Independent Predictor Of Poor Prognosis Research Articles

Developing a Siamese Network for UTIs Risk Prediction in Immobile Patients Undergoing Stroke.

Stroke patients tend to suffer from immobility, which increases the possibility of post-stroke complications. Urinary tract infections (UTIs) are one of the complications as an independent predictor of poor prognosis of stroke patients. However, the incidence of new UTIs onsets during hospitalization was rare in most datasets with a prevalence of 4%. This imbalanced data distribution sets obstacles to establishing an accurate prediction model. Our study aimed to develop an effective prediction model to identify UTIs risk in immobile stroke patients, and (2) to compare its prediction performance with traditional machine learning models. We tackled this problem by building a Siamese Network leveraging commonly used clinical features to identifying patients with UTIs risk. Model derivation and validation were based on a nationwide dataset including 3982 Chinese patients. Results showed that the Siamese Network performed better than traditional machine learning models in imbalanced datasets (Sensitivity: 0.810; AUC: 0.828).

Prognosis for Young Females with Pseudomyxoma Peritonei of Appendiceal Origin and Unilateral or Bilateral Ovaries Preserved During Cytoreductive Surgery.

ObjectiveTo determine prognosis for young female patients with peritoneal pseudomyxoma (PMP) of appendiceal origin and unilateral or bilateral ovaries preserved during cytoreductive surgery (CRS).MethodsClinical data of female patients treated with CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) at the Aerospace Center Hospital, Beijing between January, 2009 and December, 2019 were retrospectively reviewed. Patients had no changes in the bilateral ovaries on gross pathological observations or biopsy during CRS, and normal ovarian function. The demographic and clinical characteristics and prognosis of women with ovaries preserved (ovarian preservation group) or resected (ovarian resection group) during CRS were compared. Independent prognostic factors for survival were identified using univariate and multivariate analysis.Results40 patients were included in the final analysis. 19 patients chose ovarian preservation while 21 patients underwent ovarian resection. Completeness of cytoreduction (CCR) scores were CCR-0/1. There were significant differences in age (<40 vs. ≥40), symptoms, intraoperative HIPEC (Y vs. N), and histopathologic subtype of PMP (low-grade vs. high-grade) (p < 0.001) between patients in the ovarian preservation and ovarian resection groups. In the ovarian preservation group, median overall survival (OS) was 59 months (range, 53–65 months), and the 5-year survival rate was 37.9%. Median disease-free survival (DFS) was 13 months (range, 9–17 months), and the 5-year recurrence rate was 87.4%. In the ovarian resection group, the 5-year survival rate was 87.7%, and the 5-year recurrence rate was 18.3%. Median OS and median DFS were not reached. In patients with low-grade PMP, median DFS was significantly longer in patients with ovarian resection compared to ovarian preservation (p < 0.001). Univariate analysis showed histopathologic subtype of PMP (low-grade vs. high-grade, p < 0.001) was significantly associated with OS and DFS. On multivariate analysis, high-grade histopathologic subtype of PMP was an independent predictor of poor prognosis (OS and DFS).ConclusionHistopathologic subtype of PMP represents an independent predictor of prognosis in female patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during CRS. These findings imply that ovarian preservation is a more suitable option for young females with low-grade PMP compared to high-grade PMP. Further prospective studies should be done investigating the role of resection of uninvolved ovaries in PMP.

Single-cell immune mapping of adenoid cystic carcinoma (ACC) reveals potential therapeutic targets for the aggressive solid subtype.

