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Respiratory tract resident memory T cells (T RM ), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA vaccination establishes respiratory T RM . We generated a self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron–based nanoparticles. Here, we report how routes of immunization in mice, including contralateral versus ipsilateral intramuscular boosts, or intravenous and intranasal routes, influenced influenza-specific cell–mediated and humoral immunity. Parabiotic surgeries revealed that intramuscular immunization was sufficient to establish CD8 T RM in the lung and draining lymph nodes. Contralateral, compared with ipsilateral, intramuscular boosting broadened the distribution of lymph node T RM and T follicular helper cells but slightly diminished resulting levels of serum antibody. Intranasal mRNA delivery established modest circulating CD8 and CD4 T cell memory but augmented distribution to the respiratory mucosa. Combining intramuscular immunizations with an intranasal mRNA boost achieved high levels of both circulating T cell memory and lung T RM . Thus, routes of mRNA vaccination influence humoral and cell-mediated immunity, and intramuscular prime-boosting establishes lung T RM that can be further expanded by an additional intranasal immunization.

Background: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined. Methods: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria. Results: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C–E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; P trend <0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; P trend <0.001). Conclusions: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

Abstract Background Stereotactic radiosurgery (SRS) and resection are treatment options for patients with facial nerve schwannomas without mass effect. Objective This article evaluates outcomes of patients treated with SRS versus resection + SRS. Method We retrospectively compared 43 patients treated with SRS to 12 patients treated with resection + SRS. The primary study outcome was unfavorable combined endpoint, defined as worsening or new clinical symptoms, and/or tumor radiological progression. SRS (38.81 ± 5.3) and resection + SRS (67.14 ± 11.8) groups had similar clinical follow-ups. Results At the time of SRS, the tumor volumes of SRS (mean ± standard error; 1.83 ± 0.35 mL) and resection + SRS (2.51 ± 0.75 mL) groups were similar. SRS (12.15 ± 0.08 Gy) and resection + SRS (12.16 ± 0.14 Gy) groups received similar radiation doses. SRS group (42/43, 98%) had better local tumor control than the resection + SRS group (10/12, 83%, p = 0.04). Most of SRS (32/43, 74%) and resection + SRS (10/12, 83%) group patients reached a favorable combined endpoint following SRS (p = 0.52). Considering surgical associated side effects, only 2/10 patients of the resection + SRS group reached a favorable endpoint (p < 0.001).Patients of SRS group, who are > 34 years old (p = 0.02), have larger tumors (> 4 mL, 0.04), internal auditory canal (IAC) segment tumor involvement (p = 0.01) were more likely to reach an unfavorable endpoint. Resection + SRS group patients did not show such a difference. Conclusion While resection is still needed for larger tumors, SRS offers better clinical and radiological outcomes compared to resection followed by SRS for facial schwannomas. Younger age, smaller tumors, and non-IAC situated tumors are factors that portend a favorable outcome.