Search

Eka Burkadze,1 Ketevan Axobadze,1 Nino Chkhaberidze,1 Nino Chikhladze,1 Madalina Adina Coman,2 Diana Dulf,2 Corinne Peek-Asa3 1Department of Public Health, Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi, Georgia; 2Department of Public Health, College of Political, Administrative and Communication Sciences, Babes-Bolyai University, Cluj-Napoca, Romania; 3Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, USACorrespondence: Eka BurkadzeDepartment of Public Health, Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, 1 Chavchavadze Ave, Tbilisi, 0179, GeorgiaTel +995 591 11 80 90Email eka.burkadze@tsu.gePurpose: Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality worldwide, disproportionally affecting low- and middle-income countries (LMICs). Epidemiological characteristics of TBI at a national level are absent for most LMICs including Georgia. This study aimed to establish the registries and assess causes and outcomes in TBI patients presenting to two major trauma hospitals in the capital city –Tbilisi.Patients and Methods: The prospective observational study was conducted at Acad. O. Gudushauri National Medical Center and M. Iashvili Children’s Central Hospital from March, 1 through August, 31, 2019. Patients of all age groups admitted to one of the study hospitals with a TBI diagnosis were eligible for participation. Collected data were uploaded using the electronic data collection tool –REDCap, analyzed through SPSS software and evaluated to provide detailed information on TBI-related variables and outcomes using descriptive statistics.Results: Overall, 542 hospitalized patients were enrolled during the study period, about 63% were male and the average age was 17.7. The main causes of TBI were falls (58%) and struck by or against an object (22%). The 97% suffered from mild TBI (GCS 13– 15). Over 23% of patients arrived at the hospital more than 1 hour after injury and 25% after more than 4-hours post-injury. Moderate and severe TBI were associated with an increased hospital length of stay. Mortality rate of severe TBI was 54%.Conclusion: This study provides important information on the major epidemiological characteristics of TBI in Georgia, which should be considered for setting priorities for injury management.Keywords: traumatic brain injury, injury epidemiology, registry, Georgia

Fountoulakis K.N., Karakatsoulis G.N., Abraham S., Adorjan K., Ahmed H.U., Alarcón R.D., Arai K., Auwal S.S., Berk M., Bjedov S., Bobes J., Bobes-Bascaran T., Bourgin-Duchesnay J., Bredicean C.A., Bukelskis L., Burkadze A., Abud I.I.C., Castilla-Puentes R., Cetkovich M., Colon-Rivera H., Corral R., Cortez-Vergara C., Crepin P., De Berardis D., Delgado S.Z., De Lucena D., De Sousa A., Stefano R.D., Dodd S., Elek L.P., Elissa A., Erdelyi-Hamza B., Erzin G., Etchevers M.J., Falkai P., Farcas A., Fedotov I., Filatova V., Fountoulakis N.K., Frankova I., Franza F., Frias P., Galako T., Garay C.J., Garcia-Álvarez L., García-Portilla M.P., Gonda X., Gondek T.M., González D.M., Gould H., Grandinetti P., Grau A., Groudeva V., Hagin M., Harada T., Hasan T.M., Hashim N.A., Hilbig J., Hossain S., Iakimova R., Ibrahim M., Iftene F., Ignatenko Y., Irarrazaval M., Ismail Z., Ismayilova J., Jacobs A., Jakovljević M., Jakšić N., Javed A., Kafali H.Y., Karia S., Kazakova O., Khalifa D., Khaustova O., Koh S., Kopishinskaia S., Kosenko K., Koupidis S.A., Kovacs I., Kulig B., Lalljee A., Liewig J., Majid A., Malashonkova E., Malik K., Malik N.I., Mammadzada G., Mandalia B., Marazziti D., Marčinko D., Martinez S., Matiekus E., Mejia G., Memon R.S., Martínez X.E.M., Mickevičiūtė D., Milev R., Mohammed M., Molina-López A., Morozov P., Muhammad N.S., Mustač F., Naor M.S., Nassieb A., Navickas A., Okasha T., Pandova M., Panfil A.-L., Panteleeva L., Papava I., Patsali M.E., Pavlichenko A., Pejuskovic B., Da Costa M.P., Popkov M., Popovic D., Raduan N.J.N., Ramírez F.V., Rancans E., Razali S., Rebok F., Rewekant A., Flores E.N.R., Rivera-Encinas M.T., Saiz P., de Carmona M.S., Martínez D.S., Saw J.A., Saygili G., Schneidereit P., Shah B., Shirasaka T., Silagadze K., Sitanggang S., Skugarevsky O., Spikina A., Mahalingappa S.S., Stoyanova M., Szczegielniak A., Tamasan S.C., Tavormina G., Tavormina M.G.M., Theodorakis P.N., Tohen M., Tsapakis E.M., Tukhvatullina D., Ullah I., Vaidya R., Vega-Dienstmaier J.M., Vrublevska J., Vukovic O., Vysotska O., Widiasih N., Yashikhina A., Prezerakos P.E., Smirnova D.

