Trends and predictors of decompressive craniectomy in acute ischemic stroke, 2011-2020.

INTRODUCTION: Rates of decompressive craniectomy (DC) in acute ischemic stroke (AIS) have been reported to decline over time, attributed to an increase in endovascular therapy (EVT) preventing the development of malignant cerebral edema. We sought to characterize trends in DC in AIS between 2011 and 2020. MATERIAL AND METHODS: We performed a retrospective observational study of U.S. AIS hospitalizations using the National Inpatient Sample, 2011 to 2020. We calculated rates of DC per 10,000 AIS among all AIS hospitalizations, as well as AIS hospitalizations undergoing invasive mechanical ventilation (IMV). A logistic regression to determine predictors of DC was performed. RESULTS: Of ∼4.4 million AIS hospitalizations, 0.5 % underwent DC; of ∼300,000 AIS with IMV, 5.8 % underwent DC. From 2011 to 2020, the rate of DC increased from 37.4 to 59.1 per 10,000 AIS (p < 0.001). The rate of DC in patients undergoing IMV remained stable at ∼550 per 10,000 (p = 0.088). The most important factors predicting DC were age (OR 4.88, 95 % CI 4.53-5.25), hospital stroke volume (OR 2.61, 95 % CI 2.17-3.14), hospital teaching status (OR 1.54, 95 % CI 1.36-1.75), and transfer status (OR 1.53, 95 % CI 1.41-1.66); EVT status did not predict DC. CONCLUSIONS: The rate of DC in AIS has increased between 2011 and 2020. Our findings are contrary to prior reports of decreasing DC rates over time. Increasing EVT rates do not seem to be preventing the occurrence of DC. Future research should focus on the decision-making process for both clinicians and surrogates regarding DC with consideration of long-term outcomes.

Association of Do-Not-Resuscitate orders and in-hospital mortality among patients undergoing cranial neurosurgery.

BACKGROUND: Previous studies identified pre-existing DNR orders as a predictor of mortality after surgery. We sought to evaluate mortality of patients receiving cranial neurosurgery with DNR orders placed at the time of, or within 24 h of admission. METHODS: We performed a retrospective cohort study using the California State Inpatient Database, January 2018 to December 2020. We used International Classification of Diseases, 10th Revision (ICD-10) codes to identify emergent hospitalizations with principal diagnosis of brain injury, including traumatic brain injury [TBI], ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], or malignant brain tumor [mBT]. We used procedure and Diagnosis Related Group codes to identify cranial neurosurgery. Patients with DNR were one-to-one matched to non-DNR controls based on diagnosis (exact matching), age, sex, Elixhauser comorbidity index, and organ failure (coarsened matching). The primary outcome was inpatient mortality. RESULTS: In California, 30,384 patients underwent cranial neurosurgery, 2018-2020 (n = 3,112, 10% DNR). DNR patients were older, more often female, more often White, with greater comorbidity and organ system dysfunction. There were 2,505 patients with DNR orders 1:1 matched to controls. Patients with DNR had greater inpatient mortality (56% vs. 23%, p < 0.001; Hazard Ratio 3.11, 95% CI 2.50-3.86), received tracheostomy (Odds Ratio [OR] 0.37, 95% CI 0.24-0.57) and gastrostomy less (OR 0.48, 95% CI 0.39-0.58) compared to controls. Multivariable analysis of the unmatched cohort demonstrated similar results. CONCLUSION: Patients undergoing cranial neurosurgery with early or pre-existing DNR have high inpatient mortality compared to clinically similar non-DNR patients; 1 in 2 died during their hospitalization.

National Cost Estimates of Invasive Mechanical Ventilation and Tracheostomy in Acute Stroke, 2008-2017.

BACKGROUND: Patients with stroke receiving invasive mechanical ventilation (IMV) and tracheostomy incur intense treatment and long hospitalizations. We aimed to evaluate US hospitalization costs for patients with stroke requiring IMV, tracheostomy, or no ventilation. METHODS: We performed a retrospective observational study of US hospitalizations for acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage receiving IMV, tracheostomy, or none using the National Inpatient Sample, 2008 to 2017. We calculated hospitalization costs using cost-to-charge ratios adjusted to 2017 US dollars for inpatients with stroke by ventilation status (no IMV, IMV alone, tracheostomy). RESULTS: Of an estimated 5.2 million (95% CI, 5.1-5.3) acute stroke hospitalizations, 2008 to 2017; 9.4% received IMV alone and 1.4% received tracheostomy. Length of stay for patients without IMV was shorter (median, 4 days; interquartile range [IQR], 2-6) compared with IMV alone (median, 6 days; [IQR, 2-13]), and tracheostomy (median, 25 days; [IQR, 18-36]; P<0.001). Mortality for patients without IMV was 3.2% compared with 51.2% for IMV alone and 9.8% for tracheostomy (P<0.001). Median hospitalization costs for patients without IMV was $9503 (IQR, $6544-$14 963), compared with $23 774 (IQR, $10 900-$47 735) for IMV alone and $95 380 (IQR, $63 921-$144 019) for tracheostomy. Tracheostomy placement in ≤7 days had lower costs compared with placement in >7 days (median, $71 470 [IQR, $47 863-$108 250] versus $102 979 [IQR, $69 563-$152 543]; P<0.001). Each day awaiting tracheostomy was associated with a 2.9% cost increase (95% CI, 2.6%-3.1%). US hospitalization costs for patients with acute stroke were $8.7 billion/y (95% CI, $8.5-$8.9 billion). For IMV alone, costs were $1.8 billion/y (95% CI, $1.7-$1.9 billion) and for tracheostomy $824 million/y (95% CI, $789.7-$858.3 million). CONCLUSIONS: Patients with acute stroke who undergo tracheostomy account for 1.4% of stroke admissions and 9.5% of US stroke hospitalization costs. Future research should focus on the added value to society and patients of IMV and tracheostomy, in particular after 7 days for the latter procedure given the increased costs incurred and poor outcomes in stroke.

Hospital Discharge and Readmissions Before and During the COVID-19 Pandemic for California Acute Stroke Inpatients.

BACKGROUND: Acute stroke therapy and rehabilitation declined during the COVID-19 pandemic. We characterized changes in acute stroke disposition and readmissions during the pandemic. METHODS: We used the California State Inpatient Database in this retrospective observational study of ischemic and hemorrhagic stroke. We compared discharge disposition across a pre-pandemic period (January 2019 to February 2020) to a pandemic period (March to December 2020) using cumulative incidence functions (CIF), and re-admission rates using chi-squared. RESULTS: There were 63,120 and 40,003 stroke hospitalizations in the pre-pandemic and pandemic periods, respectively. Pre-pandemic, the most common disposition was home [46%], followed by skilled nursing facility (SNF) [23%], and acute rehabilitation [13%]. During the pandemic, there were more home discharges [51%, subdistribution hazard ratio 1.17, 95% CI 1.15-1.19], decreased SNF discharges [17%, subdistribution hazard ratio 0.70, 95% CI 0.68-0.72], and acute rehabilitation discharges were unchanged [CIF, p<0.001]. Home discharges increased with increasing age, with an increase of 8.2% for those ≥85 years. SNF discharges decreased in a similar distribution by age. Thirty-day readmission rates were 12.7 per 100 hospitalizations pre-pandemic compared to 11.6 per 100 hospitalizations during the pandemic [p<0.001]. Home discharge readmission rates were unchanged between periods. Readmission rates for discharges to SNF (18.4 vs. 16.7 per 100 hospitalizations, p=0.003) and acute rehabilitation decreased (11.3 vs. 10.1 per 100 hospitalizations, p=0.034). CONCLUSIONS: During the pandemic a greater proportion of patients were discharged home, with no change in readmission rates. Research is needed to evaluate the impact on quality and financing of post-hospital stroke care.

Interfacility transfers for US ischemic stroke and TIA, 2006-2014.

OBJECTIVE: To investigate changes in emergency department (ED) transfers for ischemic stroke (IS) and TIA. METHODS: We performed a retrospective observational study using the US Nationwide Emergency Department Sample to identify changes in interfacility ED transfers for IS and TIA from the perspective of the transferring ED (2006-2014). We calculated nationwide transfer rates and individual ED transfer rates for IS/TIA by diagnosis and hospital characteristics. Hospital-level fractional logistic regression examined changes in transfer rates over time. RESULTS: The population-estimated number of transfers for IS/TIA increased from 22,576 patient visits in 2006 to 54,485 patient visits in 2014 (p trend < 0.001). The rate of IS/TIA transfer increased from 3.4 (95% confidence interval [CI] 3.0-3.8) in 2006 to 7.6 (95% CI 7.2-7.9) in 2014 per 100 ED visits. Among individual EDs, mean transfer rates for IS/TIA increased from 8.2 per 100 ED visits (median 2.0, interquartile range [IQR] 0-10.2) to 19.4 per 100 ED visits (median 8.1, IQR 1.1-33.3) (2006-2014) (p trend < 0.001). Transfers were more common among IS. Transfer rates were greatest among rural (adjusted odds ratio [AOR] 3.05, 95% CI 2.56-3.64) vs urban/teaching and low-volume EDs (AOR 7.49, 95% CI 6.58-8.53, 1st vs 4th quartile). The adjusted odds of transfer for IS/TIA increased threefold (2006-2014). CONCLUSIONS: Interfacility ED transfers for IS/TIA more than doubled from 2006 to 2014. Further work should determine the necessity of IS/TIA transfers and seek to optimize the US stroke care system.

Expression Profiling of the MAP Kinase Phosphatase Family Reveals a Role for DUSP1 in the Glioblastoma Stem Cell Niche.

The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7-9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens. To resolve features specific to the tumor microenvironment, we searched the Ivy Glioblastoma Atlas Project (Ivy GAP) repository, which highlight DUSP1, DUSP5, and DUSP6 as the predominant family members induced within pseudopalisading and perinecrotic regions. The inducibility of DUSP1 in response to hypoxia, dexamethasone, or the chemotherapeutic agent camptothecin was confirmed in GB cell lines and tumor-derived stem cells (TSCs). Moreover, we show that loss of DUSP1 expression is a characteristic of TSCs and correlates with expression of tumor stem cell markers in situ (ABCG2, PROM1, L1CAM, NANOG, SOX2). This work reveals a dynamic pattern of DUSP expression within the tumor microenvironment that reflects the cumulative effects of factors including regional ischemia, chemotherapeutic exposure among others. Moreover, our observation regarding DUSP1 dysregulation within the stem cell niche argue for its importance in the survival and proliferation of this therapeutically resistant population.

Timing of Percutaneous Endoscopic Gastrostomy for Acute Ischemic Stroke: An Observational Study From the US Nationwide Inpatient Sample.

BACKGROUND AND PURPOSE: Stroke guidelines recommend time-limited trials of nasogastric feeding prior to percutaneous endoscopic gastrostomy (PEG) tube placement. We sought to describe timing of PEG placement and identify factors associated with early PEG for acute ischemic stroke. METHODS: We designed a retrospective observational study to examine time to PEG for ischemic stroke admissions in the Nationwide Inpatient Sample, 2001 to 2011. We defined early PEG placement as 1 to 7 days from admission. Using multivariable regression analysis, we identified the effects of patient and hospital characteristics on PEG timing. RESULTS: We identified 34 623 admissions receiving a PEG from 2001 to 2011, 53% of which received the PEG 1 to 7 days from admission. Among hospitals placing ≥10 PEG tubes, median time to PEG for individual hospitals ranged from 3 days to over 3 weeks (interquartile range 6-8.5 days). Older adult age groups were associated with early PEG (≥85 years versus 18-54 years: adjusted odds ratio 1.68, 95% confidence interval 1.50-1.87). Those receiving a PEG and tracheostomy were more likely to receive the PEG beyond 7 days, and these patients were more often younger compared with PEG only recipients. Those admitted to high-volume hospitals were more likely to receive their PEG early (≥350 versus <150 hospitalizations; adjusted odds ratio 1.26, 95% confidence interval 1.17-1.35). CONCLUSIONS: More than half of the PEG recipients received their surgical feeding tube within 7 days of admission. The oldest old, who may benefit most from time-limited trials of nasogastric feeding for ≥2 to 3 weeks, were most likely to receive a PEG within 7 days.