Predictors of Optical Coherence Tomography-Defined Calcified Nodules in Patients With Acute Coronary Syndrome　- A Substudy From the TACTICS Registry.

BACKGROUND: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry.Methods and Results: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN. CONCLUSIONS: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Distinct Challenges of Eruptive and Non-Eruptive Calcified Nodules in Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: To provide a summary of prevalence, pathogenesis, and treatment of coronary calcified nodules (CNs). RECENT FINDINGS: CNs are most frequently detected at the sites of hinge motion of severely calcified lesions such as in the middle segment of right coronary artery and left main coronary bifurcation. On histopathology, CNs exhibit two distinctive morphologies: eruptive and non-eruptive. Eruptive CNs, which have a disrupted fibrous cap with adherent thrombi, are biologically active. Non-eruptive CNs, which have an intact fibrous cap without thrombi, are biologically inactive, representing either healed eruptive CNs or protrusion of calcium due to plaque progression. Recent studies using optical coherence tomography (OCT) have shown a difference in the mechanism of stent failure in the two subtypes, demonstrating early reappearance of eruptive CNs in the stent (at ~ 6 months) as a unique mechanism of stent failure that does not seem to be preventable by simply achieving adequate stent expansion. The cause of CN reappearance in stent is not known and could be due to acute or subacute intrusion or continued growth of the CN. Whether modification of CN is needed, the most effective calcium modification modality and effectiveness of stent implantation in eruptive CNs has not been elucidated. In this review, we discuss pathogenesis of CNs and how intravascular imaging can help diagnose and manage patients with CNs. We also discuss medical and transcatheter therapies beyond conventional stent implantation for effective treatment of eruptive CNs that warrant testing in prospective studies.

Comparison of interventional treatment options for coronary calcified nodules: A sub-analysis of the ROTA.shock trial.

BACKGROUND: The optimal treatment for coronary calcified nodules (CNs) is still unclear. The aim of this study was to compare the modification of these lesions by coronary intravascular lithotripsy (IVL) and rotational atherectomy (RA) using optical coherence tomography (OCT). METHODS: ROTA.shock was a 1:1 randomized, prospective, double-arm multi-center non-inferiority trial that compared the use of IVL and RA with percutaneous coronary intervention (PCI) in severely calcified lesions. In 19 of the patients out of this study CNs were detected by OCT in the target lesion and were treated by either IVL or RA. RESULTS: The mean angle of CNs was significantly larger in final OCT scans than before RA (92 ± 17° vs. 68 ± 7°; p = 0.01) and IVL (89 ± 18° vs. 60 ± 10°; p = 0.03). The CNs were thinner upon final scans than in initial native scans (RA: 17.8 ± 7.8 mm vs. 38.6 ± 13.1 mm; p = 0.02; IVL: 16.5 ± 9.0 mm vs. 37.2 ± 14.3 mm; p = 0.02). Nodule volume did not differ significantly between native and final OCT scans (RA: 0.66 ± 0.12 mm3 vs. 0.61 ± 0.33 mm3; p = 0.68; IVL: 0.64 ± 0.19 mm3 vs. 0.68 ± 0.22 mm3; p = 0.74). Final stent eccentricity was high with 0.62 ± 0.10 after RA and 0.61 ± 0.09 after IVL. CONCLUSION: RA or IVL are unable to reduce the volume of the calcified plaque. CN modulation seems to be mainly induced by the stent implantation and not by RA or IVL.

Coronary artery calcification: concepts and clinical applications.

Vascular calcification is an important hallmark of atherosclerosis. Coronary artery calcification (CAC) implies the presence of coronary artery disease (CAD), irrespective of risk factors or symptoms, is concomitant with the development of advanced atherosclerosis. Coronary thrombosis is the most common clinical end event leading to acute coronary syndrome (ACS). The least common type of pathology associated with thrombosis is the calcified nodule (CN). It usually occurs in elderly patients with severely calcified and tortuous arteries. The prevalence of calcified nodules in patients with ACS may be underestimated due to the lack of easily recognisable diagnostic methods. In this review, the authors will focus on the classification, clinical significance, pathogenesis, and diagnostic evaluation and treatment of CAC to further explore the clinical significance of CN.

Pulmonary diffuse calcified multiple nodules in alveolar echinococcosis.

Alveolar echinococcosis is a potentially life-threatening parasitic disease primarily involving the liver caused by echinococcus multilocularis. Alveolar echinococcosis shows tumor-like growth that can lead to infiltration of neighboring organs. It is a slowly progressive disease and most commonly metastasizes to the lung. In this study, a 45-year-old female case of alveolar echinococcosis with bilateral pulmonary diffuse calcified multiple nodules metastases is presented.

