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Prostaglandins & Other Lipid Mediators Jun 2024Atherosclerosis is a chronic inflammatory disease forming plaques in medium and large-sized arteries. ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin...
Atherosclerosis is a chronic inflammatory disease forming plaques in medium and large-sized arteries. ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) is an extracellular-matrix remodelling enzyme involved in the degradation of versican in the arterial wall. Recent reports indicated that increased expression of ADAMTS-4 is associated with plaque progression and vulnerability. Bioactive components of dietary oil, like sesame oil, are reported to have anti-inflammatory and antioxidant properties. Here, we studied the effect of sesame oil on regulating ADAMTS-4 in high-fat diet-induced atherosclerosis rat model. Our results indicated that sesame oil supplementation improved the anti-inflammatory and anti-oxidative status of the body. It also reduced atherosclerotic plaque formation in high-fat diet-fed rats. Our results showed that the sesame oil supplementation significantly down-regulated the expression of ADAMTS-4 in serum and aortic samples. The versican, the large proteoglycan substrate of ADAMTS-4 in the aorta, was downregulated to normal control level on sesame oil supplementation. This study, for the first time, reveals that sesame oil could down-regulate the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis, imparting a new therapeutic potential for sesame oil in the management of atherosclerosis.
PubMed: 38936541
DOI: 10.1016/j.prostaglandins.2024.106862 -
International Journal of Molecular... Jun 2024Takayasu's arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The... (Review)
Review
Takayasu's arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. Advancements in technology have facilitated the identification of novel autoantibodies in TAK. Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK. Additionally, ectopic lymphoid neogenesis within the aortic wall of TAK patients exhibits functional characteristics. In recent decades, therapeutic interventions targeting B cells, notably utilizing the anti-CD20 monoclonal antibody rituximab, have demonstrated efficacy in TAK. Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. Furthermore, it examines the roles of T-helper and T follicular helper cells in humoral immunity and their potential contributions to disease mechanisms. We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients. We believe that further elucidation of the pathogenic role of autoimmune B cells and the underlying regulatory mechanisms holds promise for the development of personalized approaches to managing TAK patients.
Topics: Takayasu Arteritis; Humans; B-Lymphocytes; Immunity, Humoral; Rituximab; Autoimmunity; Animals; Autoantibodies
PubMed: 38928233
DOI: 10.3390/ijms25126528 -
Bioengineering (Basel, Switzerland) Jun 2024Autologous-engineered artificial tissues constitute an ideal alternative for radical surgery in terms of natural anticoagulation, self-repair, tissue regeneration, and... (Review)
Review
Autologous-engineered artificial tissues constitute an ideal alternative for radical surgery in terms of natural anticoagulation, self-repair, tissue regeneration, and the possibility of growth. Previously, we focused on the development and practical application of artificial tissues using "in-body tissue architecture (iBTA)", a technique that uses living bodies as bioreactors. This study aimed to further develop iBTA by fabricating tissues with diverse shapes and evaluating their physical properties. Although the breaking strength increased with tissue thickness, the nominal breaking stress increased with thinner tissues. By carving narrow grooves on the outer periphery of an inner core with narrow grooves, we fabricated approximately 2.2 m long cord-shaped tissues and net-shaped tissues with various designs. By assembling the two inner cores inside the branched stainless-steel pipes, a large graft with branching was successfully fabricated, and its aortic arch replacement was conducted in a donor goat without causing damage. In conclusion, by applying iBTA technology, we have made it possible, for the first time, to create tissues of various shapes and designs that are difficult using existing tissue-engineering techniques. Thicker iBTA-induced tissues exhibited higher rupture strength; however, rupture stress was inversely proportional to thickness. These findings broaden the range of iBTA-induced tissue applications.
PubMed: 38927834
DOI: 10.3390/bioengineering11060598 -
Biomedicines Jun 2024Pigs as laboratory animals are used in preclinical studies aimed at developing medical devices for cardiac surgery. The anatomy of the cardiovascular system of these...
