Site Of Infarction Research Articles

Risk factors and prognosis of acute ischemic stroke complicated with cerebral microbleeds

Objective: To observe the risk factors and prognosis of patients with acute ischemic stroke complicated with cerebral microbleeds (CMBs) to provide a theoretical basis for better prevention and treatment of acute ischemic stroke and reduction of bleeding risk. Methods: The clinical data of 200 patients with acute ischemic stroke who completed susceptibility weighted imaging (SWI) were retrospectively analyzed. They were divided into a CMB group and a non CMB group. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors and prognosis of acute ischemic stroke. Results: Univariate analysis showed that systolic blood pressure, fasting plasma glucose, free triiodothyronine (FT3), infarct site in the cerebral lobe and total anterior circulation infarct (TACI) (using the Oxfordshire Community Stroke Project (OCSP) classification) were correlated with acute ischemic stroke complicated with CMBs (P < 0.05). Multivariate logistic regression analysis showed that systolic blood pressure (OR: 1.02, 95% CI: 1.009–1.032), fasting blood glucose (OR: 1.174, 95% CI: 1.082–1.274) and infarct site in the cerebral lobe (OR: 12.925, 95% CI: 7.412–22.540) were independent risk factors for acute ischemic stroke complicated with CMBs (P < 0.05). TACI (OR: 0.004, 95% CI: 0.002–0.007) may not be an independent risk factor (P < 0.05). Conclusion: Systolic blood pressure, fasting blood glucose and infarct site in the cerebral lobe, but likely not TACI, were independent risk factors for acute ischemic stroke complicated with CMBs. The presence or absence of CMBs did not affect the prognosis of acute ischemic stroke.

Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site-derived extracellular vesicles from myocardial infarction patients.

Abstract Background and Aims Neutrophil extracellular traps (NETs) trigger atherothrombosis during acute myocardial infarction (AMI), but mechanisms of induction remain unclear. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE), which are targeted by specific natural immunoglobulin M (IgM), are increased at the culprit site in AMI. This study investigated EV as inducers of NETosis and assessed the inhibitory effect of natural anti-OSE–IgM in this process. Methods Blood from the culprit and peripheral site of ST-segment elevation myocardial infarction (STEMI) patients (n = 28) was collected, and myocardial function assessed by cardiac magnetic resonance imaging (cMRI) 4 ± 2 days and 195 ± 15 days post-AMI. Extracellular vesicles were isolated from patient plasma and cell culture supernatants for neutrophil stimulation in vitro and in vivo, in the presence of a malondialdehyde (MDA)-specific IgM or an isotype control. NETosis and neutrophil functions were assessed via enzyme-linked immunosorbent assay and fluorescence microscopy. Pharmacological inhibitors were used to map signalling pathways. Neutrophil extracellular trap markers and anti-OSE–IgM were measured by ELISA. Results CD45+ MDA+ EV and NET markers were elevated at the culprit site. Extracellular vesicles induced neutrophil activation and NET formation via TLR4 and PAD4, and mice injected with EV showed increased NETosis. Malondialdehyde-specific IgM levels were inversely associated with citH3 in STEMI patient blood. An MDA-specific IgM inhibited EV-induced NET release in vitro and in vivo. CD45+ MDA+ EV concentrations inversely correlated with left ventricular ejection fraction post-AMI. Conclusions Culprit site–derived EV induce NETosis, while MDA-specific natural IgM inhibit this effect, potentially impacting outcome after AMI.

Brown Adipose Stem Cell-Loaded Resilin Elastic Hydrogel Rebuilds Cardiac Function after Myocardial Infarction via Collagen I/III Reorganisation.

