Clear cell renal cell carcinoma (ccRCC), the most common histologic subtype of RCCs, demonstrates a wide spectrum of morphologic features (i.e., low-grade spindle cell, syncytial giant cells, and mucin-producing cells). However, papillary growth pattern in ccRCCs is rather a rare finding, which can present challenges in differential diagnostic work up. The aim of this study was to investigate ccRCCs with predominant papillary features from morphologic, immunohistochemical and molecular genetic perspectives. 23 clear cell renal cell carcinomas with papillary architecture were selected. Tumors were evaluated morphologically, immunohistochemically, and molecularly by next-generation sequencing (NGS). The diagnosis of MiT family translocation RCC was excluded by TFE3 immunohistochemistry. Mean age of patients was 65.2 years (range 42-81 years), and 19/23 were male. Tumor size ranged from 1.6 to 12.8 cm (median 6.5 cm). At a median follow-up of 2.5 years (range 1.5-9 years), 2 patients (8.7%) died of disease, 2 developed metastasis. Areas of papillary pattern accounted for approximately 40-100% of the tumor. CK7 was negative in non-papillary areas in majority of cases (20/23, 87%), and was only focally positive in 3/23 cases (13%). In papillary areas, AMACR was positive/focally positive in 17/23 (73.9%) cases and in the non-papillary areas it was positive/focally positive in 22/23 (95.6%) cases. CAIX was mainly negative in both non-papillary and papillary areas (15/23 [65%] and 16/23 [69.5%], respectively). Molecular analysis of 15 analyzable cases revealed the most frequently mutated gene to be VHL (in 9 cases), followed by PRBM1 (in 2 cases) and 29 other different mutations in various genes. Papillary growth pattern in ccRCC is not an uncommon situation. Papillary RCC with clear cells and MiT family (TFE3) translocation RCCs are the major differential diagnostic considerations in such scenarios. Our NGS molecular analysis supported classifying such tumors as a morphologic variant of ccRCC.
Neuroendocrine breast cancer (NEBC) is a group of rare tumors, which could benefit from therapy targeting the somatostatin receptors (SSTRs). In particular, SSTR2A and SSTR5 are potential targets given their consistent expression in gastrointestinal and pancreatic primary and metastatic neuroendocrine cancers. Currently, there are no studies describing the expression of SSTRs in NEBC. The purpose of our study was to characterize the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of NEBC. Thirty-one primary NEBC cases were analyzed, and SSTR2A and SSTR5 immunohistochemistry performed and scored using the modified immunoreactive score proposed by Remmele and Stanger. All patients were females with a mean age of 66.6 years (SD = 14). 77% of cases were histological grade 2. SSTR2A showed a weak positivity in 11 cases (35.5%), moderate positivity in 6 cases (19.4%) and strong positivity in 5 cases (16.1%). Nine cases were negative for SSTR2A (29%). SSTR5 showed a weak positivity in 16 cases (51.6%), moderate positivity in 6 cases (19.4%), while no cases showed strong positivity. Nine cases were negative for SSTR5 (29%). Five cases were negative for both SSTR2A and SSTR5. A weak to moderate SSTR2A and SSTR5 expression was observed in 50-70% of the cases. A subset of NEBCs with strong SSR2A expression may benefit from SSTRs targeted therapy. These results need further validation in a larger series including metastatic NEBC, to provide potential therapeutic targets for patients with advanced disease.
Dr. Milan Emil Amrus (1848-1919), was Austro-Hungarian physician and politician who lived and work in Sarajevo and Zagreb. Grammar school he finished in Slavonski Brod and Gymnasium in Zagreb (1-3).
On the October 31st, 2018 passed away Amela Kulenovic, full professor of Faculty of medicine of University of Sarajevo. Professor Amela Kulenovic was born in Sarajevo in 1956. She finished Grammar school and Gymnasium in Sarajevo. She graduated at the Faculty of medicine of University of Sarajevo in the 1980. During a period from 1978 to 1981, she worked as demonstrator at Cathedra of Anatomy of the Faculty of medicine at Sarajevo University. Since 1981 until 1982, she worked as associate assistant at the same Cathedra.
Medical Archives is the oldest biomedical journal in Bosnia and Herzegovina, and all important individuals of medical clinical practice have been published in the Medical Archives, and even today, in index and citation databases: Medline, PubMed, PubMed Central, Scopus, open access variants, is the main advertiser of medical sciences in Bosnia and Herzegovina. Medical Archives in the future would like to become a free-of-charge journal, which will publish open access articles, because finally, the financial component should be a deciding factor whether the article will be published or not. The journal opened the door to PhD students, which should also be an incentive for further progress. The main goal of the journal is to continuously raise the quality, with the addition of establishment as a source of quality science.
