SummaryDysregulation of plasma lipids is associated with age‐related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low‐density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg−1 day−1) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5‐treated but not L1‐treated mice. Similar to that, in Syrian hamsters with elevated serum L5 levels induced by a high‐fat diet, nuclear γH2AX deposition and senescence‐associated β‐galactosidase staining were increased in the aortic endothelium. This phenomenon was blocked in the presence of N‐acetyl‐cysteine (free‐radical scavenger) or caffeine (ATM blocker), as well as in lectin‐like oxidized LDL receptor‐1 (LOX‐1) knockout mice. In cultured human aortic endothelial cells, L5 augmented mitochondrial oxygen consumption and mitochondrial free‐radical production, which led to ATM activation, nuclear γH2AX deposition, Chk2 phosphorylation, and TP53 stabilization. L5 also decreased human telomerase reverse transcriptase (hTERT) protein levels and activity. Pharmacologic or genetic manipulation of the reactive oxygen species (ROS)/ATM/Chk2/TP53 pathway efficiently blocked L5‐induced endothelial senescence. In conclusion, L5 may promote mitochondrial free‐radical production and activate the DNA damage response to induce premature vascular endothelial senescence that leads to atherosclerosis. Novel therapeutic strategies that target L5‐induced endothelial senescence may be used to prevent and treat atherosclerotic vascular disease.

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Breast cancers with 10 or more positive lymph nodes at the time of diagnosis are staged as pathological N3a (pN3a) and they have poor prognosis. Recent studies showed five-year disease-free survival (DFS) and overall survival (OS) rates of N3a disease as 43-66 and 58-81 %, respectively. We herein present outcomes of our patients with stage pN3a breast cancer. Among 2,578 patients diagnosed with invasive breast carcinoma at Hacettepe University Hospital between 2002 and 2012, 218 patients (8.4 %) had pN3a disease and were included and analyzed retrospectively in this study. Patients with internal mammary, infraclavicular, and supraclavicular node metastasis or distant metastasis at initial diagnosis were excluded. Demographic features, tumor characteristics, treatment regimens, and patient outcomes in terms of DFS and OS were analyzed. Lymph node ratio was defined as the ratio of positive to total removed lymph nodes. The median age was 49. Most common histological subtype was ductal carcinoma (82.1 %). About 82.6 % of patients had stage T2/T3 cancers and 47.7 % (104) had grade III cancers. Estrogen and progesterone receptors were positive in 133 (61 %) and 121 (55.5 %) patients, respectively. HER2 status was known for 213 patients and was positive in 87 (39.9 %) patients. A total of 27 (12.6 %) patients had triple-negative tumors. Lymphovascular invasion, extracapsular extension, and perineural invasion were present in 106 (48.6 %), 105 (48.2 %), 20 (9.2 %) cases, respectively. A total of 18 patients (8.3 %) received neoadjuvant and 200 patients (91.7 %) received adjuvant chemotherapy, mostly with anthracycline- (95 %) and taxane (60 %)-containing regimens. A total of 210 patients (96.3 %) received radiotherapy. Median follow-up was 39.5 months. A total of 96 patients relapsed on follow-up and 64 patients died. Nineteen of the relapses were locoregional and 77 were distant relapses. The 5-year DFS rate was 46.2 % and the OS rate was 69.8 %. In multivariate Cox regression analysis, grade III disease (HR 1.899, 95 % CI 1.196-3.017, P = 0.007), perineural invasion (HR 2.519, 95 % CI 1.341-4.731, P = 0.004), and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.290, 95 % CI 1.368-3.835, P = 0.002) were significantly associated with DFS, and grade III disease (HR 2.679, 95 % CI 1.500-4.782, P = 0.001) and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.182, 95 % CI 1.211-3.932, P = 0.009) were significantly associated with OS. Patients with pN3a disease in our cohort have comparable survival rates with other reports in the literature. Within this high risk group of patients, those with grade III disease, perineural invasion, and lymph node ratio ≥ 0.9 seem to confer poorer prognosis.

Letters to the Editor Utility of lung ultrasound assessment for probable SARS-CoV-2 infection during pregnancy and universal screening of asymptomatic individuals Pregnant women are a risk group for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has been shown to be associated with increased rates of preterm delivery and Cesarean section 1. Despite reassuring safety profile, imaging modalities, such as computed tomography, are used scarcely in pregnancies with suspected SARS-CoV-2 infection due to concerns about undue exposure of the fetus to ionizing radiation. However, false-positive and false-negative results are not uncommon in reverse transcription polymerase chain reaction (RT-PCR) testing. Anecdotal reports suggest that the adjunct use of imaging modalities can help manage cases in which molecular testing results and the clinical presentation are conflicting 2. Furthermore, use of imaging modalities is suggested for the preoperative screening of emergency cases 3. Lung ultrasound (LUS) is an ionizing-radiation-free, reproducible imaging modality for evaluating lung lesions, and its results are readily available, well in advance of the RT-PCR results 4. However, the added benefit of LUS for managing symptomatic and asymptomatic patients with SARS-CoV-2 infection during pregnancy remains unclear. This was a retrospective cohort study conducted in two large SARS-CoV-2 pandemic hospitals in Turkey (

