Parallel activation of helicopter and ground transportation after dispatcher identification of suspected anterior large vessel occlusion stroke in rural areas: a proof-of-concept case with modeling from the LESTOR trial.

BACKGROUND: When stroke patients with suspected anterior large vessel occlusion (aLVO) happen to live in rural areas, two main options exist for prehospital transport: (i) the drip-and-ship (DnS) strategy, which ensures rapid access to intravenous thrombolysis (IVT) at the nearest primary stroke center but requires time-consuming interhospital transfer for endovascular thrombectomy (EVT) because the latter is only available at comprehensive stroke centers (CSC); and (ii) the mothership (MS) strategy, which entails direct transport to a CSC and allows for faster access to EVT but carries the risk of IVT being delayed or even the time window being missed completely. The use of a helicopter might shorten the transport time to the CSC in rural areas. However, if the aLVO stroke is only recognized by the emergency service on site, the helicopter must be requested in addition, which extends the prehospital time and partially negates the time advantage. We hypothesized that parallel activation of ground and helicopter transportation in case of aLVO suspicion by the dispatcher (aLVO-guided dispatch strategy) could shorten the prehospital time in rural areas and enable faster treatment with IVT and EVT. METHODS: As a proof-of-concept, we report a case from the LESTOR trial where the dispatcher suspected an aLVO stroke during the emergency call and dispatched EMS and HEMS in parallel. Based on this case, we compare the provided aLVO-guided dispatch strategy to the DnS and MS strategies regarding the times to IVT and EVT using a highly realistic modeling approach. RESULTS: With the aLVO-guided dispatch strategy, the patient received IVT and EVT faster than with the DnS or MS strategies. IVT was administered 6 min faster than in the DnS strategy and 22 min faster than in the MS strategy, and EVT was started 47 min earlier than in the DnS strategy and 22 min earlier than in the MS strategy. CONCLUSION: In rural areas, parallel activation of ground and helicopter emergency services following dispatcher identification of stroke patients with suspected aLVO could provide rapid access to both IVT and EVT, thereby overcoming the limitations of the DnS and MS strategies.

Correction: Identification of Anterior Large Vessel Occlusion Stroke During the Emergency Call: Protocol for a Controlled, Nonrandomized Trial.

[This corrects the article DOI: 10.2196/51683.].

Identification of Anterior Large Vessel Occlusion Stroke During the Emergency Call: Protocol for a Controlled, Nonrandomized Trial.

BACKGROUND: Endovascular thrombectomy (ET), combined with intravenous thrombolysis if possible, is an effective treatment option for patients with stroke who have confirmed anterior large vessel occlusion (aLVO). However, ET is mainly limited to comprehensive stroke centers (CSCs), resulting in a lack of ET capacity in remote, sparsely populated areas. Most stroke networks use the "Drip and Ship" or "Mothership" strategy, resulting in either delayed ET or intravenous thrombolysis, respectively. OBJECTIVE: This study protocol introduces the Leitstellen-Basierte Erkennung von Schlaganfall-Patienten für eine Thrombektomie und daraufhin abgestimmte Optimierung der Rettungskette (LESTOR) strategy, developed to optimize the preclinical part of the stroke chain of survival to improve the clinical outcome of patients with suspected aLVO stroke. This involves refining the dispatch strategy for identifying patients with acute aLVO stroke using a phone-based aLVO query. This includes dispatching emergency physicians and emergency medical services (EMS) to urban emergency sites, as well as dispatching helicopter EMS to remote areas. If a highly suspected aLVO is identified after a standardized aLVO score evaluation during a structured examination at the emergency scene, prompt transport to a CSC should be prioritized. METHODS: The LESTOR study is a controlled, nonrandomized study implementing the LESTOR strategy, with a stepped-wedge, cluster trial design in 6 districts in southwest Germany. In an interprofessional, iterative approach, an aLVO query or dispatch protocol intended for use by dispatchers, followed by a coordinated aLVO examination score for use by EMS, is being developed, evaluated, and pretested in a simulation study. After the training of all participating health care professionals with the corresponding final aLVO query, the LESTOR strategy is being implemented stepwise. Patients otherwise receive usual stroke care in both the control and intervention groups. The primary outcome is the modified Rankin Scale at 90 days in patients with stroke receiving endovascular treatment. We will use a generalized linear mixed model for data analysis. This study is accompanied by a cost-effectiveness analysis and a qualitative process evaluation. RESULTS: This paper describes and discusses the protocol for this controlled, nonrandomized LESTOR study. Enrollment was completed in June 2023. Data analysis is ongoing and the first results are expected to be submitted for publication in 2024. The project started in April 2020 and will end in February 2024. CONCLUSIONS: We expect that the intervention will improve the clinical outcome of patients with aLVO stroke, especially outside the catchment areas of CSCs. The results of the accompanying process evaluation and the cost-effectiveness analysis will provide further insights into the implementation process and allow for a better interpretation of the results. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022152; https://drks.de/search/de/trial/DRKS00022152. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51683.

Prognostic impact of the CD34+/CD38- cell burden in patients with acute myeloid leukemia receiving allogeneic stem cell transplantation.

In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects. Percentage of bone marrow CD34+/CD38- cell burden at diagnosis was measured using flow cytometry and was highly variable (median 0.5%, range 0%-89% of all mononuclear cells). A high CD34+/CD38- cell burden at diagnosis associated with worse genetic risk and secondary AML. Patients with a high CD34+/CD38- cell burden had shorter relapse-free and overall survival which may be mediated by residual leukemia-initiating cells in the CD34+/CD38- cell population, escaping the graft-versus-leukemia effect after allogeneic transplantation. Evaluating the CD34+/CD38- cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic transplantation. Further studies to understand leukemia-initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.