Multivariate Cox Proportional-hazards Regression Analysis Research Articles

Perioperative Blood Transfusion as a Significant Predictor of Biochemical Recurrence and Survival after Radical Prostatectomy in Patients with Prostate Cancer.

PurposeThere have been conflicting reports regarding the association of perioperative blood transfusion (PBT) with oncologic outcomes including recurrence rates and survival outcomes in prostate cancer. We aimed to evaluate whether perioperative blood transfusion (PBT) affects biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) following radical prostatectomy (RP) for patients with prostate cancer.Materials and MethodsA total of 2,713 patients who underwent RP for clinically localized prostate cancer between 1993 and 2014 were retrospectively analyzed. We performed a comparative analysis based on receipt of transfusion (PBT group vs. no-PBT group) and transfusion type (autologous PBT vs. allogeneic PBT). Univariate and multivariate Cox-proportional hazard regression analysis were performed to evaluate variables associated with BRFS, CSS, and OS. The Kaplan-Meier method was used to calculate survival estimates for BRFS, CSS, and OS, and log-rank test was used to conduct comparisons between the groups.ResultsThe number of patients who received PBT was 440 (16.5%). Among these patients, 350 (79.5%) received allogeneic transfusion and the other 90 (20.5%) received autologous transfusion. In a multivariate analysis, allogeneic PBT was found to be statistically significant predictors of BRFS, CSS, and OS; conversely, autologous PBT was not. The Kaplan-Meier survival analysis showed significantly decreased 5-year BRFS (79.2% vs. 70.1%, log-rank, p = 0.001), CSS (98.5% vs. 96.7%, log-rank, p = 0.012), and OS (95.5% vs. 90.6%, log-rank, p < 0.001) in the allogeneic PBT group compared to the no-allogeneic PBT group. In the autologous PBT group, however, none of these were statistically significant compared to the no-autologous PBT group.ConclusionsWe found that allogeneic PBT was significantly associated with decreased BRFS, CSS, and OS. This provides further support for the immunomodulation hypothesis for allogeneic PBT.

Potential protective effect of Helicobacter pylori on the development of gastrointestinal GvHD.

Previous reports ascribe a modulating capacity of the immune response to Helicobacter pylori (HP). Our hypothesis was to demonstrate in a prospective study that HP infection could have a protective effect against development of gastrointestinal GvHD in patients receiving allogeneic hematopoietic cell transplantation (HCT). Presence of HP before transplant was determined using C(13) urea breath test. Seventy-nine patients receiving an allogeneic HCT were included and 93.7% of them received PBSC; in 51.9%, the donor was unrelated. Acute gastrointestinal GvHD was diagnosed in 51.9% (n=41). In the multivariable analysis, HP infection was associated with a lower frequency of gastrointestinal GvHD (odds ratio (OR)=0.19 (95% confidence interval (CI): 0.05-0.67); in contrast, an unrelated donor was associated with a higher frequency of gastrointestinal GvHD (odds ratio=5.4 (95% confidence interval: 1.6-18.2). One year overall survival (OS) was 74%. In the multivariate Cox proportional-hazards regression analysis, stages 0-II gastrointestinal GvHD (hazards ratio (HR)=0.19), reduced intensity conditioning (HR=0.04) and tacrolimus-sirolimus GvHD prophylaxis (HR=0.06) were all associated with a better OS. In summary, HP infection could have a role in decreasing gastrointestinal GvHD in patients receiving allogeneic HCT from peripheral blood including related and unrelated donors.

Risk of Cerebrovascular Events in Pneumoconiosis Patients: A Population-based Study, 1996-2011.

Pneumoconiosis is a parenchymal lung disease that develops through the inhalation of inorganic dust at work. Cerebrovascular and cardiovascular events are leading causes of mortality and adult disability worldwide. This retrospective cohort study investigated the association between pneumoconiosis, and cerebrovascular and cardiovascular events by using a nationwide population-based database in Taiwan.The data analyzed in this study was retrieved from the Taiwan National Health Insurance Research Database. We selected 6940 patients with pneumoconiosis from the database as our study cohort. Another 27,760 patients without pneumoconiosis were selected and matched with those with pneumoconiosis according to age and sex as the comparison cohort. We used univariate and multivariate Cox proportional-hazard regression analyses to determine the association between pneumoconiosis and the risk of cerebrovascular and cardiovascular events after adjusting for medical comorbidities.After adjustment for age, sex, and comorbidities, the patients with pneumoconiosis exhibited a significantly higher incidence of ischemic stroke (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.05–1.24) than did those without pneumoconiosis. The incidence of hemorrhagic stroke was higher, but not significant, in the pneumoconiosis patients (HR 1.20, 95% CI 0.99–1.46). No statistically significant differences were observed between the pneumoconiosis and nonpneumoconiosis groups in acute coronary syndrome (HR 1.10, 95% CI 0.95–1.26).The findings of this study reveal an association between pneumoconiosis and a higher risk of cerebrovascular events after adjustment for comorbidities. Healthcare providers should control the related risk factors for primary prevention of stroke in pneumoconiosis patients.

