Objectives Ascending aortic atherosclerosis and degeneration may influence surgical management and outcome following surgery for acute Type A aortic dissection (ATAAD). The aim of this study was to evaluate the association between histologically confirmed ascending aortic atherosclerosis and postoperative outcome in patients undergoing surgery for ATAAD. Methods We retrospectively evaluated 104 patients without connective tissue disorders undergoing surgery for ATAAD at Tampere University Hospital between January 2005 and November 2019. Resected ascending aortic specimens were processed for histopathology, assessing atherosclerosis, medial degeneration, and inflammation. Patients were divided into groups based on the presence (n = 58) or absence (n = 46) of histologically confirmed atherosclerosis and compared over a median follow-up of 5.9 years (interquartile range [IQR]: 0.9-8.0). Results The median age for all patients was 67.0 years (IQR: 57.0-73.0). Patients with atherosclerosis had more frequent primary intimal tears in the aortic root (62.1% vs. 39.1%, p = 0.020), but less frequent limb malperfusion (5.2% vs. 32.6%, p < 0.001), and DeBakey I dissections (53.4% vs. 76.1%, p = 0.017) as compared to those without atherosclerosis, respectively. The presence and severity of medial degeneration were significantly greater in patients with atherosclerosis (98.3% vs. 87.0%, p = 0.042; mean severity score 2.2 vs. 1.8, p = 0.044). Postoperatively, the incidence of stroke was significantly higher in the atherosclerosis group (41.4% vs. 21.7%, p = 0.034), but the rate of aortic reintervention was significantly lower (5.2% vs. 19.6%, p = 0.023). Survival did not differ significantly between the groups (log-rank p = 0.683), and limb malperfusion was the only strong independent risk factor for all-cause mortality according to multivariable Cox regression analysis. Conclusion Ascending aortic atherosclerosis including severe medial degeneration during ATAAD is associated with distinct clinical features such as the presence of proximal aortic root tear. Instead, limb malperfusion, DeBakey I classification, and presence of ascending aortic tear suggest an ascending aorta without atherosclerosis, often associated with increased risk of aortic reinterventions after surgery for ATAAD.

OBJECTIVES:We investigated whether the extent of degeneration of the ascending aortic wall found in patients with acute type A aortic dissection is associated with the presence of organ cysts. METHODS:In total, 120 consecutive patients diagnosed for acute type A aortic dissection using computer tomography at Tampere University Hospital were evaluated, screened for organ cysts, and followed for a mean 6.7-years (SDs 4.6) after surgery. The ascending aortic wall resected in surgery in patients with and without cysts was analysed for 11 different histopathological variables expressed as point score units (PSU). Multivariable binary logistic regression analysis adjusted for age and sex was performed to investigate the association of the presence of elastic fibre thinning with the presence of cysts. RESULTS:Out of 120 patients, there were 45 patients with at least 1 cyst including ovarian, renal, liver or epididymis cysts, and 75 with none. The mean age was 65.6 years (SD 11.8). Increased extent of elastic fibre thinning and the presence of thickening of the medial layer of the vasa vasorum were often present in patients with cysts as compared with those without (2.0 [1.0-2.0] vs 1.0 [0-2.0], PSU, P = .020 and 26.7% vs 12.0%, P = .049, respectively). According to the adjusted multivariable binary logistic regression analysis, the presence of elastic fibre thinning was associated with cysts (adjusted odds ratio: 2.636, 95% CI, 1.143-9.095, P = .023). CONCLUSIONS:The presence of cysts in patients requiring surgery for acute type A aortic dissection may reflect the extent of aortic wall tissue degeneration.

