Citations

PURPOSE Multiple large clinical trials have investigated adjuvant tyrosine kinase inhibitors (TKIs) to reduce the risk of cancer recurrence and progression to metastasis in high-risk renal cell carcinoma. We sought to maintain living and interactive evidence on this topic, until a high level of certainty is reached for key clinical outcomes such that further updates become unnecessary and unlikely to change clinical practice. METHODS We created a living interactive evidence synthesis platform to maintain a continuously updated meta-analysis on TKI monotherapy in adjuvant renal cell carcinoma. We implemented an automated search strategy with weekly updates to identify randomized phase 2 and 3 clinical trials. Study selection, appraisal, and data extraction were done in duplicate. Cumulative meta-analysis was performed using Analyzer Module in Living Interactive Evidence platform. For each outcome (overall survival [OS], disease-free survival [DFS], and all-cause and treatment-related adverse events), we assessed certainty of evidence using GRADE approach and conducted trial sequential analysis. RESULTS This final update includes five randomized trials including recently updated data from PROTECT trial. Meta-analysis shows that adjuvant TKI monotherapy offers no benefit in OS (hazard ratio, 1.01; 95% CI, 0.91 to 1.12, high certainty) or DFS (hazard ratio, 0.92; 95% CI, 0.86 to 1.00, high certainty) and significantly increases adverse event risk. Lack of benefit was consistent across subgroups including highest-risk patients (test for subgroup differences: P = .32). Optimal information size criteria were met, and there was high certainty of evidence for lack of DFS and OS benefit for adjuvant TKIs. CONCLUSION There is no guidance on when to stop maintaining a living review. In this example, we used trial sequential analysis and high certainty of evidence (future clinical trials unlikely to change current conclusions) as a benchmark to conclude a living review in view of convincing evidence.

Abstract Funding Acknowledgements Type of funding sources: None. Background The incidence of respiratory failure and the provision of invasive and non-invasive mechanical ventilation (MV) in patients admitted to cardiac intensive care units (CICU) are increasing. While institutional MV volumes are associated with reduced mortality in medical and surgical ICUs, this relationship has not been characterized in the CICU population. Purpose By describing the relationship between institutional MV volume and outcomes in the CICUs, we hope to shed light on minimum volume benchmarks for providing MV. Methods National Canadian population-based data from 2005 to 2015 was used to identify patients admitted to CICUs requiring MV. CICUs were categorized into low (≤100), intermediate (101-300), and high (>300) volume centers based on spline knots identified in the association between annual MV volume and mortality (Figure). Outcomes of interests included all-cause in-hospital mortality, the proportion of patients requiring prolonged MV (>96 hours) and CICU length of stay (LOS). Results Among the 47,173 CICU admissions that required MV, 89.5% (42,200) required invasive mechanical ventilation. The median annual CICU MV volume was 127 (range 1-490). In-hospital mortality was lower in intermediate (29.2%, adjusted odds ratio [aOR] 0.84, 95% CI 0.72-0.97, p = 0.019) and high-volume (18.2%; aOR 0.82, 95% CI 0.66-1.02, p = 0.076) centers, compared to low volume centers (35.9%). The proportion of patients requiring prolonged MV was higher in low-volume (29.2%) compared to high-volume (14.8%, OR 0.70, 95% 0.55-0.89, p = 0.003) centers. Point estimates for mortality and prolonged MV were lower in PCI-capable and academic centers (Table). Significantly (p <0.01) lower CICU LOS was observed only in the subgroup of PCI-capable intermediate- and high-volume hospitals. Conclusions In a national dataset, we observed that higher CICU MV hospital volumes were associated with lower in-hospital mortality, CICU LOS, and fewer episodes of prolonged MV. Pending further validation, these data suggest minimum MV volume benchmarks for CICUs caring for patients with respiratory failure. Further research is warranted to explore these associations in more detail. Unadjusted volume-outcome relationshipsOutcomesGroup 1 Annual Volume ≤100Group 2 Annual Volume 101-300Group 3 Annual Volume >300Totalp-valueTotal N1770224351512047173In-hospital mortality6357 (35.0%)7122 (29.2%)933 (18.2%)14412 (30.6%)p < 0.0001Median CICU LOS(hours)85796679p < 0.0001Episodes of prolonged MV5161 (29.2%)5608 (23.0%)758 (14.8%)11527 (24.4%)p < 0.0001Abbreviations OR (odds ratio), RD (risk difference), CI (confidence interval), PCI (percutaneous coronary intervention), LOS (length of stay)Abstract Figure. Annual CICU MV volume and mortality

