Differences In Clinical Prognosis Research Articles

Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality. We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer characterized by metabolic reprogramming. Glutamine metabolism is pivotal in metabolic reprogramming, contributing to the significant heterogeneity observed in ccRCC. Consequently, developing prognostic markers associated with glutamine metabolism could enhance personalized treatment strategies for ccRCC patients. This study obtained RNA sequencing and clinical data from 763 ccRCC cases sourced from multiple databases. Consensus clustering of 74 glutamine metabolism related genes (GMRGs)- profiles stratified the patients into three clusters, each of which exhibited distinct prognosis, tumor microenvironment, and biological characteristics. Then, six genes (SMTNL2, MIOX, TMEM27, SLC16A12, HRH2, and SAA1) were identified by machine-learning algorithms to develop a predictive signature related to glutamine metabolism, termed as GMRScore. The GMRScore showed significant differences in clinical prognosis, expression profile of immune checkpoints, abundance of immune cells, and immunotherapy response of ccRCC patients. Besides, the nomogram incorporating the GMRScore and clinical features showed strong predictive performance in prognosis of ccRCC patients. ALDH18A1, one of the GRMGs, exhibited elevated expression level in ccRCC and was related to markedly poorer prognosis in the integrated cohort, validated by proteomic profiling of 232 ccRCC samples from Fudan University Shanghai Cancer Center (FUSCC). Conducting western blotting, CCK-8, transwell, and flow cytometry assays, we found the knockdown of ALDH18A1 in ccRCC significantly promoted apoptosis and inhibited proliferation, invasion, and epithelial-mesenchymal transition (EMT) in two human ccRCC cell lines (786-O and 769-P). In conclusion, we developed a glutamine metabolism-related prognostic signature in ccRCC, which is tightly linked to the tumor immune microenvironment and immunotherapy response, potentially facilitating precision therapy for ccRCC patients. Additionally, this study revealed the key role of ALDH18A1 in promoting ccRCC progression for the first time.

Identification of a unique stress response state of T cells-related gene signature in patients with gastric cancer.

Gastric cancer (GC), the third most lethal cancer worldwide, is often diagnosed at an advanced stage, leaving limited therapeutic options. Given the diverse outcomes among GC patients with similar AJCC/UICC-TNM characteristics, there is a pressing need for more reliable prognostic tools. Recent advances in targeted therapy and immunotherapy have underscored this necessity. In this context, our study focused on a novel stress response state of T cells, termed TSTR, identified across multiple cancers, which is associated with resistance to immunotherapy. We aimed to develop a predictive gene signature for the TSTR phenotype within the tumor microenvironment (TME) of GC patients. By categorizing GC patients into high and low TSTR groups based on the infiltration states of TME TSTR cells, we observed significant differences in clinical prognosis and characteristics between the groups. Through a multi-step bioinformatics approach, we established an eight-gene signature based on genes differentially expressed between these groups. We conducted functional validations for the signature gene PDGFRL in GC cells. This gene signature effectively stratifies GC patients into high and low-risk categories, demonstrating robustness in predicting clinical outcomes. Furthermore, these risk groups exhibited distinct immune profiles, somatic mutations, and drug susceptibilities, highlighting the potential of our gene signature to enhance personalized treatment strategies in clinical practice.

Endoplasmic reticulum stress in breast cancer: a predictive model for prognosis and therapy selection.

Breast cancer (BC) is a leading cause of mortality among women, underscoring the urgent need for improved therapeutic predictio. Developing a precise prognostic model is crucial. The role of Endoplasmic Reticulum Stress (ERS) in cancer suggests its potential as a critical factor in BC development and progression, highlighting the importance of precise prognostic models for tailored treatment strategies. Through comprehensive analysis of ERS-related gene expression in BC, utilizing both single-cell and bulk sequencing data from varied BC subtypes, we identified eight key ERS-related genes. LASSO regression and machine learning techniques were employed to construct a prognostic model, validated across multiple datasets and compared with existing models for its predictive accuracy. The developed ERS-model categorizes BC patients into distinct risk groups with significant differences in clinical prognosis, confirmed by robust ROC, DCA, and KM analyses. The model forecasts survival rates with high precision, revealing distinct immune infiltration patterns and treatment responsiveness between risk groups. Notably, we discovered six druggable targets and validated Methotrexate and Gemcitabine as effective agents for high-risk BC treatment, based on their sensitivity profiles and potential for addressing the lack of active targets in BC. Our study advances BC research by establishing a significant link between ERS and BC prognosis at both the molecular and cellular levels. By stratifying patients into risk-defined groups, we unveil disparities in immune cell infiltration and drug response, guiding personalized treatment. The identification of potential drug targets and therapeutic agents opens new avenues for targeted interventions, promising to enhance outcomes for high-risk BC patients and paving the way for personalized cancer therapy.

Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell.

Cuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified. 14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy. Based on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect. CIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy.

Prognosis of Patients with Hypertrophic Obstructive Cardiomyopathy: A Multicenter Cohort Study with Data-Driven Propensity Score Matching Analysis.

Hypertrophic obstructive cardiomyopathy (HOCM) patients are reported to have a potential risk of sudden cardiac death (SCD); however, HCM with left ventricular outflow tract (LVOT) obstruction, which is regarded as a risk indicator of SCD, is doubtful since the LVOT gradient is dynamic and may be confounded by various environmental factors and routine activities. The purpose of this study was to explore the clinical prognosis of HOCM through a multicenter cohort study with data-driven propensity score matching (PSM) analysis. The cohort included 2268 patients with HCM from 1996 to 2021 in 13 tertiary hospitals. In the present study, we excluded 458 patients who underwent alcohol septal ablation (ASA) and septal myectomy (SM) surgery so 1810 HCM patients were eventually included. We developed a data-driven propensity score using 24 demographic and clinical variables to create 1:1 propensity-matched cohorts. A Cox proportional hazard regression model was constructed to assess the effect of HOCM on mortality. After logit-matching, there were no significant differences in all-cause mortality (log-rank 2 = 1.509, p = 0.22), cardiovascular mortality/cardiac transplantation (log-rank 2 = 0.020, p = 0.89) or SCD (log-rank 2 = 0.503, p = 0.48) between patients with HOCM and hypertrophic nonobstructive cardiomyopathy (HNCM), and according to the Cox proportional hazard regression model, LVOT obstruction was not a risk predictor in patients with HCM. In both matched and unmatched cohorts, there were no significant differences in clinical prognosis between HOCM and HNCM patients, and LVOT obstruction was not an independent risk predictor of prognosis in patients with HCM. ChiCTR1800017330.

Efficacy of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of nasopharyngeal carcinoma with cervical lymph node metastasis.

First, we retrospectively compared the clinical efficacy of concurrent chemoradiotherapy combined with nimotuzumab vs. chemoradiotherapy alone in patients with nasopharyngeal carcinoma (NPC) and cervical lymph node metastasis. Second, we analyzed the value of Ki-67 as a predictor of nimotuzumab efficacy. From January 2012 to December 2019, 1250 patients with cervical lymph node metastasis eligible for enrollment were included, of whom 383 were treated with concurrent chemoradiotherapy combined with nimotuzumab (targeted therapy group), and 867 were treated with concurrent chemoradiotherapy (CRT group). A total of 381 pairs of patients were matched using 1:1 propensity score matching, and differences in clinical prognosis were compared between the two groups. Overall survival (OS) (P = 0.028), disease-free survival (DFS) (P = 0.040), and distant metastasis-free survival (DMFS) (P = 0.040) were better in the targeted therapy compared to the CRT group. Multivariate analysis revealed that clinical staging, chemotherapy, and nimotuzumab therapy were predictors of OS and DFS. In the targeted therapy group, patients with ≥ 50% Ki-67 positivity had better OS and DFS rates than those with < 50% Ki-67 positivity. In patients with stage N1-3 NPC and lymph node metastasis, the addition of nimotuzumab to concurrent chemoradiotherapy may provide additional survival benefits. Ki-67 is a potential biomarker with clinical predictive value for the efficacy of nimotuzumab combined with chemoradiotherapy.

Construction of an Immune Escape-Related Signature in Clear Cell Renal Cell Carcinoma and Identification of the Relationship between IFNAR1 and Immune Infiltration by Multiple Immunohistochemistry.

In the past decade, immunotherapy has been widely used in the treatment of various tumors, such as PD-1/PD-L1 inhibitors. Although clear cell renal cell carcinoma (ccRCC) has been shown to be sensitive to immunotherapy, it is effective only in several cases, which brings great obstacles to anti-tumor therapy for patients. Lawson et al. have successfully identified 182 "core cancer innate immune escape genes" whose deletion makes cancer cells more sensitive or resistant to T-cell attack. In this research, we sought to explore genes closely associated with ccRCC among the 182 core cancer innate immune escape genes. We used online databases to screen mutated genes in ccRCC, and then used ConsensusClusterPlus to cluster clinical samples to analyze differences in clinical prognosis and immune components between the two subgroups. In addition, the immune escape score was calculated using lasso cox regression, and a stable tumor immune escape-related nomogram was established to predict the overall survival of patients. Higher immune escape score was significantly correlated with shorter survival time. Meanwhile, through the validation of the external cohort and the correlation analysis of the immune microenvironment, we proved that IFNAR1 is the key gene regulating immune escape in ccRCC, and we also found that the function of IFNAR1 in promoting immune activation is achieved by facilitating the infiltration of CD4+ T cells and CD8+ T cells. IFNAR1 regulates the malignant behavior of ccRCC by inhibiting the proliferation and migration properties. IFNAR1 may become a key biomarker for evaluating the efficacy of ccRCC immunotherapy and may also be a potential target for immunotherapy.

Does proximal versus distal injury location of the medial ulnar collateral ligament of the elbow differentially impact elbow stability? An ultrasound-guided and robot-assisted biomechanical study.

The location (proximal vs. distal) of elbow medial ulnar collateral ligament (MUCL) tears impacts clinical outcomes of nonoperative treatment. The purposes of our study were to (1) determine whether selective releases of the MUCL could be performed under ultrasound (US) guidance without disrupting overlying soft tissues, (2) assess the difference in medial elbow stability for proximal and distal releases of the MUCL using stress US and a robotic testing device, and (3) elucidate the flexion angle that resulted in the greatest amount of medial elbow laxity after MUCL injury. Sixteen paired, fresh-frozen elbow specimens were used. Valgus laxity was evaluated with both US and robotic-assisted measurements before and after selective MUCL releases. A percutaneous US-guided technique was used to perform proximal MUCL releases in 8 elbows and to perform distal MUCL releases in their matched pairs. The robot was used to determine the elbow flexion angle at which the maximum valgus displacement occurred for both proximally and distally released specimens. Open dissection was then performed to assess the accuracy of the percutaneous releases. Percutaneous US-guided releases were successfully performed in 15 of 16 specimens. The proximal release resulted in greater valgus angle displacement (11°±2°) than the distal release (8°±2°) between flexion angles of 30° and 70° (P<.0001 at 30°, P<.0001 at 40°, P=.001 at 50°, P=.005 at 60°, and P=.020 at 70°). Valgus displacement between release locations did not reach the level of statistical significance between 80° and 120° (P=.051 at 80°, P=.131 at 90°, P=.245 at 100°, P=.400 at 110°, and P=.532 at 120°). When we compared the values for the mean increase in US delta gap (stressed - supported state) from before to after MUCL release, the proximally released elbows had larger increases than the distally released elbows (5.0 mm proximal vs. 3.7 mm distal, P=.032). After MUCL release, maximum mean valgus displacement occurred at 49° of flexion. US-guided selective releases of the MUCL can be performed reliably without violating the overlying musculature. Valgus instability is not of greater magnitude for distal releases when compared with proximal releases. This findings suggests there must be alternative factors to explain the difference in clinical prognosis between distal and proximal tears. The observed flexion angle for maximum valgus laxity could have important implications for elbow positioning during US or fluoroscopic stress examination, as well as surgical repair or reconstruction of the MUCL.

Long-term differences in clinical prognosis between crossed- and parallel-cannulated screw fixation in vertical femoral neck fractures of non-geriatric patients

Background and PurposeVertical femoral neck fractures (VFNFs) are one of the most difficult fractures to stabilize, with high non-union (17%), avascular necrosis (AVN, 21%), and femoral neck shortening (FNS, 29.0%) rates. The objective of this investigation was to directly compare the long-term clinical complication rates of VFNFs repaired by crossed (Alpha fixation) or parallel screws in non-geriatric patients. Patients and MethodsWe conducted a retrospective comparative study of VFNFs in patients (<60 years) between January 2014 and December 2017, with at least 2 years of follow-up. VFNFs were fixed with either three parallel screws (G-TRI) or augmented with a crossed screw (G-ALP). Confounding variables included age, gender, initial displacement, ISS (Injury Severity Score), general comorbidities, combined fractures, Pauwels angle, reduction quality. Complications, including non-union, AVN of the femoral head and FNS were compared as outcome indicators. Risk factors associated with these variables were further analysed using multivariate analysis. ResultsA total of 157 patients (97 G-TRI; 60 G-ALP) met inclusion criteria. G-ALP had a significantly lower rate of FNS (8.3% vs. 28.9%, p = 0.039) than that of G-TRI. non-union (3.3% vs. 11.3%), AVN (21.7% vs. 25.8%), and reoperation rates (21.7% vs. 23.7%) were lower in G-ALP than G-TRI but was not statistically significant. Multivariate analyses showed significant relationships between NU and unacceptable reduction quality (OR=7.610; 1.823–31.770, adjusted-p = 0.015); between AVN and initial displacement (Garden III and IV) (OR=7.885; 1.739–35.744, adjusted-p = 0.021); and between FNS and screw configuration (OR=5.713; 1.839–17.743, adjusted-p = 0.009). ConclusionFor the treatment of VFNFs, satisfactory reduction still remains the key surgical goal that prevents NU, while the incidence of AVN strongly depends on the initial displacement at the time of injury. Crossed screws were associated with a markedly lower FNS rate than parallel screws, which promote further randomised controlled trials to establish a guideline for optimal fixation selection in VFNFs.

Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses.

PurposeThe tumor microenvironment (TME) plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC). However, underlying compositions and functions that drive the establishment and maintenance of the TME classifications are less-well understood.MethodsA total of 766 HCC patients from three public cohorts were clustered into four immune-related subclasses based on 13 TME signatures (11 immune-related cells and 2 immune-related pathways) calculated by MCP-counter. After analyzing the landscapes of functional annotation, methylation, somatic mutation, and clinical characteristics, we built a TME-based Support Vector Machine of 365 patients (discovery phase) and 401 patients (validation phase). We applied this SVM model on another two independent cohorts of patients who received sorafenib/pembrolizumab treatment.ResultsAbout 33% of patients displayed an immune desert pattern. The other subclasses were different in abundance of tumor infiltrating cells. The Immunogenic subclass (17%) associated with the best prognosis presented a massive T cell infiltration and an activation of immune checkpoint pathway. The 13 TME signatures showed a good potential to predict the TME classification (average AUC = 88%). Molecular characteristics of immunohistochemistry from Zhejiang cohort supported our SVM classification. The optimum response to pembrolizumab (78%) and sorafenib (81%) was observed in patients belonging to the Immunogenic subclass.ConclusionsThe HCC patients from distinct immune subclass showed significant differences in clinical prognosis and response to personalized treatment. Based on tumor transcriptome data, our workflow can help to predict the clinical outcomes and to find appropriate treatment strategies for HCC patients.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for β-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

Matched analysis of the prognosis of amelanotic and pigmented melanoma in head and neck

Background: The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study.Aim: To analyze data with head and neck mucosal melanoma, and compare the prognosis of patients with and without pigment.Material and methods: The patients of amelanotic melanoma were matched with pigmented type according to age, sex, stage, location of disease, treatment history, tobacco and alcohol history. The Kaplan–Meier and Cox proportional risk regression model was used for analyzation.Results: 46 patients of amelanotic melanoma and 46 of pigmented type were included in this study. The overall survival rate and progression-free survival rate of patients with pigmented melanoma were higher than in patients with amelanotic melanoma (HR = 0.533, p = .035, 95% CI = 0.296–0.957; HR = 0.530, p = .034, 95% CI = 0.294–0.953, respectively), and the risk of distant metastases in patients with amelanotic melanoma was significantly higher than that in patients with pigmented melanoma (HR = 0.474, p = .046, 95% CI = 0.228–0.987).Conclusions and significance: The prognosis and disease-free survival of amelanotic melanoma is worse than for the pigmented type group. More identifying the differences in clinical characteristics will help to further individualized treatment decisions.

Normal and leukemic stem cell niche interactions

Normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) interact with the stem cell niche bone marrow in different ways. Understanding the potentially unique microenvironmental regulation of LSCs is key to understanding in-vivo leukemogenic mechanisms and developing novel antileukemic therapies. When leukemic cells are engrafted in the stem cell niche, the cellular nature of the niche - including mesenchymal stromal cells - is reprogramed. Altered mesenchymal cells selectively support leukemic cells and reinforce the pro-leukemic environment. As the niche plays an active role in leukemogenesis, its remodeling may significantly influence the leukemogenic pattern, and cause differences in clinical prognosis. Notably, niche cells could be stimulated to revert to a pronormal/antileukemic state, creating potential for niche-based antileukemic therapy. Bone marrow microenvironments are under dynamic regulation for normal and leukemic cells, and there is bi-directional control of leukemic cells in the niche. Leukemic cells are both protected by stroma and able to reprogram stromal cells to transform the niche to a state, which reinforces leukemogenesis. Because of its dynamic nature, the niche could be converted to an environment with antileukemic properties, making it an attractive target for therapy.

Transcranial Doppler Ultrasonography for the Management of Severe Traumatic Brain Injury After Decompressive Craniectomy

Cerebral hemodynamic transformation is a relatively common finding in patients with traumatic brain injury (TBI). Knowledge of cerebral hemodynamic disturbance may assist in predicting the management outcome. Transcranial Doppler ultrasonography (TCD) monitoring of patients with TBI can be used to reveal various pathologic hemodynamic changes. The objective of this study was to compare the clinical outcomes of postoperative routine intracranial pressure (ICP) monitoring versus ICP monitoring combined with TCD monitoring in patients with brain trauma after decompressive craniectomy. This was a retrospective study of 30 patients with TBI who underwent ICP combined with TCD monitoring (after 2015) compared with a historical control group of 30 patients who only underwent routine ICP monitoring (in 2013-2014). ICP, partial pressure of carbon dioxide, hemoglobin, and hematocrit values were monitored and recorded on a daily basis for 7 days after operation. Neuroimaging was also performed at admission. Neurologic outcome was assessed at 2 weeks and 6 months after operation using the Glasgow Outcome Score Extended (GOS-E). Unconditional multivariable logistic regression was conducted to analyze the factors for favorable clinical outcome. Two weeks after operation, there were no differences in mortality rate between the 2 groups (P=0.643). When considering the GOS-E score at 6 months, there were no differences in clinical prognosis between the 2 groups (P= 0.101), but the ICP combined with TCD monitoring group showed a higher frequency of patients with favorable outcome compared with the routine ICP monitoring group (P= 0.043). Unconditional multivariable logistic regression results showed that no factor was independently associated with GOS-E at 6 months. TCD could be helpful for the serial monitoring of cerebral hemodynamic changes after decompressive craniectomy for TBI, which could be beneficial for neurologic outcome improvement.

RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML

SummaryAcute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML.

Neoadjuvant chemotherapy followed by radical surgery as an alternative treatment to concurrent chemoradiotherapy for young premenopausal patients with FIGO stage IIB squamous cervical carcinoma.

Concurrent chemoradiotherapy (cCRT) is the standard of care for International Federation of Gynecology and Obstetrics (FIGO) stage IIB squamous cervical carcinoma (SCC). However, an increasing number of young patients with stage IIB SCC are concerned with preserving their ovarian and vaginal functions during treatment. This retrospective study aimed to compare clinical prognosis between young patients with stage IIB SCC treated with neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) and those treated with cCRT. Medical records of 244 premenopausal patients aged <45 years with FIGO stage IIB SCC treated with NACT+RS and cCRT between February 2007 and June 2009 were reviewed. All these patients completed the treatment plan. NACT+RS resulted in recurrence (35.9 versus 41.8 %, P = 0.350), progression-free survival (PFS) rate (log-rank, P = 0.456), and overall survival (OS) rate (log-rank, P = 0.637) comparable to cCRT. Compared with cCRT, NACT+RS did not show a significant statistical difference in clinical prognosis of premenopausal patients with stage IIB SCC. Therefore, NACT+RS may be considered as an alternative treatment for the young patients who are concerned with preserving endocrine function, and this alternative treatment may also be administered when radiotherapy is unavailable.

Clinical outcomes of early gastric cancer with lymphovascular invasion or positive vertical resection margin after endoscopic submucosal dissection.

In early gastric cancer (EGC) cases with lymphovascular invasion or positive vertical margins after endoscopic submucosal dissection (ESD), additional radical gastrectomy is performed on principle. However, an additional surgery is often difficult to consider if the surgical approach itself is challenging or the patient refuses surgery. In such cases, only close surveillance is performed without additional surgical procedures. This study aimed to examine the difference in clinical prognosis of EGC cases with lymphovascular invasion or positive vertical margins after ESD either with or without surgery. We retrospectively studied 83 patients with lymphovascular invasion or positive vertical margins after ESD from July 2005 to November 2013. Of the 83 patients, 45 (54.2%) underwent radical additional gastrectomy (surgical group) and 38 (45.8%) were under close surveillance without surgical or endoscopic treatments (close surveillance group.) The cancer-free survival period was 78.3 ± 3.4 months in the surgical group and 64.5 ± 4.6 months in the close surveillance group. The recurrence rates did not significantly differ between the 2 groups, at 7.9% in the surgical group and 6.7% in the non-surgical group. Close surveillance may be suggested as an option for EGC patients for whom a surgical approach is difficult, who exhibit a positive vertical margin after ESD, and who have no lymphovascular or deep submucosa invasion after ESD.

Human papillomavirus and non-small cell lung cancer.

Lung cancer is the most common cause of cancer-related deaths in the world, causing more than one million deaths worldwide each year. Human papillomavirus (HPV) are small non-enveloped DNA viruses that infect squamous epithelial cells. Relevant studies have reported lung cancer-related HPV infection rates that fluctuate between 10% and 80%, depending on the various research methods and geographical factors. Various scholars gathered statistics from global research reports and found that 22.4% of the patients with lung cancer presented with an HPV infection, which suggested that HPV infection may relate to the tumorigenesis of non-small cell lung cancer. This article will review the history and discovery of HPV, the correlation between HPV and lung cancer development, and carcinogenesis caused by HPV regulatory genes, such as p53, p21, p16INK4a, and genes related to hypermethylation and genome instability in lung cancer patients with HPV infection. In addition, because studies have highlighted the difference in clinical prognosis for HPV-positive and HPV-negative patients, articles demonstrating the correlation between HPV infection and prognosis for lung cancer patients will be reviewed.

Is a score of 10 or greater on the Beck Depression Inventory equivalent to clinically diagnosed depression?

We read with great interest the recently published article by Maaike Meurs et al. [1] about examining the relation between post myocardial infarction depression and cardiovascular prognosis using a validated prediction model for post myocardial mortality. In this study, it is regrettable that the authors just used a depression screening instrument (Beck Depression Inventory, BDI) to measure depression [1]. Although a score of 10 or greater on the BDI indicates at least mild symptoms of depression [2], it is not equivalent to clinically diagnosed depression. And the authors also agree with this viewpoint in the discussion section. Therefore, such statement “post myocardial infarction depression” in the title is not accurate enough. Furthermore, the results of this study will be more valuable if the authors used both BDI and clinically diagnosed major depression disorder (MDD) to assess the status of patients. Thus we would get the important information that how many patients whose BDI ≥10 (not diagnosed clinical depression at hospitalization) developed into clinically diagnosed depression. And it will be clear that whether there are differences in clinical prognosis of patients who have developed into clinically diagnosed depression or not. From a clinical point of view, it is of vital importance to identify vulnerable patients who have poor prognosis exhibiting depressive symptoms, even in the absence of a clinically diagnosed depression. Identification of these high risk patients can alert physicians to target interventions to reduce the short term and long term cardiovascular events. In addition, the authors pointed out that BDI continuous score is a risk factor for cardiovascular prognosis. However, this article [1] did not provide the data of whether the patients who have depressive symptoms were treated with pharmacological or psychological interventions. And these treatment strategies may influence clinical prognosis and hospital readmissions in myocardial infarction (MI) survivors [3,4]. Finally, the lack of investigating depressive symptoms of patients preceding MI is another issue. Although one study has showed that an increase in depressive symptoms after MI predicts new cardiac events irrespective of depressive symptoms before MI [5]. The effect of depressive symptoms preceding MI should be taken into consideration during the analysis. It may be thatMI patientswith depressive episodes before an onset of MI who show a larger increase in depressive symptoms after MI are at increased risk of new cardiac events. And the last point is that the main causes of depression (severity of diseases or other causes) have also not been described in this study [1]. If these data can be available, the next step to carry out a series of measures to manage patients will have important clinical significance. We agree with the conclusion of the present study [1], and we think that the resultswill bemore practical and instructive if the authors have considered and solved the above problems. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.