Exploring the Function of Epicardial Cells Beyond the Surface.

The epicardium, previously viewed as a passive outer layer around the heart, is now recognized as an essential component in development, regeneration, and repair. In this review, we explore the cellular and molecular makeup of the epicardium, highlighting its roles in heart regeneration and repair in zebrafish and salamanders, as well as its activation in young and adult postnatal mammals. We also examine the latest technologies used to study the function of epicardial cells for therapeutic interventions. Analysis of highly regenerative animal models shows that the epicardium is essential in regulating cardiomyocyte proliferation, transient fibrosis, and neovascularization. However, despite the epicardium's unique cellular programs to resolve cardiac damage, it remains unclear how to replicate these processes in nonregenerative mammalian organisms. During myocardial infarction, epicardial cells secrete signaling factors that modulate fibrotic, vascular, and inflammatory remodeling, which differentially enhance or inhibit cardiac repair. Recent transcriptomic studies have validated the cellular and molecular heterogeneity of the epicardium across various species and developmental stages, shedding further light on its function under pathological conditions. These studies have also provided insights into the function of regulatory epicardial-derived signaling molecules in various diseases, which could lead to new therapies and advances in reparative cardiovascular medicine. Moreover, insights gained from investigating epicardial cell function have initiated the development of novel techniques, including using human pluripotent stem cells and cardiac organoids to model reparative processes within the cardiovascular system. This growing understanding of epicardial function holds the potential for developing innovative therapeutic strategies aimed at addressing developmental heart disorders, enhancing regenerative therapies, and mitigating cardiovascular disease progression.

Poisson Modeling Predicts Acute Telestroke Patient Call Volume.

Background: Predicting the frequency of calls for telestroke and emergency teleneurology consultation is essential to prepare staffing for the immediate management of time-sensitive strokes. In this study, we evaluate Poisson distribution count data using a generalized linear model that predicts the volume of hourly telestroke calls over a 24-h period. Methods: We performed an Institutional Review Board approved retrospective cohort review of patients (January 2019-December 2022) from an institutional telestroke database at a large nonprofit multihospital system in the United States. All patients ≥18 years with a telestroke activation were included. Telestroke calls were quantified in frequency per day and analyzed by multiple time and date intervals. Poisson probability mass function (PMF) and cumulative distribution function (CDF) were used to predict call probabilities. A univariable Poisson regression model was fit to predict call volumes. Results: A total of 8,499 patients at 21 hospitals met inclusion criteria, the mean calls/day were 5.82 ± 2.54, and mean calls/day within each hour increment ranged from a minimum of 0.07 from 5 a.m. to 6 a.m. to a maximum of 0.45 from 7 p.m. to 8 p.m. The Poisson distribution was the most appropriate parametric probability model for these data, confirmed by the fit of the data to the expected distributions corresponding to the calculated means. The predicted probabilities of call frequencies by hour were calculated using the Poisson PMF and CDF; the probability of two or fewer calls/day by hour ranged from 98.9% to 99.9%. Univariable Poisson regression modeled an increase of future calls/day from 6.7 calls/day in July 2023 to 7.6 calls/day in October 2025. Conclusion: Poisson modeling closely fits telestroke call volumes, predicts the future volumes, and can be applied to any health system in which the mean call volume is known, which may inform the number of physicians needed to cover calls in real-time.

Extended Window Thrombolytics for Ischemic Stroke: A Telestroke versus In-person Experience.

Background and Purpose: Telestroke evaluation of patients with acute ischemic stroke is supported by American Heart and Stroke Association Guidelines. However, there is no data on outcomes or safety of administering IV thrombolytic stroke therapy using extended window criteria (>4.5 h since onset of symptoms with a hyperacute MRI diffusion T2/FLAIR mismatch) via telestroke. Here, we report adverse events and outcomes of extended-window thrombolysis by telestroke vs in-person care. Methods: We performed a retrospective cohort review from 2020 to 2022 of prospectively collected multinstitutional databases from a large, not-for-profit health system with both in-person stroke and telestroke care. The primary outcome was frequency of symptomatic intracranial hemorrhage (sICH). Secondary outcomes were favorable functional outcome at hospital discharge (modified Rankin Scale, mRS, 0-3) and discharge disposition. Results: A total of 33 patients were treated with extended-window thrombolysis (n = 20 in-person, n = 13 telestroke). The median NIH stroke scale was 6, and time since last known normal was similar (median [95% CI]: in-person 13 h [11-15 h] vs telestroke 12 h [9-16 h], P = .33). The sICH frequency was low and occurred in one patient (4.8% in-person vs 0% by telestroke). Favorable outcome at discharge was not different between in-person and telestroke care (median mRS [95% CI]: 2 [1-3] vs 1 [0-2], OR .0 [.0-1.8], P = .27), and discharge deposition was also similar. Conclusions: In patients eligible for extended window acute stroke treatment with thrombolytics, there was no difference in adverse events between telestroke and in-person care.

Deep population structure linked to host vernalization requirement in the barley net blotch fungal pathogen.