6090 Background: ACC is a common salivary gland malignancy for which there is no FDA approved therapies. Despite a quiet genome, ACC has significant tumoral heterogeneity, which may facilitate the metastatic relapse. Studies focusing on the deep profile of ACC tumor microenvironment (TME) are lacking. Here we explored the TME of ACC using imaging mass cytometry (IMC) and assessed TME attributes and its association with histology and clinical outcomes. Methods: Two tissue microarrays from 62 ACC patients (pts) were built and stained with 37 metal-tagged markers. IMC was performed with the Fluidigm Helios CyTOF instrument utilizing the Hyperion Imaging System Laser ablation. Tissue and cell segmentation and multiplex imaging analysis were performed with Visiopharm software using pre-trained artificial intelligence algorithms. Comparison of cell types and markers densities among histology sub-groups were analyzed with Wilcoxon signed-rank test and its association with overall survival (OS) with log-rank and Cox Proportional Hazards. Results: Of 62 pts, 37% (23/62) had solid histology, 19% (12/62) were metastatic at diagnosis, and 55% (30/54) had disease recurrence during follow-up. With a median follow-up of 7.9 y, the median OS was 9.3y (CI 95%, 7.8-NR). Pts with solid subtype had poorer OS than non-solid histology (5.2 vs 14.6 y, p = 0.004). The IMC final dataset comprised 507,524 single-cells. No significant differences were found in cell subpopulations density between solid and non-solid histology. The most represented cell population in the stroma were macrophages, followed by CD8+ T cells, and fibroblasts. A higher percentage of M2-macrophage was associated with poor survival (p = 0.001), whereas, a higher percentage of M1-macrophage (M1:M2 ratio) was associated with better prognosis. No other immune cell type, fibroblasts or immune cell functional markers (TIGIT, TIM3, granzyme B, and PD-L1) correlated with survival. Regarding tumor markers, a higher expression of BCL-2, B7-H4, and Ki67 in the tumor cells were associated with worst survival; and remained statistically associated after adjustment for histology and staging (all p &lt; 0.001). Solid histology had a significantly higher density of tumor cells expressing B7-H4, BCL-2, and Ki67 compared to cribriform and tubular histology. A higher expression of myoepithelial marker (p63+) were associated with a better survival when compared with tumors with low p63 expression. Conclusions: ACC’s TME is composed mainly of macrophages. Despite having no significant differences in cellular composition, a higher density of tumor cells expressing BCL-2, B7-H4 and Ki67 were found in the solid histology and these markers were independent predictors of poor prognosis. The overexpression of BCL-2 and B7-H4 in the solid histology provides a scientific rationale for BCL-2 and/or B7-H4 targeting for the most aggressive ACC.

Modified 5-Item Frailty Index Score as Prognostic Marker After Radical Cystectomy in Bladder Cancer.

A modified 5-item frailty index was recently developed as a predictor of patient comorbidity-based mortality and morbidity. We evaluate the association between preoperative modified 5-item frailty index score and prognosis after radical cystectomy for bladder cancer. In this multicenter retrospective study, we calculated modified 5-item frailty index scores of the 238 patients that underwent radical cystectomy for bladder cancer between March 2009, and March 2018. The patients were classified into high frailty index score (≥ 2) or low frailty index score (≤ 1) groups for comparison of overall and cancer-specific survival between them. To evaluate the prognostic impact of the preoperative frailty index, we also performed Cox proportional regression analyses for overall, and cancer-specific survival. Of 238 patients, 53 patients were classified into the high frailty index score group and 185 patients into the low frailty index score group. Overall, 70 patients died of bladder cancer (29%), and 21 patients died of other causes (9%). The patients with high frailty index score had significantly lower rate of overall survival than those with low frailty index score (P < .01). On the other hand, there was no significant difference in cancer-specific survival rate between the 2 groups (P=.07). Multivariable Cox proportional hazard analysis revealed that high modified 5-item frailty index score was independently associated with poor overall survival (P=.01), but not with poor cancer-specific survival (P=.15). High preoperative modified 5-item frailty index score could be a significant independent predictor of poor prognosis after radical cystectomy in patients with bladder cancer.

Spatial and Transcriptomic Analysis of Perineural Invasion in Oral Cancer.

Perineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established. To address these knowledge gaps, we investigated spatial and transcriptomic profiles of PNI-positive and PNI-negative nerves. Tissue sections from 142 patients were stained with S100 and cytokeratin antibodies. Nerves were identified in two distinct areas: tumor bulk and margin. Nerve diameter and nerve-to-tumor distance were assessed; survival analyses were performed. Spatial transcriptomic analysis of nerves at varying distances from tumor was performed with NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas. PNI is an independent predictor of poor prognosis among patients with metastasis-free lymph nodes. Patients with close nerve-tumor distance have poor outcomes even if diagnosed as PNI negative using current criteria. Patients with large nerve(s) in the tumor bulk survive poorly, suggesting that even PNI-negative nerves facilitate tumor progression. Diagnostic criteria were supported by spatial transcriptomic analyses of >18,000 genes; nerves in proximity to cancer exhibit stress and growth response changes that diminish with increasing nerve-tumor distance. These findings were validated in vitro and in human tissue. This is the first study in human cancer with high-throughput gene expression analysis in nerves with striking correlations between transcriptomic profile and clinical outcomes. Our work illuminates nerve-cancer interactions suggesting that cancer-induced injury modulates neuritogenesis, and supports reclassification of PNI based on nerve-tumor distance rather than current subjective criteria.

P285 PROGNOSTIC ROLE OF ELECTROCARDIOGRAPHIC TEMPORAL CHANGES IN PATIENTS WITH ACUTE PULMONARY EMBOLISM. DATA FROM THE ITALIAN PULMONARY EMBOLISM REGISTRY (IPER)

Abstract Background The potential prognostic role of ECG changes during the course of acute pulmonary embolism (PE) has been poorly investigated over the years. Methods Data of patients prospectively enrolled in the IPER registry, having three ECGs (the first perfromed on admission, the second after three days of hospitalization and the third at discharge) were extracted and analyzed. Results Overall, 687 patients (286 males, mean age 69.0 ± 15.5 years) were included in the study. The negativization of electrocardiographic signs of right ventricualr strain (RVS) (Right bundle branch block –RBBB), S1Q3T3 and negative T waves from V1 to V4) followed the same pattern in both non–high (i.e. hemodynamically stable) and high–risk (i.e. hemodynamically unstable) patients, showing firstly the normalization of the S1QT3 pattern followed by the resolution of the RBBB. Conversely, additional NTWs appeared between the first and second ECGs in about 20% of cases and then partially normalized at discharge. Persistence of RVS at the second ECG was associated with a higher risk of death within 30 days only in high–risk patients [HRa: 2.78 (95% CI: 1.05–7.31. P = 0.03), with a sensitivity, specificity, PPV and PPN of 90.0%, 94.1%, 85.7% and 96.0%, respectively. Furthermore, the lack of normalization of the RBBB [HRa: 2.78 (95% CI: 1.05–7.31, p = 0.003)], of the NTW [HRa: 1.63 (95% CI: 1.04–2.55), p &amp;lt; 0.0001] and of the resolution of qR complex in V1 [HRa: 12.5 (95% CI: 3.39–46.4,) p &amp;lt; 0.0001] were independent predictors of poor prognosis in the short term. High–risk patients showing at the second–ECG the persitence of RBBB and NTWs as well as disappearance of the qR complex in V1 had a higher 30–day increased risk of death [HR: 9.44, (95% CI: 5.22–17.05, p &amp;lt; 0.0001]. The C–statistic confirmed in high–risk subjects an improvement in short–term prognostic power using the persistence of all three ECG signs (0.77, 95% CI: 0.51–0.94) or they single presence (0.61, 95% CI 0.42–0.79; 0.70; 95% CI: 0.52–0.88 and 0.74, 95% CI: 0.56–0.96, RBBB, NTWs and qR in V1, respectively). Conclusions The persistence of RBBB, NTWs, and qR pattern in V1 after 3 days from the hospitalization for acute PE represent an independent prognostic factors of death within 30 days in high–risk acute PE patients. In terms of prognostic power, the single evaluation of each ECG sign was lower compared to the overall or combined assessment.

The Role of PD-L1 Expression in Prediction and Stratification of Recurrent or Refractory Extranodal Natural Killer/T-Cell Lymphoma.

Background and AimsThe clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL.MethodsA total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients.ResultsUnivariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, P = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (P = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 (P = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT (P = 0.001), PI3K-AKT (P = 0.02) and NF-kappa B (P < 0.001) pathways in RR patients were significantly higher than those in ET patients.ConclusionPatients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET.

