Mortality following mechanical thrombectomy for ischemic stroke in patients with COVID-19.

OBJECTIVES: Multiple prior studies have shown a relationship between COVID-19 and strokes; further, COVID-19 has been shown to influence both time-to-thrombectomy and overall thrombectomy rates. Using large-scale, recently released national data, we assessed the association between COVID-19 diagnosis and patient outcomes following mechanical thrombectomy. MATERIALS AND METHODS: Patients in this study were identified from the 2020 National Inpatient Sample. All patients with arterial strokes undergoing mechanical thrombectomy were identified using ICD-10 coding criteria. Patients were further stratified by COVID diagnosis (positive vs. negative). Other covariates, including patient/hospital demographics, disease severity, and comorbidities were collected. Multivariable analysis was used to determine the independent effect of COVID-19 on in-hospital mortality and unfavorable discharge. RESULTS: 5078 patients were identified in this study; 166 (3.3%) were COVID-19 positive. COVID-19 patients had a significantly higher mortality rate (30.1% vs. 12.4%, p < 0.001). When controlling for patient/hospital characteristics, APR-DRG disease severity, and Elixhauser Comorbidity Index, COVID-19 was an independent predictor of increased mortality (OR 1.13, p = 0.002). COVID-19 was not significantly related to discharge disposition (p = 0.480). Older age and increased APR-DRG disease severity were also correlated with increase morality. CONCLUSIONS: Overall, this study indicates that COVID-19 is a predictor of mortality among mechanical thrombectomy. This finding is likely multifactorial but may be related to multisystem inflammation, hypercoagulability, and re-occlusion seen in COVID-19 patients. Further research would be needed to clarify these relationships.

IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis.

After lung injury, damage-associated transient progenitors (DATPs) emerge, representing a transitional state between injured epithelial cells and newly regenerated alveoli. DATPs express profibrotic genes, suggesting that they might promote idiopathic pulmonary fibrosis (IPF). However, the molecular pathways that induce and/or maintain DATPs are incompletely understood. Here we show that the bifunctional kinase/RNase-IRE1α-a central mediator of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress is a critical promoter of DATP abundance and function. Administration of a nanomolar-potent, monoselective kinase inhibitor of IRE1α (KIRA8)-or conditional epithelial IRE1α gene knockout-both reduce DATP cell number and fibrosis in the bleomycin model, indicating that IRE1α cell-autonomously promotes transition into the DATP state. IRE1α enhances the profibrotic phenotype of DATPs since KIRA8 decreases expression of integrin αvß6, a key activator of transforming growth factor ß (TGF-ß) in pulmonary fibrosis, corresponding to decreased TGF-ß-induced gene expression in the epithelium and decreased collagen accumulation around DATPs. Furthermore, IRE1α regulates DNA damage response (DDR) signaling, previously shown to promote the DATP phenotype, as IRE1α loss-of-function decreases H2AX phosphorylation, Cdkn1a (p21) expression, and DDR-associated secretory gene expression. Finally, KIRA8 treatment increases the differentiation of Krt19CreERT2-lineage-traced DATPs into type 1 alveolar epithelial cells after bleomycin injury, indicating that relief from IRE1α signaling enables DATPs to exit the transitional state. Thus, IRE1α coordinates a network of stress pathways that conspire to entrap injured cells in the DATP state. Pharmacological blockade of IRE1α signaling helps resolve the DATP state, thereby ameliorating fibrosis and promoting salutary lung regeneration.

The effect of COVID-19 on treatment and outcomes following ischemic stroke: A national assessment.

INTRODUCTION: COVID-19 has had innumerable impacts on the healthcare system, both by worsening patient illness and impeding effective and efficient care. Further, COVID-19 has been tied to increased rates of ischemic stroke, particularly among young patients. We utilized a national database to assess associations of COVID-19 with thrombectomy rates, mortality, and discharge disposition among stroke patients. METHODS: Patients were identified from the National Inpatient Sample (NIS, 2020). Inclusion criteria selected for adult ischemic stroke patients; those with venous thrombosis or unspecified cerebral infarction were excluded. Patients were stratified by presence or absence of COVID-19 diagnosis. Outcome variables included mechanical thrombectomy, in-hospital mortality, and discharge disposition. Additional patient demographics, hospital characteristics, and disease severity metrics were collected. Statistical analysis was performed via multivariable logistic regression and log-binary regression. RESULTS: 54,368 patients were included in the study; 2116 (3.89%) were diagnosed with COVID-19. COVID-19 was associated with lower rates of mechanical thrombectomy (OR 0.94, p < 0.0001), higher rates of in-hospital mortality (OR 1.14, p < 0.0001), and unfavorable discharge disposition (OR 1.08, p < 0.0001), even when controlling for illness severity. Other relationships, such as a male predominance among stroke patients with COVID-19, were also identified. CONCLUSION: This study identified a relationship between COVID-19 diagnosis and worse outcomes for each metric assessed, including mechanical thrombectomy rates, in-hospital mortality, and discharge disposition. Several factors might underly this, ranging from systemic/multisystem inflammation and worsened disease severity to logistical barriers to treatment caused by COVID-19. Further research is needed to determine causality of these findings.

Increased time to surgery and worse perioperative outcome in benign brain tumor patients with COVID-19.

