Marital status independently predicts the overall survival in young adult patients with lymphoma: A population-based, propensity-matched study.

We predicted that marital status may have predictive effects on young adult patients with cancer. A total of 37,028 young adult patients (20-39 years old) newly diagnosed with lymphoma by positive histology between 1988 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. Patients were separated into married and unmarried groups. Multivariate regression was utilized to explore the association between marital status and overall survival, and propensity score matching and an inverse probability of treatment weighting were applied to corroborate our results. Among 37,028 eligible lymphoma patients, 12,827 married patients, and 12,827 unmarried patients, had equal propensity scores and were eventually recruited in this research. Moreover, married patients reported enhanced 10-year overall survival in the original group and the matched cohort. The multivariable Cox regression analysis revealed a vital advantageous influence of married status on overall mortality, with an adjusted hazard ratio (HR) of 0.54 (95% CI, 0.51-0.57, P < .001) and the association remained robust after propensity score matching (HR, 0.53, 95% CI 0.51-0.55, P < .001) and inverse probability of treatment weighting (HR, 0.53, 95% CI 0.51-0.56, P < .001) after adjusting for confounding factors. Marital status had predictive significance for overall survival in young adult patients with lymphoma.

PFDN2 promotes cell cycle progression via the hnRNPD-MYBL2 axis in gastric cancer.

Gastric cancer (GC) is a major health burden worldwide, but our understanding of GC is limited, and the prognosis is poor. Novel therapeutic strategies and biomarkers are urgently needed to improve GC patient outcomes. Previously, we identified PFDN2 as a novel key gene in gastric cancer based on its differential expression between cancer and normal tissues. However, the role and underlying mechanisms of PFDN2 in GC remain elusive. In this article, we demonstrated that PFDN2 is highly expressed in GC and that upregulation of PFDN2 is associated with the progression of GC. We further found that PFDN2 could promote cell cycle progression by promoting MYBL2 expression. Mechanistically, we demonstrated that PFDN2 could upregulate MYBL2 expression by facilitating the nuclear translocation of hnRNPD, and thus promoting MYBL2 transcriptional program. In conclusion, we found that PFDN2 promotes cell cycle progression via the hnRNPD-MYBL2 axis and may serve as a potential biomarker and therapeutic target for GC.

Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.

Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.

BGN/FAP/STAT3 positive feedback loop mediated mutual interaction between tumor cells and mesothelial cells contributes to peritoneal metastasis of gastric cancer.

Peritoneal metastasis (PM) is most frequent in gastric cancer (GC) and cancer-associated fibroblasts (CAFs) play a critical role in this process. However, the concrete mechanism of crosstalk between CAFs and cancer cells in PM of GC remains unclear. Microarray sequencing of GC focus and PM lesions was performed, and biglycan (BGN) was screened for further study. Clinically, BGN expression was higher in GC tissues than adjacent normal tissues, and high expression correlated with poor prognosis. In vitro experiments demonstrated that BGN promoted tumor progression and the transformation of mesothelial cells (MCs) into cancer-associated fibroblasts like cells (CAFLCs). In turn, CAFLCs-derived fibroblast activation protein (FAP) facilitated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. GC-derived BGN combined with toll like receptor 2 (TLR2)/TLR4 on MCs to activate the NF-κB pathway and promote the transformation of MCs into CAFLCs by the recovery experiment, coimmunoprecipitation assay, nuclear and cytoplasmic protein extraction assay. CAFLCs-derived FAP could activate the JAK2/STAT3 signaling pathway in GC. Finally, activated STAT3 promoted BGN transcription in GC, resulting in a BGN/FAP-STAT3 positive feedback loop. Taken together, mutual interaction between tumor cells and activated MCs mediated by a BGN/FAP-STAT3 positive feedback loop facilitates PM of GC and provides a potential biomarker and therapeutic target for GC metastasis.

LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2.

The molecular mechanism underlying gastric cancer (GC) peritoneal metastasis (PM) remains unclear. Here, we identified LINC00924 as a GC PM-related lncRNA through Microarray sequencing. LINC00924 was highly expressed in GC, and its high expression is associated with a broad range of PM. Via RNA sequencing, RNA pulldown assay, mass spectrometry, Seahorse, Lipidomics, spheroid formation and cell viability assays, we found that LINC00924 promoted fatty acid (FA) oxidation (FAO) and FA uptake, which was essential for matrix-detached GC cell survival and spheroid formation. Regarding the mechanism, LINC00924 regulated the alternative splicing (AS) of Mnk2 pre-mRNA by binding to hnRNPC. Specifically, LINC00924 enhanced the binding of hnRNPC to Mnk2 pre-mRNA at e14a, thus downregulating Mnk2a splicing and regulating the p38 MAPK/PPARα signaling pathway. Collectively, our results demonstrate that LINC00924 plays a role in promoting GC PM and could serve as a drug target.

The safety of pericardiocentesis in patients under antithrombotic therapy: A single-center experience.

Objective: This study aimed to analyze the characteristics of patients with pericardial effusion requiring pericardiocentesis and to evaluate the safety of pericardiocentesis without discontinuation of anticoagulant or antiplatelet drugs. Methods: We performed a retrospective study of patients undergoing pericardiocentesis in our hospital between 2012 and 2022. Patients were categorized into the Antithrombotic Group if they had used any antiplatelet or anticoagulant drugs on the day of pericardiocentesis; otherwise they were categorized into the Non-antithrombotic Group. All procedures were performed by experienced cardiologists with echocardiographic guidance. Bleeding events were defined using the National Institutes of Health scale of adverse events. Results: A total of 501 consecutive patients were identified and 70 cases were under antithrombotic drugs (Antithrombotic Group). Patients in Antithrombotic Group were older, had more comorbidities, presented with lower platelet counts and prolonged activated partial thromboplastin time (all p < 0.05). Malignancy was the most common etiology for pericardial effusion in both groups (28.6% in Antithrombotic Group and 54.7% in Non-antithrombotic Group) and tuberculosis was the second etiology in the Non-antithrombotic Group (21.9%), while procedure-related effusion (17.1%) accounted for the second cause in the Antithrombotic Group. Two patients in the Antithrombotic Group had mild oozing at the puncture site that resolved without interventions (2.9 vs. 0%, p = 0.019), and no bleeding events higher than Grade 1 occurred in either group. Conclusion: Although antiplatelet or anticoagulant drugs may put patients undergoing pericardiocentesis at theoretically higher risk of bleeding, our study demonstrated that they are not associated with increased major bleeding complications.

SNHG16 upregulation-induced positive feedback loop with YAP1/TEAD1 complex in Colorectal Cancer cell lines facilitates liver metastasis of colorectal cancer by modulating CTCs epithelial-mesenchymal transition.

Circulating tumor cells (CTCs) are important precursors of colorectal cancer (CRC) metastasis. The epithelial-mesenchymal transition (EMT) process facilitates CTC invasion by allowing these cells to evade antimetastatic checkpoints to mediate distant metastasis. However, the specific molecular mechanism of tumor EMT remains largely unknown. Based on our previous research on the YAP1 pathway, we further studied the upstream molecule small nucleolar RNA host gene 16 (SNHG16), whose expression was correlated with advanced TNM stage, distant metastasis, and poor prognosis in CRC patients. Furthermore, loss- and gain-of-function assays revealed that SNHG16 promoted CRC colony formation, proliferation, migration, invasion, EMT, mesenchymal-like CTC generation, and liver metastasis through YAP1. Mechanistically, SNHG16 acted as a miRNA sponge to sequester miR-195-5p on Ago2, thereby protecting YAP1 from repression. Moreover, YAP1 bound TEA domain transcription factor 1 (TEAD1) to form a YAP1/TEAD1 complex, which in turn bound two sites in the promoter of SNHG16 and regulate SNHG16 transcription. Finally, in vivo experiments showed that the inhibition of SNHG16 suppressed tumor progression, and that YAP1 rescued the effect of SNHG16 on tumor progression. Herein, we have clarified a hitherto unexplored SNHG16-YAP1/TEAD1 positive feedback loop, that may be a candidate target for CRC treatment.

MiR-192-5p/RB1/NF-κBp65 signaling axis promotes IL-10 secretion during gastric cancer EMT to induce Treg cell differentiation in the tumour microenvironment.

