Areas Of Calcification Research Articles

Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure

Carbonate apatite (CO3Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO3Ap granules is difficult because of their granular shape. Therefore, we fabricated CO3Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO3Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO3Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO3Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO3Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO3Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO3Ap HCBs. Some osteoclasts invaded the wall of CO3Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO3Ap HCBs. These findings suggest that CO3Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects.Graphical The CO3Ap HCB were gradually resorbed and replaced by newly formed bone.

Cutaneous clear cell adnexal carcinoma in two dogs: cytological and immunohistochemical evaluation

In this study, cases of cutaneous clear cell adnexal carcinoma were diagnosed on the right forepaw of a 6-year-old female dog and on the right hind paw of an 8-year-old male dog. On the cytological examination, scattered cell groups were seen on the hemorrhagic background, whose cytoplasmic borders could hardly be distinguished. Although the cells showed marked pleomorphism, but were generally oval, round, or spindle-shaped. Anisokaryosis, karyomegaly, and one or more prominent nucleoli were noted in the nuclei. Pseudoinclusions were found in some cell nuclei. Histologically, it was centrally necrotic, expansive growth consisting of lobular areas in the dermis. The neoplastic cells consisted of oval round-shaped epithelioid cells with clear cytoplasm showing marked anisocytosis, anisorkaryosis and karyomegaly. Nuclei were oval or round in shape with prominent nucleoli. Cystic changes and calcified areas in layers (psammoma bodies) were noted in these areas. Few mitoses were found. In the immunohistochemical examination, tumor cells were positive for vimentin, S-100, MART1 (Melan A), and cytokeratin (MNF116) and negative for glial fibrillary acidic protein (GFAP) and smooth muscle actin (SMA). Based on these findings and results, the tumors were diagnosed as canine clear cell adnexal carcinoma. According to the literature review, this is the first case in which we found psammoma bodies and nuclear pseudo inclusions on microscopic examination of canine cutaneous clear cell adnexal carcinoma.

A Case of Peritoneal Malignant Mesothelioma in a Dog

In this case, biopsy samples sent from a private veterinary clinic to Burdur Mehmet Akif Ersoy University Veterinary Faculty Pathology Department were evaluated. In the macroscopic examination, whitish grayish cauliflower-like lesions were seen on the samples, varying in diameter 0.5-1.5 cm. Tissue samples with lesions were examined histopathologically after going through routine follow-up. In the microscopic examination, neoplastic mesotal cells with round or cuboidal shape, vesicular nuclei, anaplasic features such as anisocytosis, anionucleosis, and multinucleolus were found in some microscope fields. It was observed that these cells exhibited solid or fence-like arrays. In the neoplastic. tissue, hyalinized connective tissue and severe calcified areas were detected in some areas. In the light of these findings, the patient was diagnosed with peritoneal malignant mesothelioma.

Prediction of optical coherence tomography-detected calcified nodules using coronary computed tomography angiography

Diagnosis of calcified nodules (CNs) is critical in the proper management of coronary artery disease, but CNs can be detected only using intracoronary imaging modalities. This study aimed to investigate the ability of coronary computed tomography angiography (CCTA) in predicting CNs detected using optical coherence tomography (OCT). From 138 patients who underwent OCT-guided percutaneous coronary intervention (PCI) after CCTA evaluation, 141 PCI target vessels were retrospectively enrolled and classified into CN (12 vessels/11 patients; CNs in the PCI culprit lesion) and non-CN (129 vessels/127 patients; without CNs) groups based on the OCT analysis. Retrospective CCTA analysis revealed significantly higher coronary artery calcification score (CACS), calcified plaque volume (CPV), and maximum calcified plaque area (MCPA) of the target vessel in the CN group than in the non-CN group. Receiver operating characteristic curve indicated that CACS ≥ 162 (area under the ROC curve (AUC 0.76, sensitivity 83.3%, specificity 54.2%), CPV ≥ 20.1 mm3 (AUC 0.83, sensitivity 100%, specificity 57.3%), and MCPA ≥ 4.51 mm2 (AUC 0.87, sensitivity 91.7%, specificity 78.3%) were the best cutoff values for predicting CNs. MCPA showed the highest AUC among all the CCTA parameters. In conclusion, CCTA is useful for predicting OCT-detected CNs in PCI target vessels.

