Hydrodynamic Assessment of Explanted Degenerated Transcatheter Aortic Valves: Novel Insights Into Noncalcific and Calcific Mechanisms.

BACKGROUND: The etiology of transcatheter aortic valve (TAV) degeneration is poorly understood, particularly noncalcific mechanisms. OBJECTIVES: The authors sought to investigate noncalcific and calcific mechanisms of TAV degeneration and evaluate their impact on leaflet function by bench testing, imaging, and histology. METHODS: TAV explants were obtained from the EXPLANT THV registry and clinical institutions. Hydrodynamic assessment was performed using a heart valve pulse duplicator system under physiological conditions. Micro-computed tomography, high-resolution photography, high speed video, and hematoxylin and eosin staining were used to evaluate the morphological appearance, leaflet kinematics, and calcium burden of TAVs. RESULTS: A total of 14 explants were evaluated: 10 self-expanding CoreValve/Evolut TAVs (Medtronic), 3 balloon-expandable SAPIEN 3 TAVs (Edwards Lifesciences), and 1 mechanically expandable Lotus TAV (Boston Scientific). The median patient age at explantation was 73.0 years (Q1-Q3: 64.5-80.0 years), with a time to explantation of 4 years 1 month (1 year 5 months to 4 years 11 months). Six TAV explants were found to have leaflet calcification (162.4 mm3; 58.8-603.0 mm3), and 8 had no calcification detectable by micro-computed tomography and histology. All samples had impaired leaflet kinematics. There was no significant difference in the hydrodynamic mean gradient between calcified (47.2 mm Hg; 26.6-74.1 mm Hg) and noncalcified (27.6 mm Hg; 15.2-36.7 mm Hg; P = 0.28) TAVs. Leaflet calcification had a weak but nonsignificant association with the hydrodynamic mean gradient (r = 0.42; P = 0.14). CONCLUSIONS: TAV function can be severely impacted by noncalcific and calcific mechanisms of tissue degeneration. Importantly, functional stenosis can occur in TAVs in the absence of obvious and significant calcification.

Assessment of malignant risk stratification for microcalcifications interpreted as "amorphous" morphology on mammography: A study based on the 5th edition of breast Imaging Reporting and Data System.

PURPOSE: To investigate the malignant risk stratification of microcalcifications interpreted as amorphous morphology on mammography according to the coexistence of punctate microcalcifications based on the 5th edition of the Breast Imaging Reporting and Data System. METHOD: Between March 2013 and September 2020, 367 microcalcifications interpreted as amorphous morphology on mammography with surgical biopsies were included. The amorphous microcalcifications were classified into a predominantly punctate group (A, <50% of amorphous), a predominantly amorphous group (B, >50% of amorphous), and an only amorphous group (C, 100% of amorphous). The distribution was classified into diffuse, regional, grouped, and linear/segmental. The reference standard was the pathology. The positive predictive values (PPV) were calculated and compared using the Chi-square's test or Fisher's exact test and Kruskal-Wallis test. RESULTS: The overall PPV of microcalcifications interpreted as having an amorphous morphology was 5.2%. The PPV across groups significantly increased in proportion to the amorphous morphology, with 1.0% in group A, 5.6% in group B, and 23.3% in group C (p <.001). Furthermore, the PPV between group A and groups B plus C (10.1%) and groups A plus B (2.8%) and group C were significantly different (p <.001). The PPV of distribution was 0% for diffuse, 4.9% for regional, 5.0% for grouped, and 11.1% for linear/segmental distributions, without statistical significance. CONCLUSIONS: Pure amorphous microcalcifications are suitable for category 4B. However, when they coexist with punctate morphology, the malignant risk decreases suitable for category 4A or lower. When amorphous microcalcifications coexist with a predominantly punctate morphology, follow-up should be considered.

Artificial Intelligence for Indication of Invasive Assessment of Calcifications in Mammography Screening. / Künstliche Intelligenz zur Indikationsstellung einer invasiven Mikrokalkabklärung im Mammografie-Screening.