Irreversible fibrosis following myocardial infarction (MI) stiffens the infarcted myocardium, which remains challenging to restore. This study aimed to investigate whether the injectable RLP12 hydrogel, derived from recombinant resilin protein, could serve as a vehicle for stem cells to enhance the function of the infarcted myocardium. The RLP12 hydrogel was prepared and injected into the myocardium of rats with MI, and brown adipose-derived mesenchymal stem cells (BADSCs) were loaded. The survival and differentiation of BADSCs in vivo were investigated using immunofluorescence one week and four weeks after treatment, respectively. The heart function, MI area, collagen deposition, and microvessel density were further assessed four weeks after treatment through echocardiography, histology, immunohistochemistry, and immunofluorescence. The RLP12 hydrogel was prepared with a shear modulus of 10-15 kPa. Four weeks after transplantation, the RLP12 hydrogel significantly improved cardiac function by increasing microvessel density and reducing infarct area size and collagen deposition in MI rats. Furthermore, the distribution ratio of collagen III to I increased in both the centre and edge areas of the MI, indicating the improved compliance of the infarct heart. Moreover, the RLP12 hydrogel also promoted the survival and differentiation of BADSCs into cardiac troponin T- and α-smooth muscle-positive cells. The RLP12 hydrogel can be utilised as an injectable vehicle of BADSCs for treating MI and regulating collagen I and III expression profiles to improve the mechanical microenvironment of the infarct site, thereby restoring heart function. The study provides novel insights into the mechanical interactions between the hydrogel and the infarct microenvironment.

Association between 24-hour blood pressure parameters and 90-day functional outcome in acute ischemic stroke patients with early anticoagulation.

This study aimed to examine the relationship between blood pressure (BP) and blood pressure variability (BPV) during the first 24 hours from admission with 90-day functional outcomes in acute ischemic stroke (AIS) patients whose onset within 24 hours and receiving early argatroban treatment. The study recruited 214 AIS patients. BP was monitored using a cuff at 1-hour fixed intervals, and BP/BPV parameters [standard deviation (SD), coefficient of variation (CV), successive variation (SV), and average real variability (ARV)] were collected. Age, the National Institutes of Health Stroke Scale (NIHSS) score at admission, previous history of diabetes mellitus (DM), and infarction site (located in anterior circulation) were identified as independent factors affecting 90-day outcomes in multiple logistic regression. After adjusting for confounding variables, association between BP/BPV and 90-day modified Rankin Scale (mRS) was assessed using logistic regression models. In model 1 (adjusted for age and NIHSS score at admission), mean-systolic blood pressure (SBP) showed association with 90-day outcomes [1.068 (1.008, 1.131), P = .025]. In model 2 (adjusted for age, NIHSS score at admission, previous history of DM), mean-SBP [1.061 (1.001, 1.123), P = .045] and max-SBP [0.951 (0.906, 0.998), P = .040] showed relatively weak association with outcomes. In model 3 [adjusted for age, NIHSS score at admission, previous history of DM, infarct site (located in anterior circulation)], all BP values were not related with outcomes, meanwhile, none of the BPV parameters calculated from SBP, diastolic blood pressure and mean arterial pressure showed association with 90-day outcomes. Future prospective studies are required to assess the relationship between early BP/BPV parameters with 90-day outcomes and further clarify the reference values for BP parameters. This is important for effective BP/BPV management and improved patient prognosis.

Nanozyme-enhanced mitophagy to improve the efficacy of mesenchymal stem cells in myocardial infarction therapy

Mesenchymal stem cell therapy has emerged as a promising approach for the treatment of myocardial infarction. However, the challenge of low cell survival and retention post injection, particularly under the high levels of reactive oxygen species (ROS) and oxidative stress at the infarct site, has hindered their clinical application. Additionally, traditional drug delivery methods, such as intravenous injection, cannot meet the demand for long-term stem cell residence at the infarct site, which is another critical issue that impedes the therapeutic efficacy of stem cells. Herein, we synthesized indocyanine green-enriched Prussian blue nanozyme, called PB@PEI@ICG, which not only possessed remarkable ROS scavenging capability but also exhibited superior fluorescent tracer property. Subsequently, we engineered mesenchymal stem cells (MSCs) with PB@PEI@ICG by co-culture and found that the introduction of the nanozyme significantly enhanced mitophagy by BNIP3 and PINK1 pathways, which in turn promoted ROS scavenging and protected MSCs from cell death induced by the harsh infarct microenvironment. Furthermore, we employed pericardial injection as an alternative delivery method to prolong the residence time of MSCs at the infarct site, enabling real-time tracking via the fluorescence property of the nanozymes. The results demonstrated that PB@PEI@ICG nanozyme could significantly improve the survival and retention of MSCs at the infarct site, thereby enhancing the therapeutic effect for myocardial infarction. In conclusion, this study presents a novel strategy for stem cell therapy in myocardial infarction by using mitophagy-enhancing nanozyme to scavenge ROS for enhancing the therapeutic potential of stem cells.

