Coronary angiography through the interosseous artery: expanding the limits of the wrist approach.

A 59-year-old diabetic man with a history of numerous coronary angiographies (CAs) and peripheral artery disease underwent CA due to a non-ST elevation myocardial infarction. Femoral, radial, and ulnar arteries were unpalpable.

Perceval-S over time. Clinical outcomes after ten years of usage.

BACKGROUND: Perceval-S has become a reliable and commonly used option in surgical aortic valve replacement (AVR) since its first implantation in humans 15 years ago. Despite the fact that this aortic valve has been proven efficient enough in the short and mid-term period, there is still lack of evidence for the long-term outcomes. MATERIALS AND METHODS: This is an observational retrospective study in a high-volume cardiovascular center. Pertinent data were collected for all the patients in whom Perceval-S was implanted from 2013 to 2020. RESULTS: The total number of patients was 205 with a mean age 76.4 years. Mean survival time was 5.5 years (SE = 0.26). The overall survival probability of patients undergoing aortic valve replacement with Perceval-S at 6 months was 91.0% (Standard Error SE = 2.0%), at one year 88.4% (SE = 2.3%) and at 5-years 64.8% (SE = 4.4%). A detrimental cardiac event leading to death was the probable cause of death in 35 patients (55.6%). The initiation of Transcatheter Aortic Valve Replacement (TAVR) program in our center in 2017 was associated with a decline in the number of very high-risk patients treated with sutureless bioprosthesis. This fact is demonstrated by the significant shift towards lower surgical risk cases, as median Euroscore II was reduced from 5,550 in 2016 to 3,390 in 2020. Mini sternotomy was implemented in 79,5% of cases favoring less invasive approach. Low incidence of reinterventions, patient prosthesis mismatch and structural valve degeneration was detected. CONCLUSIONS: The survival rate after aortic valve replacement with implantation of Perceval-S is satisfactory in the long-term follow-up. Cases of bioprosthesis dysfunction were limited. Mini sternotomy was used in the majority of cases. TAVR initiation program impacted on the proportion of patients treated with Perceval-S with reduction of high-risk patients submitted to surgery.

Atrial fibrillation post CABG and the risk of arrhythmia recurrence: the AFRODITE study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass surgery (CABG) occurs with an incidence of 20-40%. The clinical relevance of POAF remains a concern, and the need for further studies regarding the clinical management of POAF is necessary. AIM: The AFRODITE study, a prospective multicenter cohort study, had as its primary endpoint the evaluation of AF recurrence in patients post CABG over a one-year period. METHODS: Two hundred twenty-eight patients aged >50 years who underwent isolated CABG were included in the study. Patients were stratified into two groups, POAF and non-POAF, and followed for 12 months for AF recurrence, hospitalizations, and death. RESULTS: Two hundred twenty-eight patients (mean age 67 years, 88.6% male) were included in the study. 28.5% of patients experienced at least one episode of POAF during index hospitalization (POAF group) and were compared with the non-POAF group (n = 163). Multivariate stepwise logistic regression analysis showed that the strongest prognostic parameter for POAF was the CHA2DS2-VASc score (odds ratio = 1.61, p < 0.001). POAF patients had a worse in-hospital outcome, but the incidence of long-term AF recurrence was not statistically different (3.6% vs. 4.8%, p = 0.9). CONCLUSION: Interestingly, a one-year prospective follow-up of patients in the study did not reveal significant differences between POAF and non-POAF patients. A notable finding was that patients with a higher CHA2DS2-VASc score were more likely to develop POAF.