The Predictive Role of NLR and PLR in Outcome and Patency of Lower Limb Revascularization in Patients with Femoropopliteal Disease.

Background: Peripheral arterial disease (PAD) changes the arterial structure and function, and is the most common manifestation of the atherosclerotic process, except for the coronary and cerebral arterial systems. Inflammation is well known to have a role in the progression of atherosclerosis and, by extension, in PAD. Among the recently studied markers in the literature, we list the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR). This study aims to analyze the preoperative role of NLR and PLR in the medium-term outcome of patients surgically revascularized for femoropopliteal disease. Methods: A retrospective study included patients admitted to the Vascular Surgery Clinic of the County Emergency Clinical Hospital of Târgu-Mureș, Romania, between January 2017 and December 2019, diagnosed with femoropopliteal disease and having presented an indication for surgical revascularization. The patients included in the study were classified according to the 12 months primary patency in two groups: “patency” and “nonpatency”. Results: Depending on the Rutherford classification (RC), there was a higher incidence of stages II and III in the patency group and a higher incidence of stage V in the nonpatency group. Depending on the optimal cut-off value according to ROC for the 12 months primary patency, obtained from Youden’s index (3.95 for NLR (82.6% sensitivity and 89.9% specificity), and 142.13 for PLR (79.1% sensitivity and 82.6% specificity)), in all high-NLR and high-PLR groups, there was a higher incidence of all adverse outcomes. Moreover, a multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of all outcomes for all recruited patients. Furthermore, for all hospitalized patients, RC 5 was an independent predictor of poor prognosis. Conclusions: Our findings establish that a high value of preoperative NLR and PLR determined at hospital admission is strongly predictive of primary patency failure (12 months after revascularization). Additionally, elevated ratio values are an independent predictor for a higher amputation rate and death for all patients enrolled in the study, except for mortality in RC 2, and both amputation and mortality in RC 5.

Aberrant ARMCX1 Expression Is an Independent Predictor of Poor Prognosis in Gastric Cancer.

ARMCX1 (Armadillo repeat containing X-linked 1) is identified to be the novel tumor suppressor gene related to multiple tumor types. Nonetheless, its effect on gastric cancer (GC) is still poorly understood. The present work determined ARMCX1 level within GC and the relation with clinicopathological characteristics. This work also collected relevant information in The Cancer Genome Atlas (TCGA) database for investigating associations of ARMCX1 with clinicopathologic variables and then validated in our GC cohort. Receiver operating characteristic (ROC) curves were plotted for assessing whether ARMCX1 expression was significant in diagnosing GC. Kaplan-Meier (KM) and Cox regression analyses were conducted for assessing clinicopathological characteristics associated with overall survival (OS) of GC cases. The data from the Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) databases was also analyzed for further validation, and biological processes (BPs) were identified by gene set enrichment analysis (GSEA). GC tissues showed markedly decreased ARMCX1 level relative to healthy counterparts (P < 0.001). Interestingly, ARMCX1 upregulation predicted low differentiation, poor OS, increased invasion, and late tumor stage. In addition, the area under ROC curve (AUC) and P value were 0.747 and <0.001, separately. Cases showing ARMCX1 upregulation showed significantly poor prognostic outcome compared with patients showing downregulation (P = 0.007). Furthermore, multivariate analysis showed that ARMCX1 upregulation independently predicted the risk of OS (P = 0.0017, hazard ratio, 1.089). GSEA analysis identified that several cancer-related pathways, such as focal adhesion, ECM receptor interaction, JAK/STAT, melanoma, WNT, and cancer, were enriched in GCs. We conclude that ARMCX1 serves as the possibly independent biomarker to diagnose and predict GC prognostic outcome.

Lipase elevation on admission predicts worse clinical outcomes in patients with COVID-19

Background and objectivesHyperlipasemia is highly prevalent among coronavirus disease 2019 (COVID-19) patients. The aim of this study was to assess the effect of lipase activity, measured at the time of admission, on the clinical course and mortality in COVID-19 patients. MethodsThe population of this study comprised 12,139 patients who were hospitalized due to COVID-19 between June 2020 and June 2021 in a pandemic hospital. Of these, 8819 patients were excluded from the study due to missing data, four patients were excluded due to a diagnosis of acute pancreatitis (according to the revised Atlanta criteria), and 72 patients were excluded due to alcohol use or having a history of chronic pancreatitis. The final study sample consisted of the remaining 3244 COVID-19 patients. Laboratory results, intensive care unit (ICU) follow-up periods, the need for mechanical ventilation, and mortality rates were compared between the normal lipase activity and high lipase activity groups. ResultsThere were 968 (29.8%) patients with high lipase activity at the time of admission. The rate of ICU admission was 36.1% vs. 9.9% (p < 0.001), mechanical ventilation requirement rates were 33.7% vs. 8.3% (p < 0.001), and mortality rates were as 24.6% vs. 6.4% (p < 0.001) in the high lipase activity group compared to the normal lipase activity group. Multivariate regression analysis revealed that high lipase activity was an independent factor in predicting mortality in hospitalized COVID-19 patients (odds ratio [OR]: 3.191, p < 0.001). ConclusionElevated lipase activity without acute pancreatitis at the time of admission in COVID-19 patients was determined as an independent predictor of poor prognosis.

Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma

Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7–30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not significantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.

Relationship between Neurological Deterioration and Blood Pressure/Heart Rate Variability in Patients with Acute Cerebral Infarction

ObjectivesNeurological deterioration (ND) during hospitalization is an independent predictor of poor prognosis after stroke. Risk factors affecting early ND within 48 h post stroke have been intensively investigated, while few data are available on those for late ND after transfer to a wheelchair. Therefore, it was investigated whether hemodynamic factors may affect the late ND during hospitalization. Materials and methodsA retrospective study was conducted on 135 patients with atherothrombotic or cardiogenic cerebral infarction who were admitted to our hospital between April 1st, 2014 and July 31st, 2017. During hospitalization, average, maximum, and minimum values were determined for systolic blood pressure (sBP), diastolic BP (dBP), and heart rate (HR), respectively.135 patients were classified into two groups; ND (+) group, in which modified Barthel index score at the time of transfer to a wheelchair showed five points or more decrease between wheelchair transfer and discharge, and ND (−) group, which did not. Vital indices were compared between the two groups and subjected to ROC-curve analysis. ResultsThe ND (+) group included 32 patients, and the ND (−) 103. Significant differences were found between the groups in four items; sBPmin (p = 0.029), dBPmin (p = 0.019), HRave (p = 0.028), and HRmax (p < 0.01). The ND (+) group showed lower sBPmin and dBPmin, and higher HRave and HRmax than the ND (−) group. ConclusionsLate ND after transfer to a wheelchair is related to the vital indices during hospitalization and should be cautiously managed to prevent late ND

ADAM12 is an independent predictor of poor prognosis in liver cancer

Disintegrin and metalloproteinase 12 (ADAM12) is thought to trigger the occurrence and development of numerous tumours, including colorectal, breast, and pancreatic cancers. On the basis of The Cancer Genome Atlas (TCGA) datasets, in this study, the relationship between ADAM12 gene expression and hepatocellular carcinoma (HCC), the prognostic value of this relationship, and the potential mechanisms influencing HCC development were evaluated. The results showed that the ADAM12 gene was significantly and highly expressed in liver cancer tissue. The high expression of the ADAM12 gene in liver cancer tissue significantly and positively correlated with T stage, pathological stage, and residual tumour. Kaplan–Meier and Cox regression analyses revealed that ADAM12 gene expression is an independent risk factor influencing the prognosis of patients with liver cancer. Pathway analyses of ADAM12 in HCC revealed ADAM12-correlated signalling pathways, and the expression level of ADAM12 was associated with immune cell infiltration. In vitro experiments demonstrated that the expression level of ADAM12 in Huh-7 and Hep3B cells was significantly higher than that in other HCC cells. ShRNA transfection experiments confirmed that the expression levels of TGF-β and Notch pathway-related proteins were significantly decreased. An EdU cell proliferation assay showed that a low level of ADAM12 gene expression significantly inhibited the proliferative activity of HCC cells. Cell cycle experiments showed that low ADAM12 expression blocked the G1/S phase transition. Overall, this research revealed that high ADAM12 gene expression implies a poor prognosis for patients with primary liver cancer. In addition, it is a potential indicator for the diagnosis of liver cancer.