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease

BackgroundClinical implications of different types of vascular calcification are poorly understood. The two most abundant forms of calcification, nodular and sheet calcification, have not been quantitatively analyzed in relation to the clinical presentation of lower extremity arterial disease (LEAD).MethodsThe study analyzed 51 femoral artery plaques collected during femoral endarterectomy, characterized by the presence of > 90% stenosis. Comprehensive clinical data was obtained from patient records, including magnetic resonance angiography (MRA) images, toe pressure and ankle brachial index measurements and laboratory values. The plaques were longitudinally sectioned, stained with Hematoxylin and Eosin and digitized in a deep learning platform for quantification of the relative area of nodular and sheet calcification to the plaque section area. A deep learning artificial intelligence algorithm was designed and independently validated to reliably quantify nodular calcification and sheet calcification. Vessel measurements and quantity of each calcification category was compared to the risk factors and clinical presentation.ResultsOn average, > 90% stenosed vessels contained 22.4 ± 12.3% of nodular and 14.5 ± 11.8% of sheet calcification. Nodular calcification area proportion in lesions with > 90% stenosis is associated with reduced risk of critically low toe pressure (< 30 mmHg) (OR = 0.910, 95% CI = 0.835–0.992, p < 0.05), severely lowered ankle brachial index (< 0.4) (OR = 0.912, 95% CI = 0.84–0.986, p < 0.05), and semi-urgent operation (OR = 0.882, 95% CI = 0.797–0.976, p < 0.05). Sheet calcification did not show any significant association.ConclusionsLarge amount of nodular calcification is associated with less severe LEAD. Patients with nodular calcification may have better flow reserves despite local obstruction.

Sex-dependent expression of neutrophil gelatinase-associated lipocalin in aortic stenosis

BackgroundAccumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders. We aimed to analyse sex-related differences of NGAL in AS and its role in the inflammatory and fibrocalcific progression of AS.Methods and results220 (60.45% men) patients with severe AS elective for surgical aortic valve (AV) replacement were recruited. Immunohistochemistry revealed higher expression of NGAL in calcific areas of AVs and that was validated by qPCR in in 65 (60% men) donors. Valve interstitial cells (VICs) were a source of NGAL in these samples. Proteome profiler analyses evidenced higher expression of NGAL in men compared to women, and that was further validated by ELISA. NGAL expression in the AV was correlated with inflammation, oxidative stress, and osteogenic markers, as well as calcium score. The expression of NGAL, both intracellular and secreted (sNGAL), was significantly deregulated only in calcifying male-derived VICs. Depletion of intracellular NGAL in calcifying male-derived VICs was associated with pro-inflammatory profiles, dysbalanced matrix remodelling and pro-osteogenic profiles. Conversely, exogenous NGAL mediated inflammatory and dysbalanced matrix remodelling in calcifying VICs, and all that was prevented by the pharmacological blockade of NGAL.ConclusionsOwing to the over-expression of NGAL, the AV from men may be endowed with higher expression of inflammatory, oxidative stress, matrix remodelling and osteogenic markers supporting the progression of calcific AS phenotypes. The expression of NGAL in the VIC emerges as a potential therapeutic checkpoint, with its effects being potentially reverted by the pharmacological blockade of extracellular NGAL.

A calcitonin-producing pancreatic neuroendocrine neoplasm treated with distal pancreatectomy a lengthy time after a left trisectionectomy for liver metastases: a case report.