Pigs as laboratory animals are used in preclinical studies aimed at developing medical devices for cardiac surgery. The anatomy of the cardiovascular system of these animals has been well studied and acknowledged as suitable for use and the testing of new cardiovascular devices developed for humans. However, there are no morphometric characteristics of the aortic root and thoraco-abdominal part of porcine aorta. This can lead to difficulties in experimental surgery and even result in the death of experimental animals due to the mismatch in the size of the implantable devices. Thus, such information is essential to enhance the efficiency of surgical technologies used for eliminating aortic pathologies in their various sections. The purpose of our research is to study the anatomy of the aorta in mini pigs and to assess whether the size, age, and sex of the animals affect the size of the main structures in their aortas. In addition, we attempted to compare the results obtained by transesophageal echocardiography (TEE) and angiography. We studied 28 laboratory mini pigs, dividing them into three groups by body weight (40-70 kg, 71-90 kg, and 90 kg). We did not find any relationship between the external somatometric characteristics of the animals and the size of their aortas. Animals have individual anatomical variability in their cardiovascular systems, which means that they need to be examined in terms of preoperative planning by any available method-echocardiography, angiography, or multispiral computed tomography (CT).
PubMed: 38927452
DOI: 10.3390/biomedicines12061245 -
Biomolecules Jun 2024Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of...
Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4 T cells, CD8 T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1β and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1β and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.
Topics: Animals; Angiotensin II; Aortic Aneurysm, Abdominal; Mice; Male; Sulfonamides; Apolipoproteins E; Phosphate-Binding Proteins; Disease Models, Animal; Mice, Inbred C57BL; Macrophages; Indoles; Mice, Knockout, ApoE; Gasdermins
PubMed: 38927129
DOI: 10.3390/biom14060726 -
Journal of Cardiothoracic Surgery Jun 2024Perioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning...
BACKGROUND
Perioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning (ML) method has been widely used in perioperative risk predictions during cardiac surgery. However, the utilization of ML in PMI has not been studied yet. Therefore, we sought to develop and validate the performances of ML for PMI with different cut-off values in cardiac surgery with cardiopulmonary bypass (CPB).
METHODS
This was a second analysis of a multicenter clinical trial (OPTIMAL) and requirement for written informed consent was waived due to the retrospective design. Patients aged 18-70 undergoing elective cardiac surgery with CPB from December 2018 to April 2021 were enrolled in China. The models were developed using the data from Fuwai Hospital and externally validated by the other three cardiac centres. Traditional logistic regression (LR) and eleven ML models were constructed. The primary outcome was PMI, defined as the postoperative maximum cardiac Troponin I beyond different times of upper reference limit (40x, 70x, 100x, 130x) We measured the model performance by examining the area under the receiver operating characteristic curve (AUROC), precision-recall curve (AUPRC), and calibration brier score.
RESULTS
A total of 2983 eligible patients eventually participated in both the model development (n = 2420) and external validation (n = 563). The CatboostClassifier and RandomForestClassifier emerged as potential alternatives to the LR model for predicting PMI. The AUROC demonstrated an increase with each of the four cutoffs, peaking at 100x URL in the testing dataset and at 70x URL in the external validation dataset. However, it's worth noting that the AUPRC decreased with each cutoff increment. Additionally, the Brier loss score decreased as the cutoffs increased, reaching its lowest point at 0.16 with a 130x URL cutoff. Moreover, extended CPB time, aortic duration, elevated preoperative N-terminal brain sodium peptide, reduced preoperative neutrophil count, higher body mass index, and increased high-sensitivity C-reactive protein levels were identified as risk factors for PMI across all four cutoff values.
CONCLUSIONS
The CatboostClassifier and RandomForestClassifer algorithms could be an alternative for LR in prediction of PMI. Furthermore, preoperative higher N-terminal brain sodium peptide and lower high-sensitivity C-reactive protein were strong risk factor for PMI, the underlying mechanism require further investigation.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Cardiac Surgical Procedures; Cardiopulmonary Bypass; China; Machine Learning; Postoperative Complications; Retrospective Studies; Risk Assessment
PubMed: 38926872
DOI: 10.1186/s13019-024-02856-y -
Heart, Lung & Circulation Jun 2024Admission systolic blood pressure is a significant predictor of in-hospital mortality in patients with acute type A aortic dissection (ATAAD). While previous studies...
AIM
Admission systolic blood pressure is a significant predictor of in-hospital mortality in patients with acute type A aortic dissection (ATAAD). While previous studies have focussed on recording the highest blood pressure value from both arms, this study aimed to evaluate the associations between blood pressure in bilateral arms and in-hospital mortality.
METHODS
Data were analysed from 262 patients with ATAAD treated at a single centre. The relationship between bilateral arm blood pressure upon admission and in-hospital mortality was assessed in a logistic regression model. To comprehensively evaluate potential non-linear relationships, the association between admission bilateral systolic blood pressure (SBP) and the risk of in-hospital mortality was analysed using restricted cubic splines on a continuous scale.
