Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of ...previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.
IMPORTANCE: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final ...diagnosis of intracerebral hemorrhage (ICH) is unknown. OBJECTIVE: To determine the effect of direct transport to an endovascular treatment (EVT)–capable stroke center vs transport to the nearest local stroke center. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale RACE score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022. INTERVENTION: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165). MAIN OUTCOMES AND MEASURES: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 no symptoms to 6 death) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5. RESULTS: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 67.5% men; mean SD age 71.7 12.8 years; and median IQR RACE score, 7 6-8). For the primary outcome, direct transfer to an EVT-capable stroke center (mean SD mRS score, 4.93 1.38) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean SD mRS score, 4.66 1.39; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 48.9% vs 62 of 165 37.6%; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 22.6% vs 9 of 165 patients 5.6%; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients 35.8% vs 29 of 165 patients 17.6%; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02795962
The influence of the COVID-19 pandemic on attendance to out-of-hospital cardiac arrest (OHCA) has only been described in city or regional settings. The impact of COVID-19 across an entire country ...with a high infection rate is yet to be explored.
The study uses data from 8629 cases recorded in two time-series (2017/2018 and 2020) of the Spanish national registry. Data from a non-COVID-19 period and the COVID-19 period (February 1st–April 30th 2020) were compared. During the COVID-19 period, data a further analysis comparing non-pandemic and pandemic weeks (defined according to the WHO declaration on March 11th, 2020) was conducted. The chi-squared analysis examined differences in OHCA attendance and other patient and resuscitation characteristics. Multivariate logistic regression examined survival likelihood to hospital admission and discharge. The multilevel analysis examined the differential effects of regional COVID-19 incidence on these same outcomes.
During the COVID-19 period, the incidence of resuscitation attempts declined and survival to hospital admission (OR = 1.72; 95%CI = 1.46–2.04; p < 0.001) and discharge (OR = 1.38; 95%CI = 1.07–1.78; p = 0.013) fell compared to the non-COVID period. This pattern was also observed when comparing non-pandemic weeks and pandemic weeks. COVID-19 incidence impinged significantly upon outcomes regardless of regional variation, with low, medium, and high incidence regions equally affected.
The pandemic, irrespective of its incidence, seems to have particularly impeded the pre-hospital phase of OHCA care. Present findings call for the need to adapt out-of-hospital care for periods of serious infection risk.
ISRCTN10437835.
Objetivos. Comparar el proceso asistencial prehospitalario y los resultados hospitalarios de los pacientes categorizados como Código Ictus (CI) en función del tipo de ambulancia que realiza la ...primera valoración, y analizar los factores asociados con un buen resultado funcional y la mortalidad a los 3 meses. Método. Estudio observacional de cohortes prospectivo multicéntrico. Incluyó todos los CI atendidos por un sistema de emergencias prehospitalario desde enero del 2016 a abril del 2022. Se recogieron variables prehospitalarias y hospitalarias. La variable de clasificación fue el tipo de ambulancia que asiste el CI: unidad de soporte vital básico (USVB) o avanzado (USVA). Las variables de resultado principal fueron la mortalidad y el estado funcional de los ictus isquémicos sometidos a tratamiento de reperfusión a los 90 días del episodio. Resultados. Se incluyeron 22.968 pacientes, de los cuales 12.467 (54,3%) presentaron un ictus isquémico con un buen estado funcional previo. El 93,1% fueron asistidos por USVB y se solicitó una USVA en el 1,6% de los casos. A pesar de presentar diferencias en el perfil clínico del paciente atendido y en los tiempos del proceso CI prehospitalario, el tipo de unidad no mostró una asociación independiente con la mortalidad (OR ajustada 1,1; IC 95%: 0,77- 1,59) ni con el estado funcional a los 3 meses (OR ajustada 1,05; IC 95%: 0,72-1,47). Conclusiones. El porcentaje de complicaciones de los pacientes con CI atendidos por USVB es bajo. El tipo de unidad que asistió al paciente inicialmente no se asoció ni con el resultado funcional ni con la mortalidad a los 3 meses.
The accumulation of adipose tissue macrophages (ATMs) in obesity has been associated with hepatic injury. However, the ATMs contribution to hepatic fibrosis in non-alcoholic fatty liver disease ...(NAFLD) remains to be elucidated. Herein, we investigate the relationship between ATMs and liver fibrosis in NAFLD patients and evaluate the impact of ATMs modulation over hepatic fibrosis in an experimental NASH model.
Adipose tissue and liver biopsies from 42 NAFLD patients with different fibrosis stages were collected. ATMs were characterized by immunohistochemistry and flow cytometry and correlation between ATMs and liver fibrosis stages was assessed. Selective modulation of ATMs phenotype was achieved by ip administration of dextran coupled with dexamethasone in diet induced obese and NASH murine models. Chronic administration effects were evaluated by histology and gene expression analysis in adipose tissue and liver samples. In vitro crosstalk between human ATMs and hepatic stellate cells (HSC) and liver spheroids was performed.
NAFLD patients presented an increased accumulation of pro-inflammatory ATMs that correlated with hepatic fibrosis. Long term modulation of ATMs significantly reduced pro-inflammatory phenotype and ameliorated adipose tissue inflammation. Moreover, ATMs modulation was associated with an improvement in steatosis and hepatic inflammation and significantly reduced fibrosis progression in an experimental NASH model. In vitro, the reduction of the pro-inflammatory phenotype of human ATMs with dextran-dexamethasone treatment reduced the secretion of inflammatory chemokines and directly attenuated the pro-fibrogenic response in HSC and liver spheroids.
Pro-inflammatory ATMs increase in parallel with fibrosis degree in NAFLD patients and their modulation in an experimental NASH model improves liver fibrosis, uncovering the potential of ATMs as a therapeutic target to mitigate liver fibrosis in NAFLD.
We report that human adipose tissue pro-inflammatory macrophages correlate with hepatic fibrosis in NAFLD. Furthermore, the modulation of adipose tissue macrophages by dextran-nanocarrier conjugated with dexamethasone shifts the pro-inflammatory phenotype of ATM to an anti-inflammatory phenotype in an experimental murine model of NASH. This shift ameliorates adipose tissue inflammation, hepatic inflammation and fibrosis. Our results highlight the relevance of adipose tissue in NAFLD pathophysiology and unveil ATMs as a potential target for NAFLD.
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•Pro-inflammatory ATMs are associated with fibrosis in NAFLD patients.•Dextran coupled with dexamethasone administrated ip selective target ATMs•Long term ATMs modulation reduces their pro-inflammatory phenotype in obese and NASH mice•Modulation of ATMs reduces hepatic fibrosis by attenuating hepatic stellate cells activation
To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional ...outcome at 3 months.
Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode.
Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio aOR, 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47).
The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.
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