PURPOSE: Lesion-related evaluation of the diagnostic performance of an individual artificial intelligence (AI) system to assess mamographically detected and histologically proven calcifications. MATERIALS AND METHODS: This retrospective study included 634 women of one screening unit (July 2012 - June 2018) who completed the invasive assessment of calcifications. For each leasion, the AI-system calculated a score between 0 and 98. Lesions scored > 0 were classified as AI-positive. The performance of the system was evaluated based on its positive predictive value of invasive assessment (PPV3), the false-negative rate and the true-negative rate. RESULTS: The PPV3 increased across the categories (readers: 4a: 21.2 %, 4b: 57.7 %, 5: 100 %, overall 30.3 %; AI: 4a: 20.8 %, 4b: 57.8 %, 5: 100 %, overall: 30.7 %). The AI system yielded a false-negative rate of 7.2 % (95 %-CI: 4.3 %: 11.4 %) and a true-negative rate of 9.1 % (95 %-CI: 6.6 %; 11.9 %). These rates were highest in category 4a, 12.5 % and 10.4 % retrospectively. The lowest median AI score was observed for benign lesions (61, interquartile range (IQR): 45-74). Invasive cancers yielded the highest median AI score (81, IQR: 64-86). Median AI scores for ductal carcinoma in situ were: 74 (IQR: 63-84) for low grade, 70 (IQR: 52-79) for intermediate grade and 74 (IQR: 66-83) for high grade. CONCLUSION: At the lowest threshold, the AI system yielded calcification-related PPV3 values that increased across categories, similar as seen in human evaluation. The strongest loss in AI-based breast cancer detection was observed for invasively assessed calcifications with the lowest suspicion of malignancy, yet with a comparable decrease in the false-positive rate. An AI-score based stratification of malignant lesions could not be determined. KEY POINTS: · The AI-based PPV3 for calcifications is comparable to human assessment.. · AI showed a lower detection performance of screen-positive and screen-negative lesions in category 4a.. · Histological subgroups could not be discriminated by AI scores.. CITATION FORMAT: · Weigel S, Brehl AK, Heindel W et al. Artificial Intelligence for Indication of Invasive Assessment of Calcifications in Mammography Screening. Fortschr Röntgenstr 2023; 195: 38 - 46.

Biomechanical Assessment of Macro-Calcification in Human Carotid Atherosclerosis and Its Impact on Smooth Muscle Cell Phenotype.

Intimal calcification and vascular stiffening are predominant features of end-stage atherosclerosis. However, their role in atherosclerotic plaque instability and how the extent and spatial distribution of calcification influence plaque biology remain unclear. We recently showed that extensive macro calcification can be a stabilizing feature of late-stage human lesions, associated with a reacquisition of more differentiated properties of plaque smooth muscle cells (SMCs) and extracellular matrix (ECM) remodeling. Here, we hypothesized that biomechanical forces related to macro-calcification within plaques influence SMC phenotype and contribute to plaque stabilization. We generated a finite element modeling (FEM) pipeline to assess plaque tissue stretch based on image analysis of preoperative computed tomography angiography (CTA) of carotid atherosclerotic plaques to visualize calcification and soft tissues (lipids and extracellular matrix) within the lesions. Biomechanical stretch was significantly reduced in tissues in close proximity to macro calcification, while increased levels were observed within distant soft tissues. Applying this data to an in vitro stretch model on primary vascular SMCs revealed upregulation of typical markers for differentiated SMCs and contractility under low stretch conditions but also impeded SMC alignment. In contrast, high stretch conditions in combination with calcifying conditions induced SMC apoptosis. Our findings suggest that the load bearing capacities of macro calcifications influence SMC differentiation and survival and contribute to atherosclerotic plaque stabilization.

Contrast-enhanced mammography for the assessment of screening recalls: a two-centre study.

