Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.

Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis. PRC2 has a well-established role in developing tissues, orchestrating transcriptional programs via chromatin modification. PRC2 proteins are expressed in olfactory globose basal cells (GBCs) and nascent neurons. Conditional PRC2 loss perturbs lesion-induced neuron production, accompanied by altered histone modifications and misexpression of lineage-specific transcription factors in GBCs. De-repression of Sox9 in PRC2-mutant GBCs is accompanied by increased Bowman's gland production, defining an unrecognized role for PRC2 in regulating gland versus neuron cell fate. Our findings support a model for PRC2-dependent mechanisms promoting sensory neuronal differentiation in an adult neurogenic niche.

Outcomes in Patients with Minor Stroke: Diagnosis and Management in the Post-thrombectomy Era.

In the era of mechanical thrombectomy and better preventative strategies, a higher number of patients are being discharged home from the hospital with the so-called minor strokes. This has significantly changed the landscape of stroke recovery. Unfortunately, while symptoms may be categorized as mild compared to individuals with higher NIH Stroke Scale scores, the physical, cognitive, and emotional sequelae can be disabling and result in failure to return to work and poor quality of life in a population with significant potential to recover fully. In this review, we discuss the current state of minor stroke, the most common pattern of resulting deficits, what is known about the underlying pathophysiology that leads to a relatively global pattern of impaired cognition following an infarct in any location, and special considerations for treatment based on this population's unique needs. Raising awareness of the current morbidity associated with minor stroke, the need for a uniform definition that allows for comparisons of individuals across studies, and further research focused on this population to optimize outcomes, has the potential to significantly improve recovery.

The telemedicine experience: using principles of clinical excellence to identify disparities and optimize care.

ABSTRACT: The use of telemedicine has increased significantly during the Corona virus disease 2019 pandemic. This manuscript serves to identify the underlying principles of clinical excellence in telemedicine and to determine whether effective care practices can be generalized as a one-size-fits-all model or must instead be tailored to individual patient populations.A survey assessing care quality and patient satisfaction for patients using telemedicine was created and administered via email to 2 urban cohorts of varying demographics and socioeconomic backgrounds: a population of patients with prior stroke and cerebrovascular disease, and a cohort of patients followed for interstitial lung disease. Results were compared across groups to determine the generalizability of effective practices across populations.Individuals taking part in telemedicine were more likely to be White, more affluent, and woman, regardless of clinical diagnosis compared with a similar cohort of patients seen in-person the year prior. A lower-than-expected number of patients who were Black and of lower socioeconomic status followed up virtually, indicating potential barriers to access. Overall, patients who participated in televisits were satisfied with the experience and felt that the care met their medical needs; however, those who were older were more likely to experience technical difficulties and prefer in-person visits, while those with less education were less likely to feel that their questions were addressed in an understandable way.When thoughtfully designed, telemedicine practices can be an effective model for patient care, though implementation must consider population characteristics including age, education, and socioeconomic status, and strategies such as ease of access versus optimization of communication strategies should be tailored to meet individual patient needs.

The Routine Follow-up Head CT: Is it Still a Necessary Step in the Thrombolysis Pathway?

BACKGROUND: The 24-h head computed tomography (CT) scan following intravenous tissue plasminogen activator or mechanical thrombectomy (MT) is currently part of most acute stroke protocols. However, as evidence emerges regarding who is at highest risk for treatment complications, the utility of routine neuroimaging for all patients has become less clear. METHODS: Four hundred seventy-five patients presenting with acute ischemic stroke to Johns Hopkins Bayview Medical Center between 2004 and 2018 and treated with intravenous tissue plasminogen activator and/or MT were evaluated. Neuroimaging performed during the first 48 h of hospitalization was reviewed for edema, hemorrhagic transformation (HT), or other findings altering management. Early imaging (< 24 h), performed for neurologic deterioration, was compared with imaging performed per protocol (24 ± 6 h). Factors predictive of radiographically and clinically significant findings on per-protocol imaging were determined. RESULTS: One hundred fifty-three patients (32%) underwent early imaging. These patients generally had more severe strokes. HT was found in 15% of cases. For the remaining patients (n = 322), imaging at 24 h impacted acute management for only 24 patients: resulting in emergent hemicraniectomy in 1 (0.3%) and leading to additional imaging to monitor asymptomatic HT or edema in 23 (7.1%). Advanced age, higher stroke severity, MT, and atrial fibrillation were associated with significant findings on the 24-h CT scan. Only 2 of the 24 patients had an initial National Institutes of Health Stroke Scale score of < 7. CONCLUSIONS: The 24-h head CT scan does not change management for most patients, particularly those with low National Institutes of Health Stroke Scale scores who do not undergo MT. Consideration should be given to removing routine follow-up imaging from postthrombolysis protocols in favor of an examination-based approach.