The blind additive white Gaussian noise level estimation is an important and a challenging area of digital image processing with numerous applications including image denoising and image segmentation. In this paper, a novel block-based noise level estimation algorithm is proposed. The algorithm relies on the artificial neural network to perform a complex image patch analysis in the singular value decomposition (SVD) domain and to evaluate noise level estimates. The algorithm exhibits the capacity to adjust the effective singular value tail length with respect to the observed noise levels. The results of comparative analysis show that the proposed ANN-based algorithm outperforms the alternative single stage block-based noise level estimating algorithm in the SVD domain in terms of mean square error (MSE) and average error for all considered choices of block size. The most significant improvements in MSE levels are obtained at low noise levels. For some test images, such as “Car” and “Girlface”, at σ = 1 , these improvements can be as high as 99% and 98.5%, respectively. In addition, the proposed algorithm eliminates the error-prone manual parameter fine-tuning and automates the entire noise level estimation process.
Aim To investigate a correlation between resistive index (RI) level changes following extracorporeal shock wave lithotripsy (ESWL) in treated and non-treated kidneys depending on the ESWL treatment intensity. The study was conducted on 60 subjects, which were divided in two groups according to age and treatment protocol. Results In the group of patients younger than 55 years of age there was a significant increase in mean RI values, on the first (p=0.001) and second day after the treatment (p=0.007). In the group older than 55 years of age, the resulting increase in mean RI levels was also significant on the first (p=0.003) and second (p=0.011) day following the treatment. The RI values in the non-treated kidney on the first day after the treatment grew significantly (p=0.033). In the group older than 55, RI values in the non-treated kidney grew significantly on the first day after the treatment (p=0.044). In the group who received 2000 SWs, RI levels grew significantly (p=0.044) as well as in the group who received 4000 SWs during the treatment, where the significance was more pronounced (p=0.007). Conclusion There is a correlation between RI changes and the degree and localization of changes in vascular elements of the kidney. Post-ESWL treatment changes are existent and reversible, over a period of one week after the treatment.
Introduction: Violence at work has become an alarming problem worldwide. The real size of the problem is unknown because of underreporting. The aim of the survey was to estimate the prevalence of workplace violence (WPV) among primary health care professionals in the Public Institution Health Center of Sarajevo Canton (HCSC), Bosnia and Herzegovina, and determine possible association with demographic and work-related characteristics of participants. Aim: The aim of the survey was to estimate the prevalence of workplace violence (WPV) among Primary health care professionals in the Public Institution Health Center of Sarajevo Canton (HCSC), Bosnia and Herzegovina, and determine possible association with demographic and work-related characteristics of participants. Methods: A cross-sectional study was conducted between March and May 2017. The sample consisted of medical professionals employed at HCSC. The data were collected by a questionnaire with 42 questions divided into 7 blocks of topic. Descriptive statistics were used to describe the sample. Binary logistic regression analysis was used to test the association between the occurrence of violence and independent variables (gender, age, years of work experience and office setting). Results: A total of 558 out of 983 health professionals employed in Primary health care were involved in this survey. The overall prevalence of WPV was 90.3%, with 498 (89.2%) exposed to verbal violence and 417 (74.7%) exposed to indirect physical violence. Binary logistic regression analysis indicated that the following demographic and work-related characteristics were positively significantly associated with WPV: women were associated with verbal violence [Odd ratio (OR) 1.91, 95% confidence interval (CI) 1.06, 1.47] and stalking [OR= 2.06, 95% CI (1.04, 4.08)]. Office setting (urban) was significantly positively associated with indirect physical violence [OR= 1.59, 95% CI (1.03, 2.47)]. Conclusion: Almost all health professionals in Sarajevo primary health care were subjected to different types of WPV. There is a need for intervention to provide safer workplace environment. Professional, administrative, legal support and protection of health professionals by the health authorities and institution management is urgently required.
