Improving Access to Specialist Palliative Care for Patients With Catastrophic Strokes Using Best Practice Advisory- a Feasibility Study.

Background and Purpose: The American Heart Association and American Stroke Association (AHA/ASA) strongly recommend specialty palliative care (PC) for all patients hospitalized with life-threatening or life-altering strokes to provide expert symptom management, improve communication, promote shared decision-making and relieve suffering. We piloted an intervention to remind physicians about high PC needs of their patients admitted with catastrophic stroke. Methods: We worked with colleagues from medical informatics to create a "Best Practice Advisory" (BPA) to recommend a goals-of-care conversation and PC consultation for patients with a National Institutes of Health Stroke Scale (NIHSS) score of 20 or more in our electronic medical record (Epic). We evaluated the impact of this BPA, after implementation, on the number and timing of PC consults and reviewed barriers to this system change. Results: The BPA was operational in Jan 2019. Data analysis showed that it fired for all patients with an entered NIHSS score of ≥20. Though a large portion of the BPAs (more than 90%) were acknowledged without documented reason (after selecting "do not order"), PC consultations per 100 patients with triggered BPA increased from the first year of implementation (11.7 in 2019) to the next 2 years (20.7 in 2020, 15.6 in 2021). Also, the providers learned to manage BPA alerts better resulting in more than 30% reduction in the number of BPA alerts fired for each patient encounter in 2020-2021 compared to 2019.

Association between the LACE+ index and unplanned 30-day hospital readmissions in hospitalized patients with stroke.

Background: The LACE+ index is used to predict unplanned 30-day hospital readmissions, but its utility to predict 30-day readmission in hospitalized patients with stroke is unknown. Methods: We retrospectively analyzed 1,657 consecutive patients presenting with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and August 2020. The primary outcome of interest was unplanned 30-day readmission for any reason after index hospitalization for stroke. The 30-day readmission risk was categorized by LACE+ index to high risk (≥78), medium-to-high risk (59-77), medium risk (29-58), and low risk (≤ 28). Kaplan-Meier analysis, Log rank test, and multivariable Cox regression analysis (with backward elimination) were used to determine whether the LACE+ score was an independent predictor for 30-day unplanned readmission. Results: The overall 30-day unplanned readmission rate was 11.7% (194/1,657). The median LACE+ score was higher in the 30-day readmission group compared to subjects that had no unplanned 30-day readmission [74 (IQR 67-79) vs. 70 (IQR 62-75); p < 0.001]. On Kaplan-Meier analysis, the high-risk group had the shortest 30-day readmission free survival time as compared to medium and medium-to-high risk groups (p < 0.01, each; statistically significant). On fully adjusted multivariable Cox-regression, the highest LACE+ risk category was independently associated with the unplanned 30-day readmission risk (per point: HR 1.67 95%CI 1.23-2.26, p = 0.001). Conclusion: Subjects in the high LACE+ index category had a significantly greater unplanned 30-day readmission risk after stroke as compared to lower LACE+ risk groups. This supports the validity of the LACE+ scoring system for predicting unplanned readmission in subjects with stroke. Future studies are warranted to determine whether LACE+ score-based risk stratification can be used to devise early interventions to mitigate the risk for unplanned readmission.

Predicting mortality in moderate-severe TBI patients without early withdrawal of life-sustaining treatments including ICU complications: The MYSTIC-score.

PURPOSE: To develop and internally validate the MortalitY in Moderate-Severe TBI plus ICU Complications (MYSTIC)-Score to predict in-hospital mortality of msTBI patients without early (<24 h) withdrawal-of-life-sustaining treatments. METHODS: We analyzed data from a Neuro-Trauma Intensive Care Unit prospectively collected between 11/2009-5/2019. Consecutive adult msTBI patients were included if Glasgow Coma Scale≤12, and neither died nor had withdrawal-of-life-sustaining treatments within 24 h of admission (n = 485). Using univariate and multivariable logistic regression in a random-split cohort approach (2/3 derivation;1/3 validation), we identified independent predictors of in-hospital mortality while adjusting for validated predictors of mortality (IMPACT-variables). We constructed the MYSTIC-Score and examined discrimination and calibration. RESULTS: The MYSTIC-Score included the ICU complications brain edema, herniation, systemic inflammatory response syndrome, sepsis, acute kidney injury, cardiac arrest, and urinary tract infection. In the derivation cohort(n = 324), discrimination and calibration were excellent (area-under-the-receiver-operating-curve [AUC-ROC] = 0.95;Hosmer-Lemeshow p-value = 0.09, with p > 0.05 indicating good calibration). Internal validation revealed an AUC-ROC = 0.93 and Hosmer-Lemeshow-p-value = 0.76 (n = 161). CONCLUSIONS: Certain ICU complications are independent predictors of in-hospital mortality and strengthen outcome prediction in msTBI when combined with validated admission predictors of mortality. However, external validation is needed to determine robustness and practical applicability of our model given the high potential for residual confounders.