Calcitonin-producing pancreatic neuroendocrine neoplasms (PanNENs) are extremely rare. There have been no reports of a patient in whom liver metastases were the presenting finding, and a calcitonin-producing PanNEN was subsequently detected after a lengthy period. A 53-year-old man had diarrhea for several years. Computed tomography (CT) revealed multiple liver tumors. We performed a left trisectionectomy with a bile duct resection. The histologic examination showed neuroendocrine tumors G1. Immunohistochemistry was positive for calcitonin and the serum calcitonin level was elevated. Neuroendocrine neoplasms of hepatic origin are extremely rare, so a systemic exploration was performed, but no tumor was detected. CT showed a 4-mm calcification in the pancreatic body, but no contrast-enhanced mass was noted. Although the liver tumors were resected, the diarrhea and high serum calcitonin level persisted. Serial examinations were performed for 6years, but no tumor was identified; however, 6.5years after the hepatectomy the serum calcitonin level increased. CT showed a 10-mm contrast-enhanced mass in the calcified area of the pancreatic body. A distal pancreatectomy was performed. The histologic examination showed a neuroendocrine tumor G1, which mimicked the liver tumors. Immunohistochemistry was positive for calcitonin. After the distal pancreatectomy, the serum calcitonin level decreased and diarrhea resolved. The calcitonin-producing neuroendocrine neoplasm was considered the pancreatic primary and the hepatic tumors were metastases. Calcitonin-producing PanNENs may be initially recognized as liver tumors and may become evident after a lengthy period, thus long-term observation is recommended. Aggressive surgeries may contribute to long-term survival.

SPDR-5 ESTABLISHMENT OF A CONTINUOUS CULTURE METHOD FOR MENINGIOMAS AND THE EFFECTS OF THE GREM2-BMP SIGNALLING PATHWAY ON PROLIFERATION AND ANGIOGENESIS

Abstract Purpose Meningiomas are closely related to osteogenesis, including calcification and hyperostosis at the site of attachment. Signaling pathways involved in tumor formation and extension of meningioma have not yet been elucidated. Treatment options include surgical removal and radiotherapy, but there are no reports of effective drug treatment. This is due to the difficulty of culturing non-malignant meningiomas, which has made basic experiments difficult. In this study, we established a continuous culture method for meningiomas and investigated the signaling pathways involved in meningioma growth. Methods 67 consecutive cases of meningiomas treated in our department for three years from Apr, 2019 to March, 2022. Primary continuous culture was performed by modifying the conditional reprogramming (CR) method. Sixty-four cases were studied, excluding three cases in which culture was abandoned due to contamination. The mean age was 62.6 years, Grade 3 (6%), Grade 2 (14%) and Grade 1 (80%). These were used to observe morphology, proliferation and genetic analysis involved in angiogenesis. Results 1) Sustained culture lasted an average of 150 days with no differences between Grades; 2) Inhibition of BMP signaling involved in osteogenesis suppressed cell proliferation regardless of Grade, and the IC50 of the inhibitor suggested the involvement of the receptor ALK3; 3) We identified GREM2 as upstream regulator of BMP signals 4) GREM2 is highly expressed in menigotherial meningiomas and immunostaining showed strong expression around whole and calcified areas. 5) GREM2 expression is negatively correlated with MIB-1 L.I., so overexpression of GREM2 in malignant meningioma cells decreased ID, which is involved in proliferation downstream of BMP signaling, and increased angiogenic factor VEGFA, which is involved in proliferation. Conclusion A method for the continuous culture of meningiomas was established. Using this experimental system, we identified the involvement of the GREM2-BMP signaling pathway in proliferation and angiogenesis in meningiomas as well as calcification.

Successful trans-femoral retrieval of a stuck axillary Impella 5.0 device.

We describe a case in which an axillary Impella 5.0, stuck in an area of calcification in the right subclavian artery, could not be retrieved in the usual manner. However, it was successfully removed using a long 22-Fr sheath and snaring catheter by means of the trans-femoral artery. Device retrieval using the trans-femoral artery snare technique is considered a valid option for removing the Impella device in patients who exhibit this complication.