Aortic aneurysms have traditionally been studied as a single pathological entity, with emphasis on valve morphology. While histopathological differences between bicuspid (BAV) and tricuspid (TAV) aortopathy are well documented, less is known about how these mechanisms interact with aneurysm location within the ascending aorta. This gap complicates risk assessment and surgical planning beyond diameter-based criteria. We aimed to evaluate histopathological features of ascending aortic aneurysms across three topographical subgroups-root, tubular, and combined involvement-and assess modification by valve cuspidity. Using systematic criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on medial degeneration, adventitial alterations and atherosclerosis in patients undergoing ascending aortic surgery at a Finnish tertiary care center. The cohort comprised 296 patients with aneurysms located in the sinus of Valsalva (n = 122), tubular part (n = 130), and both regions (n = 44). Medial degeneration was present in all samples and predominantly moderate, with comparable median severity score of 2 (range 1-3, P = 0.829) across groups. In the overall cohort, no statistically significant differences were observed between topographical groups. Among TAV patients, tubular aneurysms demonstrated significantly higher histopathological scores for medial degeneration, elastic fiber fragmentation and loss, elastic fiber disorganisation, smooth muscle cell disorganization and nuclei loss, laminar medial collapse, medial fibrosis, adventitial fibrosis and atherosclerosis (all P < 0.05). In BAV patients, no statistical differences were found. Tubular aneurysms are characterized by more extensive wall remodeling and adventitial changes compared to root aneurysms, particularly in TAV patients. Notably, female sex emerged as a strong independent predictor of advanced medial and adventitial pathology. These findings underscore the importance of considering anatomical location, valve morphology, and sex in risk stratification and may inform surgical decision-making beyond diameter-based criteria.

This study investigated the distinguishing characteristics between acute type A aortic dissection (ATAAD) and aortic wall dilatation. Utilizing systematic histopathology criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on degeneration, atherosclerosis, and inflammation in patients undergoing surgery in a Finnish tertiary care hospital. The study included 156 patients, those undergoing surgery for ATAAD (n = 116) and those with dilatation (n = 40). Despite similar clinical characteristics, histological analysis of the aortic wall indicated a higher overall degeneration in ATAAD compared to dilatation (2.4 ± 0.6 vs. 1.9 ± 0.8, Point score unit (PSU), p < 0.001). Findings included increased intralamellar mucoid extracellular matrix accumulation (69 vs. 32, p = 0.020; extent 2.0 ± 0.3 vs. 1.7 ± 0.5, PSU, p < 0.001; severity 1.8 ± 0.6 vs. 1.5 ± 0.5, PSU, p = 0.005) elastic fiber thinning (68 vs. 9, p = 0.001; extent 1.0 ± 0.9 vs. 0.4 ± 0.8, PSU, p < 0.001; severity 0.8 ± 0.8 vs. 0.4 ± 0.8, PSU, p = 0.001), elastic fiber disorganization (89 vs. 21, p = 0.005; extent 1.2 ± 0.8 vs. 0.9 ± 0.9, PSU, p = 0.029) and laminar medial collapse (64 vs. 6, p < 0.001; type 0.7 ± 0.7 vs. 0.2 ± 0.4, PSU, p < 0.001; extent 0.9 ± 0.9 vs. 0.9 ± 0.9, PSU, p < 0.001) in ATAAD compared to dilatation. Elastic fiber pathology and laminar medial collapse are distinct features of ATAAD compared to aortic dilatation in patients undergoing ascending aorta surgery.

Background: Non-adjustable patient characteristics such as diabetes mellitus may influence surgical decision-making and outcome after acute type A aortic dissection (ATAAD). The aim of this study was to compare the degree of aortic wall atherosclerosis and surgical solutions in patients with diabetes mellitus versus those without during ATAAD. Methods: Altogether, 123 consecutive patients undergoing surgery for ATAAD at Tampere University Heart Hospital were evaluated. The ascending aortic wall resected in surgery was processed for histopathological analysis of atherosclerosis, inflammation, and medial layer degeneration. Patients with and without diabetes mellitus were compared during a mean 4.7-year follow-up. Results: There were 11 patients with diabetes mellitus and 112 without. The mean age for all patients was 63.6 years (standard deviation [SD] 13.3). Altogether, 48 patients had a conduit aortic prosthesis replacing the aortic root together with the ascending aorta, including only one patient with diabetes (p = 0.049). Nine patients received a frozen elephant trunk prosthesis to treat the aortic arch together with the ascending aorta. The severity of ascending aorta atherosclerosis was more prominent in patients with diabetes mellitus as compared to patients without (0.8 [0.4] vs. 0.3 [0.5], p = 0.009, respectively). During follow-up, 8 and 78 patients with and without diabetes died, respectively (logarithmic rank p = 0.187). Conclusions: Histopathology of the ascending aorta during ATAAD reveals distinctive severity of aortic wall atherosclerosis in patients with diabetes mellitus versus those without. The degree of atherosclerosis assessed postoperatively is associated with the extent of surgical procedure in many patients and may guide follow-up protocol.