Anticoagulation in Patients with Atrial High-rate Episodes Detected by Cardiac Implantable Electronic Devices.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias that are identified by the use of continuous rhythm monitoring devices such as pacemakers, defibrillators, or implantable cardiac monitors. Nevertheless, the therapeutic implications of these rhythm disturbances remain uncertain. The presence of AHRE is associated with an increased risk of stroke as compared to patients who do not exhibit AHRE. The utilisation of oral anticoagulation has the ability to mitigate the likelihood of stroke occurrence in patients with AHRE. However, it is important to note that this treatment approach is also linked to a severe bleeding rate of approximately 2% per year. The stroke rate among individuals diagnosed with AHRE appears to be comparatively lower when compared to patients diagnosed with atrial fibrillation. The efficacy and safety of anticoagulation in patients with AHRE have yet to be definitively established. Further research is required to provide a comprehensive understanding of the effectiveness and safety of oral anticoagulation in individuals with AHRE.

The Thyroid-cardiac Axis: Thyroid Function, Cardiac Rhythmology, and Sudden Cardiac Death.

It is well known that thyroid dysfunction increases the risk of cardiovascular mortality and morbidity. The pleiotropic effect of thyroid hormones has a profound effect on the cardiovascular system, influencing both the formation of a normal cardiac rhythm and rhythm disturbance. A number of research studies have demonstrated correlations between TSH and FT4 levels and significant cardiovascular events. The pathophysiological mechanisms underlying these complex associations are, however, inadequately defined. A system-based examination of the relationship between thyroid homeostasis and cardiovascular disease could pave the way for novel study areas and a more individualised strategy for the management of individuals at cardiovascular risk.

Development of a novel histone deacetylase inhibitor unveils the role of HDAC11 in alleviating depression by inhibition of microglial activation.

Histone deacetylases (HDACs) are key epigenetic regulators and classified into four subtypes. Despite the various roles of each HDAC isoform, the lack of selective HDAC inhibitors has limited the elucidation of their roles in biological systems. HDAC11, the sole class-IV HDAC, is highly expressed in the brain, however, the role of HDAC11 in microglia is not fully understood. Based on the modification of MC1568, we developed a novel HDAC inhibitor, 5. Interestingly, 5 suppresses lipopolysaccharide-induced microglial activation by the initiation of autophagy and subsequent inhibition of nitric oxide production. Furthermore, we demonstrated that 5 significantly alleviates depression-like behavior by inhibiting microglial activation in mouse brain. Our discovery reveals that specific pharmacological regulation of HDAC11 induces autophagy and reactive nitrogen species balance in microglia for the first time, which makes HDAC11 a new therapeutic target for depressive disorder.

Tumor Markers and Their Diagnostic Significance in Ovarian Cancer.

Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis. PURPOSE: This paper explores the diagnostic importance of various tumor markers including CA-125, CA15-3, CA 19-9, HE4,hCG, inhibin, AFP, and LDH, and their impact on disease monitoring and treatment response assessment. METHODS: Article searches were performed on PubMed, Scopus, and Google Scholar. Keywords used for the searching process were "Ovarian cancer", "Cancer biomarkers", "Early detection", "Cancer diagnosis", "CA-125","CA 15-3","CA 19-9", "HE4","hCG", "inhibin", "AFP", "LDH", and others. RESULTS: HE4, when combined with CA-125, shows improved sensitivity and specificity, particularly in early-stage detection. Additionally, hCG holds promise as a prognostic marker, aiding treatment response prediction and outcome assessment. Novel markers like microRNAs, DNA methylation patterns, and circulating tumor cells offer potential for enhanced diagnostic accuracy and personalized management. Integrating these markers into a comprehensive panel may improve sensitivity and specificity in ovarian cancer diagnosis. However, careful interpretation of tumor marker results is necessary, considering factors such as age, menopausal status, and comorbidities. Further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management. In conclusion, tumor markers such as CA-125, CA15-3, CA 19-9, HE4, and hCG provide valuable insights into ovarian cancer diagnosis, monitoring, and prognosis, with the potential to enhance early detection.

Evaluation of Vitamin D-enriched Bone Graft in Surgically-induced Critical-sized Bone Defects: An Experimental Study.