OBJECTIVES: To evaluate the potential of contrast-enhanced mammography (CEM) for reducing the biopsy rate of screening recalls. METHODS: Recalled women were prospectively enrolled to undergo CEM alongside standard assessment (SA) through additional views, tomosynthesis, and/or ultrasound. Exclusion criteria were symptoms, implants, allergy to contrast agents, renal failure, and pregnancy. SA and CEM were independently evaluated by one of six radiologists, who recommended biopsy or 2-year follow-up. Biopsy rates according to SA or recombined CEM (rCEM) were compared with the McNemar's test. Diagnostic performance was calculated considering lesions with available final histopathology. RESULTS: Between January 2019 and July 2021, 220 women were enrolled, 207 of them (median age 56.6 years) with 225 suspicious findings analysed. Three of 207 patients (1.4%) developed mild self-limiting adverse reactions to iodinated contrast agent. Overall, 135/225 findings were referred for biopsy, 90/225 by both SA and rCEM, 41/225 by SA alone and 4/225 by rCEM alone (2/4 being one DCIS and one invasive carcinoma). The rCEM biopsy rate (94/225, 41.8%, 95% CI 35.5-48.3%) was 16.4% lower (p < 0.001) than the SA biopsy rate (131/225, 58.2%, 95% CI 51.7-64.5%). Considering the 124/135 biopsies with final histopathology (44 benign, 80 malignant), rCEM showed a 93.8% sensitivity (95% CI 86.2-97.3%) and a 65.9% specificity (95% CI 51.1-78.1%), all 5 false negatives being ductal carcinoma in situ detectable as suspicious calcifications on low-energy images. CONCLUSIONS: Compared to SA, the rCEM-based work-up would have avoided biopsy for 37/225 (16.4%) suspicious findings. Including low-energy images in interpretation provided optimal overall CEM sensitivity. KEY POINTS: • The work-up of suspicious findings detected at mammographic breast cancer screening still leads to a high rate of unnecessary biopsies, involving between 2 and 6% of screened women. • In 207 recalled women with 225 suspicious findings, recombined images of contrast-enhanced mammography (CEM) showed a 93.8% sensitivity and a 65.9% specificity, all 5 false negatives being ductal carcinoma in situ detectable on low-energy images as suspicious calcifications. • CEM could represent an easily available one-stop shop option for the morphofunctional assessment of screening recalls, potentially reducing the biopsy rate by 16.4%.

Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. METHODS: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. RESULTS: We found significant difference in total plaque volume between men and women (ß=22.9 mm3 [95% CI, 15.4-30.5]; mean volume in men 1399±425 mm3, in women 1011±242 mm3). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3-6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2-4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2-7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1-5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2-8.6]). CONCLUSIONS: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.

Functional Assessment of Missense Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6-/- mouse model of pseudoxanthoma elasticum. Variants p.L420V and p.R1064W were found benign because they had abundance and plasma membrane localization in hepatocytes similar to the wild-type human ABCC6 transgene, normalized plasma inorganic pyrophosphate levels, and prevented mineralization in the dermal sheath of vibrissae in muzzle skin, a phenotypic hallmark in the Abcc6-/- mice. In contrast, p.S400F was shown to be pathogenic because it failed to normalize plasma inorganic pyrophosphate levels and had no effect on ectopic mineralization despite its normal expression and proper localization in hepatocytes. These results showed that adenovirus-mediated hepatic ABCC6 expression in Abcc6-/- mice can provide a model system to effectively elucidate the multifaceted functional consequences of human ABCC6 missense variants identified in patients with pseudoxanthoma elasticum.

Clinical management of atypical ductal hyperplasia on vacuum-assisted biopsy of microcalcifications: External validation study of a decision tree selecting patients eligible for surveillance.

BACKGROUND: Atypical lesions found on percutaneous breast biopsy raise specific management issues. The aim of this study was to validate the previous performance of a decision tree defined by Forgeard et al to select a subset of patients at low-risk of surgical diagnostic upgrade that would be eligible for surveillance. METHODS: A consecutive series of 211 patients diagnosed with ADH on vacuum-assisted biopsy (VAB) of clustered microcalcifications alone, then operated in our institution, was reviewed. Histological findings on percutaneous cores were compared with definitive diagnoses on surgical specimens. The rate of cancer underestimation on VAB was analyzed in the four arms and two management attitudes defined in the scheme, using size and quality of microcalcification removal and the number of ADH foci. RESULTS: Ninety-eight women with ADH met the inclusion criteria. Overall, 20 cancers were diagnosed at surgery, showing a malignancy rate of 44% (17/39 patients) in the surgery group and of 5% (3/59 patients) in the surveillance group, which was not significantly different from the 2% rate in the monitored reference group (p > 0.64). The malignancy rate increased significantly with the size of clustered microcalcifications (0% when < 6mm, 17% when between 6mm and 21 mm, 48% when > 21 mm, p < 0001) and the number of ADH foci on VAB (14% when ≤ 2, 45% when > 2, p < 0.005). CONCLUSION: Our results corroborate - within the limits of large confidence intervals - those obtained with the reference decision tree. Due to statistical uncertainty, however, they need to be prospectively validated in a broader series.