The previous understanding has been that atherosclerosis tends to increase distally from the ascending aorta, but recent studies and practical experience have indicated that atherosclerosis occurs in the ascending aorta more than previously thought. Medial degeneration is linked to aortic aneurysms, dissection and dilatation and has been related to increased mortality. There is a lack of data on the coexistence of atherosclerosis and medial degeneration in the ascending aorta and its outcome to clinical morbidity and mortality. Earlier studies have shown coexisting atherosclerosis and medial degeneration as significant risk indicators for coronary and cerebrovascular events. We aimed to analyze aortic specimens classified according to the consensus documents of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology particularly the comparison of variable morphological features with the atherosclerotic grade to gain more data about the coexistence of atherosclerosis and medial degeneration. We evaluated 217 specimens of human ascending aorta resected at Tampere University Heart Hospital because of aortic aneurysm, dissection or dilatation. None of the samples contained normal aortic morphology; atherosclerosis was found in a total of 75.8 % of the samples and medial degeneration in all the samples. The present study is mostly in agreement with earlier research regarding the prevalence of different histological findings, even though a higher prevalence of atherosclerosis was found compared with most studies. There was no statistically significant association between atherosclerosis and medial degeneration, but a higher atherosclerotic grade was significantly associated with the presence of smooth muscle cell nuclei loss, smooth muscle cell disorganisation, elastic fibre thinning and medial fibrosis. Our study reinforces the perception that atherosclerotic lesions significantly occur in the ascending aorta and coexist with individual components of the medial degeneration.

Chemokine-like receptor 1 (CMKLR-1) is a G-protein-coupled receptor that functions as the binding site of chemerin. It induces chemotaxis in various immune cells, and it has recently been linked to vascular remodeling in inflammation. In this study, we investigated CMKLR-1 expression in human aorta samples, focusing on its distribution across different cell types and its potential association with clinical and histomorphological data, particularly concerning aortic dissection and aneurysms. We analyzed 62 aorta samples taken from patients undergoing dissection surgery (n = 27) or aneurysm/dilatation (n = 35) using immunohistochemical CMKLR-1 staining. CMKLR-1 expression was primarily observed in the smooth muscle cells (SMCs) of the aortic media layer, and band-like coloring appeared in the unstained center section. CMKLR-1 positivity in the inner and outer parts of the media layer was observed in only a few cases. One-third of the vasa vasorum exhibited staining. Staining in lymphocytes, macrophages, and endothelia was rare. No significant differences in CMKLR-1 expression were found between the dissection and aneurysm cases, and the clinical or histomorphological data. Although CMKLR-1 expression did not distinguish between the studied conditions, its presence in the aortic media, especially in SMCs, is noteworthy.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) create a global burden in the field of cardiovascular medicine due to significant morbidity and mortality, particularly in low- and middle-income countries and the underprivileged population. Sequential surgical specimens of mitral valves excised from 19 patients with moderate to marked rheumatic mitral stenosis were included in this study and compared to eight sequential surgical myxomatous degenerative valves (control). The study group population had a mean age of 43.8 (± standard deviation (SD) 13.3) years and comprised 10 female and nine male patients. The controls included three female and five male patients with a mean age of 61.5 (± SD 16.1) years. In RHD, the lymphatic vessel size and count per mm² were increased compared to the degenerative valves. Statistical significance was found in the blood and lymphatic vessel size, and lymphatic vessel count. In RHD, the combined blood and lymphatic vessel size increased from 1.45µm² (± SD 2.52) to 4.91 µm² (± SD 6.33). The lymphatic vessel count was 1,123.86 per mm² (± SD 2,154.68) in the RHD and 213.08 per mm² (± SD 390.13) in the myxomatous degenerative valves. Angiogenesis and lymphangiogenesis characterize mitral valves in RHD.