The study included 55 cases of formalin-fixed and paraffin-embedded (FFPE) tissues of breast invasive ductal carcinoma. The following algorithm has been made for further discussion by using immunohistochemical examination: antibodies against hormonal receptors; HER2; E-cadherin, Vimentin, Beta-catenin; Ki-67; Tumour buds were evaluated by using H&E stained slides and computer software Qupath (version 0.3.2). The results of the study show that estrogen expression is different in primary tumour mass and in tumour buds and its expression is diminished in the Luminal B molecular subtype respectively. Vimentin and Beta-catenin expression is showing similar changes, the quantity is much higher in tumour microclusters compared to the primary tumour and metastatic lymph nodes. It can demonstrate features of epithelial-mesenchymal transformation. Modifications in dynamics of proliferative activity are showing the lowest proliferative activity in tumour microclusters which can be discussed as the indirect manifestation of epithelial-mesenchymal transformation.

In the study of cement-enamel junction (CEJ), as an anatomical and clinical unit, its location and evaluation play a crucial role in identifying various pathologic lesions and for their optimal treatment. Dental caries is the most common lesion of teeth, which develops in hard dental tissues. In the development of caries and non-carious lesions, the anatomical border of the cement-enamel adhesion is extremely important and shows distinct diversity. The profile of the anatomical border of the cement-enamel adhesion and its variation in the same and different teeth distinguishes predisposition to external cervical resorption (ECR). The manufacture of adhesion systems is oriented to modify such chemically functional monomers which will improve the quality of adhesion composites and enable much stronger and prolonged performance. Which itself will show much harmonic compatibility to dental strong tissues and is of utmost importance in the treatment of cervical defects.

Endometrial Carcinoma is the most common gynaecological malignancy in the female population and is considered as incidentally the second gynaecological malignancy worldwide. Based on 2018 data more than 380 000 new cases were diagnosed worldwide and almost 90 000 of them had a lethal outcome. Interaction between cancer cells and their microenvironment regulates cancer progression in multiple types of cancer. It has great value in developing endometrial cancer and its progression respectively. There is no sufficient research data about the consequences and mechanisms which are participating in endometrial cancer progression and what determines its aggressive behaviour. Molecular signals derived from stromal cells and/or extracellular matrix plays a crucial role in malignancy. The cancer microenvironment is composed of cellular components and noncellular components (extracellular matrix)as well. Cancer cell invasion and metastasizing are some of the leading reasons why endometrial cancer is hardly sensitive to the treatment and has worse overall prognoses. Identification of Signaling pathways of the local microenvironment and peptides synthesized by stromal cells has a critical role in the modification of potentially significant biomarkers for endometrial cancer metastases and high-grade malignancy. In consideration of all of the mentioned microenvironment of endometrial cancer and its single components needs deeper examination while it has a critical value in understanding cancer aetiology, progression and its prognoses.