Abstract 12340: Vascular Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries

Background and aims: The number of patients with peripheral arterial disease (PAD) is increasing, and when it develops into critical limb ischemia (CLI), the 5-year mortality rate is as high as 50%. Nevertheless, there are few histopathological reports of PAD. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) obtained from the patients who underwent low extremity amputation due to CLI. Methods: Thirty tibial arteries removed from 15 lower limb amputation specimens were examined. Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 transverse sections. Results: The distribution of calcified area per vessel area is significantly higher in PTAs than in ATAs by the soft X-ray radiography images (ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9; p &lt; 0.05). Morphological and immnunohistological examination revealed eccentric plaque with necrotic core and macrophage infiltration was prominent in ATAs than in PTAs(ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9; p &lt; 0.05) (ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9; p &lt; 0.05). Moreover, thromboembolic lesions were frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p &lt; 0.05). The proportion of intimal calcification area and medial calcification area were significantly higher in ATAs and PTAs, respectively (intima; ATAs, 0% [0-16.8] versus PTAs, 0% [0-11.7%]; p &lt;0.05, media; PTAs, 38.2% versus ATAs, 15.7%; p &lt; 0.05). Conclusions: Histological features were strikingly different among these arteries of the patients with CLI. To clarify the pathological features of CLI may contribute to establish the therapeutic strategy for PAD, particularly below the knee arteries.

Abstract 13063: Clonal Hematopoiesis Associated With TET2 and DNMT3A Gene Driver Mutations Accelerates Aortic Valve Calcification in vitro and in vivo

Calcific aortic valve disease (CAVD) is the most common age-related heart valve disease, with no medical therapy to halt progression. Age is associated with the enrichment of somatic mutations in hematopoietic stem cells leading to clonal hematopoiesis (CH). CH mutations promote inflammation, occur in more than 30% of patients with severe CAVD and CAVD patients harboring CH mutations have a worse prognosis. Single-cell RNA-sequencing of immune cells (n=127120 cells) of CAVD patients with CH-mutations showed strong proinflammatory and M1-like macrophage gene signatures (CD38, CXCL10) along with genes associated with calcification (S100A9, RUNX2, Oncostatin M=OSM) suggesting that CH might be causally involved in CAVD. Indeed, silencing of TET2 or DNMT3A in macrophages in vitro induce the prototypic osteoblastic transcription factor RUNX2 and paracrine acting genes such as OSM and S100A9, which can promote vascular calcification. Secreted factors from TET2 or DNMT3A-silenced macrophages induced osteoblastic differentiation as demonstrated by elevated calcium deposition and genes involved in the RUNX2 signaling pathway (COL1A2, ALP), which could be ablated by silencing of OSM in CH-macrophages. Atheroprone Ldlr -/- mice receiving TET2 -/- bone marrow transplants mice showed increased total calcified area along (1.49-fold) with increased numbers of calcification deposits (2.33-fold) as evidenced by von Kossa staining. Increased myeloid derived OSM and S100A9 was found in the valves of TET2 -/- BMT mice with S100A9 strongly co-occurring with OSM. This study provides insights into the development of incident CAVD for patients with CH mutations and therefore yields plausible interventions for nearly one third of CAVD cases to slow or stop disease progression.

ODP187 Doedge-Potter syndrome and papillary thyroid carcinoma: An unusual association