Targeted delivery of black phosphorus nanosheets by ROS responsive complex hydrogel based on angiogenesis and antioxidant promotes myocardial infarction repair

Myocardial infarction (MI) is one of the leading causes of death. This is attributed to the dramatic changes in the myocardial microenvironment post-MI. Therefore, effective intervention in the early stages of MI is significant for inhibiting its progression and improving cardiac function. Herein, an injectable composite hydrogel scaffold (Gel-pBP@Mg) was developed by integrating magnesium (Mg)-modified black phosphorus nanosheets (pBP@Mg) into a reactive oxygen species-responsive hydrogel (Gel). This loose and porous Gel provides a natural platform for carrying pBP@Mg. In situ, sustained release of pBP@Mg is achieved via responsive ROS degradation in the infarct site. The high ROS reactivity of Black phosphorus nanosheets (BPNSs) can effectively inhibit the progression of oxidative stress in the infarct area and reduce inflammatory response by down-regulating the NF-κB pathway. Additionally, the sustained release of Mg loaded on the surface of BPNSs can effectively promote angiogenesis in MI, which is significant for the long-term prognosis after infarction. Our developed Gel-pBP@Mg effectively blocked infarction progression and improved myocardial function by sustainably inhibiting the “oxidative stress-inflammation” reaction chain and pro-angiogenesis. This study reveals Gel-pBP@Mg composite therapeutic potential in treating MI through In vitro and In vivo studies, providing a promising modality for MI treatment.Graphical abstract

New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1

BackgroundThe current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.ObjectiveWe aimed to establish a...

Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg

Endothelial cells are a heterogeneous population with various organ-specific and conserved functions that are critical to organ development, function, and regeneration. Here we report a Sox17-Erg direct reprogramming approach that uses cardiac fibroblasts to create differentiated endothelial cells that demonstrate endothelial-like molecular and physiological functions in vitro and in vivo. Injection of these induced endothelial cells into myocardial infarct sites after injury results in improved vascular perfusion of the scar region. Furthermore, we use genomic analyses to illustrate that Sox17-Erg reprogramming instructs cardiac fibroblasts toward an arterial-like identity. This results in a more efficient direct conversion of fibroblasts into endothelial-like cells when compared to traditional Etv2-based reprogramming. Overall, this Sox17-Erg direct reprogramming strategy offers a robust tool to generate endothelial cells both in vitro and in vivo, and has the potential to be used in repairing injured tissue.

The Role of GLP-1 Affects Fate of Astrocytes Following Ischemic Stroke in Mice

Stroke is one of the leading causes of physical and intellectual disability and mortality in adults of most of the developed countries. The most of studies in ischemic stroke focus on neuronal pathological mechanisms and neuronal death trying to rescue neurons via stopping the detrimental pathological processes or enhancing neuronal viability. Although astrocytes are the most abundant cells and in mammal central nervous system (CNS), they were ignored for period of time but are return to spotlight in recent years. Astrocyte play multiple roles in maintain normal function of central nervous system and respond to all kinds of CNS injury and disease. Responses of astrocytes to CNS damage lead to both detrimental and beneficial consequences. Previous studies have reported that astrocyte inflammatory responses to ischemic stroke may devastate the ischemic lesion, but other astrocytic responses lead to anti-excitotoxicity, secreting neurotrophic factors, neurogenesis, synaptogenesis, axonal remodeling, and angiogenesis promoting neuroprotective effects. Glucagon-like peptide-1 (GLP-1) have been intensively studied on beneficial effects of neurons, but not many studies work on effects of GLP-1 to astrocytes. Our early study has found that activation of GLP-1 receptors prevented ischemia-induced brain cell death and observed newly neuronal progenitor cells were from astrocyte-lineage in penumbral area of 3-day post-ischemic mouse brains by immunohistochemistry (IHC). RT-PCR, immunoblotting, and immunofluorescent results also clearly indicated the astrocytes expressed GLP-1 receptors. Furthermore, Western blotting results showed administration of GLP-1 analogue, exendin-4 (EX-4), suppressed expression of pro-inflammatory proteins in oxygen-glucose deprivation (OGD) treated mouse primary astrocytes. Interestingly, we also observed that infarct site obtained sever DNA damage and less GFAP positive astrocytes, on contrary, the penumbral area had more GFAP positive astrocytes and less DNA damage in IHC images of stroke brains. The results implied that A1 and A2 astrocytes play certain roles in ischemic brains and recovery. The goal of this study is to determine the mechanisms of GLP-1 involving in astrocytic fate decision and approach on minimizing detrimental effects and amplifying the beneficial effects, which possibly develop innovative therapies for ischemic stroke. The study is supported by 108-2320-B-182A-005-MY3 and 112-2320-B-182A-003- from Taiwan National Science and Technology Council. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of the medial agranular cortex in unilateral spatial neglect.

