Calcified Nodules Research Articles

Progression from Nodular Calcification to Calcified Nodules Leading to Acute Myocardial Infarction

Progression from Nodular Calcification to Calcified Nodules Leading to Acute Myocardial Infarction

Cardiac Calcified Amorphous Tumor: An Unusual Etiology for Recurrent Cardioembolic Strokes (P3-5.026)

<h3>Objective:</h3> To report a patient with recurrent cardioembolic strokes, in whom an underlying calcified amorphous tumor (CAT) of the heart was detected as the etiology, 2 years after initial presentation. <h3>Background:</h3> CAT of the heart is a rare intracavitary cardiac mass characterized histologically by amorphous fibrinous material and calcification. It has a tendency for embolism. We use this illustrative case to bring awareness for this rare entity and utility of advanced cardiac imaging. <h3>Design/Methods:</h3> An 87-year-old woman with recurrent recent strokes was evaluated for her 5^th stroke. Her neuroimaging had suggested an embolic etiology, but routine cardiac workup had not identified a source. After her 5^th stroke happened despite being on anticoagulation, a trans-esophageal ECHO (TEE) was done followed by cardiac MRI. <h3>Results:</h3> TEE and MRI showed a left atrial non-enhancing calcified mass attached by a stalk to the interatrial septum suspicious for CAT. The tumor was surgically resected. Histological examination showed nodular amorphous calcification against the background of degenerating fibrinous material consistent with CAT. The immediate post-operative period was uneventful, and the patient was discharged to a rehabilitation facility on aspirin monotherapy. <h3>Conclusions:</h3> CAT is a rare cardiac tumor, and its presence is suggested by the presence of calcification of an intracardiac mass on cardiac imaging. The presence of mitral annular calcification (MAC) and renal disease can be additional clues to CAT being the cause for an intracardiac mass, which can then be identified by advanced cardiac imaging. A definitive diagnosis can be made only on pathology, and the definitive treatment is surgical. MAC-related CAT can grow rapidly, has a high embolic risk, and should be removed expeditiously to prevent embolic strokes, even in asymptomatic individuals. <b>Disclosure:</b> Mr. Sharma has nothing to disclose. Dr. Annam has nothing to disclose. Bilal Ali has nothing to disclose. Dr. Guler has nothing to disclose. Dr. Hussein has nothing to disclose.

Analysis for discharge within 2 days after thoracoscopic anatomic lung cancer surgery.

The risk and beneficial factors of early discharge after thoracoscopic anatomic lung cancer surgery are unknown, and this study aims to investigate predictors and associated 30-day readmission for early discharge. We performed a single-center retrospective analysis of 10,834 consecutive patients who underwent thoracoscopic anatomic lung cancer surgery. Two groups were determined based on discharge date: "discharged by postoperative Day 2" and "discharged after postoperative Day 2." Univariable and multivariable analysis were conducted to identify predictors for discharge. Using propensity score matching (PSM) to compare 30-day readmission rate between two cohorts. A total of 1911 patients were discharged by postoperative Day 2. Multivariable analysis identified older age (odds ratio (OR) = 1.014, p < 0.001), male sex (OR = 1.183, p = 0.003), larger tumor size (OR = 1.248, p < 0.001), pleural adhesions (OR = 1.638, p = 0.043), lymph nodes calcification (OR = 1.443, p = 0.009), advanced clinical T stage (vs. T < 2, OR = 1.470, p = 0.010), lobectomy resection (vs. segmentectomy resection, OR = 2.145, p < 0.001) and prolonged operative time (OR = 1.011, p < 0.001) as independent risk factors for discharge after postoperative Day 2. Three adjustable variables including higher FEV1 /FVC (OR = 0.989, p = 0.001), general anesthesia (GA) plus thoracic paravertebral blockade (vs. GA alone, OR = 0.823, p = 0.006) and uni-portal thoracoscopic surgery (vs. multi-portal, OR = 0.349, p < 0.001) were associated with a decreased likelihood of discharge after postoperative Day 2. Before and after a 1:1 PSM, discharged by postoperative Day 2 did not increase the risk of 30-day readmission compared to counterparts. Carefully selected patients can be safely discharged within 2 days after thoracoscopic anatomic lung cancer surgery. Three modifiable variables may be favorable for promoting discharge by postoperative Day 2.

