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International Journal of Surgery Case... May 2024Left pulmonary artery sling is an uncommon condition observed in infants. The severity of the condition is determined by the compression of the broncho-tracheal tree...
INTRODUCTION AND IMPORTANCE
Left pulmonary artery sling is an uncommon condition observed in infants. The severity of the condition is determined by the compression of the broncho-tracheal tree induced by the ring sling compression. The main goal of the treatment is to adjust the left pulmonary artery and eventually relieving the compression through surgery. The long-term outcome associated with the complexity of the anomalies.
CASE PRESENTATION
A nine-months old patient complained of worsening respiratory distress. The computed tomography scan revealed the potential presence of a left pulmonary artery sling and compression of the trachea, without any abnormalities in the trachea itself. Echocardiography study showed no intracardiac lesion. We successfully did left pulmonary artery transection and re-implantation to main pulmonary artery without cardiopulmonary bypass.
CLINICAL DISCUSSION
Pulmonary artery sling commonly treated with reimplantation of the sling to its origin that usually required cardiopulmonary bypass machine. However, in our case we delivered it without the need of cardiopulmonary bypass. The outcome result turned excellent with echo post-operative showed confluent pulmonary arteries.
CONCLUSION
The optimal approach to treating congenital pulmonary artery sling is through early surgical intervention in symptomatic patients. Following surgical repair devoid of tracheal lesion, the prognosis appears favorable, and routine follow-up is required to determine the long-term effects.
PubMed: 38669803
DOI: 10.1016/j.ijscr.2024.109692 -
The International Journal of... May 2024Repaired Tetralogy of Fallot (rTOF) patients suffer from pulmonary regurgitation and may require pulmonary valve replacement (PVR). Cardiac magnetic resonance imaging...
Repaired Tetralogy of Fallot (rTOF) patients suffer from pulmonary regurgitation and may require pulmonary valve replacement (PVR). Cardiac magnetic resonance imaging (cMRI) guides therapy, but conventional measurements do not quantify the intracardiac flow effects from pulmonary regurgitation or PVR. This study investigates intracardiac flow parameters of the right ventricle (RV) of rTOF by computational fluid dynamics (CFD). cMRI of rTOF patients and controls were retrospectively included. Feature-tracking captured RV endocardial contours from long-axis/short-axis cine. Ventricular motion was reconstructed via diffeomorphic mapping, serving as domain boundary for CFD simulations. Vorticity (1/s), viscous energy loss (ELoss, mJ/L) and turbulent kinetic energy (TKE, mJ/L) were quantified in RV outflow tract (RVOT) and RV inflow. These parameters were normalized against total RV kinetic energy (KE) and RV inflow vorticity to derive dimensionless metrics. Vorticity contours by Q-criterion were qualitatively compared. rTOF patients (n = 15) had mean regurgitant fraction 38 ± 12% and RV size 162 ± 35 mL/m. Compared to controls (n = 12), rTOF had increased RVOT vorticity (142.6 ± 75.6/s vs. 40.4 ± 11.8/s, p < 0.0001), Eloss (55.6 ± 42.5 vs. 5.2 ± 4.4 mJ/L, p = 0.0004), and TKE (5.7 ± 5.9 vs. 0.84 ± 0.46 mJ/L, p = 0.0003). After PVR, there was decrease in normalized RVOT Eloss/TKE (p = 0.0009, p = 0.029) and increase in normalized tricuspid inflow vorticity/KE (p = 0.0136, p = 0.043), corresponding to reorganization of the "donut"-shaped tricuspid ring-vortex. The intracardiac flow in rTOF patients can be simulated to determine the impact of PVR and improve the clinical indications guided by cardiac imaging.
Topics: Humans; Tetralogy of Fallot; Ventricular Function, Right; Female; Male; Pulmonary Valve Insufficiency; Retrospective Studies; Magnetic Resonance Imaging, Cine; Kinetics; Hydrodynamics; Hemodynamics; Models, Cardiovascular; Adult; Predictive Value of Tests; Young Adult; Blood Flow Velocity; Heart Ventricles; Patient-Specific Modeling; Adolescent
PubMed: 38668927
DOI: 10.1007/s10554-024-03084-0 -
BioRxiv : the Preprint Server For... Apr 2024Cerebral amyloid angiopathy (CAA) is a vasculopathy characterized by vascular β-amyloid (Aβ) deposition on cerebral blood vessels. CAA is closely linked to Alzheimer's...
