There is conflicting evidence for adverse outcomes after coronary artery bypass surgery (CABG) with prior percutaneous intervention (PCI). A literature search was performed from 1998 to 2017 and ...articles with primary or secondary outcomes of survival, major adverse cardiovascular events (MACE), and myocardial infarction in CABG patients with prior PCI were included. Forest plots were generated from odds ratios for survival, MACE, and myocardial infarction for unmatched and propensity-matched data. Heterogeneity between studies was assessed for all outcomes using I2. Funnel plots were generated for early survival, survival at 5 years, survival at >5 years, and MACE. Thirty-one studies were included over 18 years with 194,544 patients without PCI prior to CABG and 23,519 patients (12.09%) with prior PCI. Prior PCI did not adversely affect survival among the included studies (inverse rate ratio: 1.12, 95% confidence interval: 0.98–1.27, P = 0.110. MACE was significantly worse for those with prior PCI (odds ratio: 1.26, confidence interval: 1.02–1.55, P = 0.03). The relative risk of mortality associated with prior PCI has decreased significantly over the last 2 decades. Studies with higher percentage of prior PCI patients had higher relative mortalities. There was significant heterogeneity between studies for the treatment effects. PCI prior to CABG in recent times does not adversely affect survival despite adverse early and late MACE rates. However, high institutional rates of prior PCI may be associated with increasing mortality after CABG.
Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of ...synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability.
Viruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms.
Influenza pneumonia remains a common and debilitating viral infection despite vaccination programs and antiviral agents developed for prophylaxis and treatment. The neuraminidase inhibitor ...oseltamivir is frequently prescribed for established influenza A virus infections, but the emergence of neuraminidase inhibitor resistant viruses, a brief therapeutic window and competing diagnoses complicate its use. PUL-042 is a clinical stage, aerosol drug comprised of synthetic ligands for Toll-like receptor (TLR) 2/6 and TLR 9. This host-targeted, innate immune stimulant broadly protects against bacterial, fungal and viral pneumonias, including those caused by influenza, when given prophylactically to animals. This study evaluated the therapeutic antiviral effects of PUL-042 against established influenza A pneumonia, when given alone or in combination with oseltamivir. Mice were treated with PUL-042 aerosol, oseltamivir or both at varying time points before or after challenge with influenza pneumonia. Treating established, otherwise lethal influenza A pneumonia (>1 LD100) with multiple inhaled doses of PUL-042 aerosol plus oral oseltamivir resulted in greater mouse survival than treatment with either drug alone. Single agent PUL-042 also protected mice against established infections following challenges with lower viral inocula (approximately 1 LD20). Aerosolized oseltamivir further enhanced survival when co-delivered with PUL-042 aerosol. The prophylactic and therapeutic benefits of PUL-042 were similar against multiple strains of influenza virus. In vitro influenza challenge of human HBEC3kt lung epithelial cells revealed PUL-042-induced protection against infection that was comparable to that observed in vivo. These studies offer new insights into means to protect susceptible populations against influenza A pneumonia.
Increasing complexity in cardiac operations has raised the discussion on trainee autonomy and the number of cases required to achieve competency. This study compares outcomes among cases done by ...trainees vs consultants for high risk patients. 696 (trainee=158 vs consultant=438) major high risk cardiac operations (Euroscore >10) were reviewed at a single center. Observations were propensity matched to consultant or trainee based on several baseline characteristics. Euroscore was: Trainee; 12.3 ± 1.6 versus Consultant; 12.8 ± 2.2, p=.036. Multivariable analysis did not identify trainee as a risk factor for worse in-hospital mortality (OR; 0.95, CI; 0.4-2.2, p=.914) or composite outcome of length of stay >30 days, deep sternal infection, new hemodialysis, new stroke or transient ischemic attack, in-hospital death or reoperation (OR; 0.64, CI; 0.39-1.03, p=.069). NYHA class, diabetes and emergency/salvage surgery were predictors of worse composite outcome. After propensity matching (130 pairs), there was no difference in reoperation rates (3.1% versus 4.6%, p=.727), inhospital death (5.4% versus 7.7%, p=.607) or composite outcome (20.8% versus 29.2%, p=.152). There was no statistical difference in cross clamp times (Trainee; 74.0 ± 32.7 min vs Consultant; 82.6 ± 51.1, p=.229) and bypass times (Trainee; 116.3 ± 52.8 min versus Consultant 135.3 ± 72.6 min, p=.055). The length of stay was similar (18.2 ± 13.2 days versus 19.9 ± 15.6 days, p=.302). It is possible for trainees to perform high risk cardiac surgery without compromising the quality of patient care.
Background
Outcomes for high surgical risk patients who declined transcatheter aortic valve implantation (TAVI) and then reconsidered for conventional aortic valve replacement (rSAVR) for severe ...calcific aortic stenosis are not well known.
Methods
This single-centre, case–control study (rSAVR vs Conservative group) retrospectively analysed patients for rSAVR (2009–2019). Multivariable logistic regression was used to identify independent predictors of composite of neurological sequelae/renal failure/deep sternal wound infection/re-exploration and death. Survival was compared using Kaplan–Meier curves and log-rank test. A Cox proportional hazards model was used to determine predictors of survival.
