NFGNB and 78 years [IQR: 54-83] and 2 (28.6%) in Aeromonas spp. Ten (33.3%) patients with Enterobacterales, 55 (46.2%) patients with NFGNB, and 6 (85.7%) patients with Aeromonas spp. were infected cases. The others were considered as colonized. There were no patients with ICU stay or intubation in Enterobacterales, while 5 (4.2%) and 4 (3.4%) patients were in ICU and intubated in NFGNB, and 2 patients were in ICU and intubated in Aeromonas spp., respectively. All-cause 30-day mortality rates were 10% in Enterobacterales, 16.8 % in NFGNB and 28.6% in Aeromonas spp. In the infected patients, 3 patients (30%) with Enterobacterales, 12 patients (21.8%) with NFGNB and 1 patient (16.7%) with Aeromonas spp. died within 30 days after isolation. Flow diagram outlining the characteristics of the patients and species in this study. Kaplan-Meier survival curves of patients with carbapenem resistant Enterobacterales Kaplan-Meier survival curves of patients with carbapenem resistant nonfermenting gram-negative bacilli ConclusionMortality rates were high in infected cases of CR Enterobacterales, CR NFGNB and CR Aeromonas spp. Carbapenem-resistant Acinetobacter spp. was not detected, which differed from the CR epidemiology in Europe, the United States, and other Asian countries.Disclosures Sho Saito, n/a, Shionogi (Grant/Research Support) David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Yohei Doi, MD, PhD, AstraZeneca (Speaker's Bureau)bioMerieux (Consultant)FujiFilm (Advisor or Review Panel member, Speaker's Bureau)Gilead (Consultant)GSK (Consultant)Meiji (Consultant)MSD (Consultant)Shionogi (Consultant) Yohei Doi, MD, PhD, Astellas (Individual(s) Involved: Self): Grant/Research Support; AstraZeneca (Individual(s) Involved: Self): Speakers' bureau; bioMerieux (Individual(s) Involved: Self): Consultant, Speakers' bureau; Chugai (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; FujiFilm (Individual(s) Involved: Self): Advisor or Review Panel member; Gilead (Individual(s) Involved: Self): Consultant; GSK (Individual(s) Involved: Self): Consultant; Kanto Chemical (Individual(s) Involved: Self): Grant/Research Support; MSD (Individual(s) Involved: Self): Speaking Fee; Pfizer (Individual(s) Involved: Self): Grant/Research Support; Shionogi (Individual(s) Involved: Self): Grant/Research Support, Speakers' bureau; Teijin Healthcare (Individual(s) Involved: Self): Speakers' bureau; VenatoRx (Individual(s) Involved: Self): Consultant

Drug Persistence of Biologic Treatments in Psoriasis: A Swedish National Population Study.

IntroductionBiologic treatments for psoriasis are commonly switched. Treatment persistence represents an important parameter related to long-term therapeutic performance. The objective of the study was to analyse the real-world persistence with biologics over time in the treatment of psoriasis.MethodsA retrospective observational study of adults with psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Patients included were treated with a biologic between 2010 and 2018. Treatment episodes were identified from the drug’s date of dispensation recorded in the Prescribed Drug Register to the end of supply of the drug. Median persistence was estimated by Kaplan–Meier survival curves for patients who received adalimumab, etanercept, secukinumab, ustekinumab and ixekizumab. Descriptive analysis of change in persistence over time for 3-year running cohorts was also carried out.ResultsA total of 2292 patients were analysed. Patients who received ustekinumab had the longest median persistence [49.3 months, 95% confidence interval (CI) 38.0–59.1] and etanercept the shortest (16.3 months, 95% CI 14.5–19.0). Median persistence was longer in biologic-naive than biologic-exposed patients. Persistence for ustekinumab decreased by almost 50% over the study period, from a median of 62.3 (95% CI 45.6–∞) months in 2010–2011 to 32.7 (21.2–49.3) months in 2014–2016.ConclusionsPersistence with biologics was, on average, relatively low, given the chronic nature of psoriasis. Changes in persistence over time seemed to be attributable to changes in the therapeutic landscape, providing patients with more options to switch biologic treatments if their current management was considered suboptimal.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00616-7.