Association between Body Mass Index and Sputum Culture Conversion among South Korean Patients with Multidrug Resistant Tuberculosis in a Tuberculosis Referral Hospital

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is an important global health problem. Furthermore, the time to identify a positive sputum culture is an important risk factor for the spread of tuberculosis, and several factors can predict a prolonged time to culture conversion. Moreover, the relationship between poor nutritional status and infectious disease is clearly established. Therefore, the present study aimed to investigate the association between body mass index (BMI) and sputum culture conversion within 3 months among patients with MDR-TB.Materials and MethodsWe retrospectively evaluated 218 patients with MDR-TB who were treated at a large tuberculosis referral hospital in South Korea between January 2005 and December 2010. The outcome of interest was defined as sputum culture conversion within 3 months, and we analyzed the association between BMI and this outcome.ResultsAmong the 218 patients, 53 patients (24.3%) had a low BMI (<18.5 kg/m2). In the multivariate Cox proportional-hazards regression analysis, failure to achieve sputum culture conversion within 3 months was independently associated with having a low BMI (hazard ratio [HR]: 1.741, 95% confidence interval [CI]: 1.006–3.013; P = 0.047) and a positive sputum smear at the initiation of therapy (HR: 8.440, 95% CI: 1.146–62.138, P = 0.036).ConclusionLow BMI (<18.5 kg/m2) was an independent risk factor for failure to achieve sputum culture conversion within 3 months among patients with MDR-TB.

Risk factors related to late metastases in 1,372 melanoma patients disease free more than 10 years.

In many centers, Stage I-II melanoma patients are considered "cured" after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness >2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free.

Immuno-virological and clinical impacts of treating cancer in patients living with HIV.

Patients living with HIV (PLHIV) are increasingly being affected by cancer. However, data evaluating the long-term impact of cancer treatment on HIV course are sparse. To determine whether anticancer treatments detrimentally impact HIV course, we conducted a retrospective cohort study in seven hospitals in France. Adult PLHIV treated for haematological or solid malignancies were included and compared (1:1) with suitably matched (cancer-free) controls. The primary outcome was the risk of a ≥ 25% reduction in the absolute CD4+ count during follow-up. The risks for virological failure (i.e. a confirmed plasma viral load >50 copies/mL), incidental AIDS-related illnesses and death over time were also assessed. Multivariate Cox proportional-hazards regression analyses were used to identify the outcome predictors. One-hundred-and-ten patients with cancer and 110 controls were followed for a median of 4.4 years. In a Cox model, the CD4+ depletion was strongly predicted by external radiotherapy (ERT) exposure (HR = 5.1, 95% CI, 3.0-8.6, P < 0.0001) but not by chemotherapy. For patients exposed to ERT, the magnitude of the CD4+ depletion peaked 6 months after their cancer diagnosis (mean CD4+ drop at this time = -283 ± 370 cells/mm(3)). Overall, the cancer patients were also more likely to experience virological failure than the controls (HR = 1.7, 95% CI, 1.1-2.7, P = 0.03). Finally, the incidence of AIDS-related illnesses was similar for both groups. In PLHIV, cancer treatment increased the risk for prolonged CD4+ depletion and virological failure but had no impact on AIDS-related events when appropriate prophylaxes were implemented.

Co-expression of midkine and pleiotrophin predicts poor survival in human glioma

The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p<0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p=0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p=0.022 and 0.001, respectively), time to recurrence (p=0.043 and 0.011, respectively) and poor overall survival (p=0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p=0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p=0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.

OP0211 Association between Systemic Activity and Lymphoma in Primary Sjogren Syndrome: Baseline Essdai Predictors in 921 Spanish Patients (GEAS-SS Registry)

ObjectivesTo analyse the epidemiological, clinical and analytical features at diagnosis and the usefulness the new 2010 European activity index (ESSDAI) to predict the development of lymphoproliferative disease in a large...

Prognostic impact of infiltration of the vagina and/or uterus in women undergoing anterior pelvic exenteration for urothelial carcinoma of the bladder: results of a contemporary multicentre series.

To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21-82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

Building and validation of a prognostic model for predicting extracorporeal circuit clotting in patients with continuous renal replacement therapy

To develop a predictive model for circuit clotting in patients with continuous renal replacement therapy (CRRT). A total of 425 cases were selected. 302 cases were used to develop a predictive model of extracorporeal circuit life span during CRRT without citrate anticoagulation in 24 h, and 123 cases were used to validate the model. The prediction formula was developed using multivariate Cox proportional-hazards regression analysis, from which a risk score was assigned. The mean survival time of the circuit was 15.0 ± 1.3 h, and the rate of circuit clotting was 66.6 % during 24 h of CRRT. Five significant variables were assigned a predicting score according to the regression coefficient: insufficient blood flow, no anticoagulation, hematocrit ≥0.37, lactic acid of arterial blood gas analysis ≤3 mmol/L and APTT < 44.2 s. The Hosmer-Lemeshow test showed no significant difference between the predicted and actual circuit clotting (R (2) = 0.232; P = 0.301). A risk score that includes the five above-mentioned variables can be used to predict the likelihood of extracorporeal circuit clotting in patients undergoing CRRT.

Prognostic Relevance of Viable Circulating Tumor Cells Detected by EPISPOT in Metastatic Breast Cancer Patients

Detection of circulating tumor cells (CTC) in breast cancer patients is currently performed in many clinical trials, using different technologies, in particular the EpCAM-dependent CellSearch® system. The purpose of this study was to investigate the incidence and prognostic relevance of viable CTC in a large cohort of metastatic breast cancer (MBC) patients. A total of 254 MBC patients were enrolled in a prospective multicenter study at first diagnosis of metastatic disease or disease progression (before the start of a new treatment regimen). After EpCAM-independent enrichment, viable CTC releasing cytokeratin-19 as an epithelial cell marker were detected in the peripheral blood by an EPISPOT assay, and the Food and Drug Administration cleared CellSearch was used as the reference method. Using the EPISPOT assay, CTC were detected in 59% of MBC patients. The overall survival (OS) was linked with the CTC status measured by EPISPOT (P = 0.0191), which allowed stratification of MBC patients in low- and high-risk groups. This stratification could be improved by addition of the CTC status assessed by the CellSearch system. In multivariate Cox proportional-hazards regression analysis, the 3 methods used to determine the level of CTC (EPISPOT, CellSearch, and combination of EPISPOT/CellSearch) were compared by the Bayesian information criterion method. Interestingly, the combination of the EPISPOT and CellSearch assays was the strongest predictor of OS (hazard ratio, 22.6; 95% CI, 2.8-184.08). This is the first study in which CTC detection using the EPISPOT assay was evaluated on a large cohort of MBC patients, showing prognostic relevance of the presence of viable CTC.

The Prognositic Significance of Serial Renal Function Measurements in Chronic Heart Failure

Background: Impaired renal function is a strong prognostic factor in Chronic Heart Failure (CHF). Most studies of it, however, have assessed single measurements of renal function. Thus, the purpose of the present study was to determine the prognostic significance and importance of serial measurements of renal function before and after hospital discharge. Methods and results: A total of 542 consecutive patients admitted for worsening CHF (455 males, 60.6 ± 14.2 years) were studied. Estimated glomerular filtration rate (eGFR) was evaluated before discharge and 6 months later. Patients were followed-up to register cardiac death and rehospitalization due to worsening heart failure. We divided study subjects into four groups based on changes in renal function between before discharge and 6 months after. These were Group 1: normal to normal eGFR (≥60 mL/min/17.3m2), Group 2: reduced (<60 mL/min/17.3m2) to normal eGFR, Group 3: normal to reduced eGFR, and Group 4: reduced to reduced eGFR. Compared to Group 1, Groups 2, 3 and 4 had relative risks of 2.265-fold (P<0.05), 4.055-fold (P<0.001) and 3.974-fold (P<0.001), respectively, for adverse cardiac events after discharge. The multivariate Cox proportional hazard regression analysis demonstrated that log BNP at 6 months after discharge (hazard ratio [HR]: 1.768, P<0.001), peak VO2 (HR: 0.859, P<0.001) and eGFR <60 mL/min/1.73m2 at 6 months (HR: 1.854, P<0.05), but not eGFR at discharge, were independent predictors for cardiac events. Conclusion: Changes in renal function by serial measurements after discharge are important for the assessment of risk in CHF.

