Deep transfer learning for detection of breast arterial calcifications on mammograms: a comparative study.

INTRODUCTION: Breast arterial calcifications (BAC) are common incidental findings on routine mammograms, which have been suggested as a sex-specific biomarker of cardiovascular disease (CVD) risk. Previous work showed the efficacy of a pretrained convolutional network (CNN), VCG16, for automatic BAC detection. In this study, we further tested the method by a comparative analysis with other ten CNNs. MATERIAL AND METHODS: Four-view standard mammography exams from 1,493 women were included in this retrospective study and labeled as BAC or non-BAC by experts. The comparative study was conducted using eleven pretrained convolutional networks (CNNs) with varying depths from five architectures including Xception, VGG, ResNetV2, MobileNet, and DenseNet, fine-tuned for the binary BAC classification task. Performance evaluation involved area under the receiver operating characteristics curve (AUC-ROC) analysis, F1-score (harmonic mean of precision and recall), and generalized gradient-weighted class activation mapping (Grad-CAM++) for visual explanations. RESULTS: The dataset exhibited a BAC prevalence of 194/1,493 women (13.0%) and 581/5,972 images (9.7%). Among the retrained models, VGG, MobileNet, and DenseNet demonstrated the most promising results, achieving AUC-ROCs > 0.70 in both training and independent testing subsets. In terms of testing F1-score, VGG16 ranked first, higher than MobileNet (0.51) and VGG19 (0.46). Qualitative analysis showed that the Grad-CAM++ heatmaps generated by VGG16 consistently outperformed those produced by others, offering a finer-grained and discriminative localization of calcified regions within images. CONCLUSION: Deep transfer learning showed promise in automated BAC detection on mammograms, where relatively shallow networks demonstrated superior performances requiring shorter training times and reduced resources. RELEVANCE STATEMENT: Deep transfer learning is a promising approach to enhance reporting BAC on mammograms and facilitate developing efficient tools for cardiovascular risk stratification in women, leveraging large-scale mammographic screening programs. KEY POINTS: • We tested different pretrained convolutional networks (CNNs) for BAC detection on mammograms. • VGG and MobileNet demonstrated promising performances, outperforming their deeper, more complex counterparts. • Visual explanations using Grad-CAM++ highlighted VGG16's superior performance in localizing BAC.

The evolution of calcified anaerobic granular sludge bed informs the deep insight into its agglomeration process.

Calcium-induced agglomeration of anaerobic granular sludge bed (AGSB) has become a critical factor in performance decline of calcified anaerobic reactors. However, the agglomeration process of AGSB and the underlying mechanisms remain unclear and elusive. This study delved into the evolution of calcified AGSB, and four typical states of normal AGSB (Nor-AGSB), calcified dispersed AGSB (Dis-AGSB), calcified dimeric AGSB (Dim-AGSB), and calcified polymeric AGSB (Pol-AGSB) were characterized. It was found that the minimum transport velocity of Dis-AGSB was 3.14-3.79 times higher than that of Nor-AGSB, and surpassed both the superficial velocity and the bubble-induced wake velocity. This led to the sedimentation of AGS at the bottom of reactor, resulting in stable contacts with each other. Solid fillers between AGS, namely cement, were observed within Dim-AGSB and Pol-AGSB, and could be classified as tightly- and loosely- bonded cement (T- and L-cement). Further analysis revealed that T-cement was rich in extracellular polymeric substances and intertwining pili/flagella, serving as the primary driving force for robust inter-AGS adhesion. While the L-cement was primarily in the form of calcite precipitation, and blocked the convective mass transfer pathways in Pol-AGSB, leading to the decreased convective mass transfer capacity. The critical distance between calcite and AGS was further revealed as 5.33 nm to form stable initial adhesion. Consequently, the agglomeration mechanism involving the evolution of AGSB was proposed as calcium-induced sedimentation, calcium-induced adhesion, and calcium-induced stasis in order. This study is expected to offer deep insight into the calcium-induced agglomeration especially from the overlooked perspective of AGSB, and provides feasible control strategies to manage the pressing calcification issues in engineering applications.

A Dynamic Cellular Model as an Emerging Platform to Reproduce the Complexity of Human Vascular Calcification In Vitro.

