(1) Background: Patients’ experiences and satisfaction with their treatment are becoming increasingly important in the context of quality assurance, but the measurement of these parameters is accompanied by several disadvantages such as poor cross-country comparability and methodological problems. The aim of this review is to describe and summarize the process of measuring, publishing, and utilizing patient experience and satisfaction data in countries with highly developed healthcare systems in Europe (Germany, Sweden, Finland, Norway, the United Kingdom) and the USA to identify possible approaches for improvement. (2) Methods: Articles published between 2000 and 2021 that address the topics described were identified. Furthermore, patient feedback in social media and the influence of sociodemographic and hospital characteristics on patient satisfaction and experience were evaluated. (3) Results: The literature reveals that all countries perform well in collecting patient satisfaction and experience data and making them publicly available. However, due to the use of various different questionnaires, comparability of the results is difficult, and consequences drawn from these data remain largely unclear. (4) Conclusions: Surveying patient experience and satisfaction with more unified as well as regularly updated questionnaires would be helpful to eliminate some of the described problems. Additionally, social media platforms must be considered as an increasingly important source to expand the range of patient feedback.

Despite decades of promising preclinical validation and clinical translation, ischemic stroke still remains as one of the leading causes of death and disability worldwide. Within its complex pathophysiological signatures, thrombosis and inflammation, that is, thromboinflammation, are highly interconnected processes leading to cerebral vessel occlusion, inflammatory responses, and severe neuronal damage following the ischemic event. Hence, we here review the most recent updates on thromboinflammatory-dependent mediators relevant after stroke focusing on recent discoveries on platelet modulation, a potential regulation of the innate and adaptive immune system in thromboinflammation, utterly providing a thorough up-to-date overview of all therapeutic approaches currently undergoing clinical trial.

BACKGROUND: The discrepancy between experimental research and clinical trial outcomes is a persistent challenge in preclinical studies, particularly in stroke research. A possible factor contributing to this issue is the lack of standardization across experimental stroke models, leading to poor reproducibility in multicenter studies. This study addresses this gap by aiming to enhance reproducibility and the efficacy of multicenter studies through the harmonization of protocols and training of involved personnel. METHODS: We established a set of standard operating procedures for various stroke models and the Neuroscore. These standard operating procedures were implemented across multiple research centers, followed by specialized, in-person training for all participants. We measured the variability in infarct volume both before and after the implementation of these standardized protocols and training sessions. RESULTS: The standardization process led to a significant reduction in variability of infarct volume across different stroke models (40%–50% reduction), demonstrating the effectiveness of our harmonized protocols and training. Additionally, the implementation of the Neuroscore system across centers showed low variability and consistent results up to 28 days poststroke, underscoring its utility in chronic phase evaluations. CONCLUSIONS: The harmonization of protocols and surgeon training significantly reduced variability in experimental outcomes across different centers. This improvement can increase the comparability of data between research groups and enhance the statistical power of multicenter studies. Our findings also establish the Neuroscore as a reliable tool for long-term assessment in stroke research, paving the way for more consistent and impactful multicenter preclinical studies.

Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) – a key component of the KKS – in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.

BACKGROUND: Respiratory viruses, such as influenza viruses and SARS-CoV-2, cause severe infections of the respiratory system. Cohort studies and clinical observations indicate that patients with severe influenza A virus (IAV) infections are at an increased risk of developing an ischemic stroke event. However, the underlying mechanisms remain elusive. To this end, we investigated the consequences of IAV infection on cerebral damage in a mouse model of ischemic stroke. METHODS: We intranasally inoculated male C57BL6/N mice with the mouse-adapted IAV strain A/Puerto Rico 8/34 or PBS as a vehicle control. At 3, 7, and 10 days post-infection, mice were subjected to transient middle cerebral artery occlusion, followed by sacrifice 24 hours after reperfusion for subsequent analysis. The anticoagulant drug acetylsalicylic acid was administered as treatment 1 day before transient middle cerebral artery occlusion. RESULTS: Our research demonstrated a time-dependent deterioration of cerebral ischemia after transient middle cerebral artery occlusion, resulting in increased infarct volume and a worsened neurological outcome at the propagation and inflammation phases of infection. Our observations revealed an elevation in procoagulant activity and an increase in thrombosis within the microvasculature after infection and stroke. This effect was attributed to an infection-mediated inflammatory milieu and accelerated neutrophil response. Upon infection, the release of increased neutrophil extracellular traps by neutrophils had detrimental consequences for transient middle cerebral artery occlusion development. Administration of acetylsalicylic acid or control antiviral therapy prevented the IAV-induced exacerbation of stroke and reduced brain damage by reducing NETosis and coagulation. CONCLUSIONS: These findings suggest that IAV infections enhance the systemic propensity for NETosis and foster a procoagulant state, thereby increasing the risk of cerebral damage and thrombosis following stroke. Targeting a combination of neutrophils and coagulation molecules simultaneously represents a promising treatment approach for clinical stroke.

T helper (TH)17 cells, a proinflammatory subset of effector T cells, are involved in the pathogenesis of autoimmune diseases such as multiple sclerosis. Although the cytokine TGF-β has been shown to positively regulate the development of murine interleukin (IL)-17 producing CD4+ T cells, the canonical Smad-dependent intracellular signaling pathway seems to be dispensable for TH17 differentiation. By using a protein antibody array we characterized the phosphorylation status of signaling proteins downstream of the TGF-β receptor during TH17 differentiation of naïve murine CD4+CD62L+ T cells to the TH17 phenotyp. To identify Smad-independent signaling pathways we compared the protein phosphorylation between wild type T cells and T cells with overexpression of the Smad pathway inhibitor Smad7. We found that proteins of the PI3K/AKT/mTOR pathway are activated at specific phosphorylation sites during TH17 differentiation, independently of Smad signaling. Pharmacological inhibition of these pathways caused decreased IL-17 production by differentiated TH17 cells in vitro. Our data show that Smad-independent intracellular signaling pathways contribute to TGF-β-induced TH17 differentiation, and expand our understanding of inflammatory pathways relevant for multiple sclerosis.