RESULTS
Mean age was 53.6±12.5 years and 194 (74.0%) were male. Baseline and operative data showed that ages, body mass index, smoking, left-arm SBP, left-arm diastolic blood pressure (DBP), right-arm SBP, right-arm DBP, syncope, cerebral/cardiac ischaemia, retrograde brain perfusion, Bentall procedure, coronary artery bypass grafting, and aortic valve replacement significantly differed among the left-arm SBP tertiles. In-hospital mortality was 17.6% (46 of 262). Restricted cubic splines demonstrated that the relationship between presenting left-arm SBP and in-hospital mortality followed a U-shaped curve, whereas non-linearity was not detected in the right arm.
CONCLUSION
This study found a U-shaped association between admission left-arm SBP and in-hospital mortality in ATAAD surgery patients, whereas a non-linearity relationship was not detected for right-arm SBP. Low left-arm SBP independently correlated with increased in-hospital mortality, underscoring the significance of bilateral blood pressure differences in ATAAD prognosis.
PubMed: 38925995
DOI: 10.1016/j.hlc.2024.03.017 -
Journal of Vascular Surgery Jun 2024This study aimed to determine the influences of varying severity of sleep apnea syndrome (SAS) on the outcomes after thoracic endovascular aorta repair (TEVAR) in...
OBJECTIVE
This study aimed to determine the influences of varying severity of sleep apnea syndrome (SAS) on the outcomes after thoracic endovascular aorta repair (TEVAR) in patients with Stanford type B aortic dissection (TBAD).
METHODS
This observational study focused on individuals with TBAD plus SAS who received TEVAR between January 2018 and December 2022. Patients were divided into groups according to the results of the portable sleep-breathing monitoring systems (PSMS): mild SAS (MSAS) and moderate-to-severe SAS (MSSAS). Clinical profiles were collected and analyzed.
RESULTS
A total of 121 cases with TBAD plus SAS who underwent TEVAR were enrolled in this study. Two groups were formed by stratifying these cases: MSAS (74 cases) and MSSAS (47 cases). The MSSAS cases were found to be older relative to MSAS cases (51.7 ± 8.3 vs. 57.1 ± 12.8 years, p = 0.012) and had a higher body mass index (BMI; 25.7 ± 2.3 vs. 27.0 ± 2.3 kg/m, p = 0.038). The investigation did not find any appreciable differences between the MSAS and MSSAS groups in terms of complications (endoleak: p = 0.403, SINE: p = 1.000, stent displacement: p = 1.000). However, the MSSAS group exhibited a significantly higher overall mortality rate compared to MSAS group (log-rank p = 0.027). The tendency continued when examining cases with Marfan syndrome (MFS) combined with MSSAS, where the overall mortality rate was significantly greater compared to MFS cases with MSAS (log-rank p = 0.037). The absence of a significant difference was noteworthy in the freedom from reintervention between the MSAS and MSSAS groups (log-rank p = 0.278). The overall mortality rate was significantly higher in MSSAS group even after adjusting for varying potential confounders in the multivariate cox regression analysis (HR 95%CI: 1.875 [1.238-2.586], p = 0.012). A markedly higher rate of distal stent dilation in the MSSAS group was also observed compared to the MSAS group (2.5 [2, 3] vs. 4 [2, 5.5] mm/year, p = 0.029).
CONCLUSIONS
MSSAS is associated with a significantly higher risk of overall mortality and dilation rate of the distal stent after TEVAR for TBAD patients. Hence, aggressive efforts to reverse the severity of SAS in time in these individuals appear necessary.
PubMed: 38925349
DOI: 10.1016/j.jvs.2024.06.023 -
Bone Jun 2024Osteoporosis is underdiagnosed, especially in ethnic and racial minorities who are thought to be protected against bone loss, but often have worse outcomes after an...
