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PurposeMyocardial fibrosis in aortic stenosis (AS) is associated with worse survival following aortic valve replacement (AVR). We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. MethodsA total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement (LGE) and T1 mapping and global longitudinal strain (GLS) analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies (71) that were sampled at the time of AVR. ResultsCVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

BACKGROUND: The mechanisms driving the transition from inflammation to fibrosis in sarcoidosis patients are poorly understood; prognostic features are lacking. Immune cell profiling may provide insights into pathogenesis and prognostic factors of the disease. This study aimed to establish associations in simultaneous of lymphocyte subset profiles in the blood, bronchoalveolar lavage fluid (BALF), and lung biopsy tissue in the patients with newly diagnosed sarcoidosis. METHODS: A total of 71 sarcoid patients (SPs) and 20 healthy controls (HCs) were enrolled into the study. CD31, CD38, CD44, CD103 positive T lymphocytes in blood and BALF were analysed. Additionally, the densities of CD4, CD8, CD38, CD44, CD103 positive cells in lung tissue biopsies were estimated by digital image analysis. RESULTS: Main findings: (I) increase of percentage of CD3(+)CD4(+)CD38(+) in BALF and blood, and increase of percentage of CD3(+)CD4(+)CD44(+) in BALF in Löfgren syndrome patients comparing with patients without Löfgren syndrome, (II) increase of percentage of CD3(+)CD4(+)103(+) in BALF and in blood in patients without Löfgren syndrome (comparing with Löfgren syndrome patients) and increase of percentage of CD3(+)CD4(+)103(+) in BALF and in blood in more advanced sarcoidosis stage. (III) Increasing percentage of BALF CD3(+)CD4(+)CD31(+) in sarcoidosis patients when comparing with controls independently of presence of Löfgren syndrome, smoking status or stage of sarcoidosis. Several significant correlations were found. CONCLUSIONS: Lymphocyte subpopulations in blood, BALF, and lung tissue were substantially different in SPs at the time of diagnosis compared to HCs. CD3(+)CD4(+)CD31(+) in BALF might be a potential supporting marker for the diagnosis of sarcoidosis. CD3(+)CD4(+)CD38(+) in BALF and blood and CD3(+)CD4(+)CD44(+) in BALF may be markers of the acute immune response in sarcoidosis patients. CD4(+)CD103(+) T-cells in BALF and in blood are markers of the persistent immune response in sarcoidosis patients and are potential prognostic features of the chronic course of this disease.

The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.

The extracellular matrix (ECM) is amongst many tissue components affected by cancer, however, morphological changes of the ECM are not well-understood and thus, often omitted from diagnostic considerations. Polarimetric second-harmonic generation (P-SHG) microscopy allows for visualization and characterization of collagen ultrastructure in the ECM, aiding in better understanding of the changes induced by cancer throughout the tissue. In this paper, a large region of hematoxylin and eosin (H&E) stained human lung section, encompassing a tumor margin, connecting a significant tumor portion to normal tissue was imaged with P-SHG microscopy. The resulting polarimetric parameters were utilized in principal components analysis and unsupervised K-Means clustering to separate normal- and tumor-like tissue. Consequently, a pseudo-color map of the clustered tissue regions is generated to highlight the irregularity of the ECM collagen structure throughout the region of interest and to identify the tumor margin, in the absence of morphological characteristics of the cells.

Cryptogenic organising pneumonia (COP) is a rare interstitial lung disease with different onset of symptoms, which responds rapidly to glucocorticoid treatment. We present a case of COP which manifested as progressive 3-year dyspnoea that has led ultimately to acute respiratory failure. Moreover, treatment with prednisone for this patient exhibits slow onset of the effect.

The extracellular matrix (ECM) collagen undergoes major remodeling during tumorigenesis. However, alterations to the ECM are not widely considered in cancer diagnostics, due to mostly uniform appearance of collagen fibers in white light images of hematoxylin and eosin-stained (H&E) tissue sections. Polarimetric second-harmonic generation (P-SHG) microscopy enables label-free visualization and ultrastructural investigation of non-centrosymmetric molecules, which, when combined with texture analysis, provides multiparameter characterization of tissue collagen. This paper demonstrates whole slide imaging of breast tissue microarrays using high-throughput widefield P-SHG microscopy. The resulting P-SHG parameters are used in classification to differentiate tumor from normal tissue, resulting in 94.2% for both accuracy and F1-score, and 6.3% false discovery rate. Subsequently, the trained classifier is employed to predict tumor tissue with 91.3% accuracy, 90.7% F1-score, and 13.8% false omission rate. As such, we show that widefield P-SHG microscopy reveals collagen ultrastructure over large tissue regions and can be utilized as a sensitive biomarker for cancer diagnostics and prognostics studies.

Cryptogenic organizing pneumonia is a rare interstitial lung disease with different onset of symptoms, which responds rapidly to glucocorticoid treatment. We present a case of cryptogenic organizing pneumonia which manifested as a progressive 3-year dyspnea that ultimately has led to acute respiratory failure. Moreover, treatment with prednisone for this patient exhibited slow onset of the effect.

The extracellular matrix (ECM) collagen undergoes major remodeling during tumorigenesis. However, alterations to the ECM are not widely considered in cancer diagnostics, due to mostly uniform appearance of collagen fibers in white light images of hematoxylin and eosin-stained tissue sections. Polarimetric second-harmonic generation (P-SHG) microscopy enables label-free visualization and ultrastructural investigation of non-centrosymmetric molecules, which, when combined with texture analysis, provides multiparameter characterization of tissue collagen. This paper demonstrates whole slide imaging of breast tissue microarrays using high-throughput widefield P-SHG microscopy. The resulting P-SHG parameters are used in classification to differentiate tumor tissue from normal with 94.2% accuracy and F1-score, and 6.3% false discovery rate. Subsequently, the trained classifier is employed to predict tumor tissue with 91.3% accuracy, 90.7% F1-score, and 13.8% false omission rate. As such, we show that widefield P-SHG microscopy reveals collagen ultrastructure over large tissue regions and can be utilized as a sensitive biomarker for cancer diagnostics and prognostics studies.

Second-harmonic generation microscopy was used to image collagen in normal and cancerous human colon histological samples, and texture analysis was used to investigate the changes in collagen structure occurring during carcinogenesis.

Polarimetric second-harmonic generation microscopy was used to acquire images of collagen in normal and cancerous human colon histological samples, and texture analysis was applied to investigate the changes in the collagen structure.

Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome.Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death.Thirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis.This study has shown that two markers - cardiotropic viruses and myocardial inflammation - are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

Background/Aim: The prognostic role of thyroid transcription factor-1 (TTF1) in advanced lung cancer is not clearly established. The present study aimed to evaluate the associations between clinicopathological characteristics, TTF1 expression, and overall survival (OS) of patients with advanced lung adenocarcinoma. Materials and Methods: One hundred and seventy-two patients were enrolled in this retrospective study. OS was assessed according to immunohistochemical TTF1 expression in lung adenocarcinoma tissue, age, gender, performance status (PS), smoking history and status, disease stage, tumor differentiation, epidermal growth factor receptor (EGFR) mutation and EGFR tyrosine kinase inhibitor (TKI) treatment status. Results: The OS time was longer (p

Background/Aim: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice. Materials and Methods: We treated IAV-infected mice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p

Intralobarinė sekvestracija – plaucio vystymosi anomalija,pasireiskianti nefunkcionuojancios parenchimosplotu, turinciu anomalią kraujotaką. Klinikiniai simptomai yra nespecifiniai ir neretai si anomalija gali imituoti bronchektazes. Tyrimo tikslas: įvertintiintralobarinės plaucių sekvestracijos diagnostikos ir gydymo rezultatus VU MF Krūtinės chirurgijos centre. Tyrimo metodai ir tiriamieji. Į tyrimą įtraukti 44 asmenys, operuoti dėl bronchektazėms būdingų simptomų (is jų 10-ciai diagnozuota intralobarinė sekvestracija). Tyrimo rezultatai: pagrindiniai ligoniųsu intralobarine sekvestracija simptomai buvo kosulys (80%), skrepliavimas (30%), karsciavimas (30%). Diagnostikai naudoti tyrimai: krūtinės ląstosrentgenograma (100%), kompiuterinė tomografija(100%), aortografija (30%), kompiuterinės tomografijosangiografija (20%), fibrobronchoskopija (80%). Klaidinga pradinė diagnozė nustatyta pusei ligonių. Gydymas – chirurginis. Visiems ligoniams pasalinta plaucio apatinė skiltis (7 - kairiojo, 3 – desiniojo).Isvados: intralobarinė plaucių sekvestracija dažnai sukelia simptomus, identiskus sergant bronchektazėmis.Tiriant tokius ligonius būtina nustatyti,ar nėra anomalinių arterijų, patenkancių į vieną ar kitą plaucių dalį. Kompiuterinė angiografija įgalinatiksliai diagnozuoti anomalines plaucių arterijas. Jas (ją) nustacius pries operaciją, ligonis apsaugomasnuo galimo grėsmingo kraujavimo operuojant.

Polarimetric second-harmonic generation (P-SHG) microscopy is used to characterize the composition and polarity of collagen fibers in various regions of human cardiac tissue. The boundary between the cardiac conduction system and myocardium is shown to possess a distinct composition of collagen compared to other regions in the heart. Moreover, collagen fibers in this region are macroscopically organized in a unipolar arrangement, which may consequently aid in effective propagation of the electrical signal through the cardiac conduction system.

Introduction Organizing pneumonia (OP) is a rare disorder which may be associated with various clinical contexts and radiological patterns.

During the heart surgery there is a possibility to harm the conduction system of the heart (HCS), which may cause dangerous obstruction of the heart functionality. The muscular origin makes it complicated to distinguish HCS from the surrounding tissues; therefore, there is an immense necessity to visualise HCS during the operation time. Optical methods carry information about intrinsic properties of the tissue and provide the unique possibility to study the objects non-invasively. The experiments were performed on the human heart tissue specimens ex vivo. HCS, myocardium (MC), and connective tissue (CT) were preliminary marked by a pathologist and histologically approved after the spectral measurements. The spectrometer FLS920 (Edinburgh Instruments) was used for steady state and time-resolved fluorescence registration. Fluorescence was exited using a 405 nm pulsed laser. Spectral analysis revealed that at least three fluorophores are responsible for the emission in the region of 430–550 nm. According to the lifetimes, the fluorescing constituents in all tissues should be the same. The fractional components of fluorescence intensity revealed a similar composition of MC and HCS; however, quantitative differences were observed between HCS and CT.

Chronic eosinophilic pneumonia is a rare interstitial lung disorder, which causes diagnostic difficulties. Often the disease is diagnosed correctly after several weeks or months following initial presentation. The aim of the study was to prospectively evaluate peculiarities of manifestation of idiopathic chronic eosinophilic pneumonia (ICEP), which may allow to improving early diagnosis. Twenty patients with ICEP were involved in this investigation. The cases of acute eosinophilic pneumonia and cases of chronic eosinophilic pneumonia of known origin were excluded. To define archetypal signs of the idiopathic chronic eosinophilic pneumonia, 3 comparable groups were selected. They were the group of 50 patients with community-acquired pneumonia (COP); the group of 21 asthmatic patients with COP, and the cluster of 10 patients with morphologically confirmed cryptogenic organizing pneumonia (OP). Clinical and radiological manifestation of ICEP was similar to COP and cryptogenic OP manifestation. We have found that chest pain; fine rales and pleurisy were unrepresentative for ICEP. However, blood eosinophilia was typical sign of ICEP and wheezing was a frequent observation. Usually ICEP patients had relative mild clinical symptoms and moderate increased C reactive protein (CRP) level even in cases of multiple pulmonary infiltrates. In conclusion, in cases of not typical pneumonia course, i.e. non-resolving or recurrent pulmonary infiltrates; relative mild clinical symptoms and moderate increased CRP level with multiple pulmonary infiltrates; blood eosinophilia and/or signs of airway obstruction eosinophilic pneumonia should be suspected and bronchoalveolar lavage and/or bronchoscopic lung biopsy performed.

Fluorescence measurements have been employed for the spectroscopic characterization of heart tissues. Excitation at the absorption band of the aromatic amino acids allows good differentiation between tissues of the bundle of His and those of myocardium when the ratios of the fluorescence intensities measured at 340 nm to those at 450 nm are compared. Several fluorophores with overlapping fluorescence bands are responsible for autofluorescence of heart tissues in the spectral range from 350 to 550 nm. The tissues of the bundle of His and myocardium are distinguishable by fluorescence intensity under excitation in the UVA spectral region. The best conditions are ensured by the excitation range of 360–390 nm and by recording of the fluorescence signal in the 440–480 nm spectral range.

Silicosis remains a common occupational respiratory disease. Even in this era of highly sophisticated hygiene in European countries, new occupational cases of silicosis continue to be reported. Four cases of silicosis which developed after a rela� . Four cases of silicosis which developed after a rela� tively short occupational exposure to respirable silica among the members of one family are described. Four young men worked illegally abroad in mining in one of European countries. All of them were employed together in the same working conditions. One of the brothers died due to the acute form of the disease (lipoproteinosis). Two of the brothers suffered from simple nodular silicosis, and the fourth brother developed very early nodular silicosis and small airway dust disease. A one year followup revealed moderate/severe worsening of the disease in all surviving brothers.