AbstractChronic wound infections caused by biofilm‐forming microorganisms represent a major burden to healthcare systems. Treatment of chronic wound infections using conventional antibiotics is often ineffective due to the presence of bacteria with acquired antibiotic resistance and biofilm‐associated antibiotic tolerance. We previously developed an electrochemical scaffold that generates hydrogen peroxide (H2O2) at low concentrations in the vicinity of biofilms. The goal of this study was to transition our electrochemical scaffold into an H2O2‐generating electrochemical bandage (e‐bandage) that can be used in vivo. The developed e‐bandage uses a xanthan gum‐based hydrogel to maintain electrolytic conductivity between e‐bandage electrodes and biofilms. The e‐bandage is controlled using a lightweight, battery‐powered wearable potentiostat suitable for use in animal experiments. We show that e‐bandage treatment reduced colony‐forming units of Acinetobacter buamannii biofilms (treatment vs. control) in 12 h (7.32 ± 1.70 vs. 9.73 ± 0.09 log10[CFU/cm2]) and 24 h (4.10 ± 12.64 vs. 9.78 ± 0.08 log10[CFU/cm2]) treatments, with 48 h treatment reducing viable cells below the limit of detection of quantitative and broth cultures. The developed H2O2‐generating e‐bandage was effective against in vitro A. baumannii biofilms and should be further evaluated and developed as a potential alternative to topical antibiotic treatment of wound infections.

Objective This manuscript aims to explore the impact of race/ethnicity and socioeconomic status on in-hospital complication rates after left atrial appendage closure (LAAC). Methods The US National Inpatient Sample was used to identify hospitalisations for LAAC between 1 October 2015 to 31 December 2018. These patients were stratified by race/ethnicity and quartiles of median neighbourhood income. The primary outcome was the occurrence of in-hospital major adverse events, defined as a composite of postprocedural bleeding, cardiac and vascular complications, acute kidney injury and ischaemic stroke. Results Of 6478 unweighted hospitalisations for LAAC, 58% were male and patients of black, Hispanic and ‘other’ race/ethnicity each comprised approximately 5% of the cohort. Adjusted by the older Americans population, the estimated number of LAAC procedures was 69.2/100 000 for white individuals, as compared with 29.5/100 000 for blacks, 47.2/100 000 for Hispanics and 40.7/100 000 for individuals of ‘other’ race/ethnicity. Black patients were ~5 years younger but had a higher comorbidity burden. The primary outcome occurred in 5% of patients and differed significantly between racial/ethnic groups (p<0.001) but not across neighbourhood income quartiles (p=0.88). After multilevel modelling, the overall rate of in-hospital major adverse events was higher in black patients as compared with whites (OR: 1.60, 95% CI 1.22 to 2.10, p<0.001); however, the incidence of acute kidney injury was higher in Hispanics (OR: 2.19, 95% CI 1.52 to 3.17, p<0.001). No significant differences were found in adjusted overall in-hospital complication rates between income quartiles. Conclusion In this study assessing racial/ethnic disparities in patients undergoing LAAC, minorities are under-represented, specifically patients of black race/ethnicity. Compared with whites, black patients had higher comorbidity burden and higher rates of in-hospital complications. Lower socioeconomic status was not associated with complication rates.

Abstract On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.

AbstractDespite the widespread adoption of primary percutaneous intervention and modern antithrombotic therapy, ST-segment elevation myocardial infarction (STEMI) remains the leading cause of death in the United States and remains one of the most important causes of morbidity and mortality worldwide. Certain high-risk patients present a challenge for diagnosis and treatment. The widespread adoption of primary percutaneous intervention in addition to modern antithrombotic therapy has resulted in substantial improvement in the short- and long-term prognosis following STEMI. In this review, we aim to provide a brief analysis of the state-of-the-art treatment for patients presenting with STEMI, focusing on cardiogenic shock, current treatment and controversies, cardiac arrest, and diagnosis and treatment of mechanical complications, as well as multivessel and left main-related STEMI.

Abstract Aims Primary percutaneous coronary intervention (pPCI) is the gold standard, guideline-recommended revascularization strategy in patients presenting with ST-elevation myocardial infarction (STEMI). However, there are limited data on its use and effectiveness among patients with active cancer presenting with STEMI. Methods and results All STEMI hospitalizations between 2004 and 2015 from the National Inpatient Sample were retrospectively analysed, stratified by cancer type. Propensity score matching was performed to estimate the average treatment effect of pPCI in each cancer on in-hospital adverse events, including major adverse cardiovascular and cerebrovascular events (MACCE) and its individual components, and compare treatment effect between cancer and non-cancer patients. Out of 1 870 815 patients with STEMI, 38 932 (2.1%) had a current cancer diagnosis [haematological: 11 251 (28.9% of all cancers); breast: 4675 (12.0%); lung: 9538 (24.5%); colon: 3749 (9.6%); prostate: 9719 (25.0%)]. Patients with cancer received pPCI less commonly than those without cancer (from 54.2% for lung cancer to 70.6% for haematological vs. 82.3% in no cancer). Performance of pPCI was strongly associated with lower adjusted probabilities of MACCE and all-cause mortality in the cancer groups compared with the no cancer group. There was no significant difference in estimated average pPCI treatment effect between the cancer groups and non-cancer group. Conclusion Primary percutaneous coronary intervention is underutilized in STEMI patients with current cancer despite its significantly lower associated rates of in-hospital all-cause mortality and MACCE that is comparable to patients without cancer. Further work is required to assess the long-term benefit and safety of pPCI in this high-risk group.

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.