Combined assessment of pulmonary arterial enlargement and coronary calcification predicts the prognosis of patients with chronic obstructive pulmonary disease.

INTRODUCTION: In chronic obstructive pulmonary disease (COPD), chest computed tomography (CT) provides clinically important cardiovascular findings, which include diameter of pulmonary artery (PA), its ratio to the diameter of the aorta (PA:A ratio), and coronary artery calcium score (CACS). The clinical importance of these cardiovascular findings has not been fully assessed in Japan, where cardiovascular morbidity and/or mortality is reported to be much less compared with Western counterparts. METHODS: PA diameter and PA:A ratio were measured in 172 and 130 patients with COPD who enrolled in the Hokkaido COPD cohort study and the Kyoto University cohort, respectively. CACS was measured in 131 and 128 patients in each cohort. RESULTS: While the highest quartile group in PA diameter was associated with higher all-cause mortality compared to the lowest quartile group in both cohorts, individual assessments of PA:A ratio and CACS were not associated with the long-term clinical outcomes. When PA diameter and CACS were combined, patients with PA enlargement (diameter >29.5 mm) and/or coronary calcification (score >440.8) were associated with higher all-cause mortality in both cohorts. CONCLUSION: Combined assessment of PA enlargement and CACS was associated with poor prognosis, which provides a clinical advantage in management of patients with COPD even in geographical regions with lower risk of cardiovascular diseases.

In-laboratory breast specimen radiography reduces tissue block utilization and improves turnaround time of pathologic examination.

BACKGROUND: This study was performed to determine whether in-laboratory specimen radiography reduces turnaround time or block utilization in surgical pathology. METHODS: Specimens processed during a 48-day trial of an in-lab cabinet radiography device (Faxitron) were compared to a control group of specimens imaged in the mammography suite during a prior 1-year period, and to a second group of specimens not undergoing imaging of any type. RESULTS: Cases imaged in the mammography suite had longer turnaround time than cases not requiring imaging (by 1.15 days for core biopsies, and 1.73 days for mastectomies; p < 0.0001). In contrast, cases imaged in-lab had turnaround time that was no longer than unimaged cases (p > 0.05 for core biopsies, lumpectomies and mastectomies). Mastectomies imaged in-lab required submission of fewer blocks than controls not undergoing any imaging (mean reduction of 10.6 blocks). CONCLUSIONS: Availability of in-lab radiography resulted in clinically meaningful improvements in turnaround time and economically meaningful reductions in block utilization.

Age, Sex, and Valve Phenotype Differences in Fibro-Calcific Remodeling of Calcified Aortic Valve.

Background In calcific aortic valve disease on tricuspid aortic valves (TAVs), men have higher aortic valve calcification and less fibrosis than women. However, little is known in bicuspid aortic valves (BAV). We thus aimed to investigate the impact of age, sex, and valve phenotype (TAVs versus BAVs) on fibro-calcific remodeling in calcific aortic valve disease. Methods and Results We included 2 cohorts: 411 patients who underwent multidetector computed tomography (37% women) for aortic valve calcification density assessment and 138 explanted aortic valves (histological cohort; 50% women). The cohorts were divided in younger (<60 years old) or older patients with BAV (≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less aortic valve calcification density than men in each group of the multidetector computed tomography cohort (all P≤0.01). Moreover, in women, younger patients with BAV had the lowest aortic valve calcification density (both P=0.02). In multivariate analysis, aortic valve calcification density correlated with age (ß estimate±standard error: 6.5±1.8; P=0.0004) and male sex (109.2±18.4; P<0.0001), and there was a trend with TAVs (41.5±23.0; P=0.07). Women presented a higher collagen content than men (77.8±10.8 versus 69.9±12.9%; P<0.001) in the entire cohort. In women, younger patients with BAV had denser connective tissue than TAV and older patients with BAV (both P≤0.05), while no difference was observed between men. Conclusions In calcific aortic valve disease, women had less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with BAVs had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age-specific mechanisms and be influenced by the valve morphology.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.

