ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 64 No. 3, July-September 2023

1. Defining the short-term and long-term skin manifestations of COVID-19: insights after more than three years of the pandemic

Oana Maria Ica, George Mitroi, Simona Laura Ianosi, Cristina Violeta Tutunaru, Polliana Mihaela Leru, Daniela Matei, Elena Taina Avramescu, Cornelia Andreea Tanasie, Iulia Bianca Mitroi, Carmen Daniela Neagoe, Sergiu Marian Cazacu

Aim: This review aimed to assess the impact of coronavirus disease 2019 (COVID-19) on skin health to establish a classification of the skin lesions that occur most frequently during the disease and whether a particular category of skin damage is more likely to occur both in the short term and in the long term. Methods: We conducted a literature search of the PubMed database. Ultimately, 109 articles were included in this review. The exact phrases/syntax and connectors used for the database search/query were as follows: Coronavirus and skin, COVID-19 and skin, SARS-CoV-2 and skin, Coronavirus cutaneous manifestations, COVID-19 cutaneous manifestations, SARS-CoV-2 cutaneous manifestations, Coronavirus dermatology, SARS-CoV-2 and dermatology, COVID-19 and dermatology, COVID-19 and skin eruption, Coronavirus and skin rash, COVID-19 and hair, Coronavirus and hair, Coronavirus and nails, SARS-CoV-2 and hair, and SARS-CoV-2 and nails. Only articles with abstracts referring strictly to cutaneous manifestations of COVID-19 were chosen. Articles without abstracts were not considered. Results: We established six of the most frequently reported clinical patterns associated with COVID-19 and their probability of occurring during COVID-19 disease evolution based on the current literature reports. We did not identify the particular types of skin lesions that are most prone to long-term persistence; most such cases are rare, and no conclusion can be drawn based on them. Conclusions: Apart from classified COVID-19-related skin disorders, this pandemic has been a challenge for dermatologists and a wide range of cutaneous side effects related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) treatments have been reported. We are aware of other polymorphic clinical presentations, with novel data being reported periodically, but the pathophysiological mechanisms and evolution are largely unknown.

Corresponding author: George Mitroi, Associate Professor, MD, PhD; e-mail: gmitroi@yahoo.com; Simona Laura Ianosi, Professor, MD, PhD; e-mail: simonaianosi@hotmail.com

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2. Astrocytes - friends or foes in neurodegenerative disorders

Alexandra Diana Vrapciu, Mugurel Constantin Rusu, Adelina Maria Jianu, Andrei Gheorghe Marius Motoc, Mihnea Ioan Nicolescu

Astrocytes (AS) are the most abundant glial cells in the central nervous system (CNS). They have various morphologies and numerous (50-60) branching prolongations, with roles in the maintenance of the CNS function and homeostasis. AS in the optic nerve head (ONH) have specific distribution and function and are involved in the pathogenesis of glaucoma and other neural diseases, modify their morphologies, location, immune phenotype, and ultrastructure, thus being the key players in the active remodeling processes of the ONH.

Corresponding author: Mugurel Constantin Rusu, Professor, Dr.Med., Dr.Biol., Dr.Hab.; e-mail: mugurel.rusu@umfcd.ro

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3. Tumor angiogenesis in gastric cancer

Alexandru Giubelan, Marius Ionut Stancu, Sorina Octavia Hontaru, Gheorghe Dan Malaescu, Oana Badea-Voiculescu, Camelia Firoiu, Stelian Stefanita Mogoanta

Gastric cancer (GC) is still a major health problem, being one of the leading causes of cancer-related death in the world. Although the overall incidence of GC is decreasing in the United States and Western Europe, it is still high in many countries from Asia, South America, and Eastern Europe. The process of angiogenesis or the formation of new blood vessels plays an important role in cancer progression, as it allows oxygen supply, nutrients, and factors to grow tumor cells. In our study, we found that gastric neoplasms have high vascularity, with anarchic distribution, uneven in tumor stroma, sometimes with congestion vessels and microhemorrhages. Most vessels were capillaries, with a discontinuous endothelium, poorly structured basement membrane, without junctions between endothelial cells, hyperpermeable, creating the possibility of local edema in the tumor microenvironment (TME), and also extravasation of the plasma, leukocytes and even red blood cells. Angiogenesis vessels showed a low number of pericytes, which shows that they are young vessels, both morphologically and functionally immature. Tumor cells can synthesize biochemical factors [vascular endothelial growth factor-A (VEGF-A)] that stimulate the formation of new vessels (angiogenesis) to ensure their growth and metastasis. Some connective cells (tumor-associated mast cells, tumor-associated fibroblasts) are also involved in the angiogenesis process, which stimulate the progression of tumor cells and remodel the TME.

Corresponding author: Marius Ionut Stancu, MD, PhD Student; e-mail: mariusstancu86@yahoo.com; Sorina Octavia Hontaru, Lecturer; e-mail: dr.octavia1969@yahoo.com

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4. Influence of tumor topography on clinical-morphological profile of laryngeal malignancies

Eduard Andrei Gheorghe, Iancu Emil Plesea, Luminita Svetlana Welt, Georgian Halcu, Maria Camelia Foarfa, Iulica Ionita, Carmen Aurelia Mogoanta, Elena Ionita

Aim: Laryngeal cancers are redoubtable because they are still diagnosed in advanced stages which results in poor survival and the decline of life quality. The authors intend to identify if the tumor topography influences clinical behavior, the morphological profile and therapeutic strategy. Patients, Materials and Methods: The study group included 188 patients with laryngeal malignancies diagnosed and treated in an Ear, Nose and Throat (ENT) Department. The patients have been divided into four groups according to the tumor topography and extension. Three categories of parameters were defined (epidemiological, clinical, and morphological) and analyzed comparatively between the four groups using filter scales and the chi-squared correlation test. Results: Epidemiological parameters (sex, age, socio-economic status) showed no significant differences between the four groups. Clinical parameters (symptoms, lymphadenopathies, surgical procedures, and hospitalization) instead registered significant differences between the four groups. Morphological parameters (longitudinal diameter, transverse diameter, shape, gross aspect, histopathological aspect, grade, local invasion - pT, lymph node invasion - pN, metastases - pM and tumor stage), excepting shape, registered too significant differences between the four groups. The analysis of the whole set of parameters in each group revealed different, distinct profiles for each of the topographic groups, especially for glottic and large tumors. Our results concerning the entire series of tumors ranged in the limits of variation of each of the parameters observed in the literature. Conclusions: Our study revealed that tumors placed in different regions of the larynx have distinct profiles from epidemiological, clinical, and morphological points of view. However, the profile of our entire group of tumors proved to be comparable with the literature data.

Corresponding author: Iancu Emil Plesea, Professor, MD, PhD; e-mail: emil.plesea@umfcd.ro

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5. Predictor factors for recurrence in atypical meningiomas

Andrei Ionut Cucu, Claudia Florida Costea, Serban Turliuc, Laurentiu Andrei Blaj, Iulian Prutianu, Gabriela Florenta Dumitrescu, Cristina Gena Dascalu, Ion Poeata, Mihaela Cosman, Ana-Cristina Istrate, Georgiana Macovei, Ligia Gabriela Tataranu

Background and Objectives: Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS). Patients, Materials and Methods: Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors. Results: The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm(3) had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion. Conclusions: AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume >=26.4 cm(3), Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.

Corresponding author: Serban Turliuc, Associate Professor, MD, PhD; e-mail: serban_turliuc@yahoo.com; Georgiana Macovei, Associate Professor, MD, PhD; e-mail: georgiana.macovei@umfiasi.ro

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6. The significance of immune microenvironment in patients with endometriosis

Ioana Pavaleanu, Raluca Anca Balan, Adriana Grigoras, Teodora Ana Balan, Cornelia Amalinei