Abstract Hypoglycemia can occur in non-diabetic individuals. Doege-Potter is a rare paraneoplastic syndrome presented as a hypoinsulinemic hypoglycemia caused by ectopic secretion of insulin-like growth factor-2 (IGF-2) from a solitary fibrous tumor. There is recent evidence of the involvement of the IGF system in different malignancies as papillary thyroid carcinoma, being exceptional. A 69-year-old female was brought to Emergency after a routine analysis uncovered severe hypoglycemia. She mentioned a history of morning sickness, dizziness, and confusion for the last week that reverted after breakfast, and dry cough for three months. She had a 25-pack-year history of smoking, no history of alcohol use, no other antecedent of interest, no history ofdiabetes mellitus or weight loss surgery, nor chronic treatments. Physical examinations revealed diminished breath sounds in the left middle lung. A thorax radiography showed a submassive left pleural effusion and toracocentesis revealed a hemorrhagic exudate. Laboratory data showed normal GH, and cortisol levels. Despite marked hypoglycemia, insulin level was 0.4 μIU/mL (2,6-24,9), C-peptide 0.11ng/ml (1,1-4,4) and hydroxy butyrate &amp;lt;0.1 mg/dl. The serum IGF-2 level was 428μg/dL (350-1000), and the IGF-1 level was 55.4 μg/L(161-384). Anti-insulin antibodies and sulfonylureas concentration were negative. CT showed a solid mass concerning parietal pleura with areas of necrosis and calcifications, measuring 14.6×15.4×20cm. Low blood glucose with suppressed insulin, C-peptide and IGF-1 levels, elevated IGF-2/IGF-1 ratio (7,7, normal&amp;lt;3) and CT findings suggested the possibility of non-islet cell tumor hypoglycemia (NICTH). Corticoid treatment was initiated to manage the hypoglycemia. Biopsy of the mass showed a malignant solitary fibrous tumor, positive for CD34 and BCL2. After surgery, glucose and IGF-2 levels returned to normal, the patient didn't experience further episodes of hypoglycemia, and corticoid treatment was gradually suspended. A FDG-PET scan, part of extension study, found a PET-positive thyroid nodule. A thyroid ultrasound confirmed a solid, taller than wide thyroid nodule, measuring 6.7×6.4×9,5mm and fine-needle aspiration biopsy was suggestive of papillary thyroid carcinoma. Hemithyroidectomy was performed. The patient is with no evidence of disease. Doege-Potter syndrome is a rare cause of hypoglycemia, resulting from a tumor producing elevated levels of IGF-2. Diagnosis is suggested by low insulin, C-peptide and IGF-1 levels, normal or elevated IGF-2, and elevated IGF2/IGF1 ratio. High levels of ''big-IGF-2'' are associated with high risk papillary thyroid carcinoma, suggesting the relation between the IGF-system and tumor growth, nevertheless there are few cases reported describing this association. Surgical resection of the tumor is the treatment of choice. Presentation: No date and time listed

Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene.

A couple were referred for prenatal genetic testing at 31weeks' gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and a small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid. A pathogenic homozygous nonsense variant in KLHL7 (NM_001031710.2) associated with PERCHING syndrome (#617055) was identified. Whilst there are detailed descriptions of the many postnatal phenotypes seen in these patients, there are few reports of features identified during pregnancy. This report is the first published prenatal diagnosis of PERCHING syndrome and provides further information on the associated fetal phenotypes.

Biocompatibility and mineralization potential of new calcium silicate cements

Background/purposeAs calcium silicate cements (CSCs) have been successfully used in various types of vital pulp therapy, many new CSC products have been developed. The aim of this study was to evaluate the biocompatibilities and mineralization potential of new CSC. The experimental materials were NeoMTA Plus and EndoSequence Root Repair Material-Fast Set Putty (ERRM-FS) which were compared to ProRoot MTA. Materials and methodsIn vitro, the effects of the new CSC on stem cells were evaluated. Each CSC was prepared for cell viability testing, alkaline phosphatase (ALP) assay, and calcium ion release assay. In vivo, the exposed pulp model was used for the partial pulpotomy procedure. Thirty-six teeth were treated with three materials: ProRoot MTA, NeoMTA Plus, or ERRM-FS. After four weeks, the teeth were extracted and processed for histologic analysis. Dentin bridge formation, pulp inflammation, and odontoblastic cell layer were evaluated and the area of newly formed calcific barrier of each group was measured. ResultsThree CSCs demonstrated similar cell viability on stem cells and the levels of ALP and calcium release were not significantly different between tested materials. ProRoot MTA and ERRM-FS showed better tissue healing process than NeoMTA Plus after partial pulpotomy, in terms of quality of calcific barrier and pulp inflammation. The outcomes from measuring newly formed calcific area demonstrated no significant differences between the materials. ConclusionNeoMTA Plus and ERRM-FS displayed similar biocompatibilities and mineralization potential compared to ProRoot MTA. Therefore, these new CSCs can be used as desirable alternatives to ProRoot MTA.