Results
TAVI was denied in 519/1095 patients, 114(10.4%) had rSAVR (cases) and 405 (37%) were managed conservatively (controls). Mean age for rSAVR was 80 years (IQR: 73.5–85 years). The commonest reason for declining TAVI was prohibitive high risk due to multiple comorbidities. Among rSAVR, hospital mortality was 2.2% and stroke was 4.4%. Median follow-up was conservative; 14.4 months versus rSAVR; 34.8 months. Five-year survival was conservative; 12.6% versus rSAVR; and 59.5% (overall conservative; 38.0% vs. rSAVR; 60.5%, p < 0.001). rSAVR was protective (hazard ratio HR: 0.37, 95% confidence interval CI: 0.26, 0.51, p < 0.001) and high comorbidities had high hazard (HR: 1.57, 95% CI: 1.19, 2.07, p = 0.001). rSAVR had fewer hospital readmission episodes (Conservative; 13.6/patient-year vs. rSAVR; 6.9/patient-year, p = 0.002).
Conclusions
rSAVR may be considered in high surgical risk elderly patients who have been declined TAVI in centres with low operative mortality. rSAVR may be superior to conservative management in carefully selected patients.
Background Adverse neurological sequelae are a major cause of morbidity and mortality after coronary artery bypass (CABG) surgery, due to manipulation of an atherosclerotic aorta. The purpose of this ...study is to measure the impact of intraoperative epi-aortic scanning in reducing neurologic sequelae after CABG, and the patient subgroups that are benefitted the most. Methods Patients that underwent first-time CABG from July 2010 to March 2014 (n=1,989) were retrospectively reviewed and stratified by history of intraoperative epi-aortic scan (n=350) or no scan (n=1,639). Baseline characteristics, rates of adverse neurological events, and overall survival were compared among groups in both matched and unmatched cohorts and tested using Student's t -test, chi2 test, or log-rank test, respectively. Multivariable analysis using logistic regression was performed to identify potential predictors for neurological sequelae. Cumulative summation plots (CUSUM) were constructed to display the number of preventable adverse neurological events per consecutive patient that underwent CABG. A p≤0.05 was considered statistically significant. Results The use of epi-aortic scan (OR: 0.29, 95% CI: 0.09–0.99, p=0.48) was an independent predictor of adverse events. Overall rates of stroke (0.29% vs 0.55%), postoperative confusional state (1.43% vs 3.42%), or both (1.71% vs 3.72%) were lower in those scanned. CUSUM scores were higher in scanned patients, especially in those with an age above 70 years or logistic Euroscore >2. Conclusions Intraoperative epi-aortic scan is an effective assessment tool for atherosclerotic burden in the ascending aorta and can guide surgical strategy to decrease adverse neurological outcomes, particularly in high risk and elderly patients.
Background
Transfemoral aortic valve replacement (TAVR) has been studied extensively in patients with improving safety and efficacy in high to intermediate‐risk patients with aortic stenosis. TAVR ...has been now approved for patients with low surgical risk.
Objective
The purpose of this study is to integrate the evidence from randomized controlled trials (RCT) and large registry data comparing TAVR to surgical aortic valve repair (SAVR).
Methods
Seven studies (three RCTs, one post hoc study of a RCT, and three registries) were included. Incidence rate ratios (IRR) of outcomes of interest (overall mortality, 30‐day mortality, cardiovascular death, stroke, pacemaker implantation PPMI, myocardial infarction, moderate‐severe paravalvular leak PVL, and re‐intervention) were compared using a random‐effects model.
Results
The pooled analysis included 24 819 patients (TAVR, 8227 and SAVR, 16 592). 2,952 (11.9%) patients were from RCTs and 21 867 (88.1%) were registry patients. Thirty‐day mortality was lower in TAVR (logIRR, −0.43; 95% CI. −0.61 to −0.25; P < .001), whereas the rate of moderate‐severe PVL (logIRR, 1.44; 95% CI, 0.58‐2.3; P < .001) and PPMI (logIRR, 1.13; 95% CI, 1.02‐1.24; P < .001) were higher. There were no significant differences in the rates of overall mortality, reintervention, cardiovascular death, myocardial infarction, or stroke between SAVR and TAVR.
Conclusions
Early mortality is higher in SAVR while rates of PVL and PPMI are substantially higher in TAVR. There is no significant advantage with TAVR for overall survival, cardiovascular death, stroke, MI, and re‐intervention rates.
Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal ...tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes.
Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections.
Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines.
Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.
Spinal fixation is a common surgical procedure. Frequently, fixation for spinal stabilization requires use of instrumentation such as pedicle screws and fixation plates. Aerodigestive and vascular ...perforations from such procedures are infrequent albeit known complications from these procedures.
This case details an uncommon situation in which a patient with anterior cervical spine fixation in the distant past was found to have a migratory pedicle screw. The patient had symptoms of neck pain and dysphagia. Radiographic studies were helpful in demonstrating the problem. While undergoing a physical examination, the patient was witnessed to expectorate the screw. Further work up with panendoscopy was undertaken and the patient managed conservatively.
The upper aerodigestive system rarely experiences perforation from spinal stabilization hardware. When it occurs, management should include a dedicated investigation of the involved portions of the digestive system to avoid further complication.
This case presents an rare occurrence of aerodigestive perforation of a spinal pedicle screw which was self-removed.
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