Risk factors of early septic shock-related thrombocytopenia and its impact on prognosis

To investigate the risk factors and prognosis of early septic shock-related thrombocytopenia. Retrospective analysis of clinical data of patients with septic shock admitted to the department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from June 2016 to November 2020 was conducted. According to the lowest platelet count (PLT) in the early stage of septic shock (within 24 hours of using vasoactive drugs), the patients were divided into mild thrombocytopenia group [PLT (50-100)×109/L], severe thrombocytopenia group (PLT < 50×109/L) and normal platelet group (PLT > 100×109/L). The differences in general information, laboratory indicators, mechanical ventilation time, length of ICU stay, in-hospital stay, and 28-day mortality among the three groups were analyzed. Multivariate Logistic regression was used to analyze the influencing factors of thrombocytopenia, and the 28-day Kaplan-Meier survival curve of patients with different PLT levels was drawn. A total of 486 patients with septic shock were enrolled, including 123 patients with mild thrombocytopenia, 75 patients with severe thrombocytopenia and 288 patients with normal platelets. Patients with diabetes (χ2 = 30.460, P < 0.001), abdominal infection (χ2 = 15.024, P = 0.001), urinary tract infection (χ2 = 36.633, P < 0.001), bloodstream infection (χ2 = 7.755, P = 0.022), Gram negative (G-) bacilli infection (χ2 = 19.569, P < 0.001), hyperlactic acidemia (H = 23.404, P < 0.001), elevated procalcitonin (PCT, H = 43.368, P < 0.001), high acute physiology and chronic health evaluation II (APACHE II, F = 11.122, P < 0.001) and high sequential organ failure assessment (SOFA, F = 84.328, P < 0.001) were more likely to have thrombocytopenia within 24 hours of septic shock. Multivariate Logistic regression analysis of early septic shock-related thrombocytopenia showed that, diabetes [odds ratio (OR) = 0.19, 95% confidence interval (95%CI) was 0.08-0.42, P < 0.001], urinary tract infection (OR = 0.33, 95%CI was 0.13-0.83, P = 0.018), G- bacilli infection (OR = 0.20, 95%CI was 0.07-0.58, P = 0.003), hyperlactic acidemia (OR = 1.25, 95%CI was 1.07-1.46, P = 0.005) and high APACHE II score (OR = 0.85, 95%CI was 0.78-0.92, P < 0.001) were independent risk factors for platelets < 50×109/L. Abdominal infection was an independent risk factor for PLT (50-100)×109/L (OR = 0.56, 95%CI was 0.34-0.95, P = 0.03). High SOFA score was an independent risk factor for PLT ≤ 100×109/L [PLT < 50×109/L: OR = 2.03, 95%CI was 1.65-2.52, P < 0.001; PLT (50-100)×109/L: OR = 1.31, 95%CI was 1.16-1.48, P < 0.001]. There were no significant differences in mechanical ventilation time, length of ICU stay, and in-hospital stay among the three groups (H values were 0.142, 2.134, and 3.990, respectively, all P > 0.05). The 28-day mortality of septic shock patients increased with the severity of thrombocytopenia (χ2 = 40.406, P < 0.001), and the 28-day mortality of severe thrombocytopenia group and mild thrombocytopenia group was significantly higher than those of the normal platelet group [66.7% (50/75), 43.1% (53/123) vs. 27.8% (80/288), both P < 0.05]. Kaplan-Meier survival curve analysis showed that the 28-day survival rate gradually decreased with the decrease of PLT, and the 28-day survival rate was higher in the normal platelet group (Log-Rank test: χ2 = 80.667, P < 0.001). Diabetes, abdominal infection, urinary tract infection, G- bacilli infection, hyperlactic acidemia, high APACHE II score, and high SOFA score are independent risk factors for early septic shock-related thrombocytopenia. Early thrombocytopenia in patients with septic shock indicates a high risk of 28-day death.

Predictors of Outcome in Intracerebral Hemorrhage and Performance of Hemphill ICH Score and GVS Score