The etiology and pathogenesis of ovarian serous carcinomas as well as prognoses and clinical management are still under vigorous research. The data provided by many studies support the idea that ovarian serous carcinomas are mainly influenced by the changes occurring in the fallopian tube epithelium. This theory is supported by molecular lesions present in high-grade ovarian cancers and fallopian tube neoplasms. This topic needs some additional studies using pathogenetic characteristics like proliferative and apoptotic changes, which will further support and even may take it under suspicious the theory that ovarian carcinomas are originating from the fallopian tube. It is also crucial to study hormonal expressions while there is a lot of information that steroid hormones have a huge role in the pathogenesis of ovarian carcinomas but there is almost very little data on how these influences are related to the fallopian tube neoplasms. A deeper understanding of ovarian tumours and their etiological pathways are important to prevent and determine prognoses, which will enable better therapeutic methods. It has utmost importance to study additional characteristics like stem cell distribution in the fallopian tube epithelium and in ovarian neoplasms. The cancer heterogeneity need also further discussion regarding ovarian cancer novel classifications. This will finally aid the modification of better-personalized treatment.

The tumour is characterised by the presence of various amounts of lymphocytic infiltration, which is seen in different areas of cancer and has not only prognostic value the predictive value as well. Tumour-infiltrating lymphocytes (TILs) in ovarian cancer can be associated either with good prognoses or bad prognoses in some cases. The constituent which makes the tumour immune microenvironment is still under vigorous research while they may have the potential to be well modified predictive and prognostic values in ovarian cancer. The data provided by already conducted research are controversial which suggests the need for further deeper studies. Besides this fact, there is no clear determination which histological subtype of ovarian cancer is under research or in many cases all of the morphological types are united. All of these facts mentioned can clarify why the results of many pieces of research provide controversial information. It is crucial that the immune microenvironment of various morphological subtypes of ovarian carcinomas be studied separately and individually.

Endometrial Metaplasia is the process in which normal endometrioid glands are undergoing replacement by other types of benign epithelium. Endometrium can show us a diversity of metaplastic changes. Modified differentiation of Endometrial cells can be due to the presence of degenerative/reparative, hormonal or neoplastic processes. The presence of Epithelial Metaplasia can signify other concomitants benign and malignant processes. Endometrial metaplasia can be either a single process or present with other histopathological changes. There are different types of endometrial metaplasia but the most common is tubal metaplasia. The second most common can be squamous metaplasia, transitional cell metaplasia, arias-Stella reaction/changes, cellular eosinophilic changes and mucinous metaplasia. different types of metaplasia can show us the various type and intensities of expression for P16, Cyclin E, Cyclin A, Ki67, B catenin, ER, CDX2, CD10, P63. The role and importance of distinct types of endometrial metaplasia in the relapse of cancer and neoplastic progression are still unknown. There is the clinical opinion that behind every single metaplastic process there is stem cell reprogramming but the phenomenon of endometrial metaplasia needs more thorough studies.

The microbiome plays a crucial role in controlling viral infections like the Human Papillomavirus. Getting infected by HPV is not always necessary or not sufficient for the progression of cervical cancer. According to many kinds of research, it was shown that the presence of Human papillomavirus infection is not always connected to the abundance of Lactobacilli and L. gasseri. Besides that some research data suggests an association of cervicovaginal microbiome to viral infections, there are very few things clear about the exact role of the microbiome in carcinogeneses and also about mechanisms and consequences, which are responsible for the HVP persistence and elimination. Recently there are invoked some theoretical models about the Virus-Bacteria-host organism interaction and virus-associated neoplasms are classified into five major types. The characteristics, features and variability of how the cervical epithelial cells maintain to discover various types of pathogen configuration receptors are still under research such as pathogen configuration detection receptors toll-like receptor family (TLR), Retinoic acid-inducible gene 1 (RIG-1) and Nod-like receptor family (NOD). There is a lot more to study thoroughly about how all of these receptors are functioning in virus inducible lesions and what kinds of influences do they have on virus persistence and neoplastic progression

