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JACC. Cardiovascular Interventions Apr 2024Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be...
BACKGROUND
Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients.
OBJECTIVES
The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves.
METHODS
Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed.
RESULTS
A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation.
CONCLUSIONS
MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Mitral Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Mitral Valve Insufficiency; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Cardiac Catheterization
PubMed: 38599690
DOI: 10.1016/j.jcin.2024.02.012 -
Frontiers in Surgery 2024Replantation represents a treatment option for patients with severed finger pulps. However, in some cases, replantation is a challenging task.
BACKGROUND
Replantation represents a treatment option for patients with severed finger pulps. However, in some cases, replantation is a challenging task.
CASE PRESENTATION
We report a successful case of finger pulp reconstruction of the ring finger using free flaps from a nonreplantable index finger in a spare-parts procedure. A 43-year-old worker accidentally injured the index, middle and ring fingers of his left hand on a machine turntable. The severed index and middle fingers and the distal pulp of the ring finger could not be replanted due to extensive contusion of blood vessels and soft tissues. After vascular and nerve anastomosis, a free skin flap isolated from the nonreplantable index finger was transplanted to the wound of the distal pulpal defect of the ring finger. The flap survived completely postoperatively. Six months after the operation, only a slight deformity of the ring finger was observed. Moreover, sensation of the digit recovered well.
CONCLUSIONS
Spare-part surgery is a surgical approach that effectively saves and utilizes tissue that would otherwise be discarded in cases of severe limb trauma. This idea may be applied to treatment of severe injuries to multiple fingers. Additionally, in the process of tissue transplantation and repair, attention should be given to protecting the tissue in the recipient area to avoid damage to the original undamaged tissue structure, which can adversely affect healing and recovery of the tissue.
PubMed: 38596165
DOI: 10.3389/fsurg.2024.1363827 -
Andes Pediatrica : Revista Chilena de... Feb 2024Vascular rings are unusual congenital malformations. Among them, double aortic arch (DAA) is often difficult to diagnose due to its low incidence of symptoms. DAA can be...
UNLABELLED
Vascular rings are unusual congenital malformations. Among them, double aortic arch (DAA) is often difficult to diagnose due to its low incidence of symptoms. DAA can be associated with tracheal or esophageal compression and, in severe cases, could require tracheal intubation or chronic use of a nasogastric tube. This scenario favors the development of aortotracheal fistulas (ATF) or aortoe-sophageal fistulas (AEF).
OBJECTIVE
To present a clinical case with an unusual association of DAA with ATF and to reinforce the importance of maintaining high diagnostic suspicion in patients with massive aerodigestive bleeding without an obvious source.
CLINICAL CASE
A 32-week preterm newborn who required prolonged mechanical ventilation and presented intermittent episodes of massive oropharyngeal bleeding with hemodynamic compromise associated with lower airway obstruction without pulmonary hemorrhage. The patient underwent upper endoscopy and exploratory laparotomy without evidence of bleeding. Flexible nasopharyngolaryngoscopy and direct laryngoscopy also showed no abnormalities. A CT angiography showed complete DAA with indentation of the left dominant arch over the trachea, without severe stenosis or evidence of a fistula. AEF was suspected, so exploratory surgery was considered. However, the patient died before surgery due to a massive pulmonary hemorrhage. The autopsy revealed the presence of ATF.
CONCLUSIONS
In patients with massive aerodigestive bleeding without an obvious source, the presence of DAA and possible AEF/ ATF should be considered. Imaging studies have a poor performance for this diagnosis, so surgery should be considered for diagnosis and treatment in these patients.
Topics: Humans; Infant, Newborn; Vascular Ring; Esophageal Fistula; Gastrointestinal Hemorrhage
PubMed: 38587348
DOI: 10.32641/andespediatr.v95i1.5005 -
Nature Communications Apr 2024Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial...
Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.
Topics: Animals; Male; Mice; Endothelial Cells; Heart Failure; Hydroxymethylglutaryl-CoA Reductase Inhibitors; MicroRNAs; RNA, Circular; Stroke Volume
PubMed: 38580662
DOI: 10.1038/s41467-024-47327-z -
Innovations (Philadelphia, Pa.) 2024In the evolving landscape of cardiac surgery, this article explores the potential of minimally invasive mitral valve replacement procedures as a viable alternative to...