Background: The outcome of intracerebral hemorrhage (ICH) is gloomy. There are several scoring systems for predicting its outcome.&#x0D; Objective: The purpose of the present study was to observe the predictors of outcome in ICH patients and to assess the performance of ‘Hemphill ICH score’ and ‘GVS score’.&#x0D; Methodology: This cohort study involved patients of ICH admitted within 72 hours of acute event in July to December 2017 in the Department of Neurology at National Institute of Neurosciences (NINS) &amp; Hospital, Dhaka, Bangladesh. Clinical and radiological data at admission and in-hospital events were obtained from medical records. Patients who were discharged from the hospital were interviewed at 30th day after event by face to face interview or over telephone. Follow up data was not found for 4 patients.&#x0D; Results: This study involved 115 patients of ICH [median age 60 years (interquartile range, IQR 50-70); 46% (53/115) female]. In-hospital and 30-day mortality of the ICH patients was 22% (25/115: 95% CI 15-30%) and 38% (42/111; 95% CI 29–48%) respectively. There was almost perfect agreement between Hemphill ICH score and GVS score (p&lt;0.001 and κ=0.862). Kaplan-Meier survival curves of patients with different Hemphill ICH scores revealed significant difference among them; which was also true for patients with different GVS scores (by log-rank test, p&lt;0.001 for both). The area under the curve (AUC) for the Hemphill ICH score to predict mortality was 0.70 (95% CI, 0.60–0.80) and for the GVS score 0.74 (95% CI, 0.64–0.83). In bivariate logistic regression, NIHSS score, GCS score, blood glucose at admission, nosocomial pneumonia, ICH volume, midline shift along with both Hemphill ICH and GVS score were observed to predict mortality at 30 days (p&lt;0.05 for all). In two separate models adjusting for blood glucose and nosocomial pneumonia, every 1-point increase in the Hemphill ICH score and GVS score increases the mortality risk by 2.35 fold (adjusted OR: 2.35; 95% CI 1.33-4.16; p=0.003) and 2.99 fold (adjusted OR: 2.99; 95% CI 1.57-5.72; p=0.001) respectively.&#x0D; Conclusions: Both Hemphill ICH and GVS score have comparable predicting ability of outcome in ICH. In addition to components of scoring systems, occurrence of nosocomial pneumonia and blood glucose seems important.&#x0D; Journal of National Institute of Neurosciences Bangladesh, January 2021, Vol. 7, No. 1, pp. 3-9

S0010 Palliative Percutaneous Biliary Radiofrequency Ablation as Therapy for Patients With Unresectable Cholangiocarcinoma: A Meta-Analysis on Overall Survival Outcomes

INTRODUCTION: The prognosis of patients with cholangiocarcinoma (CCA) is poor with the literature demonstrating 5-year survival rates between 2–25% and a median survival of 3–6 months for unresectable disease. 70–80% of CCA cannot be surgically resected, leaving only palliative measures available for these patients. Radiofrequency ablation (RFA) delivers thermal energy to the malignant tissue via percutaneous or endoscopic approaches, resulting in locoregional coagulative necrosis and cellular death. However, there is a relative lack of literature describing the life-prolonging effects of percutaneous RFA, specifically. This meta-analysis aims to determine pooled survival outcomes in patients undergoing percutaneous biliary RFA (PRFA) for palliation of untreated, unresectable CCA. METHODS: A literature search was conducted using the PubMed database for published manuscripts and abstracts analyzing survival outcomes in patients undergoing PRFA for unresectable CCA. Only studies that provided a contingency of data allowing for extrapolation of outcomes related to cholangiocarcinoma were included. A Kaplan Meier survival curve was generated using pooled survival data and mean survival was charted using a Forest plot for comparison among the studies. RESULTS: A total of 9 studies met our criteria and were included for quantitative analysis. There were 114 patients who underwent percutaneous biliary RFA for palliative treatment of unresectable cholangiocarcinoma. The mean survival among these patients was 14.3 ± 7.5 months and median survival was 10.8 months. CONCLUSION: PRFA may be a reasonable palliative therapy for those with previously untreated unresectable cholangiocarcinoma with evidence of increased mean survival and a median survival that is greater than that in published literature in this patient demographic. However, there is a relative lack of published literature on this patient population and more data is needed to draw conclusions of survival benefit.Figure 1.: Forest Plot of the mean survival in studies assessing outcomes in patients with untreated, unresectable cholangiocarcinoma undergoing PRFA.Figure 2.: Kaplan-Meier survival curve of patients with untreated, unresectable cholangiocarcinoma undergoing PRFA.

S0007 Palliative Endoscopic Biliary Radiofrequency Ablation and Percutaneous Biliary Radiofrequency Ablation as Therapies for Patients With Unresectable Cholangiocarcinoma: A Meta-Analysis on Overall Survival Outcomes

INTRODUCTION: Cholangiocarcinoma (CCA) has an extremely poor prognosis with literature demonstrating 5-year survival rates between 2 and 25% and median survival between 3 and 6 months for unresectable disease. Up to 80% of patients presenting with CCA have unresectable disease and these patients are left with palliative treatment options. Mainstay palliative therapy (apart from systemic chemotherapy) includes percutaneous or endoscopic stenting, however these treatment options have a relatively poor survival benefit. Radiofrequency ablation is a relatively new technology that delivers thermal energy at the tumor site resulting in locoregional coagulative necrosis. This meta-analysis aims to compare survival data for patients who underwent endoscopic radiofrequency ablation (ERFA) or percutaneous radiofrequency ablation (PRFA) as a palliative therapy for unresectable CCA. METHODS: A PubMed search was conducted for manuscripts and abstracts that analyzed survival outcomes in patients undergoing either ERFA or PRFA for the treatment of unresectable CCA. Studies were included in the meta-analysis only if extrapolation of CCA specific survival was made available. Studies analyzing post-surgical disease or recurrent lesions were excluded. A Kaplan Meier curve was generated from pooled survival data and a Forest plot compiled for comparison of mean survival between studies. RESULTS: There were 23 total studies that met our criteria and included in quantitative analysis. 14 studies analyzed ERFA and the survival outcomes of 213 patients. Additionally, 9 studies analyzed 114 patients and their survival outcomes after undergoing PRFA. One study included 30 patients undergoing either PRFA or ERFA. The mean survival of the ERFA group was 12.1 ± 4.4 months and mean survival of the PRFA group was 14.3 ± 7.5 months. The combined mean survival of all 357 patients undergoing palliative ERFA or PRFA was 12.8 ± 5.4 months. The median survival of the ERFA group was 12.0 months and the median survival of the PRFA group was 10.8 months. The overall median survival of all patients undergoing biliary RFA was 10.8 months. CONCLUSION: Biliary radiofrequency ablation seems to be reasonable for palliation in those with previously untreated, unresectable CCA with evidence of increased mean and median survivals relative to published data. However further studies are required to draw meaningful conclusions regarding survival benefit.Figure 1.: Forest Plot of mean survival of patients undergoing biliary RFA (ERFA and PRFA) for treatment of unresectable cholangiocarcinoma.Figure 2.: Kaplan-Meier survival curve of patients undergoing biliary RFA (ERFA and PRFA) for treatment of unresectable cholangiocarcinoma.

S0013 Palliative Endoscopic Biliary Radiofrequency Ablation as Therapy for Patients With Unresectable Cholangiocarcinoma: A Meta-Analysis on Overall Survival Outcomes

INTRODUCTION: Cholangiocarcinoma (CCA) is a rare gastrointestinal malignancy associated with significant morbidity and mortality. Patients with unresectable disease have an associated 5-year survival between 2–25% and a median survival of 3–6 months according to published literature. The mainstay of non-systemic palliative therapy includes intraductal stenting (plastic or metal) via percutaneous or endoscopic approaches. However, these measures have had marginal life-prolonging effects. Endobiliary radiofrequency ablation (ERFA) is a novel technique that, when used in conjunction with stenting, has demonstrated significant survival benefit. This meta-analysis aims to evaluate pooled survival data of the current published literature comparing ERFA and stenting with the conventional stent-only approach. METHODS: A comprehensive literature search was conducted querying the PubMed database for published manuscripts and abstracts that analyzed survival data in patients undergoing ERFA with stenting and biliary stenting alone. Studies assessing post-surgical patients, treatment on recurrent lesions, or non-CCA related malignancies without contingency data to extrapolate CCA-specific data were excluded from the study. Pooled data was compiled to generate a Kaplan Meier curve with log-rank test performed to compare survival outcomes among the two groups. RESULTS: A total of four studies met inclusion criteria and were analyzed for quantitative outcomes. A total of 106 patients underwent ERFA with stenting compared to 101 patients that had biliary stenting alone. The mean survival of the ERFA with stenting group (11.7 ± 0.7 months) and the biliary stent control group (6.8 ± 0.3 months) differed significantly (mean difference of 4.9 ± 0.1 months, 95% CI 4.8–5.0, P < 0.0001). Likewise, median survival differed significantly between the patients undergoing ERFA with stenting (13 months) as compared to those undergoing biliary stenting alone (8 months; log-rank test z = 4.8, P < 0.0001). CONCLUSION: ERFA with biliary stenting may be a reasonable palliative therapy for those with previously untreated unresectable cholangiocarcinoma with evidence of increased mean and median survivals relative to biliary stenting alone. However, given the lack of available studies on this patient population, more longitudinal data is needed to draw conclusions of survival benefit.Figure 1.: Forest Plot of median survival of patients with untreated, unresectable cholangiocarcinoma treated with ERFA and stenting versus those treated with biliary stenting alone.Figure 2.: Kaplan-Meier survival curve of patients with untreated, unresectable cholangiocarcinoma treated with ERFA and stenting versus those treated with biliary stenting alone.