Osteoporosis is underdiagnosed, especially in ethnic and racial minorities who are thought to be protected against bone loss, but often have worse outcomes after an osteoporotic fracture. We aimed to determine the prevalence of osteoporosis by opportunistic CT in patients who underwent lung cancer screening (LCS) using non-contrast CT in the Northeastern United States. Demographics including race and ethnicity were retrieved. We assessed trabecular bone and body composition using a fully-automated artificial intelligence algorithm. ROIs were placed at T12 vertebral body for attenuation measurements in Hounsfield Units (HU). Two validated thresholds were used to diagnose osteoporosis: high-sensitivity threshold (115-165 HU) and high specificity threshold (<115 HU). We performed descriptive statistics and ANOVA to compare differences across sex, race, ethnicity, and income class according to neighborhoods' mean household incomes. Forward stepwise regression modeling was used to determine body composition predictors of trabecular attenuation. We included 3708 patients (mean age 64 ± 7 years, 54 % males) who underwent LCS, had available demographic information and an evaluable CT for trabecular attenuation analysis. Using the high sensitivity threshold, osteoporosis was more prevalent in females (74 % vs. 65 % in males, p < 0.0001) and Whites (72 % vs 49 % non-Whites, p < 0.0001). However, osteoporosis was present across all races (38 % Black, 55 % Asian, 56 % Hispanic) and affected all income classes (69 %, 69 %, and 91 % in low, medium, and high-income class, respectively). High visceral/subcutaneous fat-ratio, aortic calcification, and hepatic steatosis were associated with low trabecular attenuation (p < 0.01), whereas muscle mass was positively associated with trabecular attenuation (p < 0.01). In conclusion, osteoporosis is prevalent across all races, income classes and both sexes in patients undergoing LCS. Opportunistic CT using a fully-automated algorithm and uniform imaging protocol is able to detect osteoporosis and body composition without additional testing or radiation. Early identification of patients traditionally thought to be at low risk for bone loss will allow for initiating appropriate treatment to prevent future fragility fractures. CLINICALTRIALS.GOV IDENTIFIER: N/A.
PubMed: 38925254
DOI: 10.1016/j.bone.2024.117176 -
JMIR Cardio Jun 2024Heart failure (HF) contributes greatly to morbidity, mortality, and health care costs worldwide. Hospital readmission rates are tracked closely and determine federal...
BACKGROUND
Heart failure (HF) contributes greatly to morbidity, mortality, and health care costs worldwide. Hospital readmission rates are tracked closely and determine federal reimbursement dollars. No current modality or technology allows for accurate measurement of relevant HF parameters in ambulatory, rural, or underserved settings. This limits the use of telehealth to diagnose or monitor HF in ambulatory patients.
OBJECTIVE
This study describes a novel HF diagnostic technology using audio recordings from a standard mobile phone.
METHODS
This prospective study of acoustic microphone recordings enrolled convenience samples of patients from 2 different clinical sites in 2 separate areas of the United States. Recordings were obtained at the aortic (second intercostal) site with the patient sitting upright. The team used recordings to create predictive algorithms using physics-based (not neural networks) models. The analysis matched mobile phone acoustic data to ejection fraction (EF) and stroke volume (SV) as evaluated by echocardiograms. Using the physics-based approach to determine features eliminates the need for neural networks and overfitting strategies entirely, potentially offering advantages in data efficiency, model stability, regulatory visibility, and physical insightfulness.
RESULTS
Recordings were obtained from 113 participants. No recordings were excluded due to background noise or for any other reason. Participants had diverse racial backgrounds and body surface areas. Reliable echocardiogram data were available for EF from 113 patients and for SV from 65 patients. The mean age of the EF cohort was 66.3 (SD 13.3) years, with female patients comprising 38.3% (43/113) of the group. Using an EF cutoff of ≤40% versus >40%, the model (using 4 features) had an area under the receiver operating curve (AUROC) of 0.955, sensitivity of 0.952, specificity of 0.958, and accuracy of 0.956. The mean age of the SV cohort was 65.5 (SD 12.7) years, with female patients comprising 34% (38/65) of the group. Using a clinically relevant SV cutoff of <50 mL versus >50 mL, the model (using 3 features) had an AUROC of 0.922, sensitivity of 1.000, specificity of 0.844, and accuracy of 0.923. Acoustics frequencies associated with SV were observed to be higher than those associated with EF and, therefore, were less likely to pass through the tissue without distortion.
CONCLUSIONS
This work describes the use of mobile phone auscultation recordings obtained with unaltered cellular microphones. The analysis reproduced the estimates of EF and SV with impressive accuracy. This technology will be further developed into a mobile app that could bring screening and monitoring of HF to several clinical settings, such as home or telehealth, rural, remote, and underserved areas across the globe. This would bring high-quality diagnostic methods to patients with HF using equipment they already own and in situations where no other diagnostic and monitoring options exist.
PubMed: 38924781
DOI: 10.2196/57111