In the evolving landscape of cardiac surgery, this article explores the potential of minimally invasive mitral valve replacement procedures as a viable alternative to conventional surgical techniques. Leveraging advancements in automated suturing devices and video endoscopy, our work aims to demonstrate that minimally invasive approaches can be applied across a broad spectrum of surgical scenarios. Herein we highlight preoperative diagnostics and operative techniques, with a focus on infra-axillary anterolateral minithoracotomy as the access point. Our technique utilizes technology from LSI SOLUTIONS (Victor, NY, USA), including the RAM Device for automated suturing, which has an ergonomic design and safety features. The device's capabilities are further enhanced by the SEW-EASY Device, the RAM RING, and the COR-KNOT MINI Device, which streamline suture management and securement. This work outlines how these technological advancements can mitigate concerns about technical complexity and learning curves, thereby encouraging wider adoption of minimally invasive techniques. Clinical benefits may include reduced surgical trauma, quicker recovery, and cost-effectiveness, making it a compelling option in an era of aggressively promoted transcatheter interventions.
Topics: Humans; Minimally Invasive Surgical Procedures; Mitral Valve; Heart Valve Prosthesis Implantation; Suture Techniques; Endoscopy; Thoracotomy
PubMed: 38576096
DOI: 10.1177/15569845241237537 -
Journal of Cellular and Molecular... Apr 2024The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the... (Review)
Review
The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.
Topics: Humans; Cardiovascular Diseases; rho-Associated Kinases; Thrombosis; Vascular Diseases; Endothelial Cells
PubMed: 38568071
DOI: 10.1111/jcmm.18153 -
Circulation Apr 2024Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α),...
BACKGROUND
Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive.
METHODS
Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global -knockout and vascular smooth muscle cell-specific -knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl; 0.5 mol/L; 42 days).
RESULTS
Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II- or CaCl-treated mice. Global or vascular smooth muscle cell-specific knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. , an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II- and CaCl-induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATAC-seq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process.
CONCLUSIONS
Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA.
PubMed: 38557060
DOI: 10.1161/CIRCULATIONAHA.123.065202 -
International Immunopharmacology May 2024Emodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant,...
BACKGROUND
Emodin, a natural anthraquinone derivative isolated from the roots of Rheum officinale Baill, has many pharmacological effects including anti-inflammatory, antioxidant, antiviral, antibacterial and anti-cancer. However, little is known about the effect of emodin on acute radiation proctitis (ARP). The present study was conducted to determine its effects and elucidate its mechanisms involving AKT/MAPK/NF-κB/VEGF pathways in ARP mice.
METHODS
Total 60 C57BL/6 mice were divided randomly into control group, ARP group, AKT inhibitor MK-2206 group, and different doses of emodin groups. ARP mice were induced by 27 Gy of 6 MV X-ray pelvic local irradiation. MK-2206 was given orally for 2 weeks on alternate days. Emodin was administered daily by oral gavage for 2 weeks. Subsequently, all mice were sacrificed on day 15. The rectal tissues were obtained for further tests. The general signs score and the pathological grade were used to evaluate the severity of ARP. The expression of NF-κB, VEGF and AQP1 were determined by immunohistochemistry and western blot. The expression of p-AKT, p-ERK, p-JNK, p-p38, Bcl-2 and Bax were assessed using western blot.
RESULTS
The worse general signs and damaged tissue structure of ARP mice were profoundly ameliorated by emodin. The expression of p-AKT, p-ERK, NF-κB, VEGF and AQP1 were significantly increased, resulting in the inflammation-induced angiogenesis in ARP mice. However, the expression of p-JNK and p-p38 were decreased, leading to the reduction of apoptosis in ARP mice. Excitedly, emodin reversed these changes, not only inhibited inflammation-induced angiogenesis, but also promoted apoptosis. Notably, the effects of emodin were similar to that of AKT inhibitor MK-2206, suggesting the involvement of AKT signaling in the effect of emodin.
CONCLUSION
These results suggest that emodin attenuates ARP in mice, and the underlying mechanism might involve inhibition of the AKT/ERK/NF-κB/VEGF pathways and the induction of apoptosis mediated by JNK and p38.
Topics: Animals; Emodin; NF-kappa B; Proto-Oncogene Proteins c-akt; Mice, Inbred C57BL; Proctitis; Vascular Endothelial Growth Factor A; Mice; Signal Transduction; Radiation Injuries; Male; Anti-Inflammatory Agents; Heterocyclic Compounds, 3-Ring; Radiation Injuries, Experimental; Rectum
PubMed: 38555816
DOI: 10.1016/j.intimp.2024.111945 -
Journal of Cancer Research and... Jan 2024Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis...