Purpose: This study investigated interobserver agreement in lung ultrasonography (LUS) in pregnant women performed by obstetricians with different levels of expertise, with confirmation by an expert radiologist. Methods: This prospective study was conducted at a tertiary "Coronavirus Pandemic Hospital" in April 2020. Pregnant women suspected to have coronavirus disease 2019 (COVID-19) were included. Two blinded experienced obstetricians performed LUS on pregnant women separately and noted their scores for 14 lung zones. Following a theoretical and hands-on practical course, one experienced obstetrician, two novice obstetric residents, and an experienced radiologist blindly evaluated anonymized and randomized still images and videoclips retrospectively. Weighted Cohen's kappa and Krippendorff's alpha tests were used to assess the interobserver agreement. Results: Fifty-two pregnant women were included, with confirmed COVID-19 diagnosis rate of 82.7%. In total, 336 eligible still images and 115 videoclips were included in the final analysis. The overall weighted Cohen's kappa values ranged from 0.706 to 0.912 for the 14 lung zones. There were only seven instances of major disagreement (>1 point) in the evaluation of 14 lung zones of 52 patients (n=728). The overall agreement between the radiologist and obstetricians for the still images (Krippendorff's α=0.856, 95% confidence interval [CI], 0.797 to 0.915) and videoclips (Krippendorff's α=0.785; 95% CI, 0.709 to 0.861) was good. Conclusion: The interobserver agreement between obstetricians with different levels of experience on still images and videoclips of LUS was good. Following a brief theoretical course, obstetricians' performance of LUS in pregnant women and interpretation of pre-acquired LUS images can be considered consistent.

Aim: Ultrasound-guided fine-needle aspiration biopsy (FNAB) is a reliable, minimally invasive diagnostic method with high sensitivity and specificity in the evaluation of thyroid nodules. Our aim in this retrospective study was to determine if there was a difference in the adequacy ratio based on the number of needle passes in the thyroid FNABs in the absence of rapid on-site evaluation (ROSE) by the pathologist and to determine the optimal needle pass number for FNAB. Methods: Between November 2018 and February 2019, thyroid FNABs of 121 (99 female, 22 male) patients were evaluated retrospectively. Samples for each biopsy were numbered according to the order of retrieval, and 4 pairs of slides were prepared by the radiologist without on-site microscopic evaluation. Cytological results were determined according to the Bethesda classification. Results: The rate of adequacy in the first, second, third, and fourth passes were 76.0, 82.6, 77.7, and 71.2%, respectively. No statistically significant difference was found between these four groups in terms of adequacy (p = 0.21). The adequacy rates of the 1st, 1st+2nd, 1st+2nd+3rd, and cumulative evaluation of all four biopsies were 76.0, 87.6, 90.1, and 91.7%, respectively (p = 0.001). A statistically significant difference was found in the comparison of the 1st biopsy and the cumulative 1st+2nd biopsy in terms of adequacy rates (p = 0.019). However, there was no statistically significant difference between the cumulative 1st+2nd biopsy and the cumulative 1st+2nd+3rd biopsy in terms of adequacy rates (p = 0.54). Conclusions: In cases where ROSE cannot be performed, we recommend a minimum of 2 and a maximum of 3 needle entries for FNAB adequacy with the right technique and preparation.

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AimTo examine the intra‐ and inter‐observer variability for non‐benign thyroid cytological subcategories according to the Bethesda classification system after the second review.MethodsBetween November 2018 and May 2019, thyroid fine needle aspiration biopsies of 381 nodules were retrospectively evaluated. Among them, 74 non‐benign (category III‐VI) thyroid biopsies, analyzed according to the Bethesda system (pathologist 1:40 vs pathologist 2:34) by two independent pathologists, were reassessed by the same pathologists and by a cytopathologist. In this observer‐blinded study, weighted Cohen's kappa was used to assess the intra‐observer agreement, and Krippendorff's alpha was used to assess the inter‐observer agreement.ResultsAt the first and second evaluations of pathologists 1 and 2, the percentage agreement was 62.5% for pathologist 1 and 58.8% for pathologist 2. The intra‐observer agreement was substantial (κ = 0.705) for pathologist 1, and moderate (κ = 0.447) for pathologist 2. In the second evaluation of pathologist 1 and 2, which was compared with the cytopathologist, the agreement percentage of pathologist 1 with the cytopathologist was 50.0%, and that of pathologist 2 was 56.8%. The inter‐observer agreement was below the lowest acceptable limit for an overall agreement (α = 0.634) among the three raters. The inter‐observer agreement was only acceptable between the cytopathologist and the second pathologist, while it was low between the other raters. In the evaluation of the non‐benign nodules, the mean category score of the cytopathologist was 3.22 and lower than both pathologists (3.73 and 3.58, respectively).ConclusionsThe intra‐observer agreement of pathologists was moderate‐to‐substantial in the evaluation of non‐benign thyroid biopsies according to the Bethesda reporting system. However, the inter‐observer agreement was below the lowest acceptable limit when the cytopathologist was taken as a reference.