Oesophageal adenocarcinoma represents the 6th common cause of cancer related deaths. Frequently oesophageal adenocarcinomas are developed from Barret’s oesophagus, which represents the metaplastic lesion of the lower third of the oesophagus, when squamous epithelium is replaced by glandular epithelium. It has been shown, that Barret’s metaplasia bears the risk of progression into dysplasia and later into malignant disease. However, this risk is different in different patients. Nowadays, there are many ongoing studies investigating the molecular markers of the progression of Barret’s oesophagus, which on the other hand represents an important information for the proper clinical management of this lesion. We discuss the potential markers of Barret’s oesophagus progression and related problematic issues in presented critical review.

Conjunctival epithelial lesions vary from benign to borderline malignancy to malignant, therefore it is extremely important to detect the molecular markers of the malignant progression of conjunctival intraepithelial lesions. The aim of our study was to analyse the molecular markers of the progression of conjunctival intraepithelial lesions. We have analysed Ki67, PHH3, Bcl2, P53, P63 and CK7 using standard immunohistochemistry. In addition, we have calculated the squamous-glandular index based on the evaluation of HE stained specimens and as the ratio of P63/CK7. The results of our study indicated that the presence of squamous epithelium is significantly increased during the progression of conjunctival intraepithelial lesions, and therefore the squamous-glandular index is also increased. In addition, it is possible to divide conjunctival intraepithelial lesions as low grade and high grade lesions based on the distribution of proliferation and apoptosis markers.

Metaplasia represents the replacement of one differentiated cell type with another differentiated cell type, which is frequently seen in uterine cervix, particularly in endocervical epithelium. There are many different types of metaplasia in endocervix. It is suggested that metaplasia represents the fertile soil for the development of neoplasia. However, which cases of metaplasia transform into neoplasia, which type of metaplasia is more realted to neoplastic transformation or if there are some molecular markers which can predict the potential of neoplastic transformation, are nowadays less known. Current review represents the critical discussion of the available literature with regards to the evaluation of molecular markers and the potential of neoplastic transformation in cervical metaplasia.

Endometrial carcinoma represents the most common gynaecologic malignancy, which frequently arises from malignant progression of endometrial intraepithelial neoplasia (EIN). Nowadays, there are no defined prognostic markers for the prognosis of the malignant progression of EIN and it still represents the subject of various investigations. Different studies indicate, that sex hormone receptors, DNA damage and apoptosis proteins, as well as epithelial-mesenchymal transformation markers play an important role in the progression of EIN. However, most of the published studies are full of contradictory results, which indicates that additional studies are necessary. In current review, we will discuss the current knowledge about the mentioned markers in terms of the prognosis of EIN.

Ovarian germ-cell tumors represent about 15-20% of all ovarian tumors. They are characterised with high histological and clinical heterogeneity. Ovarian germ-cell tumors can be both benign and malignant. Nowadays, the prognostic markers of ovarian germ-cell tumors are less studied. In particular, there is only limited information about the phenotypic determinants of the malignant transformation of benign germ-cell tumors, as well as lack of information about the relapse development after treatment of malignant germ-cell tumors. In presented review article, the detailed cahracteristics of ovarian germ-cell tumors and the problematic issues in the determination of their prognostic features are discussed.