AIM
Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis factors play a pivotal role in tumor progression. We aimed to study the expression of VEGF, PDGF-B, and human epidermal growth factor receptor 2 (HER2/neu) and its association with clinicopathological features and survival in GBC.
MATERIALS AND METHODS
VEGF, PDGF-B, and HER2/neu expression was studied by immunohistochemistry (IHC) after histological evaluation in 91 GBC cases. The relationship between these markers and clinicopathological features and survival was explained through the Cox regression model and Kaplan-Meier method.
RESULTS
VEGF, PDGF-B, and HER2/neu overexpressed in 45, 79, and 68% GBC cases, respectively. VEGF was significantly overexpressed in GBC without gall stones (GS) (p = 0.007) and with moderately and poorly differentiated tumors (p = 0.012). HER2/neu was significantly overexpressed in GBC with GS (p = 0.022). Median overall survival (OS) was 39 months (95% CI: 23-55). In univariate analysis, histological type (adenocarcinoma and papillary) vs. others (signet ring/mucinous/adenosquamous) (p = 0.004), depth of tumor infiltration (p = 0.017), distant metastasis (p = 0.012), and adjuvant therapies (chemotherapy/radiotherapy) (p = 0.083) were associated with poor prognosis. Multivariate survival analysis showed histological type (p = 0.004) and distant metastasis (p = 0.032) to be independent prognostic factors for OS. Histological type (p = 0.002), distant metastasis (p = 0.003), and depth of tumor infiltration (T3-T4) (p = 0.012) showed poor median survival. Poor survival was seen in VEGF and HER2/neu positive cases.
CONCLUSION
Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.
Topics: Humans; Prognosis; Gallbladder Neoplasms; Vascular Endothelial Growth Factor A; Neoplasm Staging; Lymphatic Metastasis; Receptor, ErbB-2
PubMed: 38554345
DOI: 10.4103/jcrt.jcrt_1473_22 -
Medicine Mar 2024Current study aimed to investigate the clinical characterization, differential diagnosis, and treatment of splenic littoral cell angioma (LCA). (Review)
Review
BACKGROUND
Current study aimed to investigate the clinical characterization, differential diagnosis, and treatment of splenic littoral cell angioma (LCA).
METHODS
A retrospective analysis was performed for 10 LCA cases admitted to Huzhou Central Hospital from 2007 to 2023, for clinical manifestations, hematological tests, imaging features, pathological features, treatment methods, and prognosis along with the relevant literature was also reviewed.
RESULTS
During examinations, no specific clinical manifestations and hematological abnormalities were seen in all 10 cases of LCA. Imaging observations depicted single or even multiple spherical lesions in the spleen. Plains shown by computed tomography (CT) were found somewhat equal or slightly lower in density. On the other hand, magnetic resonance imaging (MRI) plain scans viz. T1 weighted image showed equal low and mixed signals while T2-weighted showed high and low mixed signals. Moreover, punctate low signals could be seen in high signals named "freckle sign" in MRI scans. On contrast-enhanced CT scans, the enhancement of the lesions was not obvious in the arterial phase, and some of the lesions showed edged ring-like enhancements and "filling lake" progressive enhancement during the venous phase and delayed phase. In multiple lesions, the number of enhanced scan lesions showed a variable changing pattern "less-more-less." MRI-enhanced scan showed the characteristics of "fast in and slow out." Microscopic examinations identified tumor tissue actually composed of sinus-like lacunae that anastomosed with each other in the form of a network. Furthermore, cystic expansion and pseudopapillary protrusions were also seen in the dilated sinus cavity which was lined with single-layer endothelial cells having conspicuous cytoplasmic hemosiderin. High immunophenotypic expressions of vascular endothelial cell phenotype (CD31, CD34, FVIII) and tissue cell phenotype (CD68) were also seen. Total and partial splenectomy were performed in 8 and 2 patients, respectively, and follow-up examinations showed survival in all patients with no recurrence.
CONCLUSION
LCA is a rare splenic benign lesion with atypical clinical manifestations. CT and MRI imaging are important tools in preoperative diagnosis based on pathomorphological and immunohistochemical examinations. Splenectomy is a superior therapeutic choice with significant impacts and prognosis.
Topics: Humans; Endothelial Cells; Retrospective Studies; Splenic Neoplasms; Hemangioma
PubMed: 38552075
DOI: 10.1097/MD.0000000000037550