Distinctions in bone matrix nanostructure, composition, and formation between osteoblast-like cells, MG-63, and human mesenchymal stem cells, UE7T-13

Osteoblast-like cells and human mesenchymal stem cells (hMSCs) are frequently employed as osteoprogenitor cell models for evaluating novel biomaterials in bone healing and tissue engineering. In this study, the characterization of UE7T-13 hMSCs and MG-63 human osteoblast-like cells was examined. Both cells can undergo osteogenesis and produce calcium extracellular matrix; however, calcium nodules produced by MG-63 lacked a central mass and appeared flatter than UE7T-13. The absence of growing calcium nodules in MG-63 was discovered by SEM-EDX to be associated with the formation of alternating layers of cells and calcium extracellular matrix. The nanostructure and composition analysis showed that UE7T-13 had a finer nanostructure of calcium nodules with a higher calcium/phosphate ratio than MG-63. Both cells expressed high intrinsic levels of collagen type I alpha 1 chain, while only UE7T-13 expressed high levels of alkaline phosphatase, biomineralization associated (ALPL). High ALP activity in UE7T-13 was not further enhanced by osteogenic induction, but in MG-63, low intrinsic ALP activity was greatly induced by osteogenic induction. These findings highlight the differences between the two immortal osteoprogenitor cell lines, along with some technical notes that should be considered while selecting and interpreting the pertinent in vitro model.

New Concepts on the Pathophysiology of Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is the most severe form of ischemic heart disease. Although it is caused by atherosclerotic plaque thrombosis or nonatherosclerotic causes, its pathophysiological mechanism of ACS is not fully understood, and its concept is constantly updated and developed. At present, the main pathophysiological mechanisms include plaque rupture, plaque erosion, calcified nodules (CN) and non-atherosclerotic causes such as coronary vasospasm and myocardial bridging (MB). These mechanisms may overlap and coexist in some ACS patients. Therefore, the pathophysiological mechanism of ACS is complex, and is of great significance for the diagnosis and treatment of ACS. This review will discuss the pathophysiological mechanisms of ACS to provide new thoughts on the pathogenesis, diagnosis and treatment of ACS.

Effectiveness of using both rotational atherectomy with smallest burr and orbital atherectomy system for stentless treatment of calcified nodules.

Effectiveness of using both rotational atherectomy with smallest burr and orbital atherectomy system for stentless treatment of calcified nodules.

Formation of a rare curve-shaped thoracolith documented on serial chest computed tomography images: A case report

Thoracolithiasis is a rare benign condition that manifests with one or more small nodules in the pleural cavity. In most cases, it is asymptomatic and found incidentally on chest imaging or during thoracic surgery. The thoracolithiasis formation process is rarely documented. Herein, we present a case of a rare, large, curve-shaped thoracolith, the formation of which was documented on serial computed tomography (CT) images. A 46-year-old male patient who denied any prior systemic disease was evaluated due to intermittent right-sided lateral chest pain lasting for a year. Chest radiography and CT revealed a circumscribed calcified nodule measuring 3.5 mm in the right lower lung lobe. Nodule biopsy revealed fungal infection, which was treated with antifungal medication. After 2 years of follow-up, the patient developed intermittent chest discomfort caused by pleural adhesions, and underwent video-assisted thoracic surgery with pneumolysis. Postoperatively, he developed empyema, which fully resolved with antibiotic therapy. Thereafter, he was followed up at the outpatient clinic and underwent chest CT twice per year. Over time, we observed thickening of the right distal pleura near the lower posterior mediastinum, and several sporadic calcified nodules with gradually increasing intensity, which eventually merged into a single calcified curve-shaped thoracolith measuring approximately 9 cm in length during the 5-year follow-up. This study documented the formation of a rare thoracolith shape observed for the first time.

Contribution of S100A4-expressing fibroblasts to anti-SSA/Ro-associated atrioventricular nodal calcification and soluble S100A4 as a biomarker of clinical severity.

Fibrosis and dystrophic calcification disrupting conduction tissue architecture are histopathological lesions characterizing cardiac manifestations of neonatal lupus (cardiac-NL) associated with maternal anti-SSA/Ro antibodies. Increased appreciation of heterogeneity in fibroblasts encourages re-examination of existing models with the consideration of multiple fibroblast subtypes (and their unique functional differences) in mind. This study addressed fibroblast heterogeneity by examining expression of α-Smooth Muscle Actin (myofibroblasts) and of S100 Calcium-Binding Protein A4 (S100A4). Using a previously established model of rheumatic scarring/fibrosis in vitro, supported by the evaluation of cord blood from cardiac-NL neonates and their healthy (anti-SSA/Ro-exposed) counterparts, and autopsy tissue from fetuses dying with cardiac-NL, the current study was initiated to more clearly define and distinguish the S100A4-positive fibroblast in the fetal cardiac environment. S100A4 immunostaining was observed in 4 cardiac-NL hearts with positional identity in the conduction system at regions of dystrophic calcification but not fibrotic zones, the latter containing only myofibroblasts. In vitro, fibroblasts cultured with supernatants of macrophages transfected with hY3 (noncoding ssRNA) differentiated into myofibroblasts or S100A4+ fibroblasts. Myofibroblasts expressed collagen while S100A4+ fibroblasts expressed pro-angiogenic cytokines and proteases that degrade collagen. Cord blood levels of S100A4 in anti-SSA/Ro-exposed neonates tracked disease severity and, in discordant twins, distinguished affected from unaffected. These findings position the S100A4+ fibroblast alongside the canonical myofibroblast in the pathogenesis of cardiac-NL. Neonatal S100A4 levels support a novel biomarker of poor prognosis.

MiR-20a promotes osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells and bone repair of the maxillary sinus defect model in rabbits.

Introduction: This study aimed to determine whether miR-20 promoted osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells (BMSCs) and accelerated bone formation in the maxillary sinus bone defect model in rabbits. Methods: BMSCs were transfected with miR-20a or anti-miR-20a for 12h, followed by detection of RUNX2, Sp7 mRNA, bone morphogenetic protein 2 (BMP2), and RUNX2 protein expression. Alkaline phosphatase (ALP) activity and Alizarin Red S staining were used to detect calcified nodule deposition. In the rabbit maxillary sinus bone defect model, miR-20a loaded with AAV and BMP2 protein were mixed with Bio-Oss bone powder for filling the bone defect. At 4weeks and 8weeks, bone density was detected by cone beam computed tomography (CBCT), and new bone, osteoblasts, and collagen type 1 were evaluated by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. Results: Overexpression of miR-20a enhanced the mRNA and protein levels of BMP2, RUNX2, and SP7, the activity of ALP, and the levels of matrix mineralization, whereas the levels and activity of the aforementioned factors were decreased by anti-miR-20a treatment of BMSCs. Furthermore, miR-20a significantly increased the bone density, the number of osteoblasts, and the secretion of collagen type 1 in bone defects compared with Bio-Oss bone powder in the rabbit maxillary sinus bone defect model. Conclusion: Overall, miR-20a can induce osteogenic differentiation in BMSCs and accelerate bone formation of maxillary sinus defects in rabbits.

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and β-catenin/Wnt signaling pathways.

Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and β-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and β-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and β-catenin/Wnt signaling pathways. Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and β-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

TCTAP C-048 Upfront Culotte Technique in a Short Left Main Medina 0-1-1 Lesion That Had Large Calcified Nodule at Ostial Left Circumflex

TCTAP C-048 Upfront Culotte Technique in a Short Left Main Medina 0-1-1 Lesion That Had Large Calcified Nodule at Ostial Left Circumflex

Clinical and Dermoscopic Features of Winer's Nodular Solitary Calcinosis

Aims: Solitary nodular calcinosis of Winer is a rare and benign form of localized idiopathic cutaneous calcinosis. Its dermoscopic features may be useful for early diagnosis, but have never been described in the literature to our knowledge.&#x0D; Case Report: A 5-year-old child presented to our clinic with a 2 years history of a painless keratotic and warty nodule located in the helix of the right ear. A wart was suspected and treated without any improvement. Dermoscopy was performed and showed peripheral white deposits suggestive of Winer's calcinosis, motivating an excision whose histological examination confirmed the diagnosis.&#x0D; Discussion: The subepidermal calcified nodule has been rarely described in the literature. It is not known to be associated with a disorder of phosphocalcium metabolism or other systemic diseases. Pathogenic hypotheses include calcification of preexisting skin structures, mast cell degranulation with secondary calcinosis, or prior trauma. Surgical excision with histopathological confirmation is necessary to show the dermal calcium deposits, which are usually amorphous and granular and may be surrounded by a lymphohistiocytic infiltrate or giant cells. Nevertheless, dermatoscopic evaluation can aid in rendering a timely diagnosis by showing these whitish dermal deposits.&#x0D; Conclusion: The diagnosis of Winer's nodular calcinosis has always been based on histology, but the dermoscopy described here for the first time is so suggestive that it can be used to save time and exclude other differential diagnoses.

Dantrolene inhibits lysophosphatidylcholine-induced valve interstitial cell calcific nodule formation via blockade of the ryanodine receptor.

Calcific aortic valve disease (CAVD), a fibrocalcific thickening of the aortic valve leaflets causing obstruction of the left ventricular outflow tract, affects nearly 10 million people worldwide. For those who reach end-stage CAVD, the only treatment is highly invasive valve replacement. The development of pharmaceutical treatments that can slow or reverse the progression in those affected by CAVD would greatly advance the treatment of this disease. The principal cell type responsible for the fibrocalcific thickening of the valve leaflets in CAVD is valvular interstitial cells (VICs). The cellular processes mediating this calcification are complex, but calcium second messenger signaling, regulated in part by the ryanodine receptor (RyR), has been shown to play a role in a number of other fibrocalcific diseases. We sought to determine if the blockade of calcium signaling in VICs could ameliorate calcification in an in vitro model. We previously found that VICs express RyR isotype 3 and that its modulation could prevent VIC calcific nodule formation in vitro. We sought to expand upon these results by further investigating the effects of calcium signaling blockade on VIC gene expression and behavior using dantrolene, an FDA-approved pan-RyR inhibitor. We found that dantrolene also prevented calcific nodule formation in VICs due to cholesterol-derived lysophosphatidylcholine (LPC). This protective effect corresponded with decreases in intracellular calcium flux, apoptosis, and ACTA2 expression but not reactive oxygen species formation caused by LPC. Interestingly, dantrolene increased the expression of the regulator genes RUNX2 and SOX9, indicating complex gene regulation changes. Further investigation via RNA sequencing revealed that dantrolene induced several cytoprotective genes that are likely also responsible for its attenuation of LPC-induced calcification. These results suggest that RyR3 is a viable therapeutic target for the treatment of CAVD. Further studies of the effects of RyR3 inhibition on CAVD are warranted.

Multiple cardiac calcified amorphous tumors with morphologically different characteristics complicated by aortic regurgitation: a case report

BackgroundCardiac calcified amorphous tumors (CATs) are non-neoplastic cardiac tumors of unknown origin and etiology. Several simultaneous CATs rarely occur in multiple cardiac chambers. Although CATs carry a benign prognosis, they have a risk of complications such as systemic embolism.Case presentationWe report the case of a 79-year-old woman with two CATs and aortic regurgitation due to perforations of aortic cusps. She underwent surgical tumor resection with aortic valve replacement. The CATs were macroscopically and histologically different, which may suggest different developmental stages. One CAT was in the left atrium; it was less mobile and had nodular calcifications within dense fibrous tissue. The other CAT was in the left ventricular outflow tract; it was highly mobile, with nodular calcifications surrounded by amorphous fibrin and sanguineous deposits. The highly mobile CAT mechanically damaged the aortic cusps and caused perforations. The patient has survived over 2 years with no recurrence of the cardiac masses on echocardiography.ConclusionThe patient underwent surgical resection for two CATs. The tumors occurred in different areas and had different macroscopic and histological characteristics. We recommend early resection for highly mobile CATs because of the high risks of embolization and injuries to the surrounding tissues.

Tumoral Calcinosis in the Larynx.

Tumoral calcinosis is a rare benign disease defined as calcium salt deposits in the periarticular soft tissue region. Tumoral calcinosis is rare in the neck and larynx. In this case, we described a 58-year-old man who had numerous calcified nodules in the larynx.

Combined Orbital and Rotational Atherectomy for Severe Nodular Calcification at Curved Arteries.

Combined Orbital and Rotational Atherectomy for Severe Nodular Calcification at Curved Arteries.

Bone marrow mesenchymal stem cells derived exosomal Lnc TUG1 promotes bone fracture recovery via miR-22-5p/Anxa8 axis

Bone fracture healing is a complex physiologic process that involves changes in the expression of several thousand genes. Long noncoding RNAs (lncRNAs) may have critical biological roles in this process. The objectives of the present study were to determine whether BMSC-derived exosomal lncTUG1 can enhance osteogenic differentiation and thereby promoting bone fracture recovery and to investigate its potential mechanisms of action. Bone marrow mesenchymal stromal cells were isolated from mice and cultured for the following experiments. After adipogenic and osteogenic differentiation induction, Oil Red O, alizarin red S, and alkaline phosphatase staining solutions were applied to confirm the formation of lipid droplets and calcium nodules. Western blotting analyses, real-time reverse transcription PCR assays, luciferase reporter were performed to confirm relative RNA and protein expressions and luciferase activities of transfected cells. RNA pull-down and RNA immunoprecipitation assays were also carried to verify the interaction between lncTUG1 and miR-22-5p. Additionally, a mouse model of closed femoral fractures was generated to evaluate the in vivo effect of increased lncTUG1 on fracture healing. BMSC-derived exosomal lncTUG1 enhanced the activity of osteoblasts. Overexpression of miR-22-5p reversed the osteopromoting effect of increased lncTUG1. The knockdown of Anxa8 reversed the osteogenic effect of miR-22-5p inhibitors, indicating an interaction between Anxa8 and miR-22-5p. Upregulation of lncTUG1 could promote the fracture recovery in vivo. In conclusion, the present study highlights the functional importance of BMSC-derived exosomal lncTUG1 in the process of bone fracture recovery.

Human bone marrow mesenchymal stem cell exosome-derived miR-335-5p promotes osteogenic differentiation of human periodontal ligament stem cells to alleviate periodontitis by downregulating DKK1

To observe the effect of miR-335-5p derived from human bone marrow mesenchymal stem cell (hBMMSCs) exosomes on osteogenic differentiation of human periodontal ligament stem cell (PDLSCs) model of periodontitis and explore its mechanism. The exosomes extracted from hBMMSCs were identified by transmission electron microscopy, Western blotting and PKH67 labeling. The human PDLSC model of TNF-α-induced periodontitis were co-cultured with the extracted exosomes, and qRT-PCR was performed to detect the changes in the expressions of miR-335-5p and the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) and the osteogenic marker genes (RunX2, OCN and BMP-2). Alizarin red staining and ALP staining were used to detect the formation of calcium nodules in the treated cells, and the expression level of DKK1 protein was detected with Western blotting. Dual luciferase reporter gene assay was used to verify the targeting relationship between miR-335-5p and DKK1. High expressions of CD9 and CD81 were detected in the extracted hBMMSC exosomes (P < 0.05). In TNF-α-induced hPDLSCs, treatment with the extracted exosomes significantly reduced the mRNA expressions of IL-1β, IL-6 and IL-8, enhanced the mRNA expressions of RunX2, OCN, and BMP-2, and promoted the formation of calcium nodules. MiR-335-5p was highly expressed in hBMMSC-derived exosomes, and overexpression of miR-335-5p significantly downregulated DKK1 protein expression, inhibited the mRNA expressions of IL-1β, IL-6 and IL-8, and promoted the mRNA expressions of osteogenic markers and the formation of calcium nodules in hPDLSCs. HBMMSC exosome-derived miR-335-5p promotes osteogenic differentiation of hPDLSCs and inhibits the development of periodontitis by downregulating DKK1.

Calcified coronary nodule: Tip of the iceberg on a road full of thorns.

Key Points Nodular coronary calcium (NC) is infrequent, is associated with advanced age and chronic kidney disease and may be responsible for acute coronary syndromes. NC leads to a greater incidence of stent malapposition and target lesion revascularization, and intravascular imaging often shows recurrence of the calcified nodule within the stent. Clinical outcomes are worse after stenting lesions with calcified nodules, but randomized studies are necessary to determine the best management strategy.

Effect of Different Sealers on the Cytocompatibility and Osteogenic Potential of Human Periodontal Ligament Stem Cells: An In Vitro Study.

There is tendency for unavoidable sealer extrusion in some clinical cases. This might adversely affect host stem cells and affect healing. This study aimed to investigate the effect of different sealers on the cytocompatibility and osteogenic potential of human periodontal ligament stem cells (hPDLSCs). The cytotoxic effect of the extracted elutes of VDW.1Seal (VDW.1), Endosequence BC Sealer HiFlow (ES), GuttaFlow-2 (GF), and ADSeal (AD-S) on the hPDLSCs was determined using the MTT assay. Cell proliferation and migration were assessed by the scratch wound healing assay. Osteogenic differentiation potential was assessed. Measurement of pH values and calcium ions release was performed. GF had a significantly higher percentage of viable cells. The cell migration assay showed that GF demonstrated the lowest open wound area percentage. GF and AD-S showed the highest calcium nodule deposition. GF demonstrated higher ALP activity than ES. Expression of RUNX2 and OC genes was similar for all sealers, while OPG gene expression was significantly higher for VDW.1 and GF. ES and AD-S displayed the highest pH values on day 1. Calcium ion release of ES and VDW.1 was significantly the highest. GuttaFlow-2 and VDW.1Seal sealers have favorable behavior toward host stem cells.