Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption.

Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results in lasting neurological deficits and an increased risk of autism. The impact of blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects of blood after neurovascular damage in preterm infants. Here, we show that fibrinogen, a blood-clotting protein, plays a central role in impairing neonatal cerebellar development. Longitudinal MRI of preterm infants revealed that cerebellar bleeds were the most critical factor associated with poor cerebellar growth. Using inflammatory and hemorrhagic mouse models of neonatal cerebellar injury, we found that fibrinogen increased innate immune activation and impeded neurogenesis in the developing cerebellum. Fibrinogen inhibited sonic hedgehog (SHH) signaling, the main mitogenic pathway in cerebellar granule neuron progenitors (CGNPs), and was sufficient to disrupt cerebellar growth. Genetic fibrinogen depletion attenuated neuroinflammation, promoted CGNP proliferation, and preserved normal cerebellar development after neurovascular damage. Our findings suggest that fibrinogen alters the balance of SHH signaling in the neurovascular niche and may serve as a therapeutic target to mitigate developmental brain injury after CNS hemorrhage.

Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study.

BACKGROUND: We aimed to investigate the relationship between anti-activated Factor X (anti-FXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We further investigated their association with serious bleeding and thrombotic complications. METHODS: This retrospective single-center study included 265 adults supported by VA-ECMO for refractory cardiogenic shock from January 2015 to June 2019. The concordance of anti-FXa and aPTT and their correlations were assessed in 1699 paired samples. Their independent associations with serious bleeding or thrombotic complications were also analysed in multivariate analysis. RESULTS: The concordance rate of aPTT with anti-FXa values was 50.7%, with 39.3% subtherapeutic aPTT values. However, anti-FXa and aPTT remained associated (ß = 0.43 (95% CI 0.4-0.45) 10-2 IU/mL, p < 0.001), with a significant modulation by several biological co-variables. There was no association between anti-FXa nor aPTT values with serious bleeding or with thrombotic complications. CONCLUSION: During VA-ECMO, although anti-FXa and aPTT were significantly associated, their values were highly discordant with marked sub-therapeutic aPTT values. These results should favour the use of anti-FXa. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy.

Mid-Term Survival and Risk Factors Associated With Myocardial Injury After Fenestrated and/or Branched Endovascular Aortic Aneurysm Repair.

OBJECTIVE: Myocardial injury after non-cardiac surgery (MINS) is an independent predictor of post-operative mortality in non-cardiac surgery patients and may increase health costs. Few data are available for MINS in vascular surgery patients, in general, and those undergoing fenestrated/branched endovascular aortic repairs (F/BEVAR), in particular. The incidence of MINS after F/BEVAR, the associated risk factors, and prognosis have not been determined. The aim of the present study was to help fill these knowledge gaps. METHODS: A single centre, retrospective study was carried out at a high volume F/BEVAR centre in a university hospital. Adult patients who underwent F/BEVAR between October 2010 and December 2018 were included. A high sensitivity troponin T (HsTnT) assay was performed daily in the first few post-operative days. MINS was defined as a HsTnT level ≥ 14 ng/L (MINS14) or ≥ 20 ng/L (MINS20). After assessment of the incidence of MINS, survival up to two years was estimated in a Kaplan-Meier analysis and the groups were compared according to MINS status. A secondary aim was to identify predictors of MINS. RESULTS: Of the 387 included patients, 240 (62.0%) had MINS14 and 166 (42.9%) had MINS20. In multivariable Cox models, both conditions were significantly associated with poor two year survival (MINS14: adjusted hazard ratio [aHR] 2.15, 95% confidence interval [CI] 1.10 - 4.19; MINS20: aHR 2.43, 95% CI 1.36 - 4.34). In a multivariable logistic regression, age, revised cardiac risk index, duration of surgery, pre-operative estimated glomerular filtration rate (eGFR), and haemoglobin level were independent predictors of MINS. CONCLUSION: After F/BEVAR surgery, the incidence of MINS was particularly high, regardless of the definition considered (MINS14 or MINS20). MINS was significantly associated with poor two year survival. The modifiable predictors identified were duration of surgery, eGFR, and haemoglobin level.

The Systematic Development of an Internet-Based Smoking Cessation Intervention for Adults.

Objectives The objective of this project was to determine whether intervention mapping is a suitable strategy for developing an Internet- and text message-based smoking cessation intervention. Method We used the Intervention Mapping framework for planning health promotion programs. After a needs assessment, we identified important changeable determinants of cessation behavior, specified objectives for the intervention, selected theoretical methods for meeting our objectives, and operationalized change methods into practical intervention strategies. Results We found that "social cognitive theory," the "transtheoretical model/stages of change," "self-regulation theory," and "appreciative inquiry" were relevant theories for smoking cessation interventions. From these theories, we selected modeling/behavioral journalism, feedback, planning coping responses/if-then statements, gain frame/positive imaging, consciousness-raising, helping relationships, stimulus control, and goal-setting as suitable methods for an Internet- and text-based adult smoking cessation program. Furthermore, we identified computer tailoring as a useful strategy for adapting the intervention to individual users. Conclusion The Intervention Mapping method, with a clear link between behavioral goals, theoretical methods, and practical strategies and materials, proved useful for systematic development of a digital smoking cessation intervention for adults.

"I miss the care even though I know it's just a machine": an explorative study of the relationship between an Internet-based smoking cessation intervention and its participants.

This study aimed to investigate how users perceive the different elements of an internet based smoking cessation intervention and to see if the program meet needs and expectations of people in a smoking cessation process. Nine semi-structured interviews were conducted in February 2010. Participants were recruited via the homepage of the smoking cessation program Dit Digitale Stopprogram (Your Digital Quit Program) operated by the Danish Cancer Society. The main result was that participants established a relationship to the program which influenced their smoking cessation process. Participants perceived the program as caring and found it supportive. However, the program also created feelings of frustration, disappointment and anger. Some participants in the last phase of cessation experienced text messages from the program as smoking cues. The study concluded that individual interpretations of the different elements in an Internet-based smoking cessation intervention can have both positive and negative impact on the smoking cessation process of participants.

"After all--it doesn't kill you to quit smoking": an explorative analysis of the blog in a smoking cessation intervention.

BACKGROUND: A growing body of literature demonstrates internet-based smoking cessation interventions as a promising aid in helping people quit smoking. However, the underlying mechanisms of how these interventions influence the cessation process are still relatively unknown. Several studies have indicated blogging as a potential source in providing social support to users of internet-based smoking cessation interventions and thereby enhance their change of succeeding in quitting. OBJECTIVE: The study aimed to investigate themes discussed on a blog in an internet-based smoking cessation intervention. In addition, we examined if blogging could provide social support for people in a smoking cessation process. METHOD: The study was based on messages posted from 1 January 2012 to 29 February 2012 on the blog of the internet-based smoking cessation programme DDSP, operated by the Danish Cancer Society. Messages were coded according to themes using Grounded Theory, and additionally data about bloggers were analyzed. RESULT: In total, 1663 messages were posted within the 2-month period, and we identified 16 themes. The majority of messages contained personal stories or experiences (53%), provided emotional support (34%) or congratulated other users (17%). The messages were found capable of supplying social support to members on the blog. In addition, we found that only a minority of users who viewed the blog participated actively in posting messages, and only a minority was highly active bloggers. CONCLUSIONS: The blog offers a unique platform for informal conversations about quitting smoking and is important in providing social support to people in a smoking cessation process.