S0014 Palliative Percutaneous Biliary Radiofrequency Ablation With Stenting Compared to Biliary Stenting Alone in the Treatment of Unresectable Cholangiocarcinoma: A Meta-Analysis on Survival Outcomes

INTRODUCTION: Patients diagnosed with unresectable cholangiocarcinoma (CCA) have a median survival of 3–6 months and often present with significant disease-related morbidity. Malignant biliary obstruction (MBO) is a common manifestation of CCA in which the biliary duct becomes blocked or obstructed by malignant overgrowth resulting in jaundice, pruritus, or possible infectious complications. Current palliative treatment with plastic or metal stenting offers little survival benefit to patients with unresectable disease. Percutaneous radiofrequency ablation (PRFA) is a novel palliative treatment option that, when used in conjunction with stenting, may offer significant life-prolonging results. The aim of this meta-analysis is to evaluate pooled survival data across studies comparing PRFA and stenting with conventional stenting alone. METHODS: A comprehensive literature search was made using the PubMed database for manuscripts comparing survival outcomes for patients who underwent PRFA and stenting with those who underwent stenting alone. Studies evaluating recurrent CCA, post-surgical patients, or non-CCA malignancies without contingency data to extrapolate CCA-specific related data were excluded from analysis. Data across studies was pooled to generate a Kaplan Meier curve and log rank test was performed to compare differences in survival. RESULTS: Two studies met inclusion criteria and were used for quantitative analysis. There was a total of 60 patients who were treated with palliative PRFA with stenting compared to 50 patients treated with biliary stenting alone. Mean survival of the PRFA with stenting group (7.7 ± 3.6 months) and the biliary stent control group (5.9 ± 2.5 months) differed significantly (mean difference of 1.8 ± 0.6 months, 95% CI 0.6–3.0, p = 0.004). However, median survival did not significantly differ between the patients undergoing PRFA with stenting (7.2 months) compared to those undergoing biliary stenting alone (5.2 months; log-rank test z = 1.2, p = 0.2). CONCLUSION: PRFA with concomitant biliary stenting may be a reasonable palliative therapy for those with previously untreated unresectable cholangiocarcinoma with evidence of increased mean survival. Given the lack of available studies on this patient population, more data is needed to draw conclusions of survival benefit relative to biliary stenting alone.Figure 1.: Forest Plot of Mean survival of patients with untreated, unresectable cholangiocarcinoma undergoing PRFA with biliary stenting compared to biliary stenting alone.Figure 2.: Kaplan-Meier survival curve of patients with untreated, unresectable cholangiocarcinoma undergoing PRFA with biliary stenting compared to biliary stenting alone.

Efficacy of non-surgical larynx-preservation comprehensive treatment in advanced laryngeal carcinoma.

Efficacy of non-surgical larynx-preservation comprehensive treatment in advanced laryngeal carcinoma.

Development and validation of a five-lncRNA signature with prognostic value in colon cancer.

Dysregulation of long noncoding RNAs (lncRNAs) has been found in a large number of human cancers, including colon cancer. Therefore, the implementation of potential lncRNAs biomarkers with prognostic prediction value are very much essential. GSE39582 data set was downloaded from database of Gene Expression Omnibus. Re-annotation analysis of lncRNA expression profiles was performed by NetAffx annotation files. Univariate and multivariate Cox proportional analyses helped select prognostic lncRNAs. Algorithm of random survival forest-variable hunting (RSF-VH) together with stepwise multivariate Cox proportional analysis were performed to establish lncRNA signature. The log-rank test was carried out to analyze and compare the Kaplan-Meier survival curves of patients' overall survival (OS). Receiver operating characteristic (ROC) analysis was used for comparing the survival prediction regarding its specificity and sensitivity based on lncRNA risk score, followed by calculating the values of area under the curve (AUC). The single-sample GSEA (ssGSEA) analysis was used to describe biological functions associated with this signature. Finally, to determine the robustness of this model, we used the validation sets including GSE17536 and The Cancer Genome Atlas data set.After re-annotation analysis of lncRNAs, a total of 14 lncRNA probes were obtained by univariate and multivariate Cox proportional analysis. Then, the RSF-VH algorithm and stepwise multivariate Cox analysis helped to build a five-lncRNA prognostic signature for colon cancer. The patients in group with high risk showed an obviously shorter survival time compared with patients in group with low risk with AUC of 0.75. In addition, the five-lncRNA signature can be used to independently predict the survival of patients with colon cancer. The ssGSEA analysis revealed that pathways such as extracellular matrix-receptor interaction was activated with an increase in risk score. These findings determined the strong power of prognostic prediction value of this five-lncRNA signature for colon cancer.

Prognostic value of 3-dimensional echocardiographical heart volume assessment in patients scheduled for left ventricular assist device implantation.