Cerebral amyloid angiopathy (CAA) is a vasculopathy characterized by vascular β-amyloid (Aβ) deposition on cerebral blood vessels. CAA is closely linked to Alzheimer's disease (AD) and intracerebral hemorrhage. CAA is associated with the loss of autoregulation in the brain, vascular rupture, and cognitive decline. To assess morphological and molecular changes associated with the degeneration of penetrating arterioles in CAA, we analyzed post-mortem human brain tissue from 26 patients with mild, moderate, and severe CAA end neurological controls. The tissue was optically cleared for three-dimensional light sheet microscopy, and morphological features were quantified using surface volume rendering. We stained Aβ, vascular smooth muscle (VSM), lysyl oxidase (LOX), and vascular markers to visualize the relationship between degenerative morphological features, including vascular dilation, dolichoectasia (variability in lumenal diameter) and tortuosity, and the volumes of VSM, Aβ, and LOX in arterioles. Atomic force microscopy (AFM) was used to assess arteriolar wall stiffness, and we identified a pattern of morphological features associated with degenerating arterioles in the cortex. The volume of VSM associated with the arteriole was reduced by around 80% in arterioles with severe CAA and around 60% in cases with mild/moderate CAA. This loss of VSM correlated with increased arteriolar diameter and variability of diameter, suggesting VSM loss contributes to arteriolar laxity. These vascular morphological features correlated strongly with Aβ deposits. At sites of microhemorrhage, Aβ was consistently present, although the morphology of the deposits changed from the typical organized ring shape to sharply contoured shards with marked dilation of the vessel. AFM showed that arteriolar walls with CAA were more than 400% stiffer than those without CAA. Finally, we characterized the association of vascular degeneration with LOX, finding strong associations with VSM loss and vascular degeneration. These results show an association between vascular Aβ deposition, microvascular degeneration, and increased vascular stiffness, likely due to the combined effects of replacement of VSM by β-amyloid, cross-linking of extracellular matrices (ECM) by LOX, and possibly fibrosis. This advanced microscopic imaging study clarifies the association between Aβ deposition and vascular fragility. Restoration of physiologic ECM properties in penetrating arteries may yield a novel therapeutic strategy for CAA.
PubMed: 38659767
DOI: 10.1101/2024.03.08.583563 -
Journal of Pediatric Surgery Mar 2024We evaluate long-term symptomatic improvement in vascular ring patients who underwent thoracoscopic division at a single quaternary pediatric surgery center.
OBJECTIVES
We evaluate long-term symptomatic improvement in vascular ring patients who underwent thoracoscopic division at a single quaternary pediatric surgery center.
METHODS
All pediatric patients who underwent vascular ring division without Kommerell's diverticulum resection between 01/2007-12/2022 were included. Surgeries were performed by pediatric general and thoracic surgeons. Patient demographic and clinical characteristics were obtained from retrospective chart review. Data on long-term symptomatic improvement were collected with structured telephone interviews.
RESULTS
60% of patients were male. Median age at operation was 24 months (IQR: 11, 60 months) with a median weight of 11.3 kg (IQR: 8.7, 19.8 kg). All patients were symptomatic preoperatively with dysphagia being the most frequent complaint (42%), followed by chronic cough (21%). Of 41 patients eligible for the long-term follow-up survey, 8 patients with a primary diagnosis of a double arch with an atretic segment in the non-dominant arch and 9 with a right dominant arch with left ligamentum arteriosum and aberrant left subclavian artery (LSCA) were contacted and consented for participation. Median interval from surgery to survey completion was 95 months (IQR 28, 135 months). Most patients had no, or only minor, symptoms related to breathing and swallowing at the time of long-term follow-up. 88% of patients experienced postoperative symptom improvement, and only one patient reported worsening of symptoms over time.
CONCLUSION
Division of an atretic arch and/or ligamentum for patients with an aberrant LSCA without Kommerell's resection may be adequate to ensure long-term improvement of breathing and swallowing problems attributable to vascular rings.
LEVEL OF EVIDENCE
Level IV.