BACKGROUND: Regulatory T (Treg) cells are important components of the tumour microenvironment (TME) that play roles in gastric cancer (GC) metastasis. Although tumour cells that undergo epithelial-mesenchymal transition (EMT) regulate Treg cell function, their regulatory mechanism in GC remains unclear. METHODS: The miR-192-5p was identified by examining three Gene Expression Omnibus GC miRNA expression datasets. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were conducted to identify interactions between miR-192-5p and RB1. The role of miR-192-5p/RB1 in GC progression was evaluated based on EdU incorporation, wound healing and Transwell assays. An in vitro co-culture assay was performed to measure the effect of miR-192-5p/RB1 on Treg cell differentiation. In vivo experiments were conducted to explore the role of miR-192-5p in GC progression and Treg cell differentiation. RESULTS: MiR-192-5p was overexpressed in tumour and was associated with poor prognosis in GC. MiR-192-5p bound to the RB1 3'-untranslated region, resulting in GC EMT, proliferation, migration and invasion. MiR-192-5p/RB1 mediated interleukin-10 (IL-10) secretion by regulating nuclear factor-kappaBp65 (NF-κBp65), affecting Treg cell differentiation. NF-κBp65, in turn, promoted miR-192-5p expression and formed a positive feedback loop. Furthermore, in vivo experiments confirmed that miR-192-5p/RB1 promotes GC growth and Treg cell differentiation. CONCLUSION: Collectively, our studies indicate that miR-192-5p/RB1 promotes EMT of tumour cells, and the miR-192-5p/RB1/NF-κBp65 signaling axis induces Treg cell differentiation by regulating IL-10 secretion in GC. Our results suggest that targeting miR-192-5p/RB1/NF-κBp65 /IL-10 may pave the way for the development of new immune treatments for GC.

Identification of Novel Tumor Microenvironment Regulating Factor That Facilitates Tumor Immune Infiltration in Cervical Cancer.

Cervical cancer is one of the most common gynecologic malignancies and one of the leading causes of cancer-related deaths in women worldwide. There are more than 30 categories of human papillomavirus infections in the genital tract. The recently discovered immune checkpoint suppression is a potential approach to improve clinical outcomes in these patients by altering immune cell function. However, many questions remain unanswered in terms of this method. For example, the proportion of responders is limited and the exact mechanism of action is uncertain. The tumor microenvironment (TME) has long been regarded as having nonnegligible influence on effectiveness of immunotherapy. The programmed cell death protein 1 (PD-1) pathway has received much attention due to its involvement in activating T-cell immune checkpoint responses. Since tumor cells may evade immune detection and become highly resistant to conventional treatments, anti-PD-1/PD-L1 antibodies are preferred as a kind of cancer treatment and many have just been licensed. To provide a theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of cervical cancer is necessary. In this work, immunological scores obtained from the ESTIMATE algorithm were used to differentiate between patients with high and low immune cell infiltration. We identified 11 immunologically significant differentially expressed genes (DEGs). For example, CXCR3 was found to be an important factor in CD8+ T cell recruitment and tumor immunological infiltration in cervical cancer. These results may lead to novel directions of understanding complex interactions between cancer cells and the tumor microenvironment, as well as new treatment options for cervical cancer.

Blood Urea Nitrogen for Short-Term Prognosis in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction.

Purpose: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI). Our study aimed to evaluate the short-term prognostic value of admission blood urea nitrogen (BUN) in patients with CS complicating AMI. Materials and Methods: 218 consecutive patients with CS after AMI were enrolled. The primary endpoint was 30-day mortality. The association of admission BUN and 30-day mortality and major adverse cardiovascular event (MACE) was investigated by Cox regression. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) further examined the predictive value of BUN. Results: During a period of 30-day follow-up, 105 deaths occurred. Compared to survivors, nonsurvivors had significantly higher admission BUN (p < 0.001), creatinine (p < 0.001), BUN/creatinine (p = 0.03), and a lower glomerular filtration rate (p < 0.001). The area under the curve (AUC) of the 4 indices for predicting 30-day mortality was 0.781, 0.734, 0.588, and 0.773, respectively. When compared to traditional markers associated with CS, the AUC for predicting 30-day mortality of BUN, lactate, and left ventricular ejection fraction were 0.781, 0.776, and 0.701, respectively. The optimal cut-off value of BUN for predicting 30-day mortality was 8.95 mmol/L with Youden-Index analysis. Multivariate Cox analysis indicated BUN >8.95 mmol/L was an important independent predictor for 30-day mortality (HR 2.08, 95%CI 1.28-3.36, p = 0.003) and 30-day MACE (HR 1.85, 95%CI 1.29-2.66, p = 0.001). IDI (0.053, p = 0.005) and NRI (0.135, p = 0.010) showed an improvement in the accuracy for mortality prediction of the new model when BUN was included compared with the standard model of predictors in previous scores. Conclusion: An admission BUN >8.95 mmol/L was robustly associated with increased short-term mortality and MACE in patients with CS after AMI. The prognostic value of BUN was superior to other renal markers and comparable to traditional markers. This easily accessible index might be promising for early risk stratification in CS patients following AMI.