Vascular calcification (VC) is a cardiovascular disease characterized by calcium salt deposition in vascular smooth muscle cells (VSMCs). Standard in vitro models used in VC investigations are based on VSMC monocultures under static conditions. Although these platforms are easy to use, the absence of interactions between different cell types and dynamic conditions makes these models insufficient to study key aspects of vascular pathophysiology. The present study aimed to develop a dynamic endothelial cell-VSMC co-culture that better mimics the in vivo vascular microenvironment. A double-flow bioreactor supported cellular interactions and reproduced the blood flow dynamic. VSMC calcification was stimulated with a DMEM high glucose calcification medium supplemented with 1.9 mM NaH2PO4/Na2HPO4 (1:1) for 7 days. Calcification, cell viability, inflammatory mediators, and molecular markers (SIRT-1, TGFß1) related to VSMC differentiation were evaluated. Our dynamic model was able to reproduce VSMC calcification and inflammation and evidenced differences in the modulation of effectors involved in the VSMC calcified phenotype compared with standard monocultures, highlighting the importance of the microenvironment in controlling cell behavior. Hence, our platform represents an advanced system to investigate the pathophysiologic mechanisms underlying VC, providing information not available with the standard cell monoculture.

Changes in the gut microbiota of pseudoxanthoma elasticum patients.

OBJECTIVE: Pseudoxanthoma elasticum (PXE) is a rare autosomal disorder with a variable phenotype that may be modulated by environmental factors. Plasma vitamin K (VK) levels may be involved in the ectopic calcification process observed in PXE. Since VK2 is predominantly produced by the gut microbiota, we hypothesized that changes in the gut microbiota of PXE patients might exacerbate the calcification process and disease symptoms. METHODS: Twenty PXE patients were included in the study and 60 gut microbiota profiles from the Biofortis laboratory database were used as controls. RESULTS: The Rhodospirillaceae family was more abundant in the PXE group while the Sphingomonadaceae family was more abundant in the control group. In a PXE severity subgroup analysis, microbiota dispersion was lower in "severe" than in "non-severe" patients, which was confirmed by permutation multivariate analysis of variance at the phylum, family and genus ranks. However, no significant association was found in a model incorporating relative abundance of bacterial families, severity score, and different blood and fecal VK species. CONCLUSION: These results suggest slight compositional changes in the gut microbiota of PXE patients. Further studies are needed to substantiate their impact on VK metabolism and the calcification process.

Modeling of Valve-in-Valve Transcatheter Aortic Valve Implantation after Aortic Root Replacement Using 3-Dimensional Artificial Intelligence Algorithm.

OBJECTIVE: Aortic root replacement requires construction of a composite valve-graft and reimplantation of coronary arteries. This study assessed the feasibility of valve-in-valve transcatheter aortic valve implantation after aortic root replacement. METHODS: A retrospective review was conducted on 74 consecutive patients who received a composite valve-graft at a single institution from 2019 to 2021. Forty patients had bioprosthetic valves with adequate postoperative gated computed tomographic angiography scans. Computational simulations of balloon and self-expanding transcatheter valve deployments were performed. The modeled coronary distances were compared to traditional, manually measured valve-to-coronary distances. RESULTS: There was a statistically significant difference in the modeled versus manual measurements of valve to coronary distances were for all patients regardless of valve type or coronary artery analyzed (p <0. 05). Most patients are low risk for coronary obstruction per three-dimensional modeling including those with a valve-to-coronary distance <4 millimeters. Only one patient (2.5%) was at risk for coronary obstruction for the left coronary artery using a ballonvalve. No other valve combination was considered high risk of coronary obstruction. Five patients (12.5%) were at risk for possible valve stent deformation at the outflow, due to angulation at the graft anastomosis. CONCLUSIONS: Following aortic root replacement, all patients were candidates for Valve-in-Valve using one or both types of transcatheter heart valves. Self-expanding valves may be at higher risk for stent frame deformation at graft anastomotic lines and balloon-expandable valves may be at higher risk of coronary obstruction.

Lead Acetate-Injected Mice is an Animal Model for Extrapolation of Calcifying Response to Humans Due to Low Involvement of Bone Resorption.