Aneurysmal Subarachnoid Hemorrhage: Review of the Pathophysiology and Management Strategies.

PURPOSE OF REVIEW: Aneurysmal subarachnoid hemorrhage remains a devastating disease process despite medical advances made over the past 3 decades. Much of the focus was on prevention and treatment of vasospasm to reduce delayed cerebral ischemia and improve outcome. In recent years, there has been a shift of focus onto early brain injury as the precursor to delayed cerebral ischemia. This review will focus on the most recent data surrounding the pathophysiology of aneurysmal subarachnoid hemorrhage and current management strategies. RECENT FINDINGS: There is a paucity of successful trials in the management of subarachnoid hemorrhage likely related to the targeting of vasospasm. Pathophysiological changes occurring at the time of aneurysmal rupture lead to early brain injury including cerebral edema, inflammation, and spreading depolarization. These events result in microvascular collapse, vasospasm, and ultimately delayed cerebral ischemia. Management of aneurysmal subarachnoid hemorrhage has remained the same over the past few decades. No recent trials have resulted in new treatments. However, our understanding of the pathophysiology is rapidly expanding and will advise future therapeutic targets.

12 versus 24 h bed rest after acute ischemic stroke thrombolysis: a preliminary experience.

BACKGROUND: The practice of ≥24 h of bed rest after acute ischemic stroke thrombolysis is common among hospitals, but its value compared to shorter periods of bed rest is unknown. METHODS: Consecutive adult patients with a diagnosis of ischemic stroke who had received intravenous thrombolysis treatment from 1/1/2010 until 4/13/2016, identified from the local ischemic stroke registry, were included. Standard practice bed rest for ≥24 h, the protocol prior to 1/27/2014, was retrospectively compared with standard practice bed rest for ≥12 h, the protocol after that date. The primary outcome was favorable discharge location (defined as home, home with services, or acute rehabilitation). Secondary outcome measures included incidence of pneumonia, NIHSS at discharge, and length of stay. RESULTS: 392 patients were identified (203 in the ≥24 h group, 189 in the ≥12 h group). There was no significant difference in favorable discharge outcome in the ≥24 h bed rest protocol compared with the ≥12 h bed rest protocol in multivariable logistic regression analysis (76.2% vs. 70.9%, adjusted OR 1.20 CI 0.71-2.03). Compared with the ≥24 h bed rest group, pneumonia rates (8.3% versus 1.6%, adjusted OR 0.12 CI 0.03-0.55), median discharge NIHSS (3 versus 2, adjusted p = .034), and mean length of stay (5.4 versus 3.5 days, adjusted p = .006) were lower in the ≥12 h bed rest group. CONCLUSION: Compared with ≥24 h bed rest, ≥12 h bed rest after acute ischemic stroke reperfusion therapy appeared to be similar. A non-inferiority randomized trial is needed to verify these findings.

Prevalence of Pelvic Vein Pathology in Patients with Cryptogenic Stroke and Patent Foramen Ovale Undergoing MRV Pelvis.

BACKGROUND: A substantial proportion of ischemic strokes has no any identified underlying cause. Notably, the prevalence of a patent foramen ovale (PFO) is increased in cryptogenic stroke (CS) populations, which may serve as a conduit for paradoxical emboli originating from deep vein thrombosis (DVT) including the pelvic veins. Yet, there are no published guidelines for the assessment of pelvic veins as part of the stroke workup and few studies have systematically investigated pelvic veins as a potential source for paradoxical emboli in CS patients. Further, there is a relative paucity of data regarding pelvic DVT in CS and results have been conflicting. Hence, we sought to determine the prevalence of pelvic DVT in select CS patients with PFO who underwent magnetic resonance venography (MRV). METHODS: We retrospectively identified patients (n = 50) who underwent contrast-enhanced pelvic MRV at the discretion of the treating physician for the evaluation of CS in the presence of a PFO during hospitalization at a single academic stroke center between January 2011 through December 2013. Multivariable logistic regression analyses were used to assess for factors independently associated with the presence of an abnormal MRV pelvis. RESULTS: Patients (47 ± 13 years of age) had MRV performed 4 ± 3 days after their incident stroke. Nine patients had an abnormal MRV (18%). Of these, four (8%) had pelvic vein thrombosis and 5 (10%) a May-Thurner anatomic variant. All patients with pelvic DVT were subsequently anticoagulated with warfarin (none had abnormal hypercoagulability testing). Clinical clues suggesting paradoxical embolism were present in as many as 40% of patients. On multivariable logistic regression, a history of any risk factors predisposing to DVT (OR 6.7; coefficient 1.9; BCa 95% CI 0.08-20.2; p = 0.014) as well as the number of predisposing risk factors (OR 3.9; coefficient 1.4; BCa 95% CI 0.25-4.2; p = 0.005) predicted the presence of pelvic vein pathology on MRV. CONCLUSION: We demonstrate a relatively high prevalence of pelvic DVT among select CS patients emphasizing the importance of considering the pelvic veins as a potential source for emboli particularly in the presence of risk factors known to predispose DVT. Because patients were included at the treating physician's discretion, our results reflect 'real-life' practice. Our results may be of clinical importance as inclusion of pelvic vein imaging in CS patients with PFO had impactful therapeutic and nosologic implications. Further study is needed to define patients most likely to benefit from pelvic vein imaging.