Ultrasound-Guided Vacuum-Assisted Biopsy in Small Breast: A Cost-Saving Solution.

BACKGROUND: The study aimed to evaluate the feasibility and reliability of ultrasound-guided vacuum-assisted breast biopsy (US-VABB) for sampling of microcalcifications indicative of cancer when stereotactic vacuum-assisted breast biopsy cannot be performed because of reasons such as thin breast tissue, insufficient thickness at compression, and microcalcification situated close to the chest wall or in breast tissue of the axillary tail. PATIENTS AND METHODS: The study population was selected from among 187 patients with microcalcifications detected on mammogram. The findings were classified using the American College of Radiology criteria as Breast Imaging Reporting and Data System 3, 4, or 5. 30 Thirty were not eligible for stereotactic guidance because of reasons such as small breast size, compression thickness <2 cm, or microcalcification located in the axillary tails or close to chest wall. In 23 patients microcalcifications were detected at ultrasound, and US-VABB was performed. The other 7 patients underwent surgical biopsy. In the 23 patients who underwent US-VABB, multiple core samples were taken after a specimen mammography to ensure that microcalcifications were included. RESULTS: Biopsy was successful in all cases of US-VABB. The procedure was well tolerated, and there were no complications. CONCLUSION: US-VABB should be preferred over diagnostic surgical biopsy when microcalcifications are sonographically visible and stereotactic guidance is contraindicated. The procedure appears to be reliable and accurate, with added advantages such as low cost and absence of radiation exposure.

Assessment of intraductal carcinoma in situ (DCIS) using grating-based X-ray phase-contrast CT at conventional X-ray sources: An experimental ex-vivo study.

BACKGROUND: The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. MATERIALS AND METHODS: GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. RESULTS: Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. CONCLUSIONS: GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.

Quantitative assessment of morphological changes of dental pulp components of teeth affected by occlusal trauma.

AIM: In the general economy of the stomatognathic system functionality, the occlusal function has an important role, meaning both the dental-dental reports and the dynamic reports interarch-interarch. Because of the interrelationships and inter-dependency that govern the functioning of the biological systems, a pathological change affecting a component of the stomatognathic system produces impaired functioning of the others. The aim of the present study is to assess the morphological changes occurred in the dental pulp components of teeth affected by occlusal trauma. MATERIALS AND METHODS: Fragments of dental pulp coming from 45 patients with occlusal trauma were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE), Masson's trichrome and anti-CD34 antibody immunostaining, in order to highlight the peripheral zone and central connective tissue of dental pulp morphological changes. A set of parameters namely thickness of peripheral zone components, calcifications, fibrosis and vascular density in the dental pulp were assessed individually and based on three topographical criteria namely the affected tooth, the position on the dental arches and the position according to sagittal plane. RESULTS: There was no correlation between morphological changes of dental pulp and the topography of teeth with occlusal trauma. The size of the peripheral area of the dental pulp and that of its components evolved in the same sense, whether it was growth or decrease. Decrease of the peripheral area was associated with the increase of collagen fibers density, calcium deposits and density of the capillary network. The direct correlation between the amount of collagen fibers and vascular density seems somewhat paradoxical but it can be explained by the reemergence of chronic inflammatory events located in the dental pulp. CONCLUSIONS: It seems that dental pulp morphological changes are not influenced by the teeth with occlusal trauma topography. With one exception (the components of peripheral zone), most of the correlations between the dental pulp morphological changes were only suggested but not validated statistically, which requires further studies on larger groups together with the introduction of inflammatory cell population studies.

Temporal Bone CT Scan for Malleal Ligaments Assessment.