Left ventricular assist device (LVAD) support is an increasingly important and successful therapeutic option for patients with end-stage heart failure. As chronic heart failure progresses, the left and right ventricles adapt by enlarging its volume and patients present for LVAD implantation with varying degrees of dilatation. By quantitatively assessing right ventricular (RV) and left ventricular (LV) volumes using 3D transoesophageal echocardiography and correlating the findings with clinical outcomes, we aim to investigate the prognostic value of LV and RV volumes for early survival after LVAD implantation. This is a single-centre, non-randomized diagnostic cohort study using prospectively collected clinical and 3D echocardiographic data from 65 patients scheduled for LVAD implantation, using centrifugal pumps for long-term support (HeartWare and HeartMate 3). The primary end-point for this study is 60-day mortality, with longer term survival as a secondary end-point. We divided our cohort group into survivors and non-survivors at 60 days [49 patients (75%) and 16 patients (25%), respectively]. Right to left end-diastolic ratio assessed by 2D echocardiography was significantly higher in the 60-day non-survivors group (0.70 ± 0.09 vs 0.62 ± 0.11; P = 0.01). Indexed end-diastolic volume parameters (LV, RV and overall heart) showed significant differences among the groups and were higher in the 60-day survivors group (LV volume 154 ± 51 ml/m2 vs 110 ± 40 ml/m2, P = 0.004; RV volume 96 ± 27 ml/m2 vs 80 ± 23 ml/m2, P = 0.05; heart 250 ± 64 ml/m2 vs 190 ± 57 ml/m2, P= 0.003). To investigate haemodynamic and echocardiographic parameters, the right to left end-diastolic ratio and indexed RV end-diastolic volume were associated with 60-day mortality in the logistic regression analysis. The Kaplan-Meier survival curves for patients with indexed RV end-diastolic volume >82 ml/m2 vs indexed RV end-diastolic volume ≤82 ml/m2 showed better 1-year survival (P = 0.005) for the group with more RV dilatation. Patients with moderately increased end-diastolic RV volume index carry a higher postoperative risk, while severe RV dilatation seems to be protective. In future, postoperative management of patients with moderately dilated RVs should be focussed on adjusting individually appropriate LVAD flows and providing frequent follow-up.

Increased Circulating Plasma Cells Predicts Poor Overall Survival in Symptomatic Plasma Cell Myeloma Patients

Abstract Backgrounds Flow cytometry can rapidly determine immunophenotypes of neoplastic plasma cells (PCs) and quantify PCs in patients with plasma cell myeloma. Flow cytometric immunophenotyping and quantification of neoplastic plasma cells is sensitive and reliable tool for diagnosis and disease monitoring in patients with monoclonal gammopathy. Circulating PCs (cPCs) in peripheral blood (PB) after autologous hematopoietic stem cell transplantation is a marker of high-risk disease in patients with plasma cell myeloma. We assessed the utility of quantification of cPCs using flow cytometry for risk stratification in newly diagnosed plasma cell myeloma patients in the era of novel agents. Methods PB and bone marrow (BM) aspirates of 85 newly diagnosed patients with symptomatic plasma cell myeloma from August 2013 to July 2014 were analyzed by five-color flow cytometry using monoclonal antibodies against CD45, CD19, CD56, CD38, and CD138. The gating strategy employed first used the expression of CD38 and CD138 to identify plasma cells among 100,000 to 200,000 events. cPCs in PB was determined according to the patient's specific immunophenotype of neoplastic PCs in BM. Results The median age of the patient population was 68 years (45~87) and 58% were female. Median follow-up duration was 19.2 months. Six out of 85 patients (7%) did not show cPCs. Among 79 patient (93%) who had detectable cPCs, the median cPCs was 0.09% (0.006~3.612%). Patients without cPCs or cPCs under 0.05% were assigned to low cPCs group (n=32, 38%) and others to high cPCs group (n=53, 62%) according to receiver operating characteristics analysis. High cPCs group showed higher level of BM neoplastic PCs detected by both methodologys of morphology and flow cytometry (P=0.002, 0.033, respectively), higher BM cellularity (P=0.011), higher serum M protein level (P=0.013), lower hemoglobin (P=0.008), and lower platelet level (P=0.034) than low cPCs group. High cPCs group was associated with adverse cytogenetics such as t(4;14) and monosomy 13 (P=0.008), and CD45 negative immunophenotype (P=0.007). In survival analysis, high cPCs presented shorter overall survival (OS) than low cPCs group (P=0.013) (Fig. 1). It was independent with patient age and cytogenetic risks (P =0.011). Conclusion By flow cytometry cPCs was detected in most symptomatic plasma cell myeloma patients. Increased cPCs ≥0.05% among PB leukocytes could be an independent prognostic factor showing adverse effect in overall survival in symptomatic plasma cell myeloma patients. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Disclosures No relevant conflicts of interest to declare.