BACKGROUND: Restoration of bone defects in the craniac vault may require the use of autografts, allografts, xenografts, or synthetic grafts. There are promising data that vitamin D may play a positive role in graft incorporation. The purpose of the present study is the evaluation of the impact of vitamin D addition to human-derived bone grafts in the healing of critical-sized bone defects in porcine skulls. MATERIALS AND METHODS: Four identical critical-sized defects were created in the calvaria of 8 adult Landrace Large White pigs. The first defect was left blank as control, the second defect was filled with human-derived bone graft, the third defect was filled with human-derived bone graft enriched with a low concentration of vitamin D (2 mg/mL), and the fourth defect was filled with human-derived bone graft enriched with a high concentration of vitamin D (10 mg/mL). The animals were sacrificed after 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation (bone volume/tissue volume) was quantitatively measured by histomorphometry. RESULTS: Signs of bone formation were evident in all bone sockets. Mean values of the bone volume/tissue volume of the 4 defects were 10.91%, 11.05%, 10.40% and 10.87% respectively, at 12 weeks. In 5 animals, high concentration of vitamin D caused a significant improvement in bone formation in relation to controls. In 3 animals, a high concentration of vitamin D was associated with decreased bone formation compared with controls. No statistical difference was observed in the graft healing among the 4 graft sites ( P > 0.05). CONCLUSIONS: The results of this study have shown that the addition of vitamin D to human-derived bone grafts does not have a significant effect on bone formation and graft incorporation in critical-sized bone defects of the porcine calvaria. Further high-quality studies are needed to fully elucidate the role of vitamin D in bone formation and bone graft union.

Targeted Proteomic Analysis of Patients with Ascending Thoracic Aortic Aneurysm.

BACKGROUND: There is a need for clinical markers to aid in the detection of individuals at risk of harboring an ascending thoracic aneurysm (ATAA) or developing one in the future. OBJECTIVES: To our knowledge, ATAA remains without a specific biomarker. This study aims to identify potential biomarkers for ATAA using targeted proteomic analysis. METHODS: In this study, 52 patients were divided into three groups depending on their ascending aorta diameter: 4.0-4.5 cm (N = 23), 4.6-5.0 cm (N = 20), and >5.0 cm (N = 9). A total of 30 controls were in-house populations ethnically matched to cases without known or visible ATAA-related symptoms and with no ATAA familial history. Before the debut of our study, all patients provided medical history and underwent physical examination. Diagnosis was confirmed by echocardiography and angio-computed tomography (CT) scans. Targeted-proteomic analysis was conducted to identify possible biomarkers for the diagnosis of ATAA. RESULTS: A Kruskal-Wallis test revealed that C-C motif chemokine ligand 5 (CCL5), defensin beta 1 (HBD1), intracellular adhesion molecule-1 (ICAM1), interleukin-8 (IL8), tumor necrosis factor alpha (TNFα) and transforming growth factor-beta 1 (TGFB1) expressions are significantly increased in ATAA patients in comparison to control subjects with physiological aorta diameter (p < 0.0001). The receiver-operating characteristic analysis showed that the area under the curve values for CCL5 (0.84), HBD1 (0.83) and ICAM1 (0.83) were superior to that of the other analyzed proteins. CONCLUSIONS: CCL5, HBD1 and ICAM1 are very promising biomarkers with satisfying sensitivity and specificity that could be helpful in stratifying risk for the development of ATAA. These biomarkers may assist in the diagnosis and follow-up of patients at risk of developing ATAA. This retrospective study is very encouraging; however, further in-depth studies may be worthwhile to investigate the role of these biomarkers in the pathogenesis of ATAA.

Correction to: The effect of endometriosis on fertility in an animal model.

[This corrects the article DOI: 10.25122/jml-2021-0391.].

Genome-Wide Analysis of lncRNA-mRNA Co-Expression Networks in CD133+/CD44+ Stem-like PDAC Cells.