BACKGROUND: The COVID-19 pandemic caused significant disruptions to healthcare systems around the world, due to both high resource utilization and concern for disease spread. Delays in non-emergent surgeries have also affected chronic disease management, including that of benign brain tumors such as meningiomas and pituitary adenomas. To evaluate the effect of COVID-19 infection on benign brain tumor resection rates and subsequent perioperative and inpatient outcomes, this study utilized the 2020 National Inpatient Sample (NIS) to investigate rates of surgical resection, time to surgery, and mortality among benign brain tumor patients with and without COVID-19. METHODS: Patient data from April 2020 to December 2020 was extracted from the NIS. Confirmed COVID-19 diagnosis was identified using the ICD-10 diagnosis code U07.1. Patients with benign neoplasms of the cerebral meninges, cranial nerves, pituitary gland, craniopharyngeal duct, and brain were included in the study. Patient socio-demographics, hospital characteristics, and clinical comorbidities were obtained. Outcome variables included rates of surgical resection, time to surgery, in-hospital mortality, length of stay, and discharge disposition. RESULTS: The study analysis consisted of 13,053 patients with benign intracranial neoplasms who met inclusion criteria; 597 (4.6%) patients were COVID-19 positive. Patients with COVID-19 were more likely to be older and male than COVID-19 negative patients. Patients with COVID-19 had increased overall likelihood of mortality (OR 2.36, 95% CI 1.72-3.25, p < 0.0001). Even when controlling for sociodemographic/hospital factors and comorbidities, COVID-19 positive patients had a significantly longer time to surgery (8.7 days vs. 0.9 days, p < 0.0001) than COVID negative patients, and were associated with a decreased likelihood of undergoing surgery on index admission overall (OR 0.17, 95% CI 0.10-0.29, p < 0.0001). CONCLUSIONS: As expected, COVID-19 infection was associated with worse inpatient outcomes in effectively all measured categories, including longer time to surgery, decreased likelihood of receiving surgery on index admission, and increased likelihood of in-hospital mortality. These findings emphasize the effect that COVID-19 has on other aspects of patient care and highlight the importance of appropriate avenues of care for patients who are COVID-19 positive. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome for these patients is essential in efficient triage and optimizing treatment for these patients in the future. Further study is needed to elucidate causal relationships on the outcomes of benign brain tumor patients.

Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients.

Background: The global coronavirus disease-19 (COVID-19) pandemic has resulted in procedural delays around the world; however, timely and aggressive surgical resection for malignant brain tumor patients is essential for outcome optimization. To investigate the association between COVID-19 and outcomes of these patients, we queried the 2020 National Inpatient Sample (NIS) for differences in rates of surgical resection, time to surgery, mortality, and discharge disposition between patients with and without confirmed COVID-19 infection. Methods: Patient data were taken from the NIS from April 2020 to December 2020. COVID-19 diagnosis was determined with the International Classification of Diseases, Tenth Revision, Clinical Modification code U07.1. Results: A total of 30,671 malignant brain tumor patients met inclusion criteria and 738 (2.4%) patients had a confirmed COVID-19 diagnosis. COVID-19-positive patients had lower likelihood of receiving surgery (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63, P < 0.0001), increased likelihood of mortality (OR 2.18, 95% CI 1.78-2.66, P < 0.0001), and increased likelihood of non-routine discharge (OR 1.25, 95% CI 1.13-1.39, P < 0.0001). Notably, COVID patients receiving surgery were not associated with surgical delay (P = 0.17). Conclusion: COVID-19 infection was associated with worse patient outcome in malignant brain tumor patients, including decreased likelihood of receiving surgery, increased likelihood of mortality, and increased likelihood of non-routine discharge. Our study highlights the need to balance the risks and benefits of delaying surgery for malignant brain tumor patients with COVID-19. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome provides important insight in effective triage for these patients in the situations where resources are limited.

Pediatric patients with malignant brain tumor treated at children's hospitals: association with fewer unplanned readmissions.

OBJECTIVE: Pediatric primary brain tumors are the leading cause of death among childhood cancers. Guidelines recommend specialized care with a multidisciplinary team and focused treatment protocols to optimize outcomes in this patient population. Furthermore, readmission is a key metric of patient outcomes and has been used to inform reimbursement. However, no prior study has analyzed national database-level records to evaluate the role of care in a designated children's hospital following pediatric tumor resection and its impact on readmission rates. The goal of this study was to investigate whether treatment at a children's hospital rather than a nonchildren's hospital has a significant effect on outcome. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to evaluate the effect of hospital designation on patient outcomes after craniotomy for brain tumor resection, and results are reported as national estimates. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if craniotomy for tumor resection at a designated children's hospital was independently associated with 30-day readmissions, mortality rate, and length of stay. RESULTS: A total of 4003 patients who underwent craniotomy for tumor resection were identified using the Nationwide Readmissions Database, with 1258 of these cases (31.4%) treated at children's hospitals. Patients treated at children's hospitals were associated with decreased likelihood of 30-day hospital readmission (OR 0.68, 95% CI 0.48-0.97, p = 0.036) compared to patients treated at nonchildren's hospitals. There was no significant difference in index mortality between patients treated at children's hospitals and those treated at nonchildren's hospitals. CONCLUSIONS: The authors found that patients undergoing craniotomy for tumor resection at children's hospitals were associated with decreased rates of 30-day readmission, with no significant difference in index mortality. Future prospective studies may be warranted to confirm this association and identify components contributing to improved outcomes in care at children's hospitals.