Predictive Value of Circulatingve-catherin in Coronary Artery Disease Patients with Symptomatic Moderate to Severe Chronic Heart Failure

Aim: To evaluate the prognostic value of circulating VE-catherinfor cumulative survivalin patients with ischemic chronic heart failure (CHF).Methods: A total of 154 patients withischemic symptomatic moderate-to-severe CHF were enrolled in the study on discharge from the hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. ELISA method for measurements of circulating level of VE-catherin was used. Concentrations of VEcatherinfor cumulative survival cases due to advanced CHF were tested. Additionally, all-cause mortality, and CHFrelated death were examined.Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating levels of VE-catherin in survived and died patient cohort were 0.63 ng/ml (95% confidence interval [CI] = 0.55-0.64 ng/ml) and 1.03 ng/ml (95% CI = 0.97-1.07 ng/ml) (P&lt;0.001). ROC analysis has been shown that cutoff point of VE-catherin concentration for cumulative survival function was 0.755ng/ml. It has beenfound a significantly divergence of Kaplan-Meier survival curves in patients with high (&gt;0.755 ng/ml) and low (&lt;0.755 ng/ml) concentrations of VE-catherin. Circulating VE-catherin independently predicted all-cause mortality (OR = 1.27; 95% CI = 1.08–1.59; P = 0.002), CHF-related death (OR = 1.16; 95% CI 1.02–1.50; P &lt; 0.001), and also CHF-related rehospitalisation (OR = 1.12; 95% CI = 1.07 – 1.25; P&lt;0.001) within 3 years of observation period.Conclusion: Increased circulating VE-catherinassociates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.J MEDICINE July 2015; 16 (2) : 73-78

Clinicopathological and biological significance of aberrant activation of glycogen synthase kinase-3 in ovarian cancer.

BackgroundGlycogen synthase kinase-3 (GSK-3) plays an important role in human cancer. The aim of this study is to evaluate the clinicopathological significance of expression of GSK-3α/β and pGSK-3α/βTyr279/216 in patients with epithelial ovarian cancer and to investigate whether GSK-3 inhibition can influence cell viability and tumor growth of ovarian cancer.MethodsImmunohistochemistry was used to examine expression of GSK-3α/β and pGSK-3α/βTyr279/216 in 71 human epithelial ovarian cancer tissues and correlations between protein expression, and clinicopathological factors were analyzed. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay following exposure of ovarian carcinoma cells to pharmacological inhibitors of GSK-3 or GSK-3 small interfering RNA. In vivo validation of tumor growth inhibition was performed with xenograft mice.ResultsThe expression levels of GSK-3α/β and pGSK-3α/βTyr279/216 in ovarian cancers were significantly higher than those in benign tumors. High expression of GSK-3α/β was more likely to be found in patients with advanced International Federation of Gynecology and Obstetrics (FIGO) stages and high serum cancer antigen 125. Higher expression of pGSK-3α/βTyr279/216 was associated with advanced FIGO stages, residual tumor mass, high serum cancer antigen 125, and poor chemoresponse. Worse overall survival was revealed by Kaplan–Meier survival curves in patients with high expression of GSK-3α/β or pGSK-3α/βTyr279/216. Multivariate analysis indicated that FIGO stage, GSK-3α/β expression, and pGSK-3α/βTyr279/216 expression were independent prognostic factors for overall survival. GSK-3 inhibition by lithium chloride, 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), or GSK-3 small interfering RNA can decrease viability of SKOV3 and SKOV3-TR30 ovarian cancer cells. Additionally, lithium chloride-treated SKOV3 xenograft mice had a significant reduction in tumor growth compared with control-treated animals.ConclusionOur findings suggest that overexpression and aberrant activation of GSK-3 may contribute to progression and poor prognosis in ovarian cancer. Inhibition of GSK-3 may be a potential therapy for ovarian cancer.

Prognostic Value of Conventional Magnetic Resonance Imaging for Adult Patients with Brain Tumors.

Magnetic resonance imaging (MRI) is the pivotal diagnostic step in patients with brain tumors, and is performed before histological diagnosis is available. We hypothesized that conventional MRI is as accurate as tumor histology in differentiating malignant from benign clinical course. Two neuroradiologists blinded to any clinical information evaluated the first diagnostic MRI of 244 brain tumor patients before any treatment, using a self-developed standardized list of image criteria and prospectively determined world health organization (WHO) tumor grade and tumor entity. All patients were examined with at least T1- and T2-weighted spin echo sequences before and after contrast injection on 1 and 1.5-T MRI scanners. Following the patients prospectively for 8-13 years after diagnosis, we were able to use nonsurvival at 5 years as a criterion for malignity and reference for the prognostic accuracy of both MRI and tumor tissue histology. The accuracy for predicting nonsurvival at 5 years was 91% (95% confidence interval (CI): 87-94%) for MRI and 92% (95% CI: 88-95%) for histology. The Kaplan-Meier survival curves of patients with benign and malignant brain tumors as diagnosed by MRI or histology differed significantly (p < 0.001). Histology confirmed benignity or malignity in 201 patients (82%, 95% CI: 77-87%). Sources of misdiagnosis were metastases diagnosed as astrocytoma WHO IV, atypical meningiomas, and low-grade astrocytoma with malignant transformation. MRI appears as accurate as histology in predicting survival at 5 years after diagnosis. Histological diagnosis may be more specific, however, and is needed to assess the tumor's specific biology.

Prognostic Significance of p53, mTOR, c-Met, IGF-1R, and HSP70 Overexpression after the Resection of Hepatocellular Carcinoma

Background/AimsThe current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival.MethodsWe analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs.Resultsp53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant.Conclusionsp53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.

Predictive Value of Circulating Apoptotic Microparticles in Patients with Ischemic Symptomatic Moderate-To-Severe Chronic Heart Failure

Aim: To evaluate the prognostic value of circulating CD31+/annexin V+ Microparticles (MPs) for cumulative survival in patients with ischemic Chronic Heart Failure (CHF). Methods: A total of 154 patients with ischemic symptomatic moderate-to-severe CHF were enrolled in the study on discharge from the hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. Flow cytometry analysis for quantifying the number of CD31+/annexin V+ MPs was used. CD31+/ annexin V+ MPs number for cumulative survival cases due to CHF were tested. Additionally, all-cause mortality, and CHF-related death were examined. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating levels of CD31+/annexin V+ MPs in patients who survived and subjects who died were 0.286 n/mL (95% confidence interval [CI] = 0.271-0.309 n/mL) and 0.673 n/mL (95% CI = 0.65-0.74 n/ mL) (P 0.850 n/mL). ROC analysis has been shown that cut off point of CD31+/ annexin V+ MPs number for cumulative survival function was 0.514 n/mL. Area under cure was 0.913 (Std. error = 0.025; 95% CI = 0.863-0.962), sensitivity and specificity were 89.6% and 69.7% respectively. It has been found a significantly divergence of Kaplan-Meier survival curves in patients with high quartile (MPs number >0.514 n/mL) of MPs numbers when compared with low quartiles. Using a stepwise model selection method for multivariable prediction model we investigated that CD31+/annexin V+ MPs number alone and combination of CD31+/annexin V+ MPs number with NT-pro-brain natriuretic peptide (NT-pro-BNP) remained statistically significant predictors for all-cause mortality, CHF-related death, and CHF-related re-hospitalisations, whereas combination of CD31+/annexin V+ MPs with both NT-pro-BNP and left ventricular ejection fraction did not. Conclusion: Increased circulating CD31+/annexin V+ MPs associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

Complete Revascularization Is Not a Prerequisite for Success in Current Transcatheter Aortic Valve Implantation Practice

This study sought to assess in patients undergoing transcatheter aortic valve implantation (TAVI), the prevalence and impact of incomplete coronary revascularization defined as >50% coronary artery or graft diameter stenosis on visual assessment of the coronary angiogram. TAVI is an established treatment option in elderly patients with aortic stenosis (AS) and a (very) high operative risk. Coronary artery disease (CAD) is often associated with AS. A single-center cohort of consecutive patients undergoing TAVI between November 2005 and June 2012 was evaluated for the presence of significant CAD. The decision to revascularize and pursue complete revascularization was made by heart team consensus. A total of 263 consecutive patients with a mean age of 80 ± 7 years and 51% male underwent TAVI with a median follow-up duration of 16 months (interquartile range: 4.2 to 28.1months). Significant CAD with myocardium at risk was present in 124 patients (47%), 44 of whom had had previous coronary artery bypass grafting (CABG), and the median SYNTAX score in the 81patients without previous CABG was 9.00 (2.38 to 15.63). Staged percutaneous coronary intervention (PCI) was planned in 19 (15%) and concomitant PCI with TAVI in 20 (16%). The median post-procedural residual SYNTAX score of patients without prior CABG was 5.00 (0.13 to 9.88). Overall, 99 patients (37%) (61 with no CABG and 38 CABG patients) had incomplete revascularization afterTAVI. Revascularization status did not affect clinical endpoints. Kaplan-Meier survival curves for patients with and without complete revascularization demonstrated a 1-year mortality of 79.9% versus 77.4% (p= 0.85), respectively. In an elderly patient population undergoing TAVI for severe AS, a judicious revascularization strategy selection by a dedicated heart team can generate favorable mid-term outcome obviating the need for complete coronary revascularization.