Pancreatic ductal adenocarcinoma (PDAC), the second most prevalent gastrointestinal malignancy and the most common type of pancreatic cancer is linked with poor prognosis and, eventually, with high mortality rates. Early detection is seldom, while tumor heterogeneity and microarchitectural alterations benefit PDAC resistance to conventional therapeutics. Although emerging evidence suggest the core role of cancer stem cells (CSCs) in PDAC aggressiveness, unique stem signatures are poorly available, thus limiting the efforts of anti-CSC-targeted therapy. Herein, we report the findings of the first genome-wide analyses of mRNA/lncRNA transcriptome profiling and co-expression networks in PDAC cell line-derived CD133+/CD44+ cells, which were shown to bear a CSC-like phenotype in vitro and in vivo. Compared to CD133-/CD44- cells, the CD133+/CD44+ population demonstrated significant expression differences in both transcript pools. Using emerging bioinformatic tools, we performed lncRNA target coding gene prediction analysis, which revealed significant Gene Ontology (GO), pathway, and network enrichments in many dyregulated lncRNA nearby (cis or trans) mRNAs, with reported involvement in the regulation of CSC phenotype and functions. In this context, the construction of lncRNA/mRNA networks by ingenuity platforms identified the lncRNAs ATF2, CHEK1, DCAF8, and PAX8 to interact with "hub" SC-associated mRNAs. In addition, the expressions of the above lncRNAs retrieved by TCGA-normalized RNAseq gene expression data of PAAD were significantly correlated with clinicopathological features of PDAC, including tumor grade and stage, nodal metastasis, and overall survival. Overall, our findings shed light on the identification of CSC-specific lncRNA signatures with potential prognostic and therapeutic significance in PDAC.

Residual strains in ascending thoracic aortic aneurysms: The effect of valve type, layer, and circumferential quadrant.

The stress distribution in ascending thoracic aortic aneurysms is determined by the mechanical properties, geometry, loading conditions, and zero-stress state of the aneurysmal aorta. Our objective was to fully characterize the zero-stress state of the aneurysmal aorta in twelve tricuspid aortic valve patients and eight (age/aortic diameter-matched) bicuspid aortic valve patients, for which little data are available. Opening angles and residual stretches were measured for the intact wall and individual layers according to quadrant and were similar in the two patient groups. The intact-wall and medial opening angles were comparable; their circumferential but not their axial ones peaked in the left lateral quadrant, with non-significant regional differences in the other layers. The intima's circumferential opening angles were the highest of all layers (∼300 deg) and the adventitia's the lowest (∼165 deg), with lesser layer differences in the axial opening angles. Upon radially cutting aortic rings, the released circumferential residual stretches were tensile (of large magnitude) externally and compressive (of small magnitude) internally, unlike the axial residual stretches released when cutting intact-wall strips, whose magnitude was small externally and large internally. Nevertheless, large circumferential compressive residual stretches were released in the adventitia upon layer dissection, counteracting the large circumferential tensile stretches of the intact wall externally. Moreover, the large axial tensile residual stretches of the intima counteracted the large axial compressive stretches of the intact wall internally. These layer-specific residual stretches may moderate the in-vivo stress gradients across wall thickness, serving as a protective mechanism against aortic dissection or rupture.

The Role of MicroRNA-126 in Atherosclerotic Cardiovascular Diseases.

Atherosclerotic cardiovascular diseases remain the leading cause of morbidity and mortality worldwide despite all efforts made towards their management. Other than targeting the traditional risk factors for their development, scientific interest has been shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront. MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases. Downregulated expression of this miR has been associated with highly prevalent cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the same time, its diagnostic and prognostic capability concerning coronary artery disease is still under investigation, with up-to-date data pointing towards a dysregulated expression in a stable disease state and acute myocardial infarction. Moreover, a lower expression of miR-126 may indicate a higher disease complexity, as well as an increased risk for future major adverse cardiac and cerebrovascular events. Ultimately, overexpression of miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects. However, the existing challenges in miR therapeutics need to be resolved before translation to clinical practice.