Early life stages of a Mediterranean coral are vulnerable to ocean warming and acidification

Abstract. The ability of coral populations to recover from disturbance depends on larval dispersion and recruitment. While ocean warming and acidification effects on adult corals are well documented, information on early life stages is comparatively scarce. Here, we investigate whether ocean warming and acidification can affect the larval and recruit development of the Mediterranean azooxanthellate coral Astroides calycularis. Larvae and recruits were raised for 9 months at ambient (23 ∘C) and warm (26 ∘C) temperatures and ambient (8.0) and low pH (7.7, on the total scale). The timing of the larval metamorphosis, growth of the recruit polyp by linear extension and budding, and skeletal characteristics of the 9-month-old polyps were monitored. Settlement and metamorphosis were more successful and hastened under a warm temperature. In contrast, low pH delayed the metamorphosis and affected the growth of the recruits by reducing the calcified area of attachment to the substrate as well as by diminishing the skeleton volume and the number of septa. However, skeleton density was higher under low pH and ambient temperature. The warm temperature and low-pH treatment had a negative impact on the survival, settlement, and growth of recruits. This study provides evidence of the threat represented by ocean warming and acidification for the larval recruitment and the growth of recruits of A. calycularis.

Unravelling the role of SOCS3 in aortic valve stenosis

Abstract Background Calcific aortic valve stenosis (CAVD) is the most prevalent heart valve disease worldwide and, in advanced stages, leads to clinical deterioration and poor prognosis. Until now, no medical treatment is available. Thought to be a merely degenerative disease, we now know that disease initiation and progression are actively regulated by immune cell infiltration, chronic inflammation, osteogenic differentiation of valvular interstitial cells (VIC) and endothelial-to-mesenchymal transition (EndMT) of valvular endothelial cells (VEC). Suppressor of Cytokine Signaling 3 (SOCS3) is known to be a key regulator of inflammation. It promotes the polarisation of macrophages to an inflammatory phenotype and thus, contributes to disease progression in atherosclerosis. In CAVD, not only inflammation but also heterotopic bone formation leads to the thickening and obstruction of the aortic valve cusps and as SOCS3 is one of the main regulators of physiological bone formation, it could play a critical role in the progression of CAVD. Purpose We hypothesize that SOCS3 plays a crucial role during calcification of the aortic valve through regulation of EndMT, calcification of valvular interstitial cells and macrophage polarization. Methods and results In initial screening experiments, we investigated SOCS3-protein expression in explanted human aortic valves from patients undergoing surgical aortic valve replacement. SOCS3 is expressed in both stenotic and non-stenotic valve tissues. Immunofluorescence-staining of human aortic valves shows the co-localisation of SOCS3 with the interstitial cell-marker Vimentin and SOCS1, which is known to regulate macrophage-polarisation together with SOCS3 (Fig. 1). Staining of the macrophage-marker CD68 revealed its co-localisation with calcified areas of the aortic valve cusp. We validated our findings in our in vitro model of VIC calcification using two different calcifying conditions. Upregulation of RUNX2 and BMP2 verified successful osteogenic differentiation of VICs. During osteogenic differentiation for 7 days, SOCS3 and SOCS1 are significantly upregulated (Fig. 2A). We were able to induce EndMT by stimulating VEC with either TNFα or TGFβ/IL1β in vitro. We show that EndMT leads to the loss of endothelial cell markers like eNOS and VWF and to an upregulation of interstitial cell markers (such as Vimentin and α-SMA) and markers of EndMT (SNAI2). During EndMT, we were also able to observe a significant upregulation of SOCS1 and SOCS3 after 7 days (Fig. 2B). Ongoing knockdown experiments will help to elucidate the role of SOCS1 and SOCS3 during initiation and progression of CAVD. Conclusion We aim towards a better understanding of SOCS3 and its role in inflammation and calcification as hallmarks of the pathogenesis of CAVD. Since Zoledronic acid has been shown to induce a decreased expression of SOCS3 in macrophages, this might present as a possible treatment strategy to target SOCS3 therapeutically. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft

Heritability and environmental influences on the onset of aortic valve sclerosis: a twin population study

Abstract Background Aortic valve sclerosis (AVSc) is the earliest manifestation of a life-threatening cardiovascular disorder, namely aortic valve stenosis (AS). AVSc is also recognized as a red flag linked to worse cardiovascular outcomes in high-risk coronary artery disease patients. However, the genetic background of AVSc is still unknown. Purpose To examine whether the heritability and environmental contributions play a role in the onset of AVSc using a sample of Italian twins. Methods The present study is based on the classical twin design. Twins, aged 50 to 70 years, already enrolled in the Italian Twin Register, were contacted and invited to undergo a clinical, echocardiographic, and complete carotid artery ultrasound examination at the our Center, between July 2017 and December 2021. The presence of AVSc was recognized as non-uniform thickening with or without spotty calcified areas of the aortic valve leaflets without a significant transvalvular gradient (maximum aortic velocity &amp;lt;2.5 m/s). Twin zygosity was assessed through a questionnaire on physical similarity during childhood, known to be ∼95% accurate. Tetrachoric twin correlations by zygosity were estimated with Mx Software using liability threshold saturated models and incorporating age as a covariate. Liability-threshold structural equation modelling was performed to decompose the phenotypic variance into contributions due to additive genetic (A), common environmental (C), and unique environmental (E) effects. Results A total of 216 adult twins (66 monozygotic, MZ and 42 dizygotic pairs, DZ; mean age 59.9±6.2) were enrolled in the study. The estimated prevalence rate of AVSc in the total sample was 29.2%. As significant sex differences were detected (males 45.2% and females 22.7%, p&amp;lt;0.01), the additional twin analyses were performed as intra-sex analyses. Females showed a greater tetrachoric correlation in MZ twins (r=0.37) compared to DZ twins (r=0.23), suggesting the existence of a genetic influence. Genetic factors, under the best (AE) model, accounted for 38% of the variance in liability to AVSc with the remaining contribution due to unique environmental influences (E = 62%). The contribution of the common environment (C) to the goodness of fit was negligible. The male group was too small for statistical calculation. Conclusion To our knowledge, the present study is the first to document the involvement of genetic factors in the development of AVSc. Our data also warrant further studies to both validate the findings obtained and to better explore the heritability of AVSc. Furthermore, our results provide a first evidence that an echocardiographic screening in individuals with relatives affected by AVSc has a scientific rational basis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Italian Ministry of Health

S3601 Gastric Inflammatory Myofibroblastic Tumor Presenting as Chronic Abdominal Pain in a Young Female