In-Hospital and Long-Term Outcomes of ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Introduction: We evaluated in-hospital and long-term outcomes of patients who underwent primary percutaneous coronary intervention (PCI) in a tertiary center. Patients and Methods: We examined 1550 patients (mean age= 58.5 years, 83.1% male) admitted with acute ST-segment elevation myocardial infarction (AMI) who underwent primary PCI and were followed-up prospectively. The primary outcomes were in-hospital death and major adverse cardiac events (MACE) at follow-up. Results: The mean duration of ischemia at admission was 2.85 ± 2.49 hours; 10.3% of the patients were Killip class III or IV. The mean door-to-device time was 43 (29-52) minutes. During hospitalization, all-cause mortality occurred in 73 patients (4.7%). Multivariate analysis revealed that advanced age, impaired left ventricular ejection function, high Killip functional class, hemoglobin level at admission, ventricular arrhythmias, and advanced atrioventricular block were independent predictors of poor prognosis (OR= 1.07, 0.93, 15.34, 1.44, 3.79, and 4.26 respectively). Among discharged patients with a median 49.5 (25-73) months follow-up, 12.4% of them died, 12.5% had a recurrent myocardial infarction (MI), and 2.3% had a cerebrovascular accident. The strongest independent MACE predictors were impaired left ventricular function, poor glomerular filtration rate, low albumin level, and a history of cerebrovascular disease (HR= 0.97, 0.99, 0.65, and 2.50, respectively). Secondary outcomes were contrast-induced acute kidney injury (16.7%), ventricular arrhythmias (6.1%), advanced atrioventricular block (3.7%), atrial fibrillation (7.6%), and major bleeding (1.6%). Conclusion: AMI still has a poor long-term prognosis. These results emphasize the advantages of rapid, non-delayed revascularization. Patients should be followed-up closely after discharge in both the short- and long-term.

Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer

Smad ubiquitination regulatory factor 2 (Smurf2) plays various roles in cancer progression. However, the correlation between Smurf2 and clinical outcomes has not been determined in patients diagnosed with colorectal cancer and colorectal liver metastases. We analyzed 66 patients with colorectal cancer who developed liver metastases. Smurf2 expression was assessed using immunohistochemical analysis of primary and metastatic liver tumors. High Smurf2 expression in both primary and metastatic tumors was significantly associated with longer overall survival time and time to surgical failure. Multivariate analyses revealed that low Smurf2 expression in primary tumors was an independent predictor of poor prognosis. In vitro experiments using colon cancer cell lines demonstrated that short interfering RNA knockdown of Smurf2 increased cell migration and tumor sphere formation. Western blot analyses revealed that Smurf2 knockdown increased the protein expression of epithelial cell adhesion molecule (EpCAM). Thus, in summary, high Smurf2 expression in cancer cells was found to be an independent predictor of better prognosis in patients with primary colorectal cancer and consequent liver metastases. The tumor-suppressive role of Smurf2 was found to be associated with cell migration and EpCAM expression; hence, Smurf2 can be considered a positive biomarker of cancer stem cell-like properties.