Endometriosis represents an estrogen-dependent disease of the female reproductive system and intra- and extraperitoneal regions, with chronic feature. Currently, immune cells, such as macrophages and lymphocytes, are considered to play a pivotal role in angiogenesis and invasion of endometriotic cells through matrix remodeling. Additionally, various studies have revealed the role of E-cadherin, beta-catenin, along with steroid hormone receptors in endometriosis development. In this context, our study aimed to analyze the relationship between the cellular immune profile and E-cadherin, beta-catenin, estrogen receptor alpha (ERalpha), and progesterone receptor (PR) immunoexpression in endometriosis tissues, along with an analysis of the possible association between serological parameters and immunohistochemical (IHC) markers. The study included 53 patients diagnosed with ovarian or cutaneous abdominal wall endometriosis, which have been investigated by routine histology, immunohistochemistry, and serum analysis. The IHC exam showed an increased density of cluster of differentiation (CD)4+ T-cells, CD8+ T-cells, and CD68+ macrophages, along with variable increased expressions of E-cadherin, beta-catenin, ERalpha, and PR. Statistical analysis revealed an intense positive correlation between CD68 and PR expression (p<0.05), without any other statistically significant correlations between IHC markers or between IHC and serological markers. Our study supports that endometriosis is an immune-dependent disease characterized by an abnormal morphological profile of T-cells and macrophages in endometriotic implants. Our study provides additional data useful in the understanding the immune milieu of endometriosis in the context of its complex pathogenic molecular mechanism. Further research is needed to develop new immunological therapeutic approaches, like immune checkpoint inhibitors administration or T-cell-targeted immunotherapy in these patients.

Corresponding author: Adriana Grigoras, Associate Professor, MD, PhD; e-mail: adriana.grigoras@umfiasi.ro, a_grigoras6600@yahoo.com, adriana.grigoras@umfiasi.ro; Raluca Anca Balan, Professor, MD, PhD; e-mail: raluca12usa@yahoo.com, raluca.balan@umfiasi.ro

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7. Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1alpha and PDK1 in the hypoxic microenvironment

Burcu Gunaydin, Gurkan Yigitturk, Hulya Elbe

Today, many anticancer drugs are used clinically for ovarian cancer, one of the leading causes of cancer-related deaths in women. Phenformin is an antidiabetic drug of the biguanide class. It improves the antiproliferative activity in cancer cells. Hypoxia is an important component associated with ovarian cancer and its tumor microenvironment. The aim of this study was to investigate the anticancer effects of Phenformin in SKOV-3 human ovarian cancer cells under hypoxic conditions. SKOV-3 human ovarian cancer cells treated with different doses of Phenformin (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours were subjected to WST-1 cell viability assay and Annexin V apoptosis assay. A dose-dependent decrease in cell viability with Phenformin treatment was observed. In addition, Phenformin activated percentage of apoptotic SKOV-3 cancer cells in a dose-dependent manner. In this study, Cobalt(II) chloride (CoCl2) treatment leads to increased hypoxia-inducible factor-1alpha (HIF-1alpha) expression and Phenformin can recover hypoxic condition. HIF-1alpha protein expression was significantly correlated with cell viability assay and apoptosis assay. We also found that Phenformin inhibits expression of phosphoinositide-dependent kinase 1 (PDK1) in SKOV-3 ovarian cancer cells. The ability to migrate to cancer cells was significantly reduced in a dose-dependent manner with Phenformin. This data demonstrates that Phenformin treatment can induce apoptosis and inhibit proliferation in ovarian cancer cells under hypoxic conditions. The findings reveal that HIF-1alpha is a new target for the treatment of ovarian cancer.

Corresponding author: Hulya Elbe, Associate Professor, MD; e-mail: hulya.elbe@mu.edu.tr

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8. Preliminary study of some of the main intratumor stroma components in gastric carcinomas

Mircea Litescu, Augustin Marian Marincas, George Mitroi, Iancu Emil Plesea, Victor Dan Eugen Strambu, Valentin Titus Grigorean, Virgiliu Mihail Prunoiu, Razvan Mihail Plesea, Florentina Gherghiceanu

Aim: The relationship between stromal compartment and tumor behavior in gastric carcinomas is still poorly understood and defined. Therefore, the authors started, with this preliminary study, an analysis of stromal compartment morphology and behavior in tumors arising from gastric mucosa epithelium. Materials and Methods: The study group included 75 patients operated for gastric carcinoma. Five parameters describing tumor morphology and behavior and eight parameters describing tumor stroma (TS) morphology were assessed. Histopathological examination included six serial sections of formalin-fixed, paraffin-embedded tumor tissue samples, stained with three classical stains and three antibodies to reveal the different parameters. For data comparison, Pearson s correlation test and the chi-squared correlation test were used. Results: Studied tumors were, usually, infiltrating, undifferentiated/diffuse type, invasive in subserous spaces and with a Ki67 index higher than 20%. Collagen fibers dominated the stromal components, with a predominance of mature type and an average fibrillary index of 2.7. The whole amount of stromal components accounted for around one quarter of the tumor area. Mature collagen fibers were in opposite correlation with their immature counterpart, and both were in opposite correlation with smooth muscle fibers and expressed an opposite trend of correlation with components of vascular compartment. The whole amount of stromal components had divergent behavior with the components of vascular compartment. The latter expressed generally an opposite trend of correlation with individual fibrillary stromal components. We found only isolated relationships statistically significant between stromal components and tumor characteristics. Conclusions: TS is in a continuous remodeling process in relation to the evolution of tumor parenchyma, tumors less differentiated proving to have an immature stroma, with newly formed collagen fibers and higher vascular density. Further studies are required.