Effects of vitamin B12 in culture medium for calcified nodule formation by rat dental pulp cells.

Background/purpose: Tooth or bone regeneration requires large numbers of mesenchymal stem cells (MSCs). Although dental pulp is a suitable cell source, the number of MSCs present in this tissue is limited and they require a long period for regeneration. Therefore, the present study investigated vitamin B12 (Vb12) as an osteoinductive factor for MSCs obtained from dental pulp. Materials and methods: Dental pulp tissue was removed from the root canals of the extracted mandibular incisors of three 6-week-old male Fischer 344/N Slc rats using an endodontic file and whole cells were harvested. After the primary culture, cells were sub-cultured for calcified nodule formation in MEM containing dexamethasone (Dex), ß-glycerophosphate (ß-GP), vitamin C (Vc), and Vb12. Calcified nodules were confirmed under an inverted phase-contrast microscope. The alkaline phosphatase (ALP) activity of cells and quantity of Ca2+ in calcified nodules were measured. Results were analyzed using the Tukey-Kramer test. Results: Densely arranged calcified nodules were microscopically observed after the subculture of cells with Dex, ß-GP, Vc, and Vb12. The ALP activity level was 0.077 ± 0.023 µmol/µg DNA in MEM supplemented with Vb12, which did not significantly differ from that without Vb12. A mass of calcium nodules formed in culture medium containing Dex, ß-GP, Vc, and Vb12. The quantity of Ca2+ increased from 13.04 ± 0.44 to 20.91 ± 0.56 mg/dL (P < 0.01). Conclusion: Vb12 is effective for in vitro tooth or bone regeneration by the MSCs of rats and is useful as an osteoinductive factor for MSCs.

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.

Prognostic Impact of Calcified Plaque Morphology After Drug Eluting Stent Implantation　- An Optical Coherence Tomography Study.

BACKGROUND: Optical coherence tomography (OCT) has the potential to characterize the detailed morphology of calcified coronary plaques. This study examined the prognostic impact of calcified plaque morphology in patients with coronary artery calcification (CAC) who underwent newer-generation drug-eluting stent (DES) implantation.Methods and Results:In all, 251 patients with moderate to severe CAC who underwent OCT-guided DES implantation were reviewed retrospectively and divided into 3 groups according to OCT findings of the target lesion: 25 patients (10.0%) with calcified nodules (CN), 69 patients (27.5%) with calcified protrusion (CP) without CN, and 157 patients (62.5%) with superficial calcific sheet (SC) without CN and CP. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). Kaplan-Meier survival analysis revealed that, among the 3 groups, the rates of MACE-free survival (log-rank test, P=0.0117), myocardial infarction (log-rank test, P=0.0103), and TLR (log-rank test, P=0.0455) were significantly worse in patients with CN. Multivariate Cox proportional hazards analysis demonstrated that CN was an independent predictor of MACE (hazard ratio 4.41; 95% confidence interval 1.63-10.8; P=0.0047). CONCLUSIONS: Target lesion CN was associated with higher cardiac event rates in patients who underwent newer-generation DES implantation for lesions with moderate to severe CAC.

Synovial Chondromatosis of the Temporomandibular Joint.

Synovial chondromatosis is a rare condition characterized by the presence of loose cartilaginous bodies, due to the abnormal proliferation of synovial membrane. However, its manifestation in the temporomandibular joint is a rare finding, occurring predominantly in females. This case report describes the clinical features, diagnosis and management of a case of synovial chondromatosis.

Calcified Nodules in the Superficial Femoral Artery Confirmed by Intravascular Ultrasound, Angioscopy, and Histology.

An 84-year-old man was admitted to the authors' hospital for the treatment of intermittent claudication. Angiography revealed an exophytic calcified nodules in the distal superficial femoral artery. Angioscopy also revealed abundant exophytic atherosclerotic calcification. Histology confirmed the diagnosis. (Level of Difficulty: Beginner.).

Milia-like idiopathic calcinosis cutis of the forehead in an adult without Down's syndrome successfully treated with a CO2 laser.

