Patologiniu nutukimu sergančių pacientų kepenų histologinių pokyčių vertinimas

Tyrimo tikslasĮvertinti patologiniu nutukimu sergančių pacientų kepenų histologinius pokyčius ir nustatyti galimus ryšius su demografiniais, kūno masės, laboratoriniais rodikliais bei gretutinėmis ligomis.Ligoniai ir metodaiPerspektyviajame tyrime dalyvavo 103 pacientai, kuriems buvo atlikta laparoskopinė skrandžio apjuosimo reguliuojama juosta operacija kūno masei mažinti. Jos metu 98 (95,1 proc.) pacientams buvo atlikta kepenų stulpelinė biopsija.RezultataiStatistiškai patikimas ryšys siejo histologinius kepenų rodiklius: 1) steatozę – su vyriška lytimi (p = 0,012), aspartataminotransferaze (AST) (p = 0,003), alaninaminotransferaze (ALT) (p = 0,003); 2) balioninę degeneraciją – su AST (p=0,036), gama-glutamiltransferaze (GGT) (p = 0,018); 3) skiltinį uždegimą – su cukriniu diabetu (CD) (p = 0,006); 4) portinį uždegimą – su trigliceridais (p = 0,011), hipertenzija (p = 0,01), miego apnėja (p = 0,028), hipertenzija su miego apnėja (p = 0,033); 5) fibrozę – su AST (p = 0,016), GGT (p = 0,013), trigliceridais (p = 0,011), CD (p = 0,006), hipertenzija (p = 0,04); 5) nealkoholinės kepenų suriebėjimo ligos aktyvumo indeksą – su kūno masės indeksu (p = 0,032), AST (p = 0,001), ALT (p = 0,012), GGT (p = 0,038), CD (p = 0,029); 6) fibrozės ir uždegimo indeksą – su AST (p = 0,048), hipertenzija (p = 0,007), CD (p = 0,007).IšvadosDidesnio laipsnio steatozė koreliuoja su padidėjusiais aspartataminotransferazės, alaninaminotransferazės, gama-glutamiltransferazės kiekiais. Didesnio laipsnio kepenų steatozė būdingesnė vyrams. Fibrozinių ir uždegiminių kepenų pokyčių sunkumą geriausiai atspindėjo aspartataminotransferazė ir trigliceridai. Patikimas ryšys siejo cukrinį diabetą, miego apnėją bei hipertenziją su nealkoholiniu steatohepatitu.Reikšminiai žodžiai: patologinis nutukimas, bariatrinė chirurgija, nealkoholinė kepenų suriebėjimo liga, nealkoholinis steatohepatitasThe histological liver evaluation in morbidly obese subjects ObjectiveTo evaluate histological liver changes in morbidly obese patients and to look for possible correlations with demographic, body mass, laboratory parameters, comorbidities.Material and methods103 patients included in our prospective study had been referred for the obesity surgery and 98 (95.1%) of them had liver biopsies.ResultsOur study assessed significant relations of these parameters: 1) steatosis and male gender (p = 0.012), aspartate transaminase (AST) (p = 0.003), alanine transaminase (ALT) (p = 0.003); 2) hepatocellular ballooning – AST (p = 0.036), gamma-glutamyltransferase (GGT) (p = 0.018); 3) lobular inflammation – diabetes mellitus (p = 0.006); 4) portal inflammation – triglycerides (p = 0.011), hypertension (p = 0.01), obstructive sleep apnea (p = 0.028), hypertension with obstructive sleep apnea (p = 0.033); 5) fibrosis – AST (p = 0.016), GGT (p = 0.013), triglycerides (p = 0.011), diabetes mellitus (p = 0.006), hypertension (p = 0.04); 5) non-alcoholic fatty liver disease activity score – body mass index (p = 0.032), AST (p = 0.001), ALT(p = 0.012), GGT (p = 0.038), diabetes mellitus (p = 0.029); 6) fibro-inflammation index – AST (p = 0.048), hypertension (p = 0.007), diabetes mellitus (p = 0.007).ConclusionsThe severity of liver steatosis preferably reflected aspartate transaminase, alanine transaminase, gamma-glutamyltransferase. The severe liver steatosis was more common among men. The severity of liver fibrosis and inflammation preferably reflected aspartate transaminase, triglycerides. Diabetes mellitus, obstructive sleep apnea and hypertension significantly correlated with non-alcoholic steatohepatitis.Key words: morbid obesity, bariatric surgery, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis

Renal Survival and Validation of Novel International Immunoglobulin A Nephropathy Prediction Tool in Latvian Population: Preliminary Data