Background Ascending aortic dilatation is associated with increased susceptibility to aortic events. Chronic obstructive pulmonary disease (COPD) may add to tissue degeneration and inflammation associated with the risk of increased aortic dilatation. We studied the characteristics and aortic wall degeneration of patients with COPD during ascending aortic dilatation. Methodology We enrolled 35 consecutive patients who underwent elective surgery for ascending aortic dilatation between February 2016 and November 2016. The patients were grouped according to the presence of COPD. The aortic diameters were measured for the aortic valve annulus, aortic root, sinotubular junction, ascending aorta, aortic arch, and descending aorta. An extensive analysis of ascending aortic wall histopathology was performed.  Results The patients with chronic obstructive pulmonary disease (COPD) (n=7) all had aortic valve regurgitation, while the aortic wall had more mucoid extracellular matrix accumulation, medial degeneration, elastic fiber fragmentation and loss, and adventitial fibrosis than those without COPD (5.7±1.1 vs. 4.3±1.0 point score units (PSU), p=0.006; 2.7±0.5 vs. 1.7±0.8 PSU, p=0.006; 4.5±1.2 vs. 3.3±1.2 PSU, p=0.034; and 0.5±0.5 vs. 0.1±0.3 PSU, p=0.023, respectively). Only the distal ascending aortic diameter slightly differed in patients with COPD vs. those without (36.5±3.3 vs. 32.2±3.8 mm, p=0.011), although increased aortic dilatation was otherwise present in both groups. Conclusions We identified a subgroup of patients with COPD who had increased aortic wall degeneration during ascending aortic dilatation. Risk stratification of aortic events in patients with COPD warrants further clarification.

Background The extent of aortic valve inflammation in patients undergoing aortic valve replacement (AVR) is unsettled. The significance of aortic valve histopathology in patients undergoing AVR is undetermined. Methods A total of 145 resected aortic valves of consecutive patients undergoing surgery for a local aortic valve disease with or without ascending aorta were investigated for histopathology. The extent of inflammation and degeneration were investigated. Unadjusted survival was evaluated by Kaplan–Meier analysis. Median follow-up was 2.7 years (interquartile range 1.5–3.9). Results Mean patient age was 69 (SD 11) years. Though endocarditis was apparent in only six patients preoperatively, severe aortic valve inflammation was diagnosed histologically in 32 patients of whom 12 patients had acute, subacute or chronic endocarditis. Despite complete aortic valve resection, survival was decreased in patients with severe aortic valve inflammation as opposed to those without (log rank, P = 0.044), even after exclusion of patients with endocarditis, emergency and aortic surgery. Conclusions Aortic valve tissue analysis reveals severe inflammation that may require postoperative treatment. The association of severe but local aortic valve inflammation with patient outcome after aortic valve surgery merits further investigation.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

Background: Aortic root involvement during acute type A aortic dissection (ATAAD) may depend on ascending aortic wall degeneration. Surgical decision-making for extended resection of the aortic root is clinically made without histopathology. The aim of the study was to investigate whether the degree of degeneration of the ascending aortic wall found in patients with ATAAD is associated with the aortic root involvement. Methods: Collectively, 141 consecutive patients undergoing ATAAD surgery at Tampere University Heart Hospital were investigated. The ascending aortic wall resected in surgery was processed for 11 different variables that describe medial and adventitial degeneration. In addition, atherosclerosis and inflammation were separately evaluated. Patients undergoing aortic root replacement were compared with those with supracoronary reconstruction of the ascending aorta with/without aortic valve surgery (root-sparing surgery) during a mean 4.9-year follow-up. Results: Aortic root replacement together with the ascending aortic replacement was performed in 39% of the patients (n=55). The mean age for all patients was 65 years [standard deviation (SD 13)]. Many patients with aortic root replacement had moderate to severe aortic valve regurgitation (85.5%). Most of the patients with aortic root-sparing surgery included a supracoronary tube prosthesis (89.5%), while nine patients also had aortic valve replacement. The degree of mucoid extracellular matrix accumulation was more prominent in patients with aortic root replacement compared to patients with root-sparing surgery (2.1 SD 0.4 vs. 1.9 SD 0.4, P=0.04, respectively). During follow-up, there were 52 deaths among patients (log rank P=0.79). Conclusions: Histopathology of the ascending aorta during ATAAD reveals distinctive aortic wall degeneration in patients with aortic root involvement vs. not. The degree of mucoid extracellular matrix accumulation assessed postoperatively is associated with the choice of surgical procedure in many patients.