Intravenous Tissue Plasminogen Activator in Combination With Mechanical Thrombectomy: Clot Migration, Intracranial Bleeding, and the Impact of "Drip and Ship" on Effectiveness and Outcomes.

Purpose: Intravenous tissue plasminogen activator (tPA) is indicated prior to mechanical thrombectomy (MT) to treat large vessel occlusion (LVO). However, administration takes time, and rates of clot migration complicating successful retrieval and hemorrhagic transformation may be higher. Given time-to-effectiveness, the benefit of tPA may vary significantly based on whether administration occurs at a thrombectomy-capable center or transferring hospital. Methods: We prospectively evaluated 170 individuals with LVO involving the anterior circulation who underwent MT at our Comprehensive Stroke Center over a 3.5 year period. Two thirds (n = 114) of patients were admitted through our Emergency Department (ED). The other 33% were transferred from outside hospitals (OSH). Patients meeting criteria were bridged with IV tPA; the others were treated with MT alone. Clot migration, recanalization times, TICI scores, and hemorrhage rates were compared for those bridged vs. treated with MT alone, along with modified Rankin scores (mRS) at discharge and 90-day follow-up. Multivariable regression was used to determine the relationship between site of presentation and effect of tPA on outcomes. Results: Patients presenting to an OSH had longer mean discovery to puncture/recanalization times, but were actually more likely to receive IV tPA prior to MT (70 vs. 42%). The rate of clot migration was low (11%) and similar between groups, though slightly higher for those receiving IV tPA. There was no difference in symptomatic ICH rate after tPA. TICI scores were also not significantly different; however, more patients achieved TICI 2b or higher reperfusion (83 vs. 67%, p = 0.027) after tPA, and TICI 0 reperfusion was seen almost exclusively in patients who were not treated with tPA. Those bridged at an OSH required fewer passes before successful recanalization (2.4 vs. 1.6, p = 0.037). Overall, mean mRS scores on discharge and at 90 days were significantly better for those receiving IV tPA (3.9 vs. 4.6, 3.4 vs. 4.4 respectively, p ~ 0.01) and differences persisted when comparing only patients recanalized in under 6 h. Conclusion: Independent of site of presentation, IV tPA before MT appears to lead to better radiographic outcomes, without increased rates of clot migration or higher intracranial hemorrhage risk, and overall better functional outcomes.

Shorter Intensive Care Unit Stays? The Majority of Post-Intravenous tPA (Tissue-Type Plasminogen Activator) Symptomatic Hemorrhages Occur Within 12 Hours of Treatment.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (sICH) is a life-threatening complication after treatment with intravenous tPA (tissue-type plasminogen activator) for acute stroke. Currently, patients are monitored for sICH in a neurocritical care unit or intensive care unit-like setting for 24 hours post-treatment-a costly and resource intensive practice. Because the half-life of tPA is much shorter than 24 hours, it is possible that the majority of patients do not require such intensive monitoring. In this study, we evaluate the time period of the highest risk for sICH post-tPA. METHODS: All patients receiving intravenous tPA for acute stroke between 2004 and 2017 at our institution were prospectively followed for sICH for 36 hours after treatment. The mean time from tPA administration to hemorrhage was calculated. Additional data were collected regarding: patient demographics, medical variables, and stroke characteristics. Variables significant in univariate analysis were entered into multivariable logistic regression models to determine factors associated with symptomatic hemorrhage. RESULTS: Three hundred eighty-five patients were administered intravenous tPA. Twenty-one (5.5%) developed sICH. The mean time from administration to hemorrhage was 8.5 hours. Greater than 80% of sICHs occurred before 12 hours post-treatment. The only variable significantly associated with sICH was combination therapy (intravenous tPA and intra-arterial thrombectomy). CONCLUSIONS: sICH associated with the administration of intravenous tPA typically occurs within the first 12 hours of treatment. Longer monitoring in an intensive care unit-like setting may be unnecessary for most individuals.