PU.1 Is Essential For MLL Leukemia Via Activation Of The Meis/HOX Pathway and A Monocytic Cytokine Mediated Anti-Apoptotic Inflammatory Program

Aberrant transcriptional programs play a critical role in the development of acute myeloid leukemias (AMLs). Although persistent over-expression of MEIS1 and HOXA9 has been shown to be essential for the initiation and maintenance of MLL-associated leukemia, it is still poorly understood what additional transcriptional regulators, independent of the MLL fusion-driven MEIS/HOX pathway, dictate the development of MLL leukemia. Considering that AMLs with MLL translocation are typically associated with the monocytic lineage (FAB M4 and M5), we explored the potential role of the monocytic lineage-specific transcriptional program in MLL leukemia.Using 97 genome-wide expression profiles of human MLL leukemias, we constructed an MLL distinctive transcriptional regulatory network. In addition to well-known transcriptional factors in leukemia development such as MEIS1 and HOXA family genes, we identified a highly active monocyte-specific gene signature that includes transcription factor PU.1. In our effort to determine the functional role of PU.1 in MLL leukemia, we found that lower PU.1 expression significantly delayed the onset of MLL- AF9 induced leukemia in primary bone marrow transplantation assay. MLL leukemia failed to maintain in vivo upon induced deletion of the PU.1 gene. To examine the clinical relevance of the PU.1 in AML patients, we further performed multivariate Cox proportional-hazards regression analysis in four published datasets of patients with AML, for whom gene expression and time-to-event data were available. We found that a PU.1-regulated 40-gene signature showed profound concordance with prognosis in segregating high-risk and low-risk AML patients. When specific subgroups of AMLs were examined, the PU.1 expression signature could predict patient outcome for MLL patients, but not in other major AMLs, such as t(8;21), t(15;17) and inv(16).We further explored the molecular mechanisms underlying the critical role of the PU.1 program in MLL leukemia. Functional annotation of this PU.1 expression signature identified the MEIS/HOX pathway (MEIS1, FLT3, KIT), as well as key genes in the inflammatory response (AIF1, NF-KB1 and CD180). We showed that PU.1 is required to maintain high expression of Meis1 and Pbx3 and also important downstream genes in the MEIS/HOX pathway that includes known MEIS/HOX targets c-Kit and Flt3. Using ChIP-sequencing, we demonstrated that PU.1 interacts with the MEIS/HOX regulatory program through co-binding with MEIS1 at the target genomic regions in a MLL-ENL cell line. In our effort to determine the role of PU.1-controlled inflammatory response genes, we found that the growth inhibition in PU.1 knockdown MLL leukemic cells was partially rescued by addition of the monocytic inflammatory cytokine AIF1. AIF1 provides an anti-apoptotic effect through activation of the NF-ƒÛB pathway and additional known apoptosis regulators. Interestingly, AML patients with higher expression of both AIF1 and MEIS1 had a significantly shorter overall survival time than those with lower expression of both genes. Patients with high expression of either MEIS1 or AIF1 had medium survival possibilities. Notably, the prognostic value of AIF1 and MEIS1 remained in those with monocytic AMLs (P=0.00079), but not in the non- monocytic group of patients (p=0.105). Collectively, these results strongly suggest that the monocyte-specific inflammatory cytokine AIF1 is an MEIS/HOX independent essential regulator in monocytic AMLs such as MLL leukemia.Loss of function PU.1 is leukemogenic in mouse models. Suppression of PU.1 activity is also required for the development of human myelocytic M2/M3 leukemia. Here we reveal a converse role for PU.1 as an essential positive regulator in the development of MLL myeloid leukemia, mostly M4/M5 monocytic AMLs. Our study demonstrats that the monocyte-specific PU.1-driven transcriptional program independently contributes to the development of myeloid MLL leukemia, in parallel with the MLL fusion pathway. PU.1 and downstream macrophage specific inflammatory cytokine AIF1 have important prognostic value and may serve as novel therapeutic targets for MLL leukemias. Disclosures:No relevant conflicts of interest to declare.