Invasive fungal pathogens pose a substantial threat to widely cultivated crop species, owing to their capacity to adapt to new hosts and new environmental conditions. Gaining insights into the demographic history of these pathogens and unravelling the mechanisms driving coevolutionary processes are crucial for developing durably effective disease management programmes. Pyrenophora teres is a significant fungal pathogen of barley, consisting of two lineages, Ptt and Ptm, with global distributions and demographic histories reflecting barley domestication and spread. However, the factors influencing the population structure of P. teres remain poorly understood, despite the varietal and environmental heterogeneity of barley agrosystems. Here, we report on the population genomic structure of P. teres in France and globally. We used genotyping-by-sequencing to show that Ptt and Ptm can coexist in the same area in France, with Ptt predominating. Furthermore, we showed that differences in the vernalization requirement of barley varieties were associated with population differentiation within Ptt in France and at a global scale, with one population cluster found on spring barley and another population cluster found on winter barley. Our results demonstrate how cultivation conditions, possibly associated with genetic differences between host populations, can be associated with the maintenance of divergent invasive pathogen populations coexisting over large geographic areas. This study not only advances our understanding of the coevolutionary dynamics of the Pt-barley pathosystem but also prompts further research on the relative contributions of adaptation to the host versus adaptation to abiotic conditions in shaping Ptt populations.

Impact of Local Tailoring on Acute Stroke Care in 21 Disparate Emergency Departments: A Prospective Stepped Wedge Type III Hybrid Effectiveness-Implementation Study.

BACKGROUND: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system. METHODS: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers. RESULTS: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes. CONCLUSIONS: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers.

Teleneurocritical care is associated with equivalent billable charges to in-person neurocritical care for patients with acute stroke.

INTRODUCTION: Teleneurocritical care (TNCC) provides virtual care for hospitals who do not have continuous neurointensivist coverage. It is not known if TNCC is cost effective nor which variables impact the total billed charges per patient encounter. We characterize cost, defined by charge characteristics of TNCC compared to in-person neurocritical care (NCC), for patients with acute ischemic or hemorrhagic stroke requiring ICU care. METHODS: We performed a retrospective review from 2018 to 2021 of prospectively collected multinstitutional databases from a large, integrated, not-for-profit health system with an in-person NCC and spoke TNCC sites. The primary outcome was the total billable charge per TNCC patient with acute ischemic or hemorrhagic stroke compared to in-person NCC. Secondary outcomes were functional outcome, transfer rate, and length of stay (LOS). RESULTS: A total of 1779 patients met inclusion criteria, 1062 at the hub in-person NCC hospital and 717 at spoke TNCC hospitals. Total billed patient charges of TNCC were similar to in-person NCC (median 104% of the cost per in-person NCC patient, 95% CI: 99%-108%). From 2018 to 2021, the charge difference between TNCC and NCC was not different (r2 = 0.71, p = 0.16). Both age and length stay were independently predictive of charges: for every year older the charge increased by US $6.3, and every day greater LOS the charge increased by $2084.3 (p < 0.001, both). TNCC transfer rates were low, and TNCC had shorter LOS and greater favorable functional outcome. DISCUSSION: TNCC was associated with similar patient financial charges as compared to in-person NCC. Standardization of care and the integrated hub-spoke value-focused operational procedures of TNCC may be applicable to other healthcare systems, however, further prospective study is needed.

Simultaneous analysis of retinol, six carotenoids, two tocopherols, and coenzyme Q10 from human plasma by HPLC.

Lipophilic antioxidant determination is of relevance in health and diseases. Several HPLC methods exists but rare are those including coenzyme Q10 with carotenoids, retinol and tocopherols. Here a single-step extraction was proposed for the detection of retinol, α and γ-tocopherols, lutein, zeaxanthin, trans-ß-carotene, α-carotene, ß-cryptoxanthin and lycopene as well as coenzyme Q10. A single HPLC column was used and UV-vis diode array detection was performed. Echinenone, alpha-tocopherol nicotinate and coenzyme Q4 were employed as internal standards. Intra-assay and inter-assay precision were respectively 1.4-7.9% and 2.2-15.8%. Accuracy was validated using SRM 968e. LOD (limit of detection) and LOQ (limit of quantification) obtained were sufficient for nutritional epidemiological study and routine clinical application.

Intravenous acetaminophen for postoperative supratentorial craniotomy pain: a prospective, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy. METHODS: The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded. RESULTS: A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2­98.4] and 85.5 ME [95% CI 73­97.9]; and at 48 hours: 123.5 ME [95% CI 102.9­144.2] and 134.2 ME [95% CI 112.1­156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001). CONCLUSIONS: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Reproducibility of ABC/2 method to determine infarct volume and mismatch percentage with CT perfusion.

BACKGROUND: Our aim is to implement a simple, rapid, and reliable method using computed tomography perfusion imaging and clinical judgment to target patients for reperfusion therapy in the hyper-acute stroke setting. We introduce a novel formula (1-infarct volume [CBV]/penumbra volume [MTT] × 100%) to quantify mismatch percentage. METHODS: Twenty patients with anterior circulation strokes who underwent CT perfusion and received intravenous tissue plasminogen activator (IV tPA) were analyzed retrospectively. Nine blinded viewers determined volume of infarct and ischemic penumbra using the ABC/2 method and also the mismatch percentage. RESULTS: Interrater reliability using the volumetric formula (ABC/2) was very good (intraclass correlation [ICC] = .9440 and ICC = .8510) for hemodynamic parameters infarct (CBV) and penumbra (MTT). ICC coefficient using the mismatch formula (1-MTT/CBV × 100%) was good (ICC of .635). CONCLUSIONS: The ABC/2 method of volume estimation on CT perfusion is a reliable and efficient approach to determine infarct and penumbra volumes. The 1-CBV/MTT × 100% formula produces a mismatch percentage assisting providers in communicating the proportion of salvageable brain and guides therapy in the setting of patients with unclear time of onset with potentially salvageable tissue who can undergo mechanical retrieval or intraarterial thrombolytics.