Vascular calcification affects the prognosis of patients with renal failure. Bisphosphonates are regarded as candidate anti-calcifying drugs because of their inhibitory effects on both calcium-phosphate aggregation and bone resorption. However, calcification in well-known rodent models is dependent upon bone resorption accompanied by excessive bone turnover, making it difficult to estimate accurately the anti-calcifying potential of drugs. Therefore, models with low bone resorption are required to extrapolate anti-calcifying effects to humans. Three bisphosphonates (etidronate, alendronate, and FYB-931) were characterised for their inhibitory effects on bone resorption in vivo and calcium-phosphate aggregation estimated by calciprotein particle formation in vitro. Then, their effects were examined using two models inducing ectopic calcification: the site where lead acetate was subcutaneously injected into mice and the transplanted, aorta obtained from a donor rat. The inhibitory effects of bisphosphonates on bone resorption and calcium-phosphate aggregation were alendronate > FYB-931 > etidronate and FYB-931 > alendronate = etidronate, respectively. In the lead acetate-induced model, calcification was most potently suppressed by FYB-931, followed by alendronate and etidronate. In the aorta-transplanted model, only FYB-931 suppressed calcification at a high dose. In both the models, no correlation was observed between calcification and bone resorption marker, tartrate-resistant acid phosphatase (TRACP). Results from the lead acetate-induced model showed that inhibitory potency against calcium-phosphate aggregation contributed to calcification inhibition. The two calcification models, especially the lead acetate-induced model, may be ideal for the extrapolation of calcifying response to humans because of calcium-phosphate aggregation rather than bone resorption as its mechanism.

Enoyl coenzyme a hydratase 1 attenuates aortic valve calcification by suppressing Runx2 via Wnt5a/Ca2+ pathway.

The morbidity and death rates of calcified aortic valves|calcific aortic valve (CAV) disease (CAVD) remain high for its limited therapeutic choices. Here, we investigated the function, therapeutic potential, and putative mechanisms of Enoyl coenzyme A hydratase 1 (ECH1) in CAVD by various in vitro and in vivo experiments. Single-cell sequencing revealed that ECH1 was predominantly expressed in valve interstitial cells and was significantly reduced in CAVs. Overexpression of ECH1 reduced aortic valve calcification in ApoE-/- mice treated with high cholesterol diet, while ECH1 silencing had the reverse effect. We also identified Wnt5a, a noncanonical Wnt ligand, was also altered when ECH1 expression was modulated. Mechanistically, we found that ECH1 exerted anti-calcific actions through suppressing Wnt signaling, since CHIR99021, a Wnt agonist, may significantly lessen the protective impact of ECH1 overexpression on the development of valve calcification. ChIP and luciferase assays all showed that ECH1 overexpression prevented Runx2 binding to its downstream gene promoters (osteopontin and osteocalcin), while CHIR99021 neutralized this protective effect. Collectively, our findings reveal a previously unrecognized mechanism of ECH1-Wnt5a/Ca2+ regulation in CAVD, implying that targeting ECH1 may be a potential therapeutic strategy to prevent CAVD development.

An Incidental Finding of a Sphenoid Sinolith: A Case Report.

Sinoliths are mineral deposits that occur within the paranasal sinus due to long-standing obstruction and lack of drainage. It is a rare differential diagnosis for intrasinus lesions found on imaging. On computed tomography (CT) of the head, these calcifications are visualized as dense radiopaque bodies within the sinuses. Typically, patients with sinoliths are asymptomatic, but if complications of chronic obstruction and recurring sinusitis arise, endoscopic removal of the sinolith may be recommended. Here, we present a 95-year-old female found to have a sinolith in the sphenoid sinus on incidental imaging. This report discusses the etiology, pathophysiology, clinical presentation, radiologic findings, and management of sinoliths.

LPS-induced senescence of macrophages aggravates calcification and senescence of vascular smooth muscle cells via IFITM3.

BACKGROUND: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored. AIMS: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3. METHODS: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated ß-galactosidase (SA-ß-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification. RESULTS: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process. CONCLUSIONS: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

Staging Extramitral Cardiac Damage in Mitral Annular Calcification With Mitral Valve Dysfunction.

BACKGROUND: Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. OBJECTIVES: This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. METHODS: We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. RESULTS: For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. CONCLUSIONS: Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality.