OBJECTIVE: To determine the feasibility of using temporal bone computed tomography (CT) scans to identify malleal ligaments and the prevalence of calcification in malleal ligaments. STUDY DESIGN: Retrospective case review. CT scans were blindly and retrospectively reviewed by two physicians (a radiologist and a nonradiologist). Scans differed by slice thickness, and included both conventional CT and cone beam CT (CBCT). SETTING: Ambulatory tertiary referral center. PATIENTS: One hundred fifty-one temporal bone CT scans, obtained between the years 2014 and 2017, were initially screened, which included 302 ears. Patients with previous tympanomastoid surgery or middle ear opacification were excluded, leaving 187 ears in the study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Percentage of visible normal and calcified malleal ligaments. RESULTS: Scans with submillimeter slice thickness were more likely to demonstrate all three malleal ligaments than those with 1 ml and larger slices (83.7% versus 50.0% for nonradiologist, p < 0.0001; 59.6 versus 34.8% for radiologist, p < 0.0001). Calcification was seen in 11.8% of ears reviewed. The ability to detect malleal ligaments with cone beam CT was 86.2%, while the rate with conventional CT was 71.1%, a difference that persisted when controlling for slice thickness. Interobserver agreement for the detection of malleal ligaments was 65% with a Cohen's kappa coefficient of κ = 0.27. CONCLUSION: Visualization of the malleal ligaments using CT scans is feasible in a majority of aerated ears. Detection of malleal ligaments improves with thinner slice thickness and cone-beam technique. Low interobserver agreement suggests the importance of experience and a need for standardized review.

Material Analysis and Optical Quality Assessment of Opacified Hydrophilic Acrylic Intraocular Lenses After Pars Plana Vitrectomy.

PURPOSE: Explanted hydrophilic intraocular lenses (IOLs) with clinically significant opacification after pars plana vitrectomy (PPV) were assessed for material change and optical quality, in an in vitro laboratory study. DESIGN: Retrospective observational case series. METHODS: Ten opacified IOLs after PPV with intraocular gas injection were analyzed in a laboratory setting. Analyses included evaluation of patients' medical history, optical quality assessment, light microscopy, histologic staining, scanning electron microscopy, and energy dispersive x-ray spectroscopy. RESULTS: In all 10 IOLs a thin layer of calcium phosphate that had accumulated underneath either the anterior or posterior optical surface in a central circular area of the IOL optic caused the opacification. The calcifications lead to deterioration of the modulation transfer function (MTF) across all spatial frequencies. CONCLUSION: PPV with instillation of gas into a pseudophakic eye with an acrylic hydrophilic lens seems to increase the risk for secondary calcification irrespective of the manufacturer. In these cases, IOL exchange is the only treatment option available. Since IOL exchange is associated with a high intraoperative complication rate, our results suggest to consider the risk of IOL calcification when implanting hydrophilic acrylic IOLs.

Ultra-High-Resolution Computed Tomography Angiography for Assessment of Coronary Artery Stenosis.

BACKGROUND: Limitations of coronary computed tomography (CTA) include false-positive stenosis at calcified lesions and assessment of in-stent patency. A prototype of ultra-high resolution computed tomography (U-HRCT: 1,792 channels and 0.25-mm slice thickness×128 rows) with improved spatial resolution was developed. We assessed the diagnostic accuracy of coronary artery stenosis using U-HRCT.Methods and Results:Seventy-nine consecutive patients who underwent CTA using U-HRCT were prospectively included. Coronary artery stenosis was graded from 0 (no plaque) to 5 (occlusion). Stenosis grading at 102 calcified lesions was compared between U-HRCT and conventional-resolution CT (CRCT: 896 channels and 0.5-mm slice thickness×320 rows). Median stenosis grading at calcified plaque was significantly improved on U-HRCT compared with CRCT (1; IQR, 1-2 vs. 2; IQR, 1-3, P<0.0001). Assessability of in-stent lumen was evaluated on U-HRCT in 79 stents. Stent strut thickness and luminal diameter were quantitatively compared between U-HRCT and CRCT. Of 79 stents, 83.5% were assessable on U-HRCT; 80% of stents with diameter 2.5 mm were regarded as assessable. On U-HRCT, stent struts were significantly thinner (median, 0.78 mm; IQR, 0.7-0.83 mm vs. 0.83 mm; IQR, 0.75-0.92 mm, P=0.0036), and in-stent lumens were significantly larger (median, 2.08 mm; IQR, 1.55-2.51 mm vs. 1.74 mm; IQR, 1.31-2.06 mm, P<0.0001) than on CRCT. CONCLUSIONS: U-HRCT with improved spatial resolution visualized calcified lesions with fewer artifacts. The in-stent lumen of stents with diameter ≥2.5 mm was assessable on U-HRCT.