Introduction: Inflammatory Myofibroblastic Tumor (IMT) is a rare mesenchymal tumor, commonly seen in children and adolescents. Lung is the most common site. Here we present an extremely rare case of a gastric IMT in a 28 year old lady. Case Description/Methods: Pt presented with intermittent epigastric pain for 8 years. This was associated with bloating and regurgitation and weight loss.These symptoms worsened along with new symptoms of chest pain, Cardiology workup was unremarkable. CT abdomen with contrast ordered to investigate further revealed 3.9 cm x 3.6 cm intramural mass with smooth margin and areas of internal calcification, extending into the gastric lumen of the upper stomach at the left lateral fundal region. Pt was referred to a local gastroenterologist. EGD performed showed confirmation of the lesion. Pt was referred to surgical oncologist at tertiary care hospital. EGD performed with biopsy of the lesion showed Benign gastric mucosa with small separate fragment of gastric mucosa containing smooth muscle-like tissue consistent with a tangentially section muscularis mucosa vs benign smooth muscle mass. Given the inconclusive diagnosis, partial gastrectomy was performed after detailed discussion with the patient. Gross pathology showed a submucosal mass, corresponding to the serosa lesion, measuring 4.3 x 4.2 x 3.7 cm. Microscopic pathology showed spindle cells with variable Cellularity with prominent lymphoplasmacytic infiltrates along with dystrophic calcification and osseous metaplasia. There is regional expression of ALK-1,and regional subserosal expression of SMA and MSA. Lesional cells do not express CD117, DOG-1, and desmin. The immunoprofile supports interpretation of IMT. Patient was seen eight months post surgery with resolution of all the symptoms. (Figure) Discussion: Primary gastric IMT is extremely rare. There have been a handful of cases in literature. Gastric IMT is most commonly associated with abdominal pain and upper GI bleeding. Most common treatment is partial gastrectomy. There is some potential of IMT to turn into malignancy. IMT are associated with high local recurrence rates. There are no guidelines on surveillance though common consensus is to perform EGD 6 months to a year initially followed by increasing the interval later. As GI clinicians, we should be aware of these symptoms associated with IMT.Figure 1.: CT images and Histology.

Evaluation of prevalence and dimension of Pineal Gland Calcification by cone-beam computed tomography (CBCT)

Abstract Objective: This study aimed to investigate the prevalence and dimensions of pineal gland calcification using cone-beam computed tomography (CBCT) in patients undergoing dental treatment. Materials and Methods: CBCTs that localized pineal gland in the fov range was selected in this retrospective study. The presence of pineal gland calcification (PGC) was noted. Vertical, horizontal and areal measurements were made by a single observer (M.S). Variables such as age, gender for each patient were recorded using previous clinical examination data. Results: The prevalence of pineal gland calcification was 33.64% (female to male ratio 3:2). The difference between males and females was not significant (p&amp;gt;0.05). PGC was highly seen in older patients when compared with younger patients (p:000). The average vertical and horizontal dimension of PGC was 2,56±0,98mm and 3,39±1,29 mm respectively. The average total calcified area was 5,45±3,75 mm2. Conclusion: This study did not find any correlation between age, gender, and linear measurements. However, the average calcified are in men was found to be significantly higher than in women.

Maternal obesity and placental pathology in correlation with adverse pregnancy outcome.

Maternal obesity is associated with increased maternal and fetal morbidity and mortality, with an increased risk of gestational diabetes mellitus (GDM) and preeclampsia (PE). This prospective study histopathologically analyzes the placentas obtained from 34 pregnant obese women studied between October 2016 and May 2020. The 10 cases of term placentas from obese pregnancies with GDM and the 12 cases with PE were examined by the Hematoxylin-Eosin (HE), Masson's trichrome (MT) and Periodic Acid-Schiff-Hematoxylin (PAS-H) classical stainings, and by the immunohistochemical evaluation and compared to placentae from uncomplicated term obese pregnancies (12 cases). We did not meet placental histopathological (HP) abnormalities that we could classify as characteristic only for the state of obese pregnancy, but we did find placental changes associated with PE and GDM, in the context of obese pregnancy. In the case of association with PE, there were common lesions, manifested by intra- and perivillous fibrinoid deposition, calcification, and placental infarction area, to which were added numerous syncytial knots. In the case of obese pregnancy associated with GDM, we found, in addition to common placental lesions of obesity, intravillositary vascular edema and in the terminal villi appearing chorangiosis. This study revealed a number of HP changes that occur in maternal obesity, even in uncomplicated obese pregnancies. A characteristic of obese pregnancies associated with PE was the presence of numerous syncytial knots, and in obese pregnancies associated with GDM, the most common HP lesion was placental chorangiosis. Certainly, we cannot conclude that these HP lesions are specific to a particular pathology, but they belong primarily to the status of maternal obesity.