A comparative study of shockwave intravascular lithotripsy and conventional percutaneous coronary intervention in the treatment of severe coronary artery calcification lesions.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of intravascular lithotripsy (IVL) in the treatment of severe coronary artery calcification (CAC) lesions. METHODS: In this study, we selected patients diagnosed with severe CAC lesions confirmed by coronary angiography (CAG) who were hospitalized in Yulin First People's Hospital between December 2021 and December 2022 and required percutaneous coronary intervention (PCI). Using a random number table, we divided all patients into the IVL group and the PCI group in the order of interventional therapy. We compared both groups in terms of the surgical success rate, intraoperative manipulation characteristics, procedural complication, and cumulative incidence of major adverse cardiovascular events (MACE). RESULTS: (1) There were no differences in the surgical success rate, incidence of MACE, and occurrence of procedural complication between the two groups; (2) Compared with the conventional PCI group, patients in the IVL group used fewer predilatation balloons, and the difference was statistically significant (all P < 0.05); (3) Compared with the conventional PCI group, patients in the IVL group had lesser surgery time and lesser radiation time, with lesser proportion of patients who were assisted with stent implantation using coronary artery rotational atherectomy, and this difference was statistically significant (P < 0.05); (4) The mean stent diameter and length in the IVL group was greater than those in the conventional PCI group but the difference was not statistically significant (P > 0.05). CONCLUSION: In this study, we found that IVL was a highly safe and effective procedure in the treatment of severe CAC lesions that did not increase the surgery and radiation time, and it could also reduce the use of predilatation balloons, thus improving the management of CAC lesions. Thus, IVL can be a novel choice in treating severe CAC lesions.

Complicated calcified alloplastic implants in the nasal dorsum: A clinical analysis.

BACKGROUND: In rhinoplasty, calcification around silicone implants is frequently observed in the tip dorsum (TD) area. Additionally, based on a review of various literature, it is presumed that calcification in silicone implants occurs due to both inflammatory chemical reactions and physical friction against the tissue. The calcification of nasal silicone implants not only results in the functional loss of the implants, but also leads to material deformation. However, there is a lack of research on calcification of nasal silicone implants in the current literature. AIM: To elucidate various clinical characteristics of calcification around nasal silicone implants, using histological and radiological analysis. METHODS: This study analyzed data from 16 patients of calcified nasal implants, who underwent revision rhinoplasty for various reasons after undergoing augmentation rhinoplasty with silicone implants. The collected data included information on implant duration, implant types, location of calcification, presence of inflammatory reactions, and computed tomography (CT) scans. RESULTS: The most common location of calcification, as visually analyzed, was in the TD area, accounting for 56%. Additionally, the analysis of CT scans revealed a trend of increasing Hounsfield Unit values for calcification with the duration of implantation, although this trend was not statistically significant (P = 0.139). CONCLUSION: Our study shows that reducing the frequency of calcification may be achievable by using softer silicone implants and by minimizing the damage to perioperative tissues.

Vascular Calcification Is Accelerated by Hyponatremia and Low Osmolality.

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate. The effects of low osmolality on phenotypic change and oxidative stress in the cultured VSMCs were examined. Microarray analysis was conducted to determine the main signaling pathway of osmolality-related VC. The transcellular sodium and calcium ions flux across the VSMCs were visualized by live imaging. Furthermore, the effect of osmolality on calciprotein particles (CPPs) was investigated. Associations between arterial intimal calcification and hyponatremia or low osmolality were examined by a cross-sectional study using human autopsy specimens obtained in the Hisayama Study. RESULTS: Low osmolality exacerbated calcification of the ECM (extracellular matrix) of cultured VSMCs and mouse aortic rings. Oxidative stress and osteogenic differentiation of VSMCs were identified as the underlying mechanisms responsible for low osmolality-induced VC. Microarray analysis showed that low osmolality activated the Rac1 (Ras-related C3 botulinum toxin substrate 1)-Akt pathway and reduced NCX1 (Na-Ca exchanger 1) expression. Live imaging showed synchronic calcium ion efflux and sodium ion influx via NCX1 when extracellular sodium ion concentrations were increased. An NCX1 inhibitor promoted calcifying media-induced VC by reducing calcium ion efflux. Furthermore, low osmolality accelerated the generation and maturation steps of CPPs. The cross-sectional study of human autopsy specimens showed that hyponatremia and low osmolality were associated with a greater area of arterial intimal calcification. CONCLUSIONS: Hyponatremia and low osmolality promote VC through multiple cellular processes, including the Rac1-Akt pathway activation.