BACKGROUND: Idiopathic calcinosis cutis is an uncommon form of calcinosis cutis. It may present as tumoral calcinosis, subepidermal calcified nodules or scrotal calcinosis. Subepidermal calcified nodules may also present as milia-like lesions commonly seen in children with Down's syndrome in the absence of tissue damage or metabolic disorders, it has been seldom reported in adults. The treatment of choice is surgical excision. However, a surgical approach may not always be beneficial to the patient given the cosmetic outcomes. Here, we describe the successful use of a CO2 laser in the treatment of milia-like calcinosis cutis of the forehead in an adult without Down's syndrome. AIMS: To describe the treatment of Milia-like idiopathic calcinosis cutis of the forehead in an adult without Down's syndrome successfully treated with a CO2 laser. METHODS: We report a case of a 48-year-old man who presented with skin-colored hard asymptomatic papules on the forehead that started about 9 years ago, a biopsy was performed and a diagnosis of milialike calcinosis cutis was made. Surgical excision was discarded regarding the location and the number of lesions, instead, a CO2 laser was used to treat this condition. RESULTS: Successful laser excision of the lesions with appealing cosmetic results. CONCLUSIONS: CO2 laser seems to be a valuable tool to treat milia-like calcinosis cutis lesions.

A case of mixed-pattern calcifications in multinodular goiter associated with a benign diagnosis.

BACKGROUND: Calcified nodules are often found in a goiter when performing an ultrasound of the neck. An analysis of different calcification patterns could contribute to discriminating between nodules with a lower malignancy risk and those with a higher malignancy risk. In certain cases, the results of a simple cytological analysis of a nodule are not specific enough to be completely trusted. CASE PRESENTATION: We present the case of a goiter with a mixed calcification pattern, including a type of calcification that is strongly associated with a malignant diagnosis, for which a completely benign diagnosis was determined. CONCLUSION: We believe that further studies examining a combination of ultrasound (US) and computed tomography (CT) scan presentations of thyroid nodules need to be performed.

Features and Outcomes of Patients with Calcified Nodules at Culprit Lesions of Acute Coronary Syndrome: An Optical Coherence Tomography Study.

OBJECTIVES: We sought to clarify clinical features and outcomes related to calcified nodules (CN) compared with plaque rupture (PR) and plaque erosion (PE) detected by optical coherence tomography (OCT) at the culprit lesions in patients with acute coronary syndrome (ACS). METHODS: Based on OCT findings for culprit lesion plaque morphologies, ACS patients with analyzable OCT images (n = 362) were classified as CN, PR, PE, and other. RESULTS: The prevalence of CN, PR, and PE was 6% (n = 21), 45% (n = 163), and 41% (n = 149), respectively. Patients with CN were older (median 71 vs. 65 years, p = 0.03) and more diabetic (71 vs. 35%, p = 0.002) than those without CN. In OCT findings, the distal reference lumen cross-sectional area (median 4.2 vs. 5.2 mm2, p = 0.048) and the postintervention minimum lumen cross-sectional area (median 4.5 vs. 5.3 mm2, p = 0.04) were smaller in lesions with CN than in those without. Kaplan-Meier estimate survival curves showed that the 500-day survival without target lesion revascularization (TLR) was lower (p = 0.011) for patients with CN (72.9%) than for those with PR (89.3%) or PE (94.8%). CONCLUSIONS: ACS patients with CN at the culprit lesion had more TLR compared to those with PR or PE.

A Case Report of Primary Synovial Chondromatosis with Bilateral Genu Valgum.

INTRODUCTION: Synovial chondromatosis is the rare and benign metaplasia of the synovial membrane resulting in the formation of multiple intra-articular cartilaginous loose bodies. Synovial chondromatosis is known by several other names including articular chondrosis and synovial chondrosis. CASE REPORT: An 18-year-old boy presented with complaints of difficulty in walking with growing deformity with restriction and painful movements of knee joints bilaterally. The patient gives a history of swelling which was initially there about 8 years back and was accompanied by fever. The patient has taken some treatment for the same by local medics but has not been relieved of his symptoms. Patient's symptoms are insidious in onset and have gradually progressed in its severity. The patient first noticed swelling over knee right side, which was accompanied by a fever followed by progressive deformity. He gave a history of locking in both knee joints. The patient gives no definitive history regarding any definitive treatment taken for his complaints. CONCLUSION: Curvilinear or rounded calcified lesions within a soft tissue mass in the close vicinity of the joint should always be further investigated for the possibility of primary synovial osteochondromatosis (PSC). The imaging appearance of PSC appears sufficiently unique to allow its differentiation from other causes of intra-articular pathology. Genu valgum following synovial chondromatosis is not yet reported in the literature. Probably increased vascularity and synovitis may be the cause for valgus deformity. This patient is in follow-up for the past 3 years, and no recurrence of loose bodies has been noted. This case is unique in terms of the age of presentation and developmental deformity which is rare in PSC.

Prevalence and distribution of calcified nodules in carotid arteries in correlation with clinical symptoms.

