...in previous small clinical series analyzing the effect of therapeutic hypothermia (TH) in patients who undergo PPCI, it was observed that there was an increased rate of stent thrombosis (ST) in ...TH- compared with non-TH-treated patients (2). In the present observational study, even under the prelude of greater hemodynamic support and a higher frequency of hemorrhagic complications in the PPCI-TH-treated patients, the incidence of ST was almost identical to that of patients not treated with TH. ...under the need of further prospective trials, we believe that adequate antithrombotic management could be achieved in this population with both the progressive introduction of third-generation P2Y12 inhibitors and consideration that the route (intravenous aspirin and crushed nasogastric P2Y12) (5) and time (before PPCI) of administration may influence the final result.
Summary Background Adequate prognostic markers to predict outcome of patients with lung cancer are still needed. The aim of this study was to assess whether choline kinase alpha (ChoKα) gene ...expression could identify patients with different prognoses. ChoKα is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer. Methods 60 patients with non-small-cell lung cancer (NSCLC) who had undergone surgical resection in a single centre were enrolled into the study as the training group. We used real-time reverse-transcriptase PCR (RT-PCR) to measure ChoKα gene expression and analyse the association between ChoKα expression and survival in evaluable patients. Additionally, a second group of 120 patients with NSCLC from a different hospital were enrolled into the study as the validation group. We did an overall analysis of all 167 patients who had available tissue to confirm the cut-off point for future studies. The primary endpoints were lung-cancer-specific survival and relapse-free survival. Findings Seven of the 60 patients in the training group were not evaluable due to insufficient tissue. In the 53 evaluable patients, the cut-off for those with ChoKα overexpression was defined by receiver operator under the curve (ROC) methodology. 4-year lung-cancer-specific survival was 54·43% (95% CI 28·24–80·61) for 25 patients with ChoKα expression above the ROC-defined cut-off compared with 88·27% (75·79–100) for 28 patients with concentrations of the enzyme below this cut-off (hazard ratio HR 3·14 0·83–11·88, p=0·07). In the validation group, six of the 120 enrolled patients were not evaluable due to insufficient tissue. For the other 114 patients, 4-year lung-cancer-specific survival was 46·66% (32·67–59·65) for those with ChoKα expression above the ROC-defined cut-off compared with 67·01% (50·92–81·11) for patients with concentrations of ChoKα below the cut-off (HR 1·87 1·01–3·46, p=0·04). A global analysis of all 167 patients further confirmed the association between ChoKα overexpression and worse clinical outcome of patients with NSCLC: 4-year lung-cancer-specific survival for ChoKα expression above the ROC-defined cut-off was 49·00% (36·61–60·38) compared with 70·52% (59·80–76·75) for those with concentrations of ChoKα below the cut-off (HR 1·98 1·14–3·45, p=0·01). The overall analysis confirmed the cut-off for ChoKα expression should be 1·91-times higher than concentrations noted in healthy tissues when ChoKα is used as an independent predictive factor of relapse-free and lung-cancer-specific survival in patients with early-stage NSCLC. Interpretation ChoKα expression is a new prognostic factor that could be used to help identify patients with early-stage NSCLC who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment. New treatments that inhibit ChoKα expression or activity in patients with lung cancer should be studied further.
Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression ...of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance.
This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival.
Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis.
Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.
Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.
The purpose of this study was ...to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts.
From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP Myocardial Ischaemia National Audit Project 2019 and BCIS British Cardiovascular Intervention Society 2018 to 2019).
In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 95% confidence interval: 2.04 to 5.42). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).
In this multicenter international registry, COVID-19–positive ACS patients presented later and had increased in-hospital mortality compared with a pre–COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.
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