Affiliations in Web of Science publication are different from those provided in the original journal publication. Here are given the affiliations from original publication in "Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences".The aim of the study was to determine kidney survival and validate the novel international immunoglobulin A nephropathy (IgAN) prediction tool (PT) in the Latvian population. Adults with morphologically confirmed IgAN were included. Kidney survival was analysed with the Kaplan–Meier method. PT-assigned risk was compared with calculated risk by the Cox regression model. The Kaplan–Meier analysis included 95 patients. The five-year kidney survival Q3 was 24 months. Women had longer median kidney-survival time (> 60 months) than men (58 months). Median kidney survival in participants with MEST T0 was longer than 60 months; T1 and T2 were 40 and 18 months, respectively. Median kidney survival in participants with diastolic blood pressure (DBP) < 99 mmHg was longer than 60 months, whereas in patients with DBP 100–109 and 110 mmHg, it was 40 and 24 months, respectively. Cox regression analysis included 68 patients. A moderate degree of correlation was found between predicted and observed five-year risk (p = 0.001). Gender, tubular atrophy/interstitial fibrosis, DBP are significant factors affecting kidney survival. Since there was statistically significant correlation and reliability between PT and follow-up analysis data, we conclude that PT could be applied for use in the Latvian populationpublishersversionPeer reviewe

Ultragarsinio tyrimo reikšmė sergant temporaliniu arteritu

Introduction. Temporal arteritis (TA) is usually diagnosed according to clinical criteria, and temporal artery biopsy is considered as a golden standard for the diagnosis. Temporal artery biopsy is a surgical intervention on a head site and is not well-tolerated by the patients. As an alternative for temporal artery investigation, ultrasound examination may be used. The aim of this pilot study was to evaluate the performance of ultrasound examination of a temporal artery of patients with and without TA, but with similar clinical findings. Materials and results. Thirteen patients seen at Vilnius University Hospital Santariškių Klinikos during 2006–2009 with suspicion of TA were included into this study, and ultrasound examination of their both right and left superficial temporal arteries was performed. Eight patients were diagnosed with TA according to clinical criteria, and 5 patients had headaches of another origin. Two patients had a biopsy-proven diagnosis. The thickened wall (“halo” sign) and / or stenosis / occlusion were found on ultrasound examination in three patients. The presence of abnormality was found in five patients from the setting of TA patients, and no abnormalities were detected in the control group. Although the groups were very small and the data scanty, we consider the sensitivity of the abnormalities detected by ultrasound to be 62.5%, and the specifi city was close to 100% in this pilot study. Conclusions. Authors recommend bilateral ultrasound examination of temporal arteries for patients with suspicion of giant cell arteritis (temporal arteritis). Our pilot study showed a suffi cient sensitivity of this diagnostic test, although it greatly depends on the experience and skills of the performer

The impact of IgM deposits on the outcome of Nephrotic syndrome in children

Background: The significance of IgM deposits in glomerular mesangium has been controversial since they were first described due to the variations in the both the definitions used and described impact on clinical outcome. The aim of our study was to evaluate the significance of the IgM deposits in the glomerular mesangium for outcomes of nephrotic syndrome (NS) in children. Methods: Forty-five children with NS who underwent renal biopsy at tertiary pediatric hospital from January 1st, 2000 to December 31st, 2015 and the pathology diagnosis of minimal change disease, focal segmental glomerulosclerosis and mesangial hypercellularity (MH) were retrospectively analyzed. IgM positivity was defined as >= 1+ imunofluorescence with predominantly mesangial distribution. The patients were stratified into IgM-positive (n = 18) and IgM-negative (n = 27). Results: At the end of the median follow-up 4.5 years (range 0.17-13.14), the IgM-positive group was represented by 11 patients (61.1%) in remission, 3 patients (16.7%) with active disease and normal kidney function, 2 (11.1%) patients with active disease and impaired kidney function, 2 (11.1%) patients on renal replacement therapy. Accordingly, the IgM-negative group included 13 patients (48.1%) in remission, 12 (44.4%) with active disease and normal kidney function, 1 (3.7%) with active disease and impaired kidney function, 1 (3.7%) on renal replacement therapy, with no statistical significance between groups (p = 0.186). Conclusions: This study did not reveal significant differences of the disease outcomes between IgM-positive and IgM-negative groups

Deep learning model for cell nuclei segmentation and lymphocyte identification in whole slide histology images

Anti-cancer immunotherapy dramatically changes the clinical management of many types of tumours towards less harmful and more personalized treatment plans than conventional chemotherapy or radiation. Precise analysis of the spatial distribution of immune cells in the tumourous tissue is necessary to select patients that would best respond to the treatment. Here, we introduce a deep learning-based workflow for cell nuclei segmentation and subsequent immune cell identification in routine diagnostic images. We applied our workflow on a set of hematoxylin and eosin (H&E) stained breast cancer and colorectal cancer tissue images to detect tumour-infiltrating lymphocytes. Firstly, to segment all nuclei in the tissue, we applied the multiple-image input layer architecture (Micro-Net, Dice coefficient (DC) 0.79±0.02).We supplemented the Micro-Net with an introduced texture block to increase segmentation accuracy (DC = 0.80 ± 0.02). We preserved the shallow architecture of the segmentation network with only 280 K trainable parameters (e.g. U-net with ∼1900 K parameters, DC = 0.78 ± 0.03). Subsequently, we added an active contour layer to the ground truth images to further increase the performance (DC = 0.81±0.02). Secondly, to discriminate lymphocytes from the set of all segmented nuclei, we explored multilayer perception and achieved a 0.70 classification f-score. Remarkably, the binary classification of segmented nuclei was significantly improved (f-score = 0.80) by colour normalization. To inspect model generalization, we have evaluated trained models on a public dataset that was not put to use during training. We conclude that the proposed workflow achieved promising results and, with little effort, can be employed in multi-class nuclei segmentation and identification tasks