Corresponding author: Augustin Marian Marincas, Lecturer, MD, PhD; e-mail: marian_marincas_11@yahoo.com; George Mitroi, Associate Professor, MD, PhD; e-mail: gmitroi@yahoo.com

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9. A cases series of endovascular and microsurgical combined treatment of intracranial aneurysms

Georgiana Ion, Alexandru Chiriac, Andrei Ionut Cucu, Claudia Florida Costea, Dragos Viorel Scripcariu, Ion Poeata

Objective: Our scientific paper is aimed at describing multimodal treatment of intracranial aneurysms represented by microsurgery and endovascular therapy. Patients, Materials and Methods: We report four cases of intracranial aneurysms treated in our Department of Neurosurgery by microsurgery (clipping) and endovascular treatment (coiling), through the joint efforts of a team of highly skilled neurosurgeons. Results: Mixed treatment has been imposed by the complications we were presented with, resulting from either of the two surgical methods employed. Conclusions: Although endovascular surgery is considered a newer treatment method, favored by many practitioners, and preferred by patients, there are situations where open surgery is still required. There are certain situations were using one of the surgical methods fails and a complementary procedure is required for a secure and successful treatment. The cases reported here will demonstrate the utility of combining the two procedures.

Corresponding author: Andrei Ionut Cucu, MD, PhD; e-mail: andreiucucu@yahoo.com; Claudia Florida Costea, Professor, MD, PhD; e-mail: costea10@yahoo.com

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10. Histopathological lesions induced by stroke in the encephalon

Octavian Paun, Roberta Andreea Cercel, Razvan Ilie Radu, Victor Cornel Raicea, Denisa Floriana Vasilica Pirscoveanu, Sorina Octavia Hontaru, Marian Valentin Zorila, Laurentiu Mogoanta

Strokes are conditions with a high degree of morbidity and mortality worldwide. These conditions profoundly affect the quality of life of patients; in addition to physical disabilities, patients present various mental disorders, such as mood disorders, anxiety, depression, behavioral disorders, fatigue, etc. Microscopic lesions of the brain parenchyma explain the clinical symptoms and correlate with the severity of the stroke. Our study consisted of the histopathological (HP) and immunohistochemical analysis of brain fragments, collected from 23 patients, with a clinical and imagistic diagnosis of stroke, who died during hospital admission. The microscopic analysis showed that both neurons and glial cells are affected in the ischemic focus. Neuronal death in the ischemic focus was mostly caused by cell necrosis and only about 10% by apoptosis. Regarding vascular lesions, it was observed that the most frequent HP lesion of intracerebral arterioles was arteriosclerosis. The lumen of the arterioles was reduced, and the vascular endothelium had a discontinuous aspect, which indicates a change in the blood-brain barrier. Sometimes the arteriole lumen was completely obstructed, with fibrinoid necrosis in the internal and middle tunic, or with the proliferation of fibroblasts and the formation of young intraluminal connective tissue. Intraparenchymal blood capillaries in the ischemic area showed endothelium discontinuities, lumen collapse, and sometimes massive perivascular edema. As for neuroinflammation, the presence of numerous neutrophils, lymphocytes, plasma cells and macrophages was found in the ischemic focus, forming a complex and inhomogeneous cellular mixture. Of the inflammatory cells present in the ischemic focus and in the ischemic penumbra area, the most numerous were the macrophages. The HP analysis showed that neuroinflammation is very complex and different in intensity from one patient to another, most likely due to associated comorbidities, age, treatment administered until death, etc.

Corresponding author: Marian Valentin Zorila, Lecturer, MD, PhD; e-mail: zorilavaly@yahoo.com.au; Sorina Octavia Hontaru, Lecturer; e-mail: dr.octavia1969@yahoo.com

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11. Assessment of the aortic tunica media histological changes in relation with the cause of death

Doru Adrian Seicaru, Mircea Litescu, Florentina Gherghiceanu, Mircea-Sebastian Serbanescu, Valentin Titus Grigorean, Razvan Mihail Plesea

Aim: The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. Materials and Methods: Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 micrometers and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson s correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. Results and Discussions: The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. Conclusions: The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.

Corresponding author: Mircea Litescu, Lecturer, MD, PhD; e-mail: mircealitescu@gmail.com; Florentina Gherghiceanu, Lecturer, MD, PhD; e-mail: mircealitescu@gmail.com

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12. Lung cancer and type 2 diabetes experience in Dolj County (southwest region of Romania) - a clinical, bioclinical and pathological study

Mihai Cosmin Stan, Camil-Ciprian Mirestean, Daniel Stoica, Florina-Carmen Popescu, Florinel Badulescu

Background and Aim: Type 2 diabetes (T2D) and cancer, the most important public health problems nowadays, and the mechanisms between the presence of diabetes and the development of malignancies remain unclear. The leading cause of cancer death in 2020 is attributed to lung cancer. This study aimed to highlight the impact of the association of these two diseases and the predominant histopathological type of lung cancer in the selected group, glycemic imbalance, and information about the course and outlook for these patients. Patients, Materials and Methods: The authors proposed a case-control 10-year period study, between 2007 and 2017, of two groups of patients diagnosed with T2D and lung cancer who underwent hospitalization at the Clinic of Medical Oncology, Emergency County Hospital, Craiova, Romania. Results: Our study showed a higher incidence of lung adenocarcinoma in patients diagnosed with T2D. The inflammatory syndrome is more pronounced in the diabetic group, which is supported by correlations between lactate dehydrogenase (LDH), albumin, and hemoglobin levels. Conclusions: The duration of cancer treatment in lung cancer and the survival rate is strongly influenced by the presence of diabetes as a concomitant disease.

Corresponding author: Mihai Cosmin Stan, MD, PhD Student; e-mail: mihai_csmn@yahoo.com

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13. Associated factors in pediatric patients admitted with severe iron-deficiency anemia in the last seven years - the experience of a single pediatric unit

Cristina Elena Singer, Viorel Biciusca, Jaqueline Abdul-Razzak, Iulian Alin Silviu Popescu, Cristiana Geormaneanu, Maria Madalina Singer, Cristina Maria Marginean, Mihaela Popescu

Objectives: To study the causes of iron deficiency, laboratory findings and clinical manifestation of infants aged 6-12 months and children aged 1-3 years diagnosed with severe iron-deficiency anemia. Patients, Materials and Methods: We conducted an observational, retrospective single tertiary center study between January 2015 and April 2022, which included 142 children. The control group (patients with no diagnosis of severe iron-deficiency anemia) included 71 patients and the study group (patients diagnosed with severe iron-deficiency anemia) included also 71 patients. Clinical data were retrospectively collected from hospital medical records. Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) 25.0 software. Results: Seventy-one children had hemoglobin <7 g/dL and low values of ferritin/serum iron (22 infants aged 6-12 months and 49 children aged 1-3 years). In both the study and control groups, the male gender was slightly more prevalent. Mother s age at birth and living standard is significantly lower in the study group. We note a higher frequency of premature births (14.08%) in children identified with anemia compared to control group (8.45%). We found a statistically significant distribution of cow s milk consumption among the two groups (p<0.001). Pearson s correlation test revealed a significant positive correlation, indicating that anemia is directly proportional to cow s milk consumption. Conclusions: The most frequent cause of iron-deficiency anemia in infants and children 1-3 years old was the consumption of cow s milk following incorrect diversification and incomplete prophylaxis of iron-deficiency anemia.