PURPOSE: Calcified nodules ("CN") are responsible for up to 5% of coronary-infarcts and, therefore, classified as minor criteria of "vulnerable" atherosclerotic plaque. We sought to evaluate prevalence and distribution of CN in carotid arteries in correlation with clinical symptoms. METHODS: 178 consecutive patients with unilateral ischemic stroke and carotid plaques ≥2 mm by duplex ultrasound underwent a carotid-black-blood-3T-MRI with fat-saturated pre- and post-contrast T1w-, PDw-, T2w- and TOF images using dedicated surface-coils. CN were defined as distinct calcification with an irregular, protruding, and convex luminal surface. Prevalence of CN was determined in common carotid artery ("CCA") and internal carotid artery ("ICA") in consensus by two reviewers blinded to clinical information. RESULTS: Thirty seven CN in 28 arteries of 26 patients were identified. Prevalence of CN in CCA compared to ICA was slightly higher (59 vs. 41%), but nearly similar in 66 arteries with ≥30% compared to 290 arteries with <30% stenosis (9.1 vs. 7.6%) and in the artery ipsilateral versus contralateral to stroke (7.9 vs. 7.9%; P values n.s.). Prevalence of CN was significantly higher in 40 symptomatic arteries with ≥30% stenosis compared to asymptomatic 26 arteries (15.6 vs. 0%; P = 0.04). There was a significantly higher prevalence of hypercholesterolemia and hypertension in patients with CN (57.7 vs. 36.0 and 88.5 vs. 66.7%; P values <0.05). CONCLUSION: CN were found in 7.9% of arteries with carotid-plaques ≥2 mm by duplex-ultrasound; prevalence was significantly higher in symptomatic arteries with ≥30% stenosis compared to asymptomatic with <30% stenosis, suggesting that CN play a role in pathogenesis of ischemic stroke in a small subset of patients.

Calcified Pulmonary Nodules Identified in a 350-Year-Old-Joseon Mummy: the First Report on Ancient Pulmonary Tuberculosis from Archaeologically Obtained Pre-modern Korean Samples.

We found calcified pulmonary nodules in a middle-aged female mummy discovered from 350-yr-old Joseon tomb of Korea. In the CT scan, we found six radiopaque nodules in right lung, through the levels of thoracic vertebrae 1 to 6. We also found presumptive pleural adhesions in right thoracic cavity of CT images. We re-confirmed radiological findings by our post-factum dissection on the same mummy. By the differential diagnosis, we speculate that the radiopaque calcification nodules and associated pleural adhesion could have been caused by tuberculosis. This is the first-ever report on the pulmonary tuberculosis identified in archaeologically obtained, pre-modern Korean samples.

Calcified Pulmonary Nodules Identified in a 350-Year-Old-Joseon Mummy: the First Report on Ancient Pulmonary Tuberculosis from Archaeologically Obtained Pre-modern Korean Samples

We found calcified pulmonary nodules in a middle-aged female mummy discovered from 350-yr-old Joseon tomb of Korea. In the CT scan, we found six radiopaque nodules in right lung, through the levels of thoracic vertebrae 1 to 6. We also found presumptive pleural adhesions in right thoracic cavity of CT images. We re-confirmed radiological findings by our post-factum dissection on the same mummy. By the differential diagnosis, we speculate that the radiopaque calcification nodules and associated pleural adhesion could have been caused by tuberculosis. This is the first-ever report on the pulmonary tuberculosis identified in archaeologically obtained, pre-modern Korean samples.

Pilomatrixoma of the breast, a rare lesion simulating breast cancer: a case report.

Pilomatrixoma or calcifying epithelioma of Malherbe is a rare, benign, skin tumour originating from piliferous follicles; breast localization is considered to be very rare. These lesions can origin from the peri-areolar piliferous bulbs and, due to the clinical and imaging features, be easily misdiagnosed as a breast neoplasm. We present a case of pilomatrixoma of the left breast in a woman of 43 years appearing as a firm, deep nodule in the external quadrants. The lesion had mammographic and sonographic malignant features, but histological analysis on core-needle biopsy and surgical specimens revealed this unusual benign lesion.

Primary synovial osteochondromatosis of the surapatellar pouch of knee. Correlation of imaging features with surgical findings.

A 31 years old female presented with swelling and pain above the right knee for three years. On examination, there was a tender swelling over the right knee more pronounced over the suprapatellar region. Plain X-ray, US, CT scan and MRI of the knee were suggestive of Primary synovial osteochondromatosis (PSC) of the suprapatellar pouch. Patient underwent total synovectomy and the diagnosis of synovial osteochondromatosis was confirmed histopathologically. Recognizing the imaging appearances of PSC is important to improve patient management.