Tumor collagen framework from bright-field histology images predicts overall survival of breast carcinoma patients

Within the tumor microenvironment, specifically aligned collagen has been shown to stimulate tumor progression by directing the migration of metastatic cells along its structural framework. Tumor-associated collagen signatures (TACS) have been linked to breast cancer patient outcome. Robust and affordable methods for assessing biological information contained in collagen architecture need to be developed. We have developed a novel artificial neural network (ANN) based approach for tumor collagen segmentation from bright-field histology images and have tested it on a set of tissue microarray sections from early hormone receptor-positive invasive ductal breast carcinoma stained with Sirius Red (1 core per patient, n = 92). We designed and trained ANNs on sets of differently annotated image patches to segment collagen fibers and extracted 37 features of collagen fiber morphometry, density, orientation, texture, and fractal characteristics in the entire cohort. Independent instances of ANN models trained on highly differing annotations produced reasonably concordant collagen segmentation masks and allowed reliable prognostic Cox regression models (with likelihood ratios 14.11-22.99, at p-value < 0.05) superior to conventional clinical parameters (size of the primary tumor (T), regional lymph node status (N), histological grade (G), and patient age). Additionally, we noted statistically significant differences of collagen features between tumor grade groups, and the factor analysis revealed features resembling the TACS concept. Our proposed method offers collagen framework segmentation from bright-field histology images and provides novel image-based features for better breast cancer patient prognostication

Nitrate removal in woodchip denitrification bioreactor – an approach combining mathematical modelling and PI control

A mathematical model of nitrate removal in woodchip denitrification bioreactor based on field experiment measurements was developed in this study. The approach of solving inverse problem for nonlinear system of differential convection-reaction equations was applied to optimize the efficiency of nitrate removal depending on bioreactor’s length and flow rate. The approach was realized through the developed algorithm containing a nonlocal condition with an incorporated PI controller. This allowed to adjust flow rate for varying inflow nitrate concentrations by using PI controller. The proposed model can serve as a useful tool for bioreactor design. The main outcome of the model is a mathematical relationship intended for bioreactor length selection when nitrate concentration at the inlet and the flow rate are known. Custom software was developed to solve the system of differential equations aiming to ensure the required nitrate removal efficiency

Associations between physical function, bone density, muscle mass and muscle morphology in older men with sarcopenia: a pilot study

Background and Objectives: It is thought that muscle and bone interact only on a biomechanical level, however, some research is now emerging that links bone and muscle on a cellular level. The aim of this study was to explore associations between physical function, muscle mass and bone density in community-dwelling elderly men with sarcopenia. A secondary goal was to analyze if muscle morphology was associated with bone density and physical functioning. Materials and Methods: Body composition was measured by dual-energy X-ray absorptiometry (DXA). Bone density was evaluated according to WHO criteria. Sarcopenia was diagnosed according to European Working Group on Sarcopenia in Older People (EWGSOP) criteria: low muscle mass and low muscle strength or low physical performance. Microbiopsy of musculus vastus lateralis was performed with a disposable muscle microbiopsy system. The perimeter and cross-sectional area of muscle fibers were calculated using image analysis software in whole slide images; type of fibers and their distribution were evaluated as well. Results: A total of 151 men, 60 years or older were included in this study. Mean age of the subjects was 72.9 ± 8.02 years. Sarcopenia was diagnosed in 45 (29.8%) men. Multiple significant correlations were found between bone mineral density, lean mass, appendicular lean mass, arm and leg lean mass, gait speed, balance test and handgrip strength in sarcopenic men. Lean mass was associated with femoral neck BMD (bone mineral density; r = 0.418, p = 0.006) and handgrip strength (r = 0.553, p < 0.001). In the sarcopenia group, 25 muscle biopsies were examined. In 9 sarcopenic men with T-scores equal or below −2.5, the muscle fiber area had a significant correlation with the balance test (r = 0.73, p = 0.025). Conclusions: In men with sarcopenia, low lean muscle mass was associated with low femoral neck BMD and low muscle strength. In sarcopenic men with osteoporosis, low muscle fiber area was associated with low scores in a balance test

Frequent Methylation of RASSF1 and RARB in Urine Sediments From Patients with Early Stage Prostate Cancer

Background. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. Material and Methods. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. Results. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). Conclusions. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa