Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and ...chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.
Background
Prolonged length of stay (LOS) and post‐acute care after percutaneous coronary intervention (PCI) is common and costly. Risk models for predicting prolonged LOS and post‐acute care have ...limited accuracy. Our goal was to develop and validate models using artificial neural networks (ANN) to predict prolonged LOS > 7days and need for post‐acute care after PCI.
Methods
We defined prolonged LOS as ≥7 days and post‐acute care as patients discharged to: extended care, transitional care unit, rehabilitation, other acute care hospital, nursing home or hospice care. Data from 22 675 patients who presented with ACS and underwent PCI was shuffled and split into a derivation set (75% of dataset) and a validation dataset (25% of dataset). Calibration plots were used to examine the overall predictive performance of the MLP by plotting observed and expected risk deciles and fitting a lowess smoother to the data. Classification accuracy was assessed by a receiver‐operating characteristic (ROC) and area under the ROC curve (AUC).
Results
Our MLP‐based model predicted prolonged LOS with an accuracy of 90.87% and 88.36% in training and test sets, respectively. The post‐acute care model had an accuracy of 90.22% and 86.31% in training and test sets, respectively. This accuracy was achieved with quick convergence. Predicted probabilities from the MLP models showed good (prolonged LOS) to excellent calibration (post‐acute care).
Conclusions
Our ANN‐based models accurately predicted LOS and need for post‐acute care. Larger studies for replicability and longitudinal studies for evidence of impact are needed to establish these models in current PCI practice.
Abstract
Objectives
To describe the prevalence and nature of bacterial co-infections in COVID-19 patients within 48 hours of hospital admission and assess the appropriateness of empirical antibiotic ...treatment they received.
Methods
In this retrospective observational cohort study, we included all adult non-pregnant patients who were admitted to two acute hospitals in North West London in March and April 2020 and confirmed to have COVID-19 infection within 2 days of admission. Results of microbiological specimens taken within 48 hours of admission were reviewed and their clinical significance was assessed. Empirical antibiotic treatment of representative patients was reviewed. Patient age, gender, co-morbidities, inflammatory markers at admission, admission to ICU and 30 day all-cause in-hospital mortality were collected and compared between patients with and without bacterial co-infections.
Results
Of the 1396 COVID-19 patients included, 37 patients (2.7%) had clinically important bacterial co-infection within 48 hours of admission. The majority of patients (36/37 in those with co-infection and 98/100 in selected patients without co-infection) received empirical antibiotic treatment. There was no significant difference in age, gender, pre-existing illnesses, ICU admission or 30 day all-cause mortality in those with and without bacterial co-infection. However, white cell count, neutrophil count and CRP on admission were significantly higher in patients with bacterial co-infections.
Conclusions
We found that bacterial co-infection was infrequent in hospitalized COVID-19 patients within 48 hours of admission. These results suggest that empirical antimicrobial treatment may not be necessary in all patients presenting with COVID-19 infection, although the decision could be guided by high inflammatory markers.
Acute myocardial infarction (AMI) complicated by cardiogenic shock is associated with substantial morbidity and mortality. Although intravascular microaxial left ventricular assist devices (LVADs) ...provide greater hemodynamic support as compared with intra-aortic balloon pumps (IABPs), little is known about clinical outcomes associated with intravascular microaxial LVAD use in clinical practice.
To examine outcomes among patients undergoing percutaneous coronary intervention (PCI) for AMI complicated by cardiogenic shock treated with mechanical circulatory support (MCS) devices.
A propensity-matched registry-based retrospective cohort study of patients with AMI complicated by cardiogenic shock undergoing PCI between October 1, 2015, and December 31, 2017, who were included in data from hospitals participating in the CathPCI and the Chest Pain-MI registries, both part of the American College of Cardiology's National Cardiovascular Data Registry. Patients receiving an intravascular microaxial LVAD were matched with those receiving IABP on demographics, clinical history, presentation, infarct location, coronary anatomy, and clinical laboratory data, with final follow-up through December 31, 2017.
Hemodynamic support, categorized as intravascular microaxial LVAD use only, IABP only, other (such as use of a percutaneous extracorporeal ventricular assist system, extracorporeal membrane oxygenation, or a combination of MCS device use), or medical therapy only.
The primary outcomes were in-hospital mortality and in-hospital major bleeding.
Among 28 304 patients undergoing PCI for AMI complicated by cardiogenic shock, the mean (SD) age was 65.0 (12.6) years, 67.0% were men, 81.3% had an ST-elevation myocardial infarction, and 43.3% had cardiac arrest. Over the study period among patients with AMI, an intravascular microaxial LVAD was used in 6.2% of patients, and IABP was used in 29.9%. Among 1680 propensity-matched pairs, there was a significantly higher risk of in-hospital death associated with use of an intravascular microaxial LVAD (45.0%) vs with an IABP (34.1% absolute risk difference, 10.9 percentage points {95% CI, 7.6-14.2}; P < .001) and also higher risk of in-hospital major bleeding (intravascular microaxial LVAD 31.3% vs IABP 16.0%; absolute risk difference, 15.4 percentage points 95% CI, 12.5-18.2; P < .001). These associations were consistent regardless of whether patients received a device before or after initiation of PCI.
Among patients undergoing PCI for AMI complicated by cardiogenic shock from 2015 to 2017, use of an intravascular microaxial LVAD compared with IABP was associated with higher adjusted risk of in-hospital death and major bleeding complications, although study interpretation is limited by the observational design. Further research may be needed to understand optimal device choice for these patients.
Objectives This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions. Background Acute kidney ...injury (AKI) is a serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention. Methods A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI. Results Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio OR: 2.60; 95% confidence interval CI: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p < 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained independent predictors of in-hospital mortality. Conclusions Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure.
Bleeding is the most common complication after percutaneous coronary intervention (PCI) and is associated with increased morbidity and health care costs. The incidence of bleeding-related mortality ...after PCI has not been described in a nationally representative population. Furthermore, the relationships among bleeding risk, bleeding site, and mortality are unclear.
To describe the association between bleeding events and in-hospital mortality after PCI and to estimate the adjusted population attributable risk (estimated as the proportion of mortality risk associated with bleeding events), risk difference, and number needed to harm (NNH) for bleeding-related in-hospital mortality after PCI.
Data from 3,386,688 procedures in the CathPCI Registry performed in the United States between 2004 and 2011 were analyzed. The population attributable risk was calculated after adjustment for baseline demographic, clinical, and procedural variables. To calculate the NNH for bleeding-related mortality, a propensity-matched analysis was performed.
In-hospital mortality.
There were 57,246 bleeding events (1.7%) and 22,165 in-hospital deaths (0.65%) in 3,386,688 PCI procedures. The adjusted population attributable risk for mortality related to major bleeding was 12.1% (95% CI, 11.4%-12.7%) in the entire CathPCI cohort. The propensity-matched population consisted of 56,078 procedures with a major bleeding event and 224 312 controls. In this matched cohort, major bleeding was associated with increased in-hospital mortality (5.26% vs 1.87%; risk difference, 3.39% 95% CI, 3.20%-3.59%; NNH = 29 95% CI, 28-31; P < .001). The association between major bleeding and in-hospital mortality was observed in all strata of preprocedural bleeding risk (low: 1.62% vs 0.17%; risk difference, 1.45% 95% CI, 1.13%-1.77%, NNH = 69 95% CI, 57-88, P < .001; intermediate: 3.27% vs 0.71%; risk difference, 2.56% 95% CI, 2.33%-2.79%, NNH = 39 95% CI, 36-43, P < .001; and high: 8.16% vs 3.45%; risk difference, 4.71% 95% CI, 4.35%-5.07%, NNH = 21 95% CI, 20-23, P < .001). Although both access-site and non-access-site bleeding were associated with increased in-hospital mortality (2.73% vs 1.87%; risk difference, 0.86% 95% CI, 0.66%-1.05%, NNH = 117 95% CI, 95-151, P < .001; and 8.25% vs 1.87%; risk difference, 6.39% 95% CI, 6.04%-6.73%, NNH = 16 95% CI, 15-17, P < .001, respectively), the NNH was lower for nonaccess bleeding.
In a large registry of patients undergoing PCI, postprocedural bleeding events were associated with increased risk of in-hospital mortality, with an estimated 12.1% of deaths related to bleeding complications.
Both Legionella pneumophila and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause pneumonia. L. pneumophila is acquired from water sources, sometimes in healthcare settings. We ...report 2 fatal cases of L. pneumophila and SARS-CoV-2 co-infection in England. Clinicians should be aware of possible L. pneumophila infections among SARS-CoV-2 patients.
This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions.
Acute kidney injury (AKI) is a ...serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention.
A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI.
Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio OR: 2.60; 95% confidence interval CI: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p < 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained independent predictors of in-hospital mortality.
Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure.
Key Points
Acute myocardial infarction with cardiogenic shock is a costly condition associated with poor clinical outcomes.
This analysis used Medicare cost data for selected patients with acute ...myocardial infarction complicated by cardiogenic shock treated with the percutaneous left ventricular assist device (pVAD) or extracorporeal membrane oxygenation (ECMO) and found that the pVAD was associated with lower costs and better outcomes.
Patients treated with ECMO tend to have more severe shock than those treated with pVAD, and unmeasured confounders make any comparison challenging to interpret.
PDF