A Rare Case of Calcinosis Cutis Presenting to a Tertiary Care Hospital in Rural Maharashtra.

Calcinosis cutis is a common ailment of the skin, caused by the accumulation of calcium salts in the subcutaneous regions, though there are rare case reports from rural Maharashtra region. This condition is usually asymptomatic and might manifest as a single growth or several different-sized growths. Its clinical presentation is observed as nodules or plaques without causing injury to underlying tissues. The condition is reported to be a secondary presentation to trauma, malignancies, and connective tissue diseases and has multifactorial underlying etiologies. Recommendation for treatments including both medical and surgical procedures is contingent upon the manifestation and severity of the condition. The final decision can be based on the results obtained from diagnostic modalities like fine needle aspiration and radiological imaging. This is the case of a 35-year-old male with a swelling on his left foot for the past two years without any associated medical history. The patient was managed by surgical incision and had a good recovery.

Correlation between coronary artery calcification and COVID-19.

Background: Coronary heart disease (CHD) is an underlying cardiac condition contributing to increased COVID-19 mortality and morbidity which can be assessed by several diagnosis methods including coronary artery calcification (CAC). The goal of this study was to find out if there were potential links between CAC, clinical findings, severity of COVID-19, and in-hospital outcomes. Methods: This retrospective study evaluated 551 suspected patients admitted to teaching hospitals of the Babol University of Medical Sciences, Babol, Iran, from March to October 2021. Data included previous diseases, comorbidities, clinical examinations, routine laboratory tests, demographic characteristics, duration of hospitalization, and number of days under ventilation were recorded in a checklist. Results: Findings of current study provide evidence of a significant relationship between coronary artery calcification (CAC) and in-hospital mortality. Additionally, we observed significant correlations between CAC and several clinical parameters including age, duration of hospitalization, pulse rate, maximum blood pressure, erythrocyte sedimentation rate (ESR), blood urea nitrogen (BUN), neutrophil count, white blood cell (WBC) count, and oxygen saturation. However, we did not observe a significant association between CAC and the severity index of COVID-19. In addition, logistic regression tests did not find a significant value of CAC to predict in-hospital mortality. Conclusion: Our findings showed a significant relationship between CAC and in-hospital mortality.

Impact of pericardial calcification on early postoperative outcomes after pericardiectomy: a retrospective observational study.

BACKGROUND: Owing to the lack of understanding of the clinical significance of pericardial calcification during pericardiectomy, whether pericardial calcification should be considered when determining the optimal timing for pericardiectomy is debatable. We aimed to investigate the effect of pericardial calcification on early postoperative outcomes in patients who underwent pericardiectomy for constrictive pericarditis. METHODS: Altogether, 44 patients who underwent pericardiectomy for constrictive pericarditis were enrolled. After excluding three patients who underwent concurrent surgeries, a total of 41 patients were categorized into two groups based on the presence of pericardial calcification as determined by preoperative computed tomography and pathological examination. Preoperative clinical and imaging characteristics, intraoperative data, and early postoperative outcomes were compared between the two groups. A multivariable analysis was performed to identify the factors associated with postoperative complications. RESULTS: The group with and without PC comprised 21 and 20 patients, respectively. No significant differences were observed in 30-day mortality (n = 1 [5%]) in the group with pericardial calcification and no mortality in the group without pericardial calcification (p > 0.999). Other early postoperative outcome variables did not demonstrate any significant differences between the two groups. However, the use of cardiopulmonary bypass was associated with postoperative complications (p < 0.009, odds ratio: 63.5, 95% confidence interval: 5.13-3400). CONCLUSIONS: Pericardial calcification did not significantly affect the postoperative outcomes after pericardiectomy. Further comprehensive studies, including those with larger sample sizes and longitudinal designs, are necessary to determine whether pericardial calcification can significantly influence the timing of surgical intervention.

Scalp vein sign caused by intracranial dural arteriovenous fistula.

A 68-year-old man presented with a headache that had started 1 month earlier. The scalp vein dilatation was observed at presentation. The findings of computed tomography and magnetic resonance imaging raised suspicion of a dural arteriovenous fistula, leading to the definitive diagnosis by digital subtraction angiography. Scalp vein signs can be a useful clue to suspect intracranial abnormalities, including dural arteriovenous fistula.