BACKGROUND:The classification terminology systems for pulmonary cytology specimens have recently emerged. Inadequate samples, classified as "nondiagnostic," raise challenges in determining the threshold of cell numbers and the risk of malignancy (ROM).METHODS:The study retrospectively reviewed 248 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples: 46 insufficient samples, 60 low cellularity samples, and 142 adequate samples. Characteristics as cellularity, number of benign and malignant cells, and background features were assessed. Receiver operating characteristic curve analysis was performed to establish cell sufficiency thresholds for the diagnosis.RESULTS:Out of the 248 samples analyzed, 108 were classified as benign, 94 as malignant, and 46 as insufficient. The study found that the cellularity thresholds for diagnosis in cell blocks and cytological samples were ≥50 cells and ≥100 cells, respectively. The thresholds for tumor cell counts were ≥1 - 10 cells for both types of cells, respectively. Considerably, some low cellularity samples were initially classified as insufficient despite meeting the diagnostic thresholds upon revision. The ROM varied across sample categories, with insufficient samples having a ROM of 10.9%, benign samples 15.7%, suspicious samples 92.0%, and malignant samples 100%.CONCLUSION:Insufficient EBUS-TBNA samples raise challenges in diagnosis and management. This study identified the root cause of insufficient samples, including factors related to humans, diagnostic methods, sampling, and laboratory processing. By understanding the root causes, diagnostic recommendations can be developed to improve the diagnostic process. The findings emphasize the importance of standardized classification and terminology systems for clear communication among healthcare professionals and institutions, ultimately improving patient care and enabling quality assurance measures.

A diagnostic challenge is presented: Distinguishing ectopic thyroid tissue from metastatic well-differentiated follicular carcinoma in cytological material. Two cases of thyroid tissue in mediastinal lymph nodes were sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Later, the cases were presented in Labquality's nongynecological external quality scheme rounds in the years 2017, 2019, and 2020. The same case was presented two times, both in the 2017 and in the 2020 rounds. The results of the three rounds and the discussion of diagnostic pitfalls of ectopic thyroid tissue are presented. A total of 112 individual laboratories worldwide participated in the external quality assurance rounds with whole-slide scanned images and digital still images of alcohol-fixed Papanicolaou-stained cytospin specimens in the years 2017, 2019, and 2020. Fifty-three laboratories participated in both the 2017 (53 of 70, 75.71%) and the 2020 (53 of 85, 62.35%) rounds. The given Pap classes between rounds were compared. Twelve (12 of 53, 22.6%) of the laboratories gave the same Pap class value, whereas 32 (32 of 53, 60.4%) were in the range of ±1 class difference (Cohen's kappa −0.035, p < 0.637). When comparing the diagnoses, 21 (21 of 53, 39.6%) laboratories gave the same diagnosis in 2017 and in 2020 (Cohen's kappa 0.039, p < 0.625). Thirty-two of the laboratories gave the same diagnosis both in 2017 and in 2020 (Cohen's kappa 0.004, p < 0.979). Ten (10 of 53, 18.9%) laboratories changed their diagnose from malignant to benign, and 11 (11 of 53, 20.8%) changed their diagnose from benign to malignant between the 2017 and the 2020 rounds. In conclusions, the expert reference diagnosis was thyroid tissue in mediastinal lymph node. Thyroid tissue in mediastinal lymph node may be either of ectopic or of neoplastic origin. The diagnostic work-up should include cytomorphological, immunohistochemical, laboratory, and imaging results. If a neoplastic change is excluded, the benign category is the most feasible one. The quality assurance rounds showed a large variability in the given Pap classes. Mirroring the problematic issue both inter- and intralaboratory of such cases both in routine diagnostics and in the classification terminologies is requiring multidisciplinary evaluation approach in the diagnostics.