LAMC1-mediated preadipocytes differentiation promoted peritoneum pre-metastatic niche formation and gastric cancer metastasis.

Gastric cancer is anatomically proximal to peritoneum. Gastric cancer peritoneal metastasis is a complex biological process which is corresponded with disharmony within dysfunctional adipose tissue and metabolism reprogramming. Laminin gamma 1 (LAMC1) is highly expressed in cancer cells of peritoneal metastatic sites, however, the mechanism of LAMC1-metiated gastric cancer metastases to adipose tissue-rich peritoneum remains unclear. In our study, immunohistochemical staining, single cell sequencing, a co-culture model, luciferase reporter, RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (CHIP) and single-molecular magnetic tweezers assays were conducted, and our results showed that LAMC1 related to Perilipin-1 content was highly expressed in peritoneal metastatic sites and mainly secreted by tumor cells. Gastric cancer cells secreted LAMC1 in an autocrine manner to detached from the primary site and promoted preadipocytes mature, rupture and release of free fatty acids (FFAs) in the peritoneal microenvironment to form pre-metastatic niche by the paracrine pathway. Reversely, differentiated preadipocyte-derived conditioned medium inhibited glycolysis and enhanced fatty acid oxidation (FAO) rate to promote cell proliferation, mesenchymal-epithelial transformation which led to tumor peritoneal colonization. In terms of biological mechanisms, one of differentiated preadipocyte-derived FFAs, palmitic acid-activated STAT3 inhibited miR-193a-3p by binding to its promoter directly; Using single-molecular magnetic tweezers, this binding manner was proved to be stable, reversable and ATP-dependent. Moreover, miR-193a-3p regulated LAMC1 in a post-translational manner. Furthermore, high LAMC1 expression in serum predicted a higher risk of peritoneal metastasis. In conclusion, our results illustrated that palmitic acid/p-STAT3/miR-193a-3p/LAMC1 pathway promotes preadipocyte differentiation, pre-metastatic niche formation and gastric cancer cell colonization to peritoneum.

The lncRNA SEMA3B-AS1/HMGB1/FBXW7 Axis Mediates the Peritoneal Metastasis of Gastric Cancer by Regulating BGN Protein Ubiquitination.

Peritoneal metastasis (PM) is one of the main causes of a poor prognosis in patients with advanced gastric cancer (GC). lncRNAs have been confirmed to play a very crucial role in the occurrence, development, and metastasis of many human cancers, including gastric cancer. However, the mechanism of lncRNA in PM of GC is rarely studied. We explored the mechanism of PM of GC through lncRNA gene sequencing and protein profiling analysis to detect PM-associated lncRNAs and proteins. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify the mRNA expression of SEMA3B-AS1 and BGN in GC tissues and adjacent normal tissues. The biological function of SEMA3B-AS1 in the PM of GC was identified through gain- and loss-of-function assays. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and coimmunoprecipitation (co-IP) assays was carried out to demonstrate the potential mechanism between SEMA3B-AS1 and its downstream genes, including HMGB1, FBXW7, and BGN. Finally, the biological function of SEMA3B-AS1 was demonstrated in animal experiments. The mRNA expression level of SEMA3B-AS1 was downregulated in GC and PM tissues compared to normal stomach tissues; however, BGN was highly expressed at the mRNA level. SEMA3B-AS1 was closely related to PM and the overall survival (OS) of GC patients. Functionally, the overexpression of SEMA3B-AS1 was related to GC progression, PM, and prognosis. Mechanistically, SEMA3B-AS1 could combine with HMGB1 to regulate the transcription of FBXW7, thus facilitating the ubiquitination of BGN. In conclusion, our study demonstrated that the SEMA3B-AS1/HMGB1/FBXW7 axis plays an inhibitory role in the PM of GC by regulating BGN protein ubiquitination. It also provides a new biological marker for the diagnosis and treatment of the PM of GC.

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination.

Ferroptosis is a novel form of cell death that is closely associated with the formation of many tumors. Our study focused on the mechanism by which long noncoding RNAs (lncRNAs) regulate ferroptosis in gastric cancer (GC) peritoneal metastasis (PM). We utilized lncRNA sequencing and protein profiling analysis to identify ferroptosis-associated lncRNAs and proteins. qRT-PCR was used to analyze the expression of BDNF-AS and FBXW7 in GC tissues and adjacent normal tissues. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and coimmunoprecipitation (co-IP) assays were performed to investigate the interaction between BDNF-AS and its downstream targets. Finally, the function of BDNF-AS was validated in vivo . We demonstrated that BDNF-AS was highly expressed in GC and PM tissues. High BDNF-AS expression was positively related to GC progression and poor prognosis. Functionally, BDNF-AS overexpression protected GC cells from ferroptosis and promoted the progression of GC and PM. Mechanistically, BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in GC by affecting VDAC3 ubiquitination. BDNF-AS might be a biomarker for the evaluation of GC prognosis and the treatment of GC.

Incidence, Clinical Characteristics and Short-Term Prognosis in Patients With Cardiogenic Shock and Various Left Ventricular Ejection Fractions After Acute Myocardial Infarction.

The 2016 European Society of Cardiology Guidelines introduced a new term, mid-range left ventricular ejection fraction (mrEF) heart failure, however, the clinical characteristics and short-term outcomes in cardiogenic shock patients with mrEF after acute myocardial infarction remain unclear. This retrospective study analyzed the baseline characteristics, management, and outcomes according to the left ventricular ejection fraction (LVEF), reduced LVEF (rEF) ≤40%, mrEF 41% to 49%, and preserved LVEF (pEF) ≥50% in patients with acute myocardial infarction complicated by cardiogenic shock. The primary end point was 30-day all-cause mortality and the secondary end point was the composite events of major adverse cardiovascular events (MACEs). In 218 patients, 71 (32.6%) were patients with mrEF. Compared with those with pEF, patients with mrEF had some similar clinical characteristics to that of rEF. The 30-day all-cause mortality in patients with rEF, mrEF, and pEF were 72.7%, 56.3%, and 32.0%, respectively (p = 0.001). The 30-day MACE were 90.9%, 69.0%, and 60.2%, respectively (p = 0.001). After multivariable adjustment, patients with mrEF and rEF had comparable 30-day all-cause mortality (hazard ratio [HR] = 0.81, 95% confidence interval [CI] 0.50 to 1.33, p = 0.404), and pEF was associated with decreased risk of 30-day all-cause mortality compared with rEF (HR = 0.41, 95% CI 0.24 to 0.71, p = 0.001). In contrast, the risk of 30-day MACE in mrEF and pEF were lower than that of rEF (HR = 0.62, 95% CI 0.40 to 0.96, p = 0.031 and HR = 0.53, 95% CI 0.34 to 0.80, p = 0.003, respectively). In conclusion, 1/3 of patients with acute myocardial infarction complicated by cardiogenic shock were mrEF. The clinical characteristics and short-term mortality in patients with mrEF were inclined to that of rEF and the occurrence of early left ventricular systolic dysfunction is of prognostic significance.

The prognostic value of admission D-dimer level in patients with cardiogenic shock after acute myocardial infarction.

Background: Shock is associated with the activation of the coagulation and fibrinolytic system, and D-dimer is the degradation product of cross-linked fibrin. However, the prognostic value of D-dimer in patients with cardiogenic shock (CS) after acute myocardial infarction (AMI) remains unclear. Methods: We retrospectively analyzed the data of consecutive patients with CS complicating AMI. The primary endpoint was 30-day mortality and the secondary endpoint was the major adverse cardiovascular events (MACEs) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage, and non-fatal stroke. Restricted cubic spline (RCS) analyses were performed to assess the association between admission D-dimer and outcomes. A multivariable Cox regression model was performed to identify independent risk factors. The risk predictive potency with D-dimer added to the traditional risk scores was evaluated by C-statistics and the net reclassification index. Results: Among 218 patients with CS complicating AMI, those who died during the 30-day follow-up presented with worse baseline characteristics and laboratory test results, including a higher level of D-dimer. According to the X-tile program result, the continuous plasma D-dimer level was divided into three gradients. The 30-day all-cause mortality in patients with low, medium, and high levels of D-dimer were 22.4, 53.3, and 86.2%, respectively (p < 0.001 for all). The 30-day incidence of MACEs was 46.3, 77.0, and 89.7%, respectively (p < 0.001). In the multivariable Cox regression model, the trilogy of D-dimer level was an independent risk predictor for 30-day mortality (median D-dimer cohort: HR 1.768, 95% CI 0.982-3.183, p = 0.057; high D-dimer cohort: HR 2.602, 95% CI 1.310-5.168, p = 0.006), a similar result was observed in secondary endpoint events (median D-dimer cohort: HR 2.012, 95% CI 1.329-3.044, p = 0.001; high D-dimer cohort: HR 2.543, 95% CI 1.452-4.453, p = 0.001). The RCS analyses suggested non-linear associations of D-dimer with 30-day mortality. The enrollment of D-dimer improved risk discrimination for all-cause death when combined with the traditional CardShock score (C-index: 0.741 vs. 0.756, p difference = 0.004) and the IABP-SHOCK II score (C-index: 0.732 vs. 0.754, p difference = 0.006), and the GRACE score (C-index: 0.679 vs. 0.715, p difference < 0.001). Similar results were acquired after logarithmic transformed D-dimer was included in the risk score. The improvements in reclassification which were calculated as additional net reclassification index were 7.5, 8.6, and 12.8%, respectively. Conclusion: Admission D-dimer level was independently associated with the short-term outcome in patients with CS complicating AMI and addition of D-dimer brought incremental risk prediction value to traditional risk prediction scores.

Leukocyte and its Subtypes as Predictors of Short-Term Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI. METHODS: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis. RESULTS: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 × 109/L) (HR 1.815; 95%CI 1.134, 2.903; P = 0.013), low eosinophil (<0.3%) (HR 2.562; 95%CI 1.412, 4.648; P = 0.002) and low basophil (≤0.1%) (HR 1.694; 95%CI 1.106, 2.592; P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 × 109/L) (HR 1.894; 95%CI 1.285, 2.791; P = 0.001), low eosinophil (<0.3%) (HR 1.729; 95%CI 1.119, 2.670; P = 0.014) and low basophil (≤0.1%) (HR 1.560; 95%CI 1.101, 2.210; P = 0.012) were independently associated with increased risk of 30-day MACE. CONCLUSIONS: Leukocyte and its subtypes changed significantly in patients with CS complicating AMI. In addition to leukocyte, eosinophil and basophil also served as independent prognostic factors for 30-day outcomes. Moreover, as the composite of leukocyte and its subtypes increased the predictive power, thus leukocyte and its subtypes, especially eosinophil and basophil should be taken into consideration for the current risk stratification model.

The Association of Thyroid Hormones With Cardiogenic Shock and Prognosis in Patients with ST Segment Elevation Myocardial Infarction (STEMI) Treated with Primary PCI.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. METHODS: A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore the relationship between CS and thyroid hormones. RESULTS: Patients who developed CS (n=103) had lower FT3 and higher FT4 upon admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 (<2.25 pg/ml) or higher FT4 (>1.25 ng/dl) were correlated with higher prevalence of CS. Over 2.5 years' follow-up, patients (n=294) with low FT3 (<2.85 pg/ml) and high FT4 (>=0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend <0.0001). CONCLUSIONS: Both FT3 and FT4 were independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in long-term follow-up.

The Association between Thyroid-Stimulating Hormone and Long-Term Outcomes in Patients with ST Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

OBJECTIVE: Thyroid hormones are closely related to the cardiovascular system. Our study aimed to explore the impact of admission thyroid-stimulating hormone (TSH) levels on long-term outcomes in patients with acute ST segment elevation myocardial infarction (STEMI) by detailed stratifications of TSH. METHODS: Consecutive STEMI patients admitted to our hospital were divided into four groups: Group 1 (TSH <0.35 mIU/L), Group 2 (TSH 0.35-1.0 mIU/L), Group 3 (TSH 1.0-3.5 mIU/L), and Group 4 (TSH >3.5 mIU/L). The primary endpoint was all-cause mortality during follow-up, and the median follow-up was 2.5 years. Cox proportional hazard regression models were performed to identify the prognostic value of TSH. RESULTS: A total of 1186 patients were included. Group 4 was presented with higher systolic and diastolic blood pressure (all P < 0.001), and Group 1 had more patients complicated by heart failure (Killip class >I, P = 0.014). During follow-up, 138 deaths occurred. Patients in Group 4 had the worst long-term outcomes (P < 0.001). The cumulative survival in Group 4 was remarkably lower (Log rank P < 0.001), whereas the other three groups were comparable (Log rank P = 0.365). Through Cox regression analysis, only TSH >3.5 mIU/L was identified as an independent risk factor for long-term mortality after STEMI. CONCLUSION: Only TSH elevation beyond the normal range was associated with worse long-term prognosis in STEMI patients, while high-normal TSH or reduced TSH did not alter long-term prognosis of STEMI patients. TSH >3.5 mIU/L was an independent risk factor for long-term mortality in STEMI.

Associations of Lipoprotein(a) With Coronary Atherosclerotic Burden and All-Cause Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

Background: The coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) has been identified as the main predictor of prognosis. However, the association of lipoprotein(a) [Lp(a)], a well-established proatherogenic factor, with atherosclerotic burden in patients with STEMI is unclear. Methods: In total, 1,359 patients who underwent percutaneous coronary intervention (PCI) for STEMI were included in analyses. Three prespecified models with adjustment for demographic parameters and risk factors were evaluated. Generalized additive models and restricted cubic spline analyses were used to assess the relationships of Lp(a) with Gensini scores and the no-reflow phenomenon. Kaplan-Meier curves were generated to explore the predictive value of Lp(a) for long-term all-cause mortality. Furthermore, mRNA expression levels of LPA in different groups were compared using the GEO database. Results: Patients in the highest tertile according to Lp(a) levels had an increased incidence of heart failure during hospitalization. Furthermore, patients with high levels of Lp(a) (>19.1 mg/dL) had sharply increased risks for a higher Gensini score (P for trend = 0.03) and no-reflow (P for trend = 0.002) after adjustment for demographic parameters and risk factors. During a median follow-up of 930 days, 132 deaths (9.95%) were registered. Patients with high levels of Lp(a) (>19.1 mg/dL) had the worst long-term prognosis (P for trend < 0.0001). In a subgroup analysis, patients with higher Lp(a) still had the highest all-cause mortality. Additionally, the mRNA expression levels of LPA in patients with STEMI with lower cardiac function were higher than those in other groups (P = 0.003). A higher coronary atherosclerotic burden was correlated with higher LPA expression (P = 0.01). Conclusion: This study provides the first evidence that Lp(a) (at both the protein and mRNA levels) is independently associated with coronary atherosclerotic lesions and prognosis in patients with STEMI treated with PCI. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028516.

Prognostic value of neutrophil-lymphocyte ratio in cardiogenic shock complicating acute myocardial infarction: A cohort study.

BACKGROUNDS: Cardiogenic shock (CS) is the most severe complication after acute myocardial infarction (AMI) with mortality above 50%. Inflammatory response is involved in the pathology of CS and AMI. In this study, we aimed to evaluate the prognostic value of admission neutrophil-lymphocyte ratio (NLR) in patients with CS complicating AMI. METHODS: Two hundred and seventeen consecutive patients with CS after AMI were divided into two groups according to the admission NLR cut-off value ≤7.3 and >7.3. The primary outcome was 30-day all-cause mortality and the secondary end-point was the composite events of major adverse cardiovascular events (MACE), including all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal haemorrhage and non-fatal stroke. Cox proportional hazard models were performed to analyse the association of NLR with the outcome. NLR cut-off value was determined by Youden index. RESULTS: Patients with NLR > 7.3 were older and presented with lower lymphocyte count, higher admission heart rate, B-type natriuretic peptide, leucocyte, neutrophil and creatinine (all P < .05). During a period of 30-day follow-up after admission, mortality in patients with NLR > 7.3 was significantly higher than in patients with NLR ≤ 7.3 (73.7% vs. 26.3%, P < .001). The incidence of MACE was also remarkably higher in patients with NLR > 7.3 (87.9% vs. 53.4%, P < .001). After multivariable adjustment, NLR > 7.3 remained an independent predictor for higher risk of 30-day mortality (HR 2.806; 95%CI 1.784, 4.415, P < .001) and MACE (HR 2.545; 95%CI 1.791, 3.617, P < .001). CONCLUSIONS: Admission NLR could be used as an important tool for short-term prognostic evaluation in patients with CS complicating AMI and higher NLR is an independent predictor for increased 30-day all-cause mortality and MACE.