Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy

BackgroundThe association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).MethodsFrom a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.ResultsWith a 3.3-years’ median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm³/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm³/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.ConclusionsThe rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.     

Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

Purpose

The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy.

Materials and Methods

Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) ≥2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile).

Results

The amount of perioperative blood loss was 937±313 mL, 1014±340 mL, and 1076±383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC ≥2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027).

Conclusion

A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel.     

Anaplastic Thyroid Cancer: Ultrasonographic Findings and the Role of Ultrasonography-Guided Fine Needle Aspiration Biopsy

Purpose

To investigate the ultrasonographic (US) features of anaplastic thyroid cancer (ATC) and the diagnostic performance of US-guided fine needle aspiration biopsy (FNAB) therein.

Materials and Methods

Eighteen cases of ATC diagnosed between January 2001 and May 2011 were included. FNAB was performed in all cases. Initial FNAB results were divided into three groups: 1) the cytological ATC group, cytological diagnosis of ATC; 2) the underestimated group, cytological diagnoses of malignancy other than ATC; and 3) the false negative group, cytological diagnoses of atypical, benign and non-diagnostic lesions. We retrospectively reviewed US findings and compared treatment modalities between each group.

Results

Among the 18 patients, there were nine in the initially cytological ATC group, four in the underestimated group and five in the false negative group. The most common US features of ATC were a solid (64.7%) and irregular shaped (88.2%) mass with lymph node involvement (76.4%). However, except for lymph node involvement (p=0.003), US findings for each group were not statistically different. The initial cytological diagnostic accuracy of ATC was 50% (9/18). Surgery was performed less in the ATC group (11%) and the false negative group (20%) than the underestimated group (75%).

Conclusion

The US features of ATC were not especially different from other types of aggressive thyroid cancer. A correct diagnosis of ATC by initial US-FNAB was made in 50% of the patients, which is significant in that therapeutic surgery can be undertaken in lower numbers if correctly diagnosed.     

Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas

We aimed to determine the pathogenesis of gastric mixed adenoneuroendocrine carcinoma (MANEC) and pure neuroendocrine carcinoma (NEC), which is largely unknown. Targeted DNA sequencing was performed on 34 tumor samples from 21 patients – 13 adenocarcinoma (ADC)/NEC components from MANECs and eight pure NECs – and 21 matched non‐neoplastic gastric tissues. Mutational profiles of MANECs/NECs were compared with those of other tumors using public databases. The majority (64.1%; 59/92) of mutations in MANEC were shared by both ADC and NEC components. TP53 was the most commonly mutated gene in MANEC (69.2%, 9/13) and pure NEC (87.5%, 8/9). All TP53 mutations in MANEC were pathogenic mutations and were shared by both ADC and NEC components. A subset of TP53^WT MANECs had a microsatellite‐unstable phenotype or amplifications in various oncogenes including ERBB2 and NMYC, and the only TP53^WT pure NEC harbored MYC amplification. Compared to NEC in other organs, NECs arising from the stomach had unique features including less frequent RB1 mutations. Differentially altered genes of MANEC ADC components were significantly associated with receptor tyrosine kinase signaling pathways, while differentially altered genes of MANEC NEC components were significantly associated with the NOTCH signaling pathway. Our data provide evidence suggesting a possible clonal origin of ADC and NEC components of MANEC, and we found that gastric MANECs and pure NECs are distinct entities with unique mutational profiles and underlying protein networks. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Torsional Resistance of WaveOne Gold and Reciproc Blue according to the Loading Methods

IntroductionThis study aimed to compare the torsional resistances and fracture modes of WaveOne Gold (Dentsply Sirona, Ballaigues, Switzerland) and Reciproc Blue (VDW, Munich, Germany) using the repetitive torsional loading (RTL) method and the conventional single-rotation (STL) method.MethodsA 3-mm file tip was fixed with a brass plate, and a torsional load was applied using a custom device. In the RTL method, the file was driven counterclockwise at 50 rpm until it achieved the preset torque of 0.5 Ncm; thereafter, it was returned to its original position. This recovery of the file to its original position was defined as 1 torsional loading cycle; the number of repetitive load cycles until fracture was counted. In the STL method, the files were rotated at a constant rate of 2 rpm in a counterclockwise direction until file fracture. The fragments fractured by the 2 methods were compared under a scanning electron microscope to examine the topographic features of the fractured surfaces and longitudinal aspects.ResultsWith the RTL method, Reciproc Blue showed a higher number of repetitive load cycles until fracture than WaveOne Gold (P < .05). With the STL method, Reciproc Blue also had a higher ultimate strength than WaveOne Gold (P < .05). Scanning electron microscopic findings of the fractured specimens from the 2 test methods showed different features of torsional failure.ConclusionsWithin the study limitations, both the RTL and STL methods conferred similar torsional resistance. Therefore, the clinically relevant RTL method with repetitive and reciprocation motion can be used for testing torsional resistance.     

Association of Carotid Intraplaque Hemorrhage and Territorial Acute Infarction in Patients with Acute Neurological Symptoms Using Carotid Magnetization-Prepared Rapid Acquisition with Gradient-Echo

Objective

The purpose of our study was to assess prevalence of carotid intraplaque hemorrhage (IPH) and associations between territorial acute infarction and IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) in patients with acute neurologic symptoms.

Methods

83 patients with suspected acute neurologic symptoms were evaluated with both brain diffusion weighted imaging (DWI) and carotid MPRAGE sequences. Carotid plaque with high signal intensity on MPRAGE of >200% that of adjacent muscle was categorized as IPH. We analyzed the prevalence of IPH and its correlation with territorial acute infarction.

Results

Of 166 arteries, 39 had a carotid artery plaque. Of these arteries, 26 had carotid artery stenosis less than 50%. In all carotid arteries, MR-depicted IPH was found in 7.2% (12/166). High-signal intensity on DWI was found in 17.5% (29/166). Combined lesion with ipsilateral high-signal intensity on DWI and IPH on carotid MPRAGE sequence was found in 6 lesions (6/166, 3.6%). Of patients with carotid artery plaque, MR-predicted IPH was found in 30.8% (12/39) and match lesions with high-signal intensity on DWI and MPRAGE was found in 15.4% (6/39). MR-predicted IPH was significantly higher prevalence in high-grade stenosis group (p=0.010). Relative risk between carotid MPRAGE-positive signal and ipsilateral high-signal intensity on DWI in arteries with carotid artery plaques was 6.8 (p=0.010).

Conclusion

Carotid MPRAGE-positive signal in patients was associated with an increased risk of territorial acute infarction as detected objectively by brain DWI. The relative risk of stroke was increased in high-grade stenosis categories.