Corresponding author: Iulian Alin Silviu Popescu, Lecturer, MD, PhD; e-mail: alinpope09@gmail.com; Cristiana Geormaneanu, Lecturer, MD, PhD; e-mail: cristianageormaneanu@yahoo.com

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14. Preserving periodontal tissue in the treatment of a large peripheral ossifying fibroma: a case study

Emine Cansu Topcuoglu, Tugce Cevik Sonmez, Tulay Koc, Omer Fahrettin Goze

Peripheral ossifying fibroma (POF) is a reactive, benign gingival enlargement. Its etiology is not fully known. It can be seen in many different sizes in the mouth. The histopathological appearance of POF is mineralized tissue and fibrous proliferation. All relevant soft and hard tissues must be removed to prevent recurrence. Periodontal tissue remaining after excision is important for tooth preservation. With large lesions, the loss of healthy periodontal tissue is also large. Periodontal surgical approaches are important to preserve the remaining periodontal tissue. The positive effects of autogenously obtained titanium-prepared platelet-rich fibrin (T-PRF) and connective tissue graft (CTG) on soft tissue are well known. A 34-year-old woman presented with a fibrous and pedunculated gingival mass in the upper left canine premolar region. The operation was performed with complete excision of the lesion down to the bone along with the surrounding healthy tissue. Periodontal treatment of the large defect created after excision of a large POF lesion was performed with laterally positioned flap, CTG and T-PRF. The periodontal tissue and defect were noted to heal in a healthy manner at the 6-month follow-up. POF is a benign lesion; however, it has a high recurrence rate. Complete elimination of the lesion is crucial to prevent recurrence. Periodontal surgical methods and biomaterials applied after surgical excision are significant to maintain the periodontal health of the remaining teeth and tissues.

Corresponding author: Tugce Cevik Sonmez, Assistant Professor; e-mail: tugce.cevik@giresun.edu.tr

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15. Mandibular lateral incisor-first premolar transposition in early mixed dentition: a rare case

Oana Cella Andrei, Mirela Ileana Dinescu, Catalina Farcasiu, Adriana Bisoc, Daniela Ioana Tarlungeanu, Ruxandra Margarit

Dental transposition is an anomaly of eruption which is usually seen in the maxilla and rarely in the mandible. The mandibular lateral incisor s transposition with the permanent canine has a prevalence of less than 0.03%. The following case presents an even rarer situation, of a right lateral mandibular incisor that erupted in the place of the first premolar, in transposition with the temporary canine. In the first phase, a series of extractions have been performed, to ensure the necessary free space for moving the lateral incisor closer to its appropriate place, and after that a fixed orthodontic appliance was used. The biomechanics for intra-arch tooth movement was ingenious enough to ensure a perfect alignment of all permanent teeth and a functional Class I canine and molar final occlusion. Early intervention and successful move of the permanent canine in its correct position ensured the functionality of the mandibular movements and a good long-term prognosis.

Corresponding author: Adriana Bisoc, Lecturer, DMD, PhD; e-mail: adry_bis@yahoo.com; Daniela Ioana Tarlungeanu, Assistant Professor, DMD, PhD; e-mail: ioanatarlungeanu@gmail.com

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16. An atypical anatomy of permanent mandibular second molar with five roots

Cristina Coralia Nistor, Paula Perlea, Lucian Toma Ciocan, Alexandru Burcea, Alexandru Andrei Iliescu

Especially in molars that may have sometimes aberrant additional root canals, the complexity of tooth internal morphology in individual cases sometimes does not match to admitted classification rules and underlines the risk of missed anatomy during the endodontic management. To our knowledge, a permanent mandibular second molar with independent five roots, three mesial and two distal, each of them harboring a single canal, was not yet reported. Despite the treatment difficulties this tooth could be successfully approached by using dental operative microscope and cone-beam computed tomography (CBCT) with small field of view. Though CBCT is not a routine imagistic examination, in case of atypical tooth anatomy aiming to establish adequate diagnosis and treatment plan, the successful clinical outcome prevails over the irradiation dose.

Corresponding author: Lucian Toma Ciocan, Associate Professor, DMD, PhD; e-mail: lucian.ciocan@umfcd.ro; Alexandru Burcea, Associate Professor, DDS, MSc, PhD; e-mail: alexandru.burcea@prof.utm.ro

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17. Letter to the Editor: Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy

Maria Filofteia Mercut, Cornelia Andreea Tanasie, Andreea Mihaela Nicolcescu, Oana Maria Ica, Carmen Luminita Mocanu, Alexandra Oltea Dan

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Corresponding author: Cornelia Andreea Tanasie, Teaching Assistant, MD, PhD; e-mail: corici.andreea@gmail.com; Oana Maria Ica, Teaching Assistant, MD, PhD; e-mail: oana.ica@umfcv.ro

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