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among various positions of the lesions, the recovery from USN during recovery periods (postoperative day; POD 10-18) tended to be slower in cases with more rostral lesions in the AGm (r = - 0.302; p = 0.028). Moreover, the total number of arm entries and maximum moving speed did not significantly differ between before and after AGm infarction. According to these results, the anterior lesions may slowly recover from USN-like behavior, and there may be a weak association between the AGm infarct site and recovery rate. In addition, all unilateral focal infarctions in the AGm induced USN-like behavior without motor deficits.

Salidroside promotes angiogenesis after cerebral ischemia in mice through Shh signaling pathway

AimsThe purpose of this study was to explore the impacts of salidroside on vascular regeneration, vascular structural changes and long-term neurological recuperation following cerebral ischemia and its possible mechanism. Main methodsFrom Day 1 to Day 28, young male mice with middle cerebral artery blockage received daily doses of salidroside and measured neurological deficits. On the 7th day after stroke, the volume of cerebral infarction was determined using TTC and HE staining. Microvascular density, astrocyte coverage, angiogenesis and the expression of the Shh signaling pathway were detected by IF, qRTPCR and WB at 7, 14 and 28 days after stroke. Changes in blood flow, blood vessel density and diameter from stroke to 28 days were measured by the LSCI and TPMI. Key findingsCompared with the dMACO group, the salidroside treatment group significantly promoted the recovery of neurological function. Salidroside was found to enhance cerebral blood flow perfusion and reduce the infarct on the 7th day after stroke. From the 7th to the 28th day after stroke, salidroside treatment boosted the expression of CD31, CD31+/BrdU+, and GFAP in the cortex around the infarction site. On the 14th day after stroke, salidroside significantly enhanced the width and density of blood vessels. Salidroside increased the expression of histones and genes in the Shh signaling pathway during treatment, and this effect was weakened by the Shh inhibitor Cyclopamine. SignificanceSalidroside can restore nerve function, improve cerebral blood flow, reduce cerebral infarction volume, increase microvessel density and promote angiogenesis via the Shh signaling pathway.

68Ga-DOTA-D-Alanine-BoroPro Radiotracer for Imaging of the Fibroblast Activation Protein in Malignant and Non-Malignant Diseases.

Recently, we reported a new fibroblast activation protein (FAP) inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-HYNIC-D-Alanine-BoroPro)(99mTc-HYNIC-iFAP) structure for tumor microenvironment SPECT imaging. This research aimed to synthesize 68Ga-[2,2',2″,2‴-(2-(4-(2-(5-(((S)-1-((S)-2-boronopyrrolidin-1-yl)-1-oxopropan-2-yl)carbamoyl)pyridin-2-yl)hydrazine-1-carbothioamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid] (68Ga-DOTA-D-Alanine-BoroPro)(68Ga-iFAP) as a novel radiotracer for PET imaging and evaluate its usefulness for FAP expression in malignant and non-malignant tissues. The coupling of p-SCN-benzene DOTA with HYNIC-iFAP was used for the chemical synthesis and further labeling with 68Ga. Radiochemical purity was verified by radio-HPLC. The specificity of 68Ga-iFAP was evaluated in HCT116 cells, in which FAP expression was verified by immunofluorescence and Western blot. Biodistribution and biokinetic studies were performed in murine models. 68Ga-iFAP uptake at the myocardial level was assessed in mice with induced infarction. First-in-human images of 68Ga-iFAP in healthy subjects and patients with myocardial infarction, glioblastoma, prostate cancer, and breast cancer were also obtained. DOTA-D-Alanine BoroPro was prepared with a chemical purity of 98% and was characterized by UPLC mass spectroscopy, FT-IR, and UV-vis. The 68Ga-iFAP was obtained with a radiochemical purity of >95%. In vitro and in vivo studies demonstrated 68Ga-iFAP-specific recognition for FAP, rapid renal elimination, and adequate visualization of the glioblastoma, breast tumor, prostate cancer, and myocardial infarction sites. The results of this research justify further dosimetry and clinical trials to establish the specificity and sensitivity of 68Ga-iFAP PET for FAP expression imaging.