Risks of subsequent epilepsy among patients with hypertensive encephalopathy: A nationwide population-based study

BackgroundTo determine whether the diagnosis of hypertensive encephalopathy (HE) is linked to an increased risk of subsequent epilepsy by using a nationwide population-based retrospective study. MethodsOur study featured a study cohort and a comparison cohort. The study cohort consisted of all patients with newly diagnosed HE between 1997 and 2010, compiled from universal insurance claims data on patients with hypertension taken from the National Health Insurance Research Database. The comparison cohort comprised the remaining hypertensive patients without encephalopathy. The follow-up period was terminated following the development of epilepsy, death, withdrawal from the National Health Insurance system, or the end of 2010. We determined the cumulative incidences and hazard ratios (HRs) of epilepsy development. ResultsThe incidence of subsequent epilepsy was 2.25-fold higher in the patients with HE than in comparisons (4.17 vs. 1.85 per 1000person-years), with an adjusted HR of 2.06 (95% CI=1.66–2.56) in the multivariable Cox proportional-hazards regression analysis. The incidence of epilepsy was higher in men, younger patients with HE, and those with brain disorders. ConclusionsWe found that, in Taiwan, patients with HE are at an increased risk of subsequent epilepsy. Physicians should be aware of HE's link to epilepsy when assessing patients with HE.

Potential effect of physiotherapeutic treatment on mortality rate in patients with severe sepsis and septic shock: A retrospective cohort analysis

PurposeThe aim of the study was to examine the onset and frequency of physiotherapeutic interventions (PTI) and their potential effects on the intensive care unit (ICU) mortality rate in patients with severe sepsis or septic shock. Material and MethodsRetrospective data analysis. Univariate and multivariate Cox proportional-hazards regression analyses were performed. ResultsAbout 6.2% of all patients (n = 999, length of ICU stay 12 days, averaged SOFA score 14) developed sepsis within three years. Of these, 77% received at least once PTI. The relative number of PTI (RNPTI index, individually calculated by the number of PTI/length of stay) in patients with sepsis was 42%. The first physiotherapeutic treatment was five days after ICU admission. Cox regression multivariate analysis adjusted by disease severity scores, sedation state and other clinical variables found RNPTI index as significant risk factor for the ICU mortality rate (hazard ratio, 0.982; 95% confidence interval, 0.974-0.990; P < .001). ConclusionsPhysiotherapists routinely assess and treat patients with sepsis. The frequency of PTI was associated with an improved outcome. Prospective studies are necessary to confirm the potential favorable impact.

A 3-year retrospective cohort study of predictors of relapse in first-episode psychosis in Hong Kong

Relapses in psychosis are costly and may have irreversible consequences. Relapse prevention is thus critical in the treatment of schizophrenia. Apart from medication discontinuation, a consistent relapse predictor has not been identified due to limitations in previous studies. We aim to investigate relapse predictors in a large cohort of patients with first-episode psychosis. This is a retrospective cohort study designed to evaluate relapses in first-episode psychosis patients in 3 years. A total of 1400 patients' case records were retrieved from a hospital database. Potential relapse predictors including demographic variables, baseline clinical measures, medication adherence, and residual positive symptoms upon clinical stabilization were collected. The cumulative relapse rates were 19.3% by year 1, 38.4% by year 2, and 48.1% by year 3. Multivariate Cox-proportional hazards regression analysis revealed that medication non-adherence, smoking, schizophrenia diagnosis, younger age, and shorter baseline hospitalization were associated with an increased risk of relapse in 3 years. Nearly half of patients relapsed after 3 years following their first-episode psychosis. Smoking as a predictor of relapse is an intriguing new finding supportive of a link between nicotinic receptors and the dopamine system. Their relationship deserves further investigations with potential clinical implications for relapse prevention.

Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma

Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play an important role in the development of human gliomas. However, their prognostic values are not clear. The aim of this study was to investigate whether co-expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas. Immunohistochemistry and western blot were used to investigate the expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both significantly higher (both P < 0.001) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis, which was confirmed by the western blot analysis. Additionally, the overexpression of either MMP-14 or MMP-19 was significantly associated with the advanced WHO grade (both P = 0.02), the low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the poor overall survival (both P = 0.01). Moreover, the Multivariate Cox proportional-hazards regression analysis revealed that the increased expressions of MMP-14 and MMP-19 were both independent prognostic factors for poor overall survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was additively and more significantly (P = 0.006) associated with adverse prognosis in patients with gliomas than respective expression of MMP-14 and MMP-19. These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.

Upregulation of Gp96 Correlates with the Radiosensitivity and Five-Year Survival Rate of Nasopharyngeal Carcinoma

Gp96 (GRP94) is a chaperone that is responsible for molecular folding and assembly of proteins. To investigate correlations among Gp96 expression, sensitivity to radiotherapy and clinical features of nasopharyngeal carcinoma (NPC), the expression of Gp96 in 98 NPC samples was analyzed by immunohistochemistry and Western blotting at the protein level, and by real-time PCR at the mRNA level. Clinicopathological features, including stage, sex, grade and survival, were compared between the high and low Gp96 expression groups. As a result, Gp96 was expressed at a higher level in NPC tissues than in noncancerous nasopharyngeal mucosa (p = 0.001). Univariate analysis suggested that a higher Gp96 expression level was associated with significantly decreased disease-free and 5-year survival rates (p = 0.000, p = 0.000, respectively). Multivariate Cox proportional-hazard regression analysis, which adjusts for clinicopathological variables, indicated that it was only associated with the 5-year overall survival rate (p = 0.002). Furthermore, patients with high Gp96 expression levels were significantly more resistant to radiotherapy (p = 0.001). These data are the first indication of a positive correlation between Gp96 expression levels and radiosensitivity and 5-year survival rate. Gp96 might serve as a novel candidate marker for predicting the long-term prognostic outcome of NPC.

Intraoperative Blood Transfusion Contributes to Decreased Long‐Term Survival of Patients With Esophageal Cancer

Several prognostic factors for patients who have undergone esophagectomy owing to esophageal squamous cell carcinoma have been suggested, including intraoperative blood loss. There are few data, however, suggesting such an association with the prognosis following radical esophagectomy. Patients with esophageal squamous cell carcinoma who underwent radical esophagectomy were divided into two groups based on the median value of the intraoperative blood loss (510g). A multivariate Cox proportional-hazard regression analysis was performed to determine if intraoperative blood loss could be an independent prognostic factor for long-term survival following radical esophagectomy. Kaplan-Meier survival analysis with a log-rank test was performed between the groups. From April 2005 to May 2009, a total of 37 patients underwent radical esophagectomy for the treatment of esophageal squamous cell carcinoma at the Juntendo Shizuoka Hospital and were assigned either to one of two groups: those with ≥510g blood loss [bleeding group (BG), n=19] or of those with <510g blood loss [less bleeding group (LBG), n=18]. The distribution of the stage of disease, the number of positive lymph nodes, and the presence of lymphatic and vascular invasion was comparable between the groups, but the Kaplan-Meier survival analysis demonstrated that survival was significantly worse in the BG group than in the LBG group (p=0.00295). This was supported by the multivariate analysis, which indicated that intraoperative blood loss was independently associated with long-term survival after radical esophagectomy. Intraoperative blood loss could be a useful prognostic factor following radical esophagectomy in patients with esophageal squamous cell carcinoma.

Prognostic value of soluble ST2 in an unselected cohort of patients admitted to an intensive care unit — The Linz Intensive Care Unit (LICU) study

BackgroundSoluble ST2 (sST2) has emerged as a prognostic biomarker in patients with heart disease. We tested the hypothesis that sST2 is an independent predictor of mortality in patients admitted to an intensive care unit (ICU). MethodsWe performed measurements of sST2 plasma concentrations in 530 consecutive patients admitted to a medical ICU of a tertiary care hospital during a study period of one year. The patients recruited during the first six months were used for the derivation cohort (n=274) and the patients recruited during the second six months were used for the validation cohort (n=256). The endpoint was defined as 90-day all-cause mortality. ResultsIn the derivation cohort, sST2 was higher among decedents (n=56; median, 146U/mL) than survivors (n=218; median 42U/mL, p<0.001). In multivariate Cox proportional-hazard regression analysis (offering age, sex, BMI, APACHE II score, SAPS II, CRP, IL-6, PCT, creatinine, total cholesterol, albumin, hs-cTnT, BNP and sST2 as independent variables), sST2 was a significant predictor of mortality (risk ratio 1.48, 95% CI 1.15–1.90; p=0.002 per 1SD increase in log transformed values). In this statistical model, only sST2 and SAPS II contributed independently to mortality prediction. We further observed an additive effect of an sST2 plasma concentration of >84U/mL and an increased SAPS II for mortality prediction. The findings from the derivation cohort were confirmed in the independent validation cohort. In those patients with a length of stay of >48h at the ICU (n=225), sST2 obtained two days after baseline measurement had a better capability than baseline sST2 to predict mortality. ConclusionsIn an unselected cohort of patients admitted to the ICU, sST2 was an independent predictor of 90-day all-cause mortality and added prognostic information to the SAPS II.