PRPF8 Expression is an Independent Predictor for Poor Prognosis in Patients with Kidney Renalclear Cell Carcinoma

Background: Alternative splicing is an important process associated with disease including tumors. PRPF8 is a conserved protein in splice some component U5 snRNP that plays an important role in tumor cell growth. Materials and Methods: The data in The Cancer Genome Atlas was downloaded and analyzed by R Studio. The box plots showed the expression pattern of PRPF8. The chi-square test was used to manifest the association between PRPF8 expression and clinical parameters. The diagnostic value was assessed using ROC curve. The Kaplan-Meier curves and the Cox regression analysis elucidated the difference of overall survival and relapse-free survival between high expression and low expression and the prognostic value. Results: We downloaded the PRPF8 expression and the clinical data of 50 healthy individuals and 537 patients from TCGA database. We found PRPF8 expression is lower in tumor tissues than that in normal tissues and is related to age, histologic grade, pathologic stage, M classification, T classification and vital status. The Kaplan Meier curves showed the patients with lower PRPF8 expression has a poorer overall survival and relapse-free survival. The Univariate and Multivariate analysis suggested PRPF8 expression was an independent prognostic factor for overall survival and relapse-free survival in kidney renal clear cell carcinoma. Conclusion: Low PRPF8 expression is an independent predictor for overall survival and relapse-free survival in kidney renal clear cell carcinoma.

The Prognostic Role of CDK9 in Bladder Cancer.

Simple SummaryIn this article, we investigated the prognostic role of cyclin-dependent kinase 9 expression in urothelial carcinoma. High CDK9 expression has recently been associated with shorter patient survival time, but its role in urothelial carcinoma has not yet been explored. The expression of CDK9 was higher in cancer than in normal urothelial tissue and correlated with tumor grade, stage, and invasiveness. To our surprise, patients with high CDK9 expression lived longer than patients with low CDK9 expression. In The Cancer Genome Atlas database cohort, high CDK9 RNA concentration correlates with longer survival of patients and CDK9 status remained a statistically significant prognostic factor in multivariate analysis. It seems that CDK9 not only regulates the expression of anti-apoptotic genes, leading to longer survival of cancer cells, it also facilitates DNA repair, preventing the build-up of genomic instability, crucial in the initiation and progression of bladder cancer. The results suggest that CDK9 overexpression is not always associated with a worse prognosis, while cell maturity and disease stage may influence the efficacy of potential targeted therapy.Introduction: Most patients with urothelial carcinoma are diagnosed with non-invasive tumors, but the prognosis worsens with the progression of the disease. Overexpression of cyclin-dependent kinase 9 has been recently linked to increased cancer proliferation, faster progression, and worse prognosis. However, some cancers seem to contradict this rule. In this work, we explored the prognostic role of CDK9 expression in urothelial carcinoma. Materials and Methods: We performed immunohistochemical analysis on 72 bladder cancer samples. To assess a larger group of patients, the Cancer Genome Atlas (TCGA) database containing 406 cases and transcriptomics information through the Human Pathology Atlas were analyzed. Results: CDK9 is overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High CDK9 expression was observed in low-stage, low-grade, and non-muscle-invasive tumors (p < 0.05). The patients with high CDK9 expression had a significantly higher 5-year overall survival rate than those with low CDK9 expression (77.54% vs. 53.6% in the TMA group and 57.75% vs. 35.44% in the TCGA group, respectively) (p < 0.05). The results were consistent in both cohorts. Multivariate Cox regression analysis indicated that low CDK9 status was an independent predictor for poor prognosis in the TCGA cohort (HR 1.60, CL95% 1.1–2.33, p = 0.014). Conclusions: High CDK9 expression predicts a favorable prognosis in urothelial carcinoma and is associated with clinicopathological features characteristic for early-stage disease. The decrease in CDK9 expression can be associated with the build-up of genetic instability and may indicate a key role for CDK9 in the early stages of urothelial carcinoma.

Expression of TMED3 is independently associated with colorectal cancer prognosis.

Colorectal cancer (CRC) is the third most common cancer type and one of the deadliest cancers worldwide. Transmembrane p24 trafficking protein 3 (TMED3) has previously been indicated to suppress CRC metastasis, but its clinical significance has remained undetermined. In the present study, the expression of TMED3 was indicated to be elevated at the mRNA and protein levels in CRC tumor samples relative to that in para-cancerous healthy tissue samples (P<0.05). Furthermore, Kaplan-Meier survival analysis revealed a significant negative association between elevated TMED3 protein levels and overall survival of patients with CRC (P<0.001, log-rank test). Multivariate Cox regression analysis additionally determined that elevated TMED3 expression in primary CRC tumors was an independent predictor of poor prognosis (P<0.05). These results revealed that elevated TMED3 expression in CRC was associated with patient survival outcomes, suggesting that TMED3 may be a potential prognostic biomarker for this cancer type.

Effectiveness and Predictors of Poor Prognosis Following Intravenous Thrombolysis in Patients with Wake-Up Ischemic Stroke Guided by Rapid MRI.

PurposeOur aim was to investigate the effectiveness and predictors of poor prognosis in WUIS patients who received alteplase thrombolysis under the guidance of diffusion-weighted imaging (DWI)-T2-weighted imaging (T2WI) mismatch.Patients and MethodsWe recruited patients within 4.5 h of acute ischemic stroke (AIS) and WUIS patients with uncertain onset times from two stroke centers. To evaluate effectiveness, we compared National Institutes of Health Stroke Scale (NIHSS) scores between the two groups at admission and at 24 h, 3 days, and 1 week thereafter. We also compared the two groups with respect to the modified Rankin Scale (mRS) score at 90 days after thrombolysis. The WUIS patients were divided into a favorable prognosis group (mRS score: 0–1 points) and a poor prognosis group (mRS score ≥2 points). Data were compared between the two subgroups to identify factors that influence poor prognoses. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of factors related to poor prognosis.ResultsA total of 114 patients with WUIS and 316 patients with AIS were enrolled in the study. There were no significant differences between the two groups in terms of NIHSS or 90-day mRS scores (p > 0.05). Baseline NIHSS score (odds ratio [OR] = 1.490, 95% confidence interval [CI] 1.248–1.779, p < 0.001) and atrial fibrillation (OR = 3.825, 95% CI 1.218–12.016, p = 0.022) were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients. The combined ROC diagnosis of these two variables had an area under the curve of 0.850.ConclusionThe DWI-T2WI sequence is an effective method to guide intravenous thrombolytic therapy for WUIS. Baseline NIHSS score and atrial fibrillation were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients.

Sec62 promotes gastric cancer metastasis through mediating UPR-induced autophagy activation.

Sec62 is a membrane protein of the endoplasmic reticulum that facilitates protein transport. Its role in cancer is increasingly recognised, but remains largely unknown. We investigated the functional role of Sec62 in gastric cancer (GC) and its underlying mechanism. Bioinformatics, tissue microarray, immunohistochemistry (IHC), western blotting (WB), quantitative polymerase chain reaction (qPCR), and immunofluorescence were used to examine the expression of target genes. Transwell, scratch healing assays, and xenograft models were used to evaluate cell migration and invasion. Transmission electron microscopy and mRFP-GFP-LC3 double-labeled adenoviruses were used to monitor autophagy. Co-immunoprecipitation (CO-IP) was performed to evaluate the binding activity between the proteins. Sec62 expression was upregulated in GC, and Sec62 upregulation was an independent predictor of poor prognosis. Sec62 overexpression promoted GC cell migration and invasion both in vitro and in vivo. Sec62 promoted migration and invasion by affecting TIMP-1 and MMP2/9 balance. Moreover, Sec62 could activate autophagy by upregulating PERK/ATF4 expression and binding to LC3II with concomitant FIP200/Beclin-1/Atg5 activation. Furthermore, autophagy blockage impaired the promotive effects of Sec62 on GC cell migration and invasion, whereas autophagy activation rescued the inhibitory effect of Sec62 knockdown on GC metastasis. Notably, Sec62 inhibition combined with autophagy blockage exerted a synergetic anti-metastatic effect in vitro and in vivo. Sec62 promotes GC metastasis by activating autophagy and subsequently regulating TIMP-1 and MMP2/9 balance. The activation of autophagy by Sec62 may involve the unfolded protein response (UPR)-related PERK/ATF4 pathway and binding of LC3II during UPR recovery involving FIP200/Beclin-1/Atg5 upregulation. Specifically, the dual inhibition of Sec62 and autophagy may provide a promising therapeutic strategy for GC metastasis.