BACKGROUND:The cardiac conduction system (CCS) creates and propagates electrical signals generating the heartbeat. This study aimed to assess the collagen content, vasculature, and innervation in the human sinoatrial and atrioventricular CCS, and surrounding tissue. MATERIALS AND METHODS:Ten sinoatrial and 17 atrioventricular CCS samples were collected from 17 adult human autopsied hearts. Masson trichrome stain was used to examine collagen, cardiomyocytes, and fat proportions. Immunohistochemically, vessels and lymphatics were studied by CD31 (pan-endothelial marker) and D2-40 (lymphatic endothelium marker) antibodies. General nerve densities were assessed by S100, while sympathetic nerves were studied using tyrosine hydroxylase, parasympathetic nerves with choline acetyltransferase, and GAP43 (neural growth marker) antibodies looked at these components. All components were quantified with QuPath software (Queens University, Belfast, Northern Ireland). RESULTS:Interstitial collagen was more than two times higher in the sinoatrial vs. atrioventricular CCS (55% vs. 22%). The fat content was 6.3% in the sinoatrial CCS and 6.5% in the atrioventricular CCS. The lymphatic vessel density was increased in the sinoatrial and atrioventricular CCS compared to the surrounding tissue and was lower in the sinoatrial vs. atrioventricular CCS (P=.043). The overall vasculature density did not differ between the SA and AV CCS. The overall innervation and neural growth densities were significantly increased in the CCS compared to the surrounding tissue. The overall innervation was higher in the atrial vs. ventricular CCS (P=.018). The neural growth was higher in the atrial vs. ventricular CCS (P=.018). The sympathetic neural supply was dominant in all the studied regions with the highest density in the sinoatrial CCS. CONCLUSIONS:Our results provide new insights into the unique morphology of the human CCS collagen, fat, vasculature, and innervation. A deeper understanding of the CCS anatomical components and morphologic substrates' role will help in elucidating the causes of cardiac arrhythmias and provide a basis for further therapeutic interventions.

A diagnostic challenge is presented: Distinguishing ectopic thyroid tissue from metastatic well-differentiated follicular carcinoma in cytological material. Two cases of thyroid tissue in mediastinal lymph nodes were sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Later, the cases were presented in Labquality's nongynecological external quality scheme rounds in the years 2017, 2019, and 2020. The same case was presented two times, both in the 2017 and in the 2020 rounds. The results of the three rounds and the discussion of diagnostic pitfalls of ectopic thyroid tissue are presented. A total of 112 individual laboratories worldwide participated in the external quality assurance rounds with whole-slide scanned images and digital still images of alcohol-fixed Papanicolaou-stained cytospin specimens in the years 2017, 2019, and 2020. Fifty-three laboratories participated in both the 2017 (53 of 70, 75.71%) and the 2020 (53 of 85, 62.35%) rounds. The given Pap classes between rounds were compared. Twelve (12 of 53, 22.6%) of the laboratories gave the same Pap class value, whereas 32 (32 of 53, 60.4%) were in the range of ±1 class difference (Cohen's kappa -0.035, p < 0.637). When comparing the diagnoses, 21 (21 of 53, 39.6%) laboratories gave the same diagnosis in 2017 and in 2020 (Cohen's kappa 0.039, p < 0.625). Thirty-two of the laboratories gave the same diagnosis both in 2017 and in 2020 (Cohen's kappa 0.004, p < 0.979). Ten (10 of 53, 18.9%) laboratories changed their diagnose from malignant to benign, and 11 (11 of 53, 20.8%) changed their diagnose from benign to malignant between the 2017 and the 2020 rounds. In conclusions, the expert reference diagnosis was thyroid tissue in mediastinal lymph node. Thyroid tissue in mediastinal lymph node may be either of ectopic or of neoplastic origin. The diagnostic work-up should include cytomorphological, immunohistochemical, laboratory, and imaging results. If a neoplastic change is excluded, the benign category is the most feasible one. The quality assurance rounds showed a large variability in the given Pap classes. Mirroring the problematic issue both inter- and intralaboratory of such cases both in routine diagnostics and in the classification terminologies is requiring multidisciplinary evaluation approach in the diagnostics.

OBJECTIVE:Acute volume overload (AVO) induces early ischemia-like changes in intramyocardial arteries. We investigated whether the Factor Xa (FXa) inhibitor apixaban interacts with the myocardium early after AVO.METHODS:Fifty-five syngeneic Fisher rats underwent surgical abdominal aortocaval fistula to induce AVO. Among them, 17 rats were treated with apixaban (10 mg/kg/day). The myocardial outcome was studied using histological analysis and by measuring atrial natriuretic peptide (ANP) and matrix metalloprotease 9 (MMP9) gene expression.RESULTS:After 3 days, the total number of intramyocardial arteries was significantly increased in the AVO+apixaban (AVO+A) group compared with that in the AVO group (12.0  ±  1.2 and 10.2 ± 1.5, point score units, respectively). In the AVO+A group, there were significantly more edematous nuclei in myocardial arteries in the right and left ventricle compared with that in the AVO group. ANP and MMP9 expression levels continued to increase significantly in the AVO+A group compared with those in the AVO group.CONCLUSION:Apixaban interacts with intramyocardial arteries in the left and right ventricles after AVO and ANP and MMP9 expression levels increased. Thus, the myocardial effect of Factor Xa inhibition needs to be monitored after AVO.

Abstract Background The magnitude of ascending aortic degeneration in patients with bicuspid aortic valves (BAV) is controversial. Methods The aim of this study was to investigate ascending aortic wall degeneration in patients with BAV as compared with tricuspid aortic valves (TAV). The ascending aortic wall of 67 consecutive patients was processed for histology and immunohistochemistry. The extent of surgery and wall degeneration were investigated. Unadjusted survival was evaluated by Kaplan–Meier analysis. Median follow-up for patients with BAV and TAV was 3.8 years (interquartile range [IQR] 3.5–4.1) and 3.7 years (IQR 3.4–3.9), respectively. Results There were 33 patients with BAV and 34 with TAV. Mid-ascending aorta diameter was 54 mm (IQR 50–60). Replacement of the aortic valve, together with an ascending aortic prosthesis, was more frequent in BAV vs TAV patients (24% vs. 3%, P = 0.013). However, medial fibrosis, elastic fiber thinning, incremental medial degeneration and smooth muscle cell nuclei loss were less prominent in BAV vs TAV patients (0.1 ± 0.4 vs. 0.8 ± 1.4, P = 0.016; 0.6 ± 1.4 vs. 1.6 ± 2.0, P = 0.027; 1.7 ± 0.7 vs. 2.2 ± 0.8, P = 0.045 and 2.3 ± 1.5 vs. 3.2 ± 1.3, P = 0.026, respectively). Conclusions Since degeneration of the ascending aortic wall was seldom prominent, histopathology alone may not support the need for surgery of the dilated ascending aorta in BAV patients as compared with TAV patients.

Unloading the heart may aid recovery after acute cardiac volume-overload (AVO). We experimentally investigated whether unloading the heart after AVO by heterotopic transplantation histologically impacts myocardial outcome. Thirty-two syngeneic Fisher 344 rats underwent surgery for abdominal arterial-venous fistula to induce AVO. Seven hearts were heterotopically transplanted one day after AVO to simulate a non-working state of the left ventricle (AVO+Tx). In addition, six rats without AVO or surgery (Normal) and five rats with sham surgery (Sham) served as controls. Myocardial outcome was studied using histology and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis for hypoxia inducible factor 1alpha (HIF1α), inducible nitric oxide synthase (iNOS), E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), vascular endothelial growth factor alpha (VEGFα), matrix metalloprotease 9 (MMP9), chitinase-3-like protein (YKL-40) and transforming growth factor beta (TGFβ). Relative ischemia of the right ventricle and septal intramyocardial arteries was decreased in AVO+Tx as compared with AVO (0.04±0.01 vs. 0.09±0.02, PSU, P=0.040 and 0.04±0.01 vs. 0.16±0.02, PSU, P=0.008, respectively). Quantitative RT-PCR showed an increase in the expression of iNOS, YKL-40 and VEGFα, and decrease in ANP in AVO+Tx as compared with AVO (5.78±1.23 vs. 2.46±0.81, P=0.039, 22.39±5.22 vs. 10.79±1.70, P=0.039 and 1.15±0.22 vs. 0.60±0.08, P=0.030, and 1.32±0.16 vs. 2.85±0.70, P=0.039, respectively). Unloading the heart by heterotopic transplantation induces early ischemic recovery of intramyocardial arteries after AVO. A non-working state reverses acute ischemic myocardial injury after AVO.