Pilot contamination due to pilot reuse in adjacent cells is a very serious problem in massive multi-input multiple-output (MIMO) systems. Therefore, proper pilot allocation is essential for improving system performance. In this paper, we formulate the pilot allocation optimization problem so as to maximize uplink sum rate of the system. To reduce the required complexity inherent in finding the optimum pilot allocation, we propose a low-complexity pilot allocation algorithm, where the formulated problem is decoupled into multiple subproblems; in each subproblem, the pilot allocation at a given cell is optimized while the pilot allocation in other cells id held fixed. This process is continued until the achievable sum rate converges. Through multiple iterations, the optimum pilot allocation is found. In addition, to improve users’ fairness, we formulate fairness-aware pilot allocation as maximization problem of sum of user’s logarithmic rate and solve the formulated problem using a similar algorithm. Simulation results show that the proposed algorithms match the good performance of the exhaustive search algorithm, meanwhile the users’ fairness is improved. key words: pilot contamination, massive MIMO, pilot allocation
Introduction: The Femoral angle of anteversion (FAA) is responsible for the medial and anterior direction of the femoral neck and therefore the femoral head towards the acetabulum. The aim of this study was to determine the difference in FAA between male and female samples, the correlation between the FAA and biomechanically relevant parameters and to provide a review of relevant clinical features related to FAA. Methods: We included 100 human dry femora and analyzed FAA, Angle of Inclination (AI), Femoral Head Diameter (FHD), Femoral Biomechanical Length (FBL) and Linear Condylar Parameters (Epicondylar Breadth Width (EBW), Lateral Condyle Depth and Medial Condyle Depth). The measurements were made using a goniometer, sliding calipers and pieces of colored string. Results: Mean FAA values were 9.84±7.97° and 8.72±8.23° for the male and female samples, respectively (p<0.05). FAA and AI in both male and female correlated negatively (-0.076), while there was a positive correlation between FAA and FHD (0.069), FAA and FBL (0.072), FAA and EBW (0.029), while the correlation was negative between FAA and LCD (-0.072), FAA and MCD (-0.063). Conclusion: The difference in FAA between male and female femora was found to be significant. This finding may help better understanding such as hip impingement, total hip arthroplasty failure, and design of femoral endoprosthesis parts.
Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ’ and clinicians’ unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union’s Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ’ preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.
The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). While small-molecule JAK inhibitors (Jakinibs) are currently under investigation for SLE, results of recent studies suggest, that the efficacy of drugs such as methotrexate (MTX) may also be due to their ability to suppress phosphorylation of STAT proteins. A previously identified STAT5 phosphorylation (pSTAT5) and STAT1 protein expression »signature« in circulating CD4+ T cells of patients with SLE was associated with perturbed homeostasis between conventional (Tcon) and activated regulatory (aTreg) subset and with time-adjusted cumulative disease activity during follow-up. Initial observations in SLE patient cohort were validated with additional markers of disease severity and patients were stratified according to medication status. Preliminary results show that lower CD4+ T-cell counts in patients with SLE are associated with higher pSTAT5 levels and Tcon homeostatic proliferation, which was previously found to drive lymphopenia associated autoimmunity. Relapsing disease was better predicted by pSTAT5 levels than CD4 counts. Further, significant correlation was found between mean pSTAT5 levels during follow- up and the markers of disease severity. As patients with SLE, also patients with rheumatoid arthritis (RA) not receiving methotrexate, had significantly higher increase in CD4+ T-cell pSTAT5 levels compared to patients not receiving this specific therapy. However, the difference in pSTAT5 between Tcon and aTreg was independent of treatment with MTX and significantly increased only in patients with SLE. CD4 depletion, driving homeostatic proliferation of Tcon subset, is therefore associated with higher pSTAT5 levels, which confer worse prognosis in patients with SLE. While treatment with MTX may decrease overall pSTAT5 levels in CD4+ T-cells also from patients with RA, increased pSTAT5 levels in Tcon relative to aTreg subset are specific for SLE.
The term ‘undifferentiated connective tissue disease’ (UCTD) is generally used to describe clinical entities characterised by clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for defined connective tissue diseases (CTDs). In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the ERN ReCONNET project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. No specific CPG on UCTD were found, potential areas of intervention are absence of a consensus definition of UCTD, need for specific monitoring and therapeutic protocols, stratification of UCTD based on the risk of developing a defined CTD and preventive measure for the future development of a more severe condition. Patients feel uncertainty regarding the name of the disease and feel the need of a better education and understanding of these conditions and its possible changes over time.
Aim To identify rates of most common pre-analytical errors and to document possible (different) error rates between inpatients and outpatients. Methods This retrospective study was conducted at the Department of Medical Biochemistry and Immunology Diagnostics, Cantonal Hospital Zenica, from December 2016 until March 2017. Data on rejected blood samples in the laboratory information system were analysed. Results During the 3-month period 35,343 patient blood samples (25,545 inpatients and 9,798 outpatients) were received in the laboratory. The study identified 602 (1.70%) rejected samples because of pre-analytical errors, mostly due to haemolysis, 292 (48.50%), and clotted samples, 240 (39.87%). The remaining 70 (11.63%) samples were rejected because of inappropriate sample volume, inappropriate container and identification errors (7.81%, 2.16% and 1.66%, respectively). The proportion of inpatient rejected samples was 8.7-fold higher than in the outpatient samples. The proportion of inpatient rejected samples because of haemolysis, clotted samples, inappropriate sample volume and inappropriate containers were higher than in the outpatient samples (20.5-, 12.1-, 2.3- and 1.3-fold higher, respectively); proportion of rejected samples because of identification errors was 8.0-fold higher in the outpatient (collection sites outside the hospital) than in the inpatient samples. Conclusion Higher pre-analytical sample error rates were connected with inpatient samples, while higher identification error rates were connected with outpatient samples. Establishment of periodic stuff training and introduction of information technology could reduce pre-analytical errors.
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