Rapid unexpected brain herniation in association with renal replacement therapy in acute brain injury: caution in the neurocritical care unit.

INTRODUCTION: We aim to raise awareness for the potential for rapid brain edema and herniation in acutely brain-injured patients undergoing renal replacement therapy (RRT), including one case undergoing continuous veno-venous hemofiltration. Dialysis disequilibrium syndrome (DDS) may have been a possible cause for the brain edema. METHODS: We retrospectively reviewed four consecutive neurocritically ill patients in acute renal failure undergoing RRT between 2011 and 2013. Imaging, blood pressure, and laboratory data pre-, during, and post-RRT are presented in graphical form. We performed an extensive literature review. RESULTS: All patients suffered rapidly progressive herniation and death from global brain edema closely related in time to RRT, without other identifiable causes even after detailed review by three neurointensivists. Common clinical symptoms included sudden onset fixed and dilated pupils with apnea, consistent with brain stem compression. Herniation was not reversed by high-dose osmotherapy, and all patients died. Our detailed literature review provides plausible mechanisms for DDS as the most likely cause for our patients' brain edema. CONCLUSIONS: Even today, sudden brain edema and herniation may occur in association with RRT in neurocritically ill patients. We call for the establishment of RRT guidelines in patients with acute neurological injuries.

Heat-shock-mediated conditional regulation of hedgehog/gli signaling in zebrafish.

BACKGROUND: Hedgehog (Hh) signaling is required for embryogenesis and continues to play key roles postembryonically in many tissues, influencing growth, stem cell proliferation, and tumorigenesis. Systems for conditional regulation of Hh signaling facilitate the study of these postembryonic Hh functions. RESULTS: We used the hsp70l promoter to generated three heat-shock-inducible transgenic lines that activate Hh signaling and one line that represses Hh signaling. Heat-shock activation of these transgenes appropriately recapitulates early embryonic loss or gain of Hh function phenotypes. Hh signaling remains activated 24 hr after heat shock in the Tg(hsp70l:shha-EGFP) and Tg(hsp70l:dnPKA-BGFP) lines, while a single heat shock of the Tg(hsp70l:gli1-EGFP) or Tg(hsp70l:gli2aDR-EGFP) lines results in a 6- to 12-hr pulse of Hh signal activation or inactivation, respectively. Using both in situ hybridization and quantitative polymerase chain reaction, we show that these lines can be used to manipulate Hh signaling through larval and juvenile stages. A ptch2 promoter element was used to generate new reporter lines that allow clear visualization of Hh responding cells throughout the life cycle, including graded Hh responses in the embryonic central nervous system. CONCLUSIONS: These zebrafish transgenic lines provide important new experimental tools to study the embryonic and postembryonic roles of Hh signaling.

A dynamic Gli code interprets Hh signals to regulate induction, patterning, and endocrine cell specification in the zebrafish pituitary.

Hedgehog (Hh) signaling is necessary for the induction and functional patterning of the pituitary placode, however the mechanisms by which Hh signals are interpreted by placodal cells are unknown. Here we show distinct temporal requirements for Hh signaling in endocrine cell differentiation and describe a dynamic Gli transcriptional response code that interprets these Hh signals within the developing adenohypophysis. Gli1 is required for the differentiation of selected endocrine cell types and acts as the major activator of Hh-mediated pituitary induction, while Gli2a and Gli2b contribute more minor activator functions. Intriguingly, this Gli response code changes as development proceeds. Gli1 continues to be required for the activation of the Hh response anteriorly in the pars distalis. In contrast, Gli2b is required to repress Hh target gene expression posteriorly in the pars intermedia. Consistent with these changing roles, gli1, gli2a, and gli2b, but not gli3, are expressed in pituitary precursor cells at the anterior neural ridge. Later in development, gli1 expression is maintained throughout the adenohypophysis while gli2a and gli2b expression are restricted to the pars intermedia. Given the link between Hh signaling and pituitary adenomas in humans, our data suggest misregulation of Gli function may contribute to these common pituitary tumors.