Noninvasive Assessment of Carotid Plaques Calcification by 18F-Sodium Fluoride Accumulation: Correlation with Pathology.

BACKGROUD: Vascular calcification is currently recognized as an important pathobiological process in atherosclerosis, but the mechanism remains elusive. Given the similarities in vascular calcification and bone formation, 18F-sodium fluoride (18F-NaF) is now considered a novel marker of vascular calcification. This study aimed to correlate 18F-NaF accumulation with the histological characterization of vascular calcification in carotid plaques. METHODS: A total of 8 patients who were undergoing carotid endarterectomy (CEA) for carotid artery stenosis were recruited. Before CEA, 18F-NaF positron emission tomography and computed tomography (PET-CT) studies were conducted. 18F-NaF uptake was measured by the maximum standardized uptake value and the target-to-background ratio. The Hounsfield unit (HU) value was also measured. Postoperative carotid plaques were investigated by hematoxylin and eosin staining, alizarin red staining, and immunohistochemistry (alpha-smooth muscle actin and CD68). RESULTS: 18F-NaF uptake was observed in the bilateral carotid bifurcation of all patients. Compared with the pathology results, there was a significant correlation between tracer activity in the carotid plaques and the calcification in the corresponding histological sections (integrated optical density [IOD]: r = .781, P = .022; positive area: r = .765, P = .027). A negative correlation was observed between 18F-NaF uptake and smooth muscle cell staining (IOD: r = -.710, P = .049). 18F-NaF uptake did not correlate with carotid artery stenosis, HU value, or inflammation. CONCLUSIONS: 18F-NaF PET-CT is a noninvasive imaging method for the assessment of calcification in human carotid atherosclerotic plaques and a promising approach to studying calcification in atherosclerotic lesions.

A novel restorative pulmonary valved conduit in a chronic sheep model: Mid-term hemodynamic function and histologic assessment.

OBJECTIVE: To evaluate the safety and the short-term function of a novel pulmonary valved conduit (Xeltis Pulmonary Valved Conduit; XPV) up to 12 months in a sheep model. METHODS: XPV and Hancock bioprosthetic valved conduits (H, used as control) were implanted in adult sheep in the pulmonary artery position. Animals were killed at 2 months (n = 6 XPV), 6 months (n = 6 XPV and n = 3 H), and 12 months (n = 6 XPV) and examined histologically. During follow-up, function of the device as well as diameter of both XPV and H were assessed by transthoracic echocardiography. RESULTS: Of 18 animals that received an XPV, 15 survived until they were killed; 3 animals that received H survived the planned observational interval. XPV showed mild neointimal thickening and degradation beginning at 2 months with an ongoing process until 12 months. Only 1 of the 18 animals with XPV had significant calcification at 6 months. Pathologic specimen did not show any significant narrowing of the conduit whereas neointimal thickness showed a peak at 6 months. Inflammatory process reached a maximum at 6 months and the degradation process at 12 months. Gel permeation chromatography analysis showed molecular weight loss beginning at 2 months with a peak at 12 months for the conduit with slower absorption for the leaflets. The wall of the H conduits showed more neointimal thickening, narrowing, and calcification compared with XPV, but the leaflets demonstrated minimal changes. CONCLUSIONS: Both conduits demonstrated an acceptable safety and functionality. Significant calcification was rarely observed in the XPV, whereas the H developed more neointimal thickness with calcification of the porcine aortic root portion of the wall.