Urothelial carcinoma represents the most common type of bladder cancer (90%) and is the most frequent malignancy of the urinary tract. Most of the urothelial carcinomas are non-invasive at the time of diagnosis, however they are characterised with the risk of recurrence after surgical treatment. The aim of our study was to investigate the characteristics of tumor heterogeneity and markers of its progression in urothelial papillary carcinomas. Study included following groups: normal urothelial epithelium, urothelial papilloma, urothelial neoplasms with low malignant potential (PUNLM), non-invasive low grade papillary urothelial carcinomas (LGPUC) and non-invasive high grade papillary urothelial carcinomas (HGPUC). In addition, study included relapsed cases of non-invasive LGPUC and HGPUC. Nuclear features and mitotic counts was assessed using digital pathology software QuPath in standard HE stained specimens. In addition, the presence of mitosis was detected as PHH3 labelled cells by immunohistochemistry. Proliferation was measured as Ki67 labelling index by immunohistochemistry. Tumor heterogeneity was investigated by the differential expression pattern of CK5, CK7 and CK20 by immunohistochemistry. Study results showed, that Nuclear features, as well as the number of mitosis, proliferation index and intratumoral heterogeneity significantly correlate with the presence of higher grade non-invasive urothelial lesions. In addition, it is possible to distinguish two major groups of non-invasive LGPUC and HGPUC, based on nuclear and phenotypic heterogeneity and mitotic and proliferative activity, I group which is characterised with higher intratumoral heterogeneity, higher mitotic count and higher proliferative activity, represents the high risk group of non-invasive LGPUC and HGPUC recurrence.

Different studies indicate that tumor infiltrating lymphocytes (TILs) and tumor associated neutrophils (TANs) play an important role during the progression of malignant tumors. We have analysed the distribution of tumor associated neutrophils (TANs) and tumor infiltrating lymphocytes (TILs) in different conjunctival lesions, with different proliferation and apoptotic characteristics. The distribution of TILs and TANs were evaluated in standard haematoxylin and eosin (HE) stained sections using the digital pathology software QuPathin normal conjunctiva, actinic keratosis, pterigea, conjunctival intraepithelial neoplasias (CoIN1-3) and conjunctival squamous cell carcinoma (CSCC). In addition, the expression of following markers were investigated using standard immunohistochemistry: Ki67, Bcl2, p53, CD3, CD8 and Foxp3. The study results indicated that the number of TILs and TANs are significantly increased during the progression of conjunctival intraepithelial lesions. Also, the number of TILs and TANs significantly correlate with higher proliferation index, lower apoptotic index and the p53 mutation status.

Nowadays, adenomyosis represents one of the most common pathology of female genital system. It occurs at different ages, including nulliparous, infertile and multiparous women. The etiology of adenomyosis is still under investigation. Despite the fact that there are many different theories, none of them fully explain the mechanisms of adenomyoisis development. The pathogeneis of adenomyosis is also less studied. Many studies indicate the involvement of female sex hormone receptors, cell proliferation and apoptosis, as well as the involvement of inflammation. Some investigators describe the malignant transformation of adenomyosis, which makes the study of the disease etiology and pathogenesis more important. In current review, we discuss the different theories of adenomyosis development, as well as the risk of malignant transformation.

Uterine leiomyomas decrease the quality of life by causing significant morbidity among women of reproductive age. Histologically various types of leiomyoma's can be differentiated. We have analysed the histopathological, proliferation, apoptotic and hormonal profile in different types of leiomyomas. Study included altogether 140 cases distributed into following groups: group I - normal myometrium (20 cases), group II-classic leiomyoma (69 cases), group III-cellular leiomyoma (15 cases), group IV - bizarre cell/atypical leiomyoma (22 cases), group V - smooth muscle tumors of uncertain malignancy potential (STUMP) (8 cases) and group VI - leiomyosarcoma (6 cases). Together with classic histopathological features such as nuclear atypia, cellularity, presence of mitoses, vasculature and necrosis, immunohistochemical phenotype using antibodies against Ki67, Cas3, ER and PR were analysed. The results of our study showed that leiomyomas are characterised with variable histopathological and immunohistochemical phenotype. Especially, two entities, bizzare/atypical leiomyoma and STUMP, which can be divided into two subgroups according to the presence of the degree of atypia and the expression of proliferation, apoptosis and hormonal markers, which might be the explanation of their different prognosis. Presented histopathological and immunohistochemical features should be considered in the diagnosis of myometrial smooth muscle tumors.