Exploring the effect of high pressure in the denaturation of casein micelles by in-situ SERS.

To investigate the structural changes of casein in response to the pressurization process under varying pressure levels, this study carried out both ex-situ and in-situ high-pressure experiments. In the in-situ experiments, the surface-enhanced Raman scattering (SERS) technique was combined with a diamond anvil cell (DAC). The high-pressure experiments indicated that significant dissociation of casein occurred at 200 MPa. Over the range of 0-302 MPa, casein exhibited both dissociation and aggregation behaviors. However, casein tended towards aggregation at pressures of 302-486 MPa, with a further increase observed beyond 486 MPa.

Comprehensive investigation of pressure-induced gelatinization of starches using in situ and ex-situ technical analyses.

The pressure-induce gelatinization of pea starch, potato starch and corn starch was investigated by a combination of in situ and ex-situ technical analyses. According to in-situ observation of gelatinization process and the analysis of granular morphology by scanning electronic microscopy (SEM), the pressure that caused potato starch gelatinization was the highest at 600 MPa. This was followed by pea starch, and the pressure that caused the gelatinization of corn starch was the lowest at 400 MPa. In situ Raman spectral analysis revealed the molecular mechanism of starch gelatinization. This indicated that high pressure treatment resulted in the modification of the structure of the double helical polymers and the degree of a double helix of the starch crystalline varied as well. This study dynamically monitors the starch gelatinization process, aiming to better understand the gelatinization mechanism and provide a theoretical basis for the application of pressure in the starch field.

Genome-Wide Identification and Characterization of the HAK Gene Family in Quinoa (Chenopodium quinoa Willd.) and Their Expression Profiles under Saline and Alkaline Conditions.

The high-affinity K+ transporter (HAK) family, the most prominent potassium transporter family in plants, which involves K+ transport, plays crucial roles in plant responses to abiotic stresses. However, the HAK gene family remains to be characterized in quinoa (Chenopodium quinoa Willd.). We explored HAKs in quinoa, identifying 30 members (CqHAK1-CqHAK30) in four clusters phylogenetically. Uneven distribution was observed across 18 chromosomes. Furthermore, we investigated the proteins' evolutionary relationships, physicochemical properties, conserved domains and motifs, gene structure, and cis-regulatory elements of the CqHAKs family members. Transcription data analysis showed that CqHAKs have diverse expression patterns among different tissues and in response to abiotic stresses, including drought, heat, low phosphorus, and salt. The expressional changes of CqHAKs in roots were more sensitive in response to abiotic stress than that in shoot apices. Quantitative RT-PCR analysis revealed that under high saline condition, CqHAK1, CqHAK13, CqHAK19, and CqHAK20 were dramatically induced in leaves; under alkaline condition, CqHAK1, CqHAK13, CqHAK19, and CqHAK20 were dramatically induced in leaves, and CqHAK6, CqHAK9, CqHAK13, CqHAK23, and CqHAK29 were significantly induced in roots. Our results establish a foundation for further investigation of the functions of HAKs in quinoa. It is the first study to identify the HAK gene family in quinoa, which provides potential targets for further functional study and contributes to improving the salt and alkali tolerance in quinoa.

Risk-adjusted management in catheterization procedures for non-ST-segment elevation myocardial infarction: A standard operating procedure pilot study.

BACKGROUND: The effects of standardized risk-adjusted periprocedural management of cardiac catheterization procedures in Non-ST segment elevation myocardial infarction (NSTEMI) remain unknown. We implemented a standard operating procedure (SOP) specifying risk assessment (RA, using National Cardiovascular Data Registry (NCDR) risk models) and risk-adjusted management (RM, e.g. intensified monitoring) in 2018 and aimed to investigate staff SOP adherence and associations with patient outcomes. METHODS AND RESULTS: All 430 invasively managed NSTEMI patients (mean age 72y; 70.9% male) in 2018 were analyzed for staff SOP adherence and in-hospital clinical outcomes. 207 patients (48.1%; RM+) received both RA and RM; 92 patients (21.4%; RM-) received RA but no RM; 131 patients (30.5%; RA-) received neither RA nor RM. Lower staff adherence to RA was associated with emergency settings (51.9% (RA-) vs. 22.1% (RA+); p<0.01), presentation in cardiogenic shock (17.6% (RA-) vs. 6.4% (RA+); p<0.01) and invasive mechanical ventilation (12.2% (RA-) vs. 3.3% (RA+); p<0.01). Early sheath removal (87.9% (RM+) vs. 56.5% (RM-); p<0.01) and intensified monitoring (p<0.01) were more frequent in the RM+ group. All-cause mortality was not different (1.4% (RM+) vs. 4.3% (RM-); p=0.13), but there were fewer major bleeding events with associated with RM (2.4% (RM+) vs. 12% (RM-); p<0.01), which remained independently associated with RM in a multivariate logistic regression model correcting for confounders (p<0.01). CONCLUSION: In an all-comer patient cohort with NSTEMI, staff adherence to risk-adjusted periprocedural management was independently associated with fewer major bleeding events. Staff adherence to SOP-specified risk assessment was frequently neglected in more critical clinical situations.

Knowledge of HbA1c and LDL-C treatment goals, subjective level of disease-related information and information needs in patients with atherosclerotic cardiovascular disease.

BACKGROUND/HYPOTHESIS: Risk factor control of diabetes mellitus (DM) and especially dyslipidemia remains unsatisfactory in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to analyze the knowledge of low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin (HbA1c) treatment goals, subjective level of information, and information needs in very high-risk patients with ASCVD. METHODS: ASCVD patients (n = 210; 75 ± 9 years; 71.4% male; 89.5% coronary disease) with DM (96.7% type 2) completed a questionnaire assessing knowledge of HbA1c and LDL-C treatment goals and subjective level of information and information needs on disease-related topics of DM and ASCVD. Serum LDL-C and HbA1c were measured. RESULTS: HbA1c goal (<7.0% in 60.6%) was attained more frequently than LDL-C goal (<70 mg/dl in 39.9%; p < .01). Significantly more participants named the correct goal for HbA1c compared to LDL-C (52.9% vs. 2.4%; p < .01). Subjective levels of information were higher and information needs were lower for DM than for ASCVD (p < .01 for all topics). No associations of knowledge of treatment goals and level of information with the attainment of treatment goals for HbA1c and LDL-C were found. However, in multivariate regression, higher levels of education were associated with knowledge of treatment goals (HbA1c: odds ratio [OR] 1.32, 95% confidence interval [CI] 1.01-1.72, p = .04; LDL-C: OR 2.32, 95% CI 1.07-5.03; p = .03). CONCLUSION: In very high-risk patients with ASCVD, a deficit of knowledge of treatment goals to control dyslipidemia exists when compared to DM, patients felt significantly better informed for topics of DM than for ASCVD and display higher information needs for topics of ASCVD.

Meta-analysed numbers needed to treat of novel antidiabetic drugs for cardiovascular outcomes.

AIMS: Absolute treatment effects-i.e. numbers needed to treat (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta-analysis of digitalized individual patient outcomes to display and compare absolute treatment effects. METHODS AND RESULTS: Individual patient time-to-event information from Kaplan-Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random-effects meta-analysis generated Meta-NNT with 95% confidence intervals. Sixteen CVOTs reported time-to-event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta-analysed for CM: At the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to -223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta-analysed for HHF: At the median follow-up of 29 months, estimated Meta-NNTs were -644 (229 to ∞ to -134) for DPP-4 inhibitors, 441 (184 to ∞ to -1100) for GLP-1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta-NNT 25 (19 to 39)] vs. primary diabetes populations [Meta-NNT 233 (167 to 385)] at 16 months of follow-up. CONCLUSIONS: We found only modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication.

Clinical efficacy and safety outcomes of bempedoic acid for LDL-C lowering therapy in patients at high cardiovascular risk: a systematic review and meta-analysis.

OBJECTIVES: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched. STUDY SELECTION: Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included. MAIN OUTCOMES AND MEASURES: Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function. RESULTS: Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39). CONCLUSION: BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.

National Cardiovascular Data Registry-Acute Kidney Injury (NCDR) vs. Mehran risk models for prediction of contrast-induced nephropathy and need for dialysis after coronary angiography in a German patient cohort.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major adverse event in patients undergoing coronary angiography. The Mehran risk model is the gold-standard for CIN risk prediction. However, its performance in comparison to more contemporary National Cardiovascular Data Registry-Acute Kidney Injury (NCDR-AKI) risk models remains unknown. We aimed to compare both in this study. METHODS AND RESULTS: Predictions of Mehran and NCDR-AKI risk models and clinical events of CIN and need for dialysis were assessed in a total of 2067 patients undergoing coronary angiography with or without percutaneous coronary intervention. Risk models were compared regarding discrimination (receiver operating characteristic analysis), net reclassification improvement (NRI) and calibration (graphical and statistical analysis). The NCDR risk model showed superior risk discrimination for predicting CIN (NCDR c-index 0.75, 95% CI 0.72-0.78; vs. Mehran c-index 0.69, 95% CI 0.66-0.72, p < 0.01), and continuous NRI (0.22; 95% CI 0.12-0.32; p < 0.01) compared to the Mehran model. The NCDR risk model tended to underestimate the risk of CIN, while the Mehran model was more evenly calibrated. For the prediction of need for dialysis, NCDR-AKI-D also discriminated risk better (c-index 0.85, 95% CI 0.79-0.91; vs. Mehran c-index 0.75, 95% CI 0.66-0.84; pNCDRvsMehran < 0.01), but continuous NRI showed no benefit and calibration analysis revealed an underestimation of dialysis risk. CONCLUSION: In German patients undergoing coronary angiography, the modern NCDR risk model for predicting contrast-induced nephropathy showed superior discrimination compared to the Mehran model while showing less accurate calibration. Results for the outcome 'need for dialysis' were equivocal.

Modern NCDR and ACTION risk models outperform the GRACE model for prediction of in-hospital mortality in acute coronary syndrome in a German cohort.

BACKGROUND AND PURPOSE: Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. METHODS AND RESULTS: A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, pGRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; pACTIONvsNCDR < 0.0001; pGRACEvsNCDR < 0.0001) and showed superior performance compared to GRACE in NSTEMI and STEMI subgroups (pGRACEvsNCDR both < 0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, pGRACEvsACTION = 0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); pGRACEvsACTION = 0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models. CONCLUSIONS: In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model.

Biological Inoculant of Salt-Tolerant Bacteria for Plant Growth Stimulation under Different Saline Soil Conditions.

Using salt-tolerant bacteria to protect plants from salt stress is a promising microbiological treatment strategy for saline-alkali soil improvement. Here, we conducted research on the growthpromoting effect of Brevibacterium frigoritolerans on wheat under salt stress, which has rarely been addressed before. The synergistic effect of B. frigoritolerans combined with representative salttolerant bacteria Bacillus velezensis and Bacillus thuringiensis to promote the development of wheat under salt stress was also further studied. Our approach involved two steps: investigation of the plant growth-promoting traits of each strain at six salt stress levels (0, 2, 4, 6, 8, and 10%); examination of the effects of the strains (single or in combination) inoculated on wheat in different salt stress conditions (0, 50, 100, 200, 300, and 400 mM). The experiment of plant growth-promoting traits indicated that among three strains, B. frigoritolerans had the most potential for promoting wheat parameters. In single-strain inoculation, B. frigoritolerans showed the best performance of plant growth promotion. Moreover, a pot experiment proved that the plant growth-promoting potential of co-inoculation with three strains on wheat is better than single-strain inoculation under salt stress condition. Up to now, this is the first report suggesting that B. frigoritolerans has the potential to promote wheat growth under salt stress, especially combined with B. velezensis and B. thuringiensis.

Uninterrupted anticoagulation during catheter ablation for atrial fibrillation: no difference in major bleeding and stroke between direct oral anticoagulants and vitamin K antagonists in an updated meta-analysis of randomised controlled trials.

BACKGROUND: Periprocedural uninterrupted anticoagulation for catheter ablation of atrial fibrillation (AF) became standard after positive results of vitamin K antagonist (VKA) trials. Previous studies of uninterrupted direct oral anticoagulants (DOACs) vs. VKA have given controversial results. We thus aimed to elucidate the risk/benefit ratio of uninterrupted DOAC vs. VKA during catheter ablation of AF in an updated meta-analysis of randomised controlled trials (RCTs). METHODS: Online databases were searched for RCTs comparing uninterrupted DOAC to VKA in patients undergoing catheter ablation of AF. Data from retrieved studies were analysed in a comprehensive meta-analysis. Primary safety outcome was major bleeding; primary efficacy outcome was stroke or transient ischaemic attack (TIA). Secondary outcomes included a composite of major bleeding and stroke or TIA, minor bleeding, acute cerebral lesions on magnetic resonance imaging (MRI), and mortality. RESULTS: Six eligible RCTs comprising 2,369 patients were included. There were no significant differences in DOAC vs. VKA concerning the rates of major bleeding (2.2% vs. 3.8%; odds ratio (OR) 0.69, 95% confidence interval (CI) 0.30-1.56; p = .37) and stroke or TIA (0.2% vs. 0.2%; OR 0.97, CI 0.20-4.72; p = .97). Pooled meta-analysis of secondary outcomes revealed no significant differences (OR 0.73, p = .49 for composite of major bleeding and stroke or TIA; OR 1.08, p = .52 for minor bleeding; OR 1.12, p = .59 for acute cerebral lesions on MRI; and OR 0.60, p = .64 for all-cause mortality). CONCLUSION: Our meta-analysis suggests that uninterrupted DOAC is not superior to VKA in patients undergoing catheter ablation of AF with comparable rates of major bleeding and stroke.

Cancer-testis antigen lactate dehydrogenase C4 in hepatocellular carcinoma: a promising biomarker for early diagnosis, efficacy evaluation and prognosis prediction.

Expressions and clinical implications of cancer-testis antigen (CTA) lactate dehydrogenase (LDH)-C4 in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, expressions of LDHC mRNA in the serum and serum-derived exosomes of early-stage HCC patients were determined using qRT-PCR, and the expression of LDH-C4 protein in HCC tissues was detected using high-throughput tissue microarray analysis. It was found that positive rates of LDHC mRNA expressions in the serum and serum exosomes of HCC patients were 68% and 60%, respectively. The AUCs of serum and exosomal LDHC in differentiating HCC patients from healthy controls were 0.8382 and 0.9451, respectively. The serum and exosomal LDHC levels in HCC patients in the treatment group were higher than the levels in the preliminary diagnosis group, but lower than those in the recurrence group. Survival analysis showed that the expression of LDH-C4 was negatively correlated with the prognosis of HCC. The Cox regression analysis showed that an LDH-C4 level was an independent risk factor for the prognosis of HCC patients. Therefore, serum and exosomal LDHC can be used as a biomarker for early diagnosis, efficacy evaluation and recurrence prediction of HCC. Moreover, LDH-C4 can be used as an important reference indicator for monitoring the prognosis of HCC.

Virtual reality-assisted conscious sedation during transcatheter aortic valve implantation: a randomised pilot study.

AIMS: Virtual reality (VR) has been used successfully in different clinical settings to treat anxiety. This prospective, randomised pilot study aimed to investigate the feasibility and safety of VR in patients undergoing conscious sedation during transfemoral transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Thirty-two patients were included and randomised to VR intervention (n=16) or control (n=16). In the intervention group, patient-selected relaxing 3D videos were projected during the TAVI procedure; pain and anxiety before and after TAVI were measured using visual analogue scales (VAS; 0-10). The median age was 83 years (IQR 78.25-87). Patients' baseline characteristics did not differ significantly between the groups. During TAVI under conscious sedation, the median duration of VR intervention was 30.5 minutes (IQR 23.5-46); 81.3% of the patients watched the videos until device implantation, 37.5% during the whole procedure. The VR intervention group reported significantly less anxiety after the procedure (VAS 2 [IQR 0-3.75] vs 5 [IQR 2-8], p=0.04) than patients randomised to control. In the intervention group, 93.8% would use VR during TAVI again. Nausea and vomiting did not occur more frequently compared to control. CONCLUSIONS: VR interventions during TAVI to assist conscious sedation are safe and feasible, even in very old and frail patients. In this small cohort, there was a significant reduction in periprocedural anxiety.

Kidney function stratified outcomes of percutaneous left atrial appendage occlusion in patients with atrial fibrillation and high bleeding risk.

Background: Patients with chronic kidney disease (CKD) and atrial fibrillation have increased risks for stroke and bleeding under oral anticoagulation (OAC). We investigated an alternative therapy of percutaneous left atrial appendage occlusion (LAAO) in CKD patients in this study.Methods: Consecutive patients undergoing LAAO were included in a retrospective analysis and stratified for kidney function into CKD/Non-CKD groups (cutoff eGFR 60 ml/min). Procedural characteristics, in-hospital and follow-up events were analysed and compared between groups.Results: LAAO was performed in 146 patients (81 CKD; 65 Non-CKD), mean follow-up was 391 days. Groups differed in eGFR (40.1 (CKD) vs. 75.1 (Non-CKD) ml/min) and CHA2DS2VASc scores (4.65 ± 1.3 (CKD) vs. 4.06 ± 1.4 (Non-CKD)). Procedural success was 98.6%, contrast-induced acute kidney injury was significantly more frequent in CKD patients (11.1% vs. 0%; p = .004). Follow-up mortality was higher in CKD (10.5/100 PY vs. 4.2/100 PY; p = .156). Follow-up stroke rates were 2.3/100 (CKD) patient-years (PY) and 1.4/100 PY (Non-CKD) (p = 1.000), corresponding to a relative risk reduction (RRR) of 60% (all), 68% (CKD) and 71% (Non-CKD) compared to expected stroke rates. Follow-up major bleeding rates were 3.5/100 PY (CKD) and 4.2/100 PY (Non-CKD), corresponding to RRR of 57% (all), 61% (CKD) and 53% (Non-CKD) compared to OAC.Conclusions: Left atrial appendage occlusion shows comparable efficacy for stroke and bleeding prevention in CKD and Non-CKD patients. CKD patients experience more adverse events during follow-up and a significantly increased risk for periprocedural contrast-induced acute kidney injury.

Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer.

BACKGROUND: Lactate dehydrogenase C4 (LDH-C4) as a cancer/testis antigen (CTA) is abnormally expressed in some malignant tumors. However, the expression and clinical significance of LDH-C4 in breast cancer (BC) has not been characterized. METHODS: We determined LDHC mRNA expression in serum and serum-derived exosomes of BC patients by quantitative RT-PCR. We also evaluated the protein expression of LDH-C4 in BC tissues using high-throughput tissue microarray analysis and immunohistochemistry. RESULTS: Our results showed high mRNA expression level of LDHC in serum and serum-derived exosomes of BC patients. The LDHC level in serum and exosomes could distinguish BC cases from healthy individuals based on their AUCs of 0.9587 and 0.9464, respectively. Besides, the LDHC level in exosomes of BC patients associated with tumor size, and positively correlated with HER2 and Ki-67 expressions (all with P < 0.05). Serum and exosomal level of LDHC negatively correlated with medical treatment and positively with the recurrence of BC. Survival analysis showed that LDH-C4 expression negatively correlated with BC prognosis. CONCLUSION: Serum and exosomal LDHC may be an effective indicator for the diagnosis, efficacy evaluation, and monitoring the recurrence of BC. LDH-C4 may act as a biomarker that predicts BC prognosis.

Validation of National Cardiovascular Data Registry risk models for mortality, bleeding and acute kidney injury in interventional cardiology at a German Heart Center.

BACKGROUND AND PURPOSE: The National Cardiovascular Data Registry (NCDR) risk scores for mortality, bleeding and acute kidney injury (AKI) are accurate outcome predictors of coronary catheterization procedures in North American populations. However, their application in German clinical practice remained elusive and we thus aimed to verify their use. METHODS: NCDR scores for mortality, bleeding and AKI and corresponding clinical outcomes were retrospectively assessed in patients undergoing catheterization for ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or for elective coronary procedures at a German Heart Center from 2014 to 2017. Risk model performance was assessed using receiver-operating-characteristic curves (discrimination) and graphical analysis/logistic regression (calibration). RESULTS: A total of 1637 patients were included, procedures were performed for STEMI (565 patients, 34.5%), NSTEMI (572 patients, 34.9%) and elective purposes (500 patients, 30.5%); 6% (13% of STEMI and 5% of NSTEMI patients) presented in cardiogenic shock and 3% with resuscitated cardiac arrest. Radial access was used in 38% of procedures and cross-over was necessary in 5%; PCI was performed in 60% of procedures. In-hospital mortality was 6.3% (STEMI 14.5%; NSTEMI 3.7%; elective 0%) and major bleedings occurred in 5.6% (STEMI 10.6%; NSTEMI 5.4%; elective 0.2%); AKI was detected in 18.1% of patients (STEMI 23.7%; NSTEMI 27.3%; elective 1.4%), amounting to KDIGO stage I/II/III in 11.5%/3.5%/3.2%. NCDR risk models discriminated very well for mortality [AUC 0.93 with 95% confidence interval (CI) 0.91-0.95] and well for major bleeding (AUC 0.82, CI 0.78-0.86) and any AKI (AUC 0.83, CI 0.81-0.86). Discrimination in the subgroup of patients with PCI was comparable (mortality: AUC 0.90; major bleeding: AUC 0.78; any AKI: AUC 0.79). However, calibration showed considerable underestimation of mortality and AKI in high-risk patients, while major bleeding was consistently overestimated (Hosmer-Lemeshow p < 0.02 for all outcomes). CONCLUSIONS: The NCDR risk models showed excellent performance in discriminating high-risk from low-risk patients in contemporary German interventional cardiology. Model calibration for adverse event probability prediction, however, is limited and demands recalibration, especially in high-risk patients.

Identification of adriamycin resistance genes in breast cancer based on microarray data analysis.

BACKGROUND: Breast cancer is a common malignant tumor with increasing incidence worldwide. This study aimed to investigate the molecular mechanisms of the adriamycin (ADR) resistance in breast cancer. METHODS: The GSE76540 dataset downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database was adopted for analysis. Differentially expressed genes (DEGs) in chemo-sensitive cases and chemo-resistant cases were identified using the GEO2R online tool respectively. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were carried out by using the DAVID online tool. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized with Cytoscape software. The impact of key tumor genes on the survival and prognosis were described. RESULTS: A total of 1,481 DEGs were excavated, including 549 up-regulated genes and 932 down-regulated genes. According to the GO analysis, the DEGs were significantly enriched in: extracellular matrix organization, positive regulation of transcription from RNA polymerase II promoter, lung development, positive regulation of gene expression, axon guidance and so on. The results of KEGG pathway enrichment analysis showed that the most enriched DEGs can be detected in: pathways in cancer, PI3K/AKT signaling pathway, focal adhesion, Ras signaling pathway and so on. In the PPI network analysis, hub genes of CDH1, ESR1, SOX2, AR, GATA3, FOXA1, KRT19, CLDN7, AGR2, ESRP1, RAB25, CLDN4, IGF1R, CLDN3 and IRS1 were detected. Finally, there is a correlation filter out these hub genes in resistance of ADR. CONCLUSIONS: Hub genes associated with ADR resistance were identified using bioinformatic techniques. The results of this study may contribute to the development of targeted therapy for breast cancer.

Routine Glycoprotein IIb/IIIa Inhibitor Therapy in ST-Segment Elevation Myocardial Infarction: A Meta-analysis.

BACKGROUND: Guidelines recommend adjunct glycoprotein IIb/IIIa inhibitors (GPIs) only in selected patients with acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate routine GPI use in STEMI treated with primary percutaneous coronary intervention. METHODS: Online databases were searched for randomized controlled trials of routine GPI vs control therapy in STEMI. Data from retrieved studies were abstracted and evaluated in a comprehensive meta-analysis. Twenty-one randomized controlled trials with 8585 patients were included: 10 trials randomized tirofiban, 9 abciximab, 1 trial eptifibatide, and 1 trial used abciximab+tirofiban; only 1 trial used dual antiplatelet therapy with prasugrel/ticagrelor. RESULTS: Routine GPI use was associated with a significant reduction in all-cause mortality at 30 days (2.4% [GPI] vs 3.2%; risk ratio [RR], 0.72; P = 0.01) and 6 months (3.7% vs 4.8%; RR, 0.76; P = 0.02), and a reduction in recurrent myocardial infarction (1.1% vs 2.1%; RR, 0.55; P = 0.0006), repeat revascularization (2.5% vs 4.1%; RR, 0.63; P = 0.0001), thrombolysis in myocardial infarction flow <3 after percutaneous coronary intervention (5.4% vs 8.2%; RR, 0.61; P < 0.0001), and ischemic stroke (RR, 0.42; P = 0.04). Major (4.7% vs 3.4%; RR, 1.35; P = 0.005) and minor bleedings (7.2% vs 5.1%; RR, 1.39; P = 0.006) but not intracranial bleedings (0.1% vs 0%; RR, 2.7; P = 0.37) were significantly increased under routine GPI. CONCLUSIONS: Routine GPI administration in STEMI resulted in a reduction in mortality, driven by reductions in recurrent ischemic events-however predominantly in pre-prasugrel/ticagrelor trials. Trials with contemporary STEMI management are needed to confirm these findings.

Endovascular Thrombectomy as a Means to Improve Survival in Acute Ischemic Stroke: A Meta-analysis.

Importance: Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. Objective: To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perform a meta-analysis. Data Sources: All randomized clinical trials cited for recommendations on EVT vs medical therapy in the latest 2018 American Stroke Association/American Heart Association guidelines. Study Selection: Ten American Stroke Association/American Heart Association guideline-relevant randomized clinical trials of EVT vs medical therapy were selected for inclusion. Two EVT trials were excluded owing to infrequent use of EVT. Data Extraction and Synthesis: Data were abstracted by 2 independent investigators and double-checked by 4 others. Singular study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% CIs. Main Outcomes and Measures: Risk of 90-day mortality and 90-day intracranial hemorrhage was analyzed; sensitivity analyses were performed in early-window EVT trials (which included patients from the onset of symptoms onward) vs late-window EVT trials (which included patients from 6 hours after onset of symptoms onward). Results: In 10 trials with 2313 patients, EVT significantly reduced the risk for 90-day mortality by 3.7% compared with medical therapy (15.0% vs 18.7%; RR, 0.81; 95% CI, 0.68-0.98; P = .03). Trends were similar in early-window (RR, 0.83; 95% CI, 0.67-1.01; P = .06) and late-window trials only (RR, 0.76; 95% CI, 0.41-1.40; P = .38). There was no difference in the risk for intracranial hemorrhage in EVT vs medical therapy (4.2% vs 4.0%; RR, 1.11; 95% CI, 0.71-1.72; P = .65). Limitations of the studies include trial protocol heterogeneity and bias originating from prematurely terminated trials. Conclusions and Relevance: This meta-analysis of all evidence on EVT cited in the 2018 American Stroke Association/American Heart Association guidelines shows significant benefits for survival during the first 90 days after acute ischemic stroke compared with medical therapy alone.