The effect of endometriosis on fertility in an animal model.

The present experimental model aimed to investigate the possible effect of endometriosis on ovarian function by altering follicular maturation and development. This single-blind, randomized study included twenty-four female Sprague Dawley mice, 2.5 months old, weighing 160-200 grams. The animals were randomly separated into four groups on the day of the surgery. Each group consisted of 6 mice. The first group (A) consisted of healthy female mice (control group). The second group (B) consisted of mice subjected to surgical insertion of ovarian endometrioma. The third group (C) consisted of mice subjected to surgically induced diffuse intraperitoneal endometriosis, and the fourth group (D) consisted of mice subjected to surgically induced extraperitoneal endometriosis. According to our experimental model, endometriosis may affect ovarian function by increasing the number of luteinized unruptured follicles (follicles that have undergone luteinization without prior rupture).

Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens.

AIMS: Inflammatory dysregulation of mechanosensitive developmental genes may be central to atherogenesis. In the present seven-week model, we utilized colchicine regimens to curtail aortic atherogenesis in New Zealand White rabbits. We also explored the effect of colchicine regimens on atheroprotective (Klotho, HOXA5, NOTCH1, and OCT4) and proatherogenic (HIF1a, SOX2, BMP4, and NANOG) genes. METHODS: The control (n = 6) and group A (n = 6) received standard and cholesterol-enriched chow, respectively. Groups B (n = 8) and C (n = 8) were fed hypercholesterolemic diet and were treated with colchicine plus fenofibrate or N-acetylcysteine (NAC), respectively. RESULTS: Group A developed significantly greater thoracic and abdominal aortic atherosclerosis compared to groups B (p < 0.001) and C (p < 0.001). Combining colchicine with NAC resulted in stronger atheroprotection both in the thoracic and the abdominal aorta. In group A thoracic aortas, Klotho was downregulated compared to controls (95% CI: 1.82-15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p < 0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (95% CI: -8.09 to -0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (95% CI: 0.37-8.29). In the abdominal aorta, hypercholesterolemic diet resulted in significant downregulation of HOXA5 (95% CI: 0.03-2.74) which was reversed with colchicine/NAC back to baseline (95% CI: -1.19 to 1.51). Colchicine/fenofibrate downregulated HIF1a compared to baseline (95% CI: 0.83-6.44). No significant differences were noted in terms of BMP4, SOX2, and OCT4. CONCLUSIONS: Overall, the aortic expression pattern of mechanosensitive genes seems to be spatially influenced by a hyperlipidemic diet and can be modified using colchicine-based therapy.

Stem cell genes in atheromatosis: The role of Klotho, HIF1α, OCT4, and BMP4.

During fetal development, shear stress regulates several aspects of vascular development. Alterations in signaling pathways due to disturbed flow in atheroprone regions closely mirror phenomena seen during embryogenesis. This flow-dependent dysregulation of developmental genes appears to promote atherogenesis by mediating inflammatory phenomena, cell cycle progression, apoptosis, cell migration, and oxidative stress. Indeed, several stem cell genes have been implicated in vascular health and atheromatosis. Klotho is key in maintaining endothelial integrity, reducing oxidative stress, and sustaining endothelial nitric oxide production. In atherosclerotic lesions, OCT4 mediates the conversion of vascular smooth muscle cells from contractile to a de-dedifferentiated proliferative phenotype with phagocytic ability. HIF1α drives atherosclerotic plaque progression by promoting intraplaque angiogenesis. BMP4 promotes osteochondrogenic development and arterial calcification. Strategic extracellular matrix changes are also seen during the various phases of atherosclerosis. The aforementioned conceptual framework explains how proatherogenic inflammation develops in response to low shear stress. In the present review, we explored the effect of cardinal atheroprotective (Klotho, OCT4) and proatherogenic (HIF1α, BMP4) genes in mediating proatherogenic inflammation.