PubMed: 38658219
DOI: 10.1016/j.jpedsurg.2024.03.057 -
Molecular Immunology Jun 2024Endothelial cell injury and dysfunction lead to cholesterol and lipid accumulation and atherosclerotic plaque formation in the arterial wall during atherosclerosis (AS)...
BACKGROUND
Endothelial cell injury and dysfunction lead to cholesterol and lipid accumulation and atherosclerotic plaque formation in the arterial wall during atherosclerosis (AS) progression, Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), a DNA methylation regulator, was strongly upregulated in atherosclerotic plaque lesions in mice. This study aimed to investigate the precise biological functions and regulatory mechanisms of UHRF1 on endothelial dysfunction during AS development.
METHODS
UHRF1 levels in the atherosclerotic plaque tissues and normal arterial intima from AS patients were tested with Western blot analysis and immunohistochemistry assays. Human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized low-density lipoprotein (ox-LDL) to induce an injury model and then transfected with short hairpin RNA targeting UHRF1 (sh-UHRF1). Cell proliferation, migration, apoptosis, the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the protein levels adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured. Moreover, co-immunoprecipitation assay was used to determine the interactions between UHRF1 and DNA methyltransferases 1 (DNMT1), As well as mothers against DPP homolog 7 (SMAD7) and yes-associated protein 1 (YAP1). SMAD7 promoter methylation was examined with methylation-specific PCR. In addition, we established an AS mouse model to determine the in vivo effects of UHRF1 on AS progression.
RESULTS
UHRF1 was upregulated in atherosclerotic plaque tissues and ox-LDL-treated HUVECs. UHRF1 knockdown mitigated ox-LDL-induced proliferation and migration inhibition, apoptosis and the production of TNF-α, IL-6, VCAM-1, and ICAM-1 in HUVECs. Mechanistically, UHRF1 promoted DNMT1-mediated SMAD7 promoter methylation and inhibited its expression. SMAD7 knockdown abolished the protective effects of UHRF1 knockdown on ox-LDL-induced HUVEC injury. Moreover, SMAD7 interacted with YAP1 and inhibited YAP1 expression by promoting YAP1 protein ubiquitination-independent degradation in HUVECs. YAP1 overexpression abrogated SMAD7 overexpression-mediated protective effects on ox-LDL-induced HUVEC injury. Finally, UHRF1 knockdown alleviated atherosclerotic plaque deposition and arterial lesions in AS mice.
CONCLUSION
UHRF1 inhibition mitigates vascular endothelial cell injury and ameliorates AS progression in mice by regulating the SMAD7/YAP1 axis.
Topics: Animals; Humans; Male; Mice; Adaptor Proteins, Signal Transducing; Apoptosis; Atherosclerosis; CCAAT-Enhancer-Binding Proteins; Cell Proliferation; Human Umbilical Vein Endothelial Cells; Lipoproteins, LDL; Mice, Inbred C57BL; Plaque, Atherosclerotic; Signal Transduction; Smad7 Protein; Ubiquitin-Protein Ligases; YAP-Signaling Proteins
PubMed: 38657333
DOI: 10.1016/j.molimm.2024.04.001 -
The Plant Cell Jul 2024Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms,...
Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin-producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms.
Topics: Lignin; Cytochromes b5; Plant Proteins; Phylogeny; Cytochrome P-450 Enzyme System; Evolution, Molecular; Magnoliopsida; Embryophyta; Charophyceae
PubMed: 38657101
DOI: 10.1093/plcell/koae120 -
Annals of Clinical and Translational... Jun 2024Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial...
OBJECTIVE
Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients.
METHODS
The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real-time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model.
RESULTS
We detected a statistically significant (p < 0.000001) up-regulation of Angiopoietin-2 (Ang-2) in CSF and stenotic middle cerebral arteries (RQ >2) of MA patients compared to controls. A high Ang-2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang-2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable-from-progressive MA. Consistently, MA cellular model showed a significant up-regulation (RQ >2) of Ang-2 in RNF213 silenced condition.
INTERPRETATION
Our results pointed out Ang-2 as a reliable biomarker mirroring arterial steno-occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.