Predictors of atrial fibrillation detection in embolic stroke of undetermined source patients with implantable loop recorder.

Covert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR. This observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection. Overall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection. Our study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.

Long-Term Percutaneous Coronary Intervention Outcomes in Chronic Versus Acute Coronary Syndromes (TARGET All Comers Trial)

In the Targeted therapy with a localised abluminal coated, low-dose sirolimus-eluting, biodegreadable polymer coronary stent (TARGET; NCT02520180) All Comers trial the biodegradable polymer (BP) sirolimus-eluting FIREHAWK stent was noninferior to the durable polymer (DP) everolimus-eluting XIENCE stent with respect to target lesion failure (TLF) at 1 and 5 years; however, the long-term safety and efficacy in the setting of acute coronary syndromes (ACS) are not known. We sought to assess the long-term outcomes in ACS versus chronic coronary syndromes (CCS) with BP sirolimus-eluting stent (SES) versus DP everolimus-eluting stent (EES). The TARGET AC study was a multicenter, open-label, noninferiority trial of all comer patients randomly allocated 1:1 to BP SES or DP EES (stratified by ST-elevation myocardial infarction and study site). In this predefined substudy, the outcomes were compared based on clinical presentation (ACS vs CCS) and treatment allocation. A total of 1,653 patients were enrolled (728 with ACS and 922 with CCS), with 94% completing the 5-year follow-up. The baseline characteristics were well-matched between the 2 stent types; however, co-morbidities were more prevalent in the CCS than in the ACS population. TLF (15.5% vs 17.7%, p = 0.24), patient-oriented outcomes (32.0% vs 34.4%, p = 0.31), and stent thrombosis (4.1% vs 3.3%, p = 0.40) were similar between patients with ACS and patients with CCS. In the ACS cohort, the outcomes at 5 years for BP SES versus DP EES were similar for TLF (16.0% vs 14.9%, p = 0.70), ischemia-driven target lesion revascularization (5.6% vs 8.3%, p = 0.17), and definite/probable stent thrombosis (2.7% vs 4.6%, p = 0.18). The same was true for the CCS cohort, with 5-year outcomes for BP SES versus DP EES for TLF (18.0% vs 17.4%, p = 0.82), ischemia-driven target lesion revascularization (6.4% vs 5.0%, p = 0.37), and definite/probable stent thrombosis (3.0% vs 1.8%, p = 0.26). In conclusion, in the TARGET AC trial, 1 in 3 patients had a major adverse event at 5 years, irrespective of CCS or ACS presentation. Long-term, the BP sirolimus-eluting FIREHAWK stent was as safe and effective as the DP everolimus-eluting XIENCE stent across the spectrum of clinical presentations.

The impact of the site of myocardial infarction on in-hospital outcomes for patients with STEMI.

The territory and vessel involved in ST-elevation myocardial infarction (STEMI) is an important and there are limited contemporary studies from the national perspective. A retrospective cohort study was undertaken of national representative hospital admission in the National Inpatient Sample with a diagnosis of anterior or non-anterior STEMI between 2017 and 2020. Multiple logistic regression and multiple linear regressions were used to determine if there are any differences in in-hospital mortality, length of stay (LOS) and cost for anterior and non-anterior STEMI. A total of 655 915 admissions with STEMI were included in the analysis (267 920 anterior STEMI, and 387 995 non-anterior STEMI). Non-anterior STEMI was associated with a significant reduction in mortality (OR 0.91 95% CI 0.89-0.99, P = 0.011) and LOS (coefficient -0.15 95% CI -0.22 to -0.08, P < 0.001) compared to anterior STEMI but there was no significant difference in healthcare costs (-297 95% CI -688 to 74). Analyses considering the infarct-related artery showed that the worse outcomes were associated with left main lesions and left-sided lesions had worse outcomes than right coronary artery lesions. Non-anterior STEMI is associated with reduced mortality and LOS compared to anterior STEMI. Left-sided coronary lesions had worse outcomes, compared to right coronary lesions. STEMI should be considered in terms of the vessel or territory affected, in relation to outcomes and healthcare costs.