Topics: Humans; Moyamoya Disease; Angiopoietin-2; Male; Female; Adult; Middle Aged; Prognosis; Biomarkers; Ubiquitin-Protein Ligases; Young Adult; Adenosine Triphosphatases
PubMed: 38655722
DOI: 10.1002/acn3.52076 -
Korean Journal of Anesthesiology Apr 2024Bleeding incidents during percutaneous dilatational tracheostomy are concerning, and most cases occur in patients with unrecognized and unanticipated anatomical...
BACKGROUND
Bleeding incidents during percutaneous dilatational tracheostomy are concerning, and most cases occur in patients with unrecognized and unanticipated anatomical variations in the vascular anatomy. However, the extent of this variation remains unclear. To address this knowledge gap, our study aimed to comprehensively map laryngeal vascular anatomy in a cohort of adult patients.
METHODS
Ultrasound assessments of the soft tissue in the neck were performed, spanning from the thyroid cartilage to the third tracheal ring and extending 2 cm laterally on both sidesperformed. We subdivided this area into 12 zones comprising four medial and eight lateral sections. A pre-planned form was used to document the presence of arteries or veins in each zone. The results are reported as odds ratios, 95% CIs, and corresponding P-values.
RESULTS
Five-hundred patients were enrolled from August 14, 2023, to November 13, 2023, at the University Hospital of Padua. Arteries and veins were identified in all investigated zones (varying from a minimum of 1.0%-46.4%). The presence of invessels progressively increased from the cricothyroid membrane to the third tracheal ring and from the midline to the paramedian laryngeal area.
CONCLUSIONS
Given the prevalence of arteries and veins, particularly in areas where tracheostomies are commonly performed, we strongly advocate for routine ultrasound assessments before such procedures are performed.
PubMed: 38653329
DOI: 10.4097/kja.23900 -
Proceedings of the National Academy of... Apr 2024The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These...
The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, we identified that decorin down-regulated a cluster of tumor-associated genes involved in lymphatic vessel (LV) development when systemically delivered to mice harboring breast carcinoma allografts. We found that Lyve1 and Podoplanin, two established markers of LVs, were markedly suppressed at both the mRNA and protein levels, and this suppression correlated with a significant reduction in tumor LVs. We further identified that soluble decorin, but not its homologous proteoglycan biglycan, inhibited LV sprouting in an ex vivo 3D model of lymphangiogenesis. Mechanistically, we found that decorin interacted with vascular endothelial growth factor receptor 3 (VEGFR3), the main lymphatic RTK, and its activity was required for the decorin-mediated block of lymphangiogenesis. Finally, we identified that Lyve1 was in part degraded via decorin-evoked autophagy in a nutrient- and energy-independent manner. These findings implicate decorin as a biological factor with antilymphangiogenic activity and provide a potential therapeutic agent for curtailing breast cancer growth and metastasis.
Topics: Decorin; Lymphangiogenesis; Animals; Mice; Humans; Female; Breast Neoplasms; Lymphatic Vessels; Cell Line, Tumor; Disease Progression; Vesicular Transport Proteins; Membrane Glycoproteins; Gene Expression Regulation, Neoplastic
PubMed: 38652741
DOI: 10.1073/pnas.2317760121 -
Cureus Mar 2024Embolization of entrapped intracardiac air represents a significant risk to the patient undergoing open-heart surgery. Entrapment of as little as 0.5 mL of gas in the...
Embolization of entrapped intracardiac air represents a significant risk to the patient undergoing open-heart surgery. Entrapment of as little as 0.5 mL of gas in the heart can cause temporary myocardial dysfunction, cardiac arrhythmias, and systemic emboli. In contrast, larger emboli can disrupt the evaluation of heart function by limiting visualization during echocardiography. We present the case of a 67-year-old male who presented with dizziness, nausea, and chest pain. A left heart catheterization revealed multi-vessel disease. Undergoing general anesthesia, the patient received three-vessel coronary artery bypass grafting, mitral valve repair, ring annuloplasty, and left atrial appendage closure. Upon aortic unclamping, transgastric echocardiography showed significant gas almost wholly obscuring the left heart chambers despite de-airing maneuvers. Successful resolution relied upon higher mean blood pressure and time, demonstrating the importance of intraoperative imaging and interdisciplinary collaboration.
PubMed: 38646393
DOI: 10.7759/cureus.56525