Establishment and validation of an extracellular volume model without blood sampling in ST-segment elevation myocardial infarction patients.

Recent studies have shown that extracellular volume (ECV) can also be obtained without blood sampling by the linear relationship between haematocrit (HCT) and blood pool R1 (1/T1). However, whether this relationship holds for patients with myocardial infarction is still unclear. This study established and validated an ECV model without blood sampling in ST-segment elevation myocardial infarction (STEMI) patients. A total of 398 STEMI patients who underwent cardiac magnetic resonance (CMR) examination with T1 mapping and venous HCT within 24 h were retrospectively analysed. All patients were randomly divided into a derivation group and a validation group. The mean CMR scan time was 3 days after primary percutaneous coronary intervention. In the derivation group, a synthetic HCT formula was obtained by the linear regression between HCT and blood pool R1 (R 2 = 0.45, P < 0.001). The formula was used in the validation group; the results showed high concordance and correlation between synthetic ECV and conventional ECV in integral (bias = -0.12; R 2 = 0.92, P < 0.001), myocardial infarction site (bias = -0.23; R 2 = 0.93, P < 0.001), and non-myocardial infarction sites (bias = -0.09; R 2 = 0.94, P < 0.001). In STEMI patients, synthetic ECV without blood sampling had good consistency and correlation with conventional ECV. This study might provide a convenient and accurate method to obtain the ECV from CMR to identify myocardial fibrosis.

Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction.

After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB. This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels. The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

2,5-Dimethyl-celecoxib induces early termination of inflammatory responses by transient macrophage accumulation and inhibits the progression of cardiac remodeling in a mouse model of cryoinjury-induced myocardial infarction

In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM-C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart failure, including myocardial infarction (MI). The inflammatory response after MI affects the progression of cardiac remodeling, wherein the immune cells, mainly macrophages, play crucial roles. Therefore, we evaluated the effect of DM-C on macrophages in a cryoinjury-induced myocardial infarction (CMI) mouse model. We observed that DM-C attenuated the deterioration of left ventricular ejection fraction and cardiac fibrosis 14 d after CMI. Gene expression of pro-inflammatory cytokines at the infarct site was reduced by DM-C treatment. Analysis of macrophage surface antigens revealed that DM-C induced transient accumulation of macrophages at the infarct site without affecting their polarization. In vitro experiments using peritoneal monocytes/macrophages revealed that DM-C did not directly increase the phagocytic ability of the macrophages but increased their number, thereby upregulating the clearance capacity. Moreover, DM-C rapidly excluded the cells expressing necrotic cell marker from the infarct site. These results suggested that DM-C enhanced the clearance capacity of macrophages by transiently increasing their number at the infarct site, and terminated the escape from the inflammatory phase earlier, thereby suppressing excessive cardiac remodeling and ameliorating cardiac dysfunction.

A Biomimetic Nanocarrier Strategy Targets Ferroptosis and Efferocytosis During Myocardial Infarction.

Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI. In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation. The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function. Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI.

Osteomielite em Pacientes com Doença Falciforme

Objective: identify clinical and laboratory characteristics of osteomyelitis (OM) in 3 patients with sickle cell disease (SCD). Metodology: Retrospective evaluation of medical records of a tertiary University Hospital in São Paulo. Discussion: The cases described were comparable to Weisman, 2020, regarding age and the higher frequency of involvement of long bones, and 2 of the 3 patients are homozygous for SCD. The three patients had leukocytosis similar to those found in the literature (Fontalis et al, 2019), and all showed an increase in CRP as the OM progressed, showing reduction in values ??when treatment started. Pain and local edema were present in the reported cases, and two of them presented pain in different sites, being diagnosed in these cases. In this study, no agent was isolated in blood cultures, as reported by Fontalis 2019. In case 1, the imaging exam showed expected changes, while in cases 2 and 3, the patients had involvement of long bones, the most common sites of previous bone infarction, acute and chronic alterations were found (Al Farii et al., 2020). Conclusion: SCD patients are at increased risk for osteomyelitis. The differential diagnosis between bone infarction related to vaso-occlusive crisis is a challenge, as the initial clinical presentation is similar. Osteomyelitis should be suspected in patients with SCD who present a vaso-occlusive crisis in only one site, with prolonged fever and an increase in inflammatory evidence. Early antibiotic therapy directed at the most frequent agents can avoid complications and allow for better prognosis.