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Papers accepted for publication

1. Adenocarcinoma of the ileum: literature insights on pyloric gland metaplasia

Bogdan Stancu, Razvan Alexandru Ciocan, Marius George Teodorescu, Doinita Crisan, Florin Vasile Mihaileanu, Stefan Ursu, Liviu Tartacovschi, Stefan Lucian Popa, Claudia Diana Gherman, Octavian Aurel Andercou

Adenocarcinoma (ADK) of the ileum is an infrequent cancer that poses significant diagnostic and treatment difficulties. This article analyses the existing case literature to investigate the correlation between pyloric gland metaplasia (PGM) and the onset of ileal ADK. PGM, defined by the atypical transformation of intestinal epithelial cells into gastric-type mucosa, has been recognized as a possible precursor lesion in the spectrum of several gastrointestinal malignancies. We intend to clarify the clinical characteristics, histological results, and outcomes linked to ileal ADK originating from PGM through an exhaustive examination of recorded cases. Our findings indicate that early identification of metaplastic alterations may be essential for enhancing prognosis and informing therapeutic choices. This study emphasizes the need for additional research to elucidate the mechanisms driving this transition and to improve diagnostic precision in clinical practice.

Corresponding author: Razvan Alexandru Ciocan, Lecturer, MD, PhD; e-mail: razvan.ciocan@umfcluj.ro

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2. The burden of cancer in metabolic dysfunction-associated steatotic liver disease

Bianca Florentina Pirvu, Diana Clenciu, Luiza Andreea Beldie, Cristina Camelia Dica, Marilena Alexandra Burticala, Tiberiu Stefanita Tenea-Cojan, Adina Mitrea, Anca Maria Amzolini, Ion Cristian Efrem, Gabriel Florin Razvan Mogos, Ionela Mihaela Vladu

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and has become a major public health problem. MASLD frequently progresses to cirrhosis and hepatocellular carcinoma, but recent studies also show a frequent association with extrahepatic cancers. One of the mechanisms involved in both locations is insulin resistance and hyperinsulinemia. The aim of this narrative review was to present the main etiopathogenic mechanisms involved in cancer development in patients with MASLD.

Corresponding author: Tiberiu Stefanita Tenea-Cojan, Associate Professor, MD, PhD; e-mail: doctortts@yahoo.com; Adina Mitrea, Teaching Assistant, MD, PhD; e-mail: adina.mitrea@umfcv.ro

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3. Clinicopathological correlations and prognostic insights in osteosarcoma: a retrospective analysis

Stefan Adrian Niculescu, Alexandru Florian Grecu, Alex Emilian Stepan, Madalina Iuliana Musat, Aritina-Elvira Morosanu, Tudor Adrian Balseanu, Michael Hadjiargyrou, Dan Cristian Grecu

Osteosarcoma (OS) is the most prevalent primary bone malignancy, predominantly affecting adolescents and young adults, and presents significant clinical challenges due to its aggressive nature and high potential for metastasis. This retrospective study analyzed 34 cases of primary OS, aged 10 to 65 years, to identify clinicopathological correlations that could inform future research and treatment strategies. The findings aim to guide larger cohort studies, essential for validating these correlations and developing tailored approaches that enhance patient outcomes. The analysis focused on demographic factors, sex, tumor grade, stage, size, and histological subtype, utilizing criteria established by the American Joint Committee on Cancer (AJCC) and the World Health Organization (WHO). The results revealed a predominance of the disease in males under 25 years of age, with the femur being the most common site of occurrence. Conventional osteoblastic OS emerged as the most frequent subtype, accounting for 50% of the cases, predominantly presenting as high-grade (G3) tumors. Over 70% of the tumors were T1 in extension (<=8 cm) and classified as stage IIA, indicating a locally advanced disease state. Correlations were observed between histological type, grade, and stage, underscoring the importance of detailed histopathological (HP) assessments in determining prognosis and guiding treatment. The findings highlight correlations between histological subtype, grade, and stage, reaffirming the critical role of detailed HP assessments in prognosis and treatment planning. While the limited sample size necessitates cautious interpretation, this study provides valuable regional and age-specific insights that could inform clinical decision-making. Future research should prioritize multi-center studies and delve into the genetic and molecular underpinnings of OS subtypes to enhance understanding and develop targeted therapies.

Corresponding author: Aritina-Elvira Morosanu, Lecturer, MD, PhD; e-mail: aritina.morosanu@umfcv.ro; Tudor Adrian Balseanu, Professor, MD, PhD; e-mail: adrian.balseanu@umfcv.ro

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4. Electrophysiological parameters in patients with hepatic cirrhosis

Dragos Lupu, Cristian Stanescu, Danut Laurentiu Nedelcu, George Alin Stoica, Mihai-Marius Botezat, Andreea-Stefania Lupu

Various electrophysiological abnormalities are noted in patients with cirrhosis, the most prevalent consisting of QT prolongation and autonomic dysfunction. This study aims to thoroughly evaluate these abnormalities in cirrhotic patients by utilizing various parameters and compare them with healthy individuals. We evaluated 60 patients with hepatic cirrhosis using a resting electrocardiogram (ECG), ECG during and after the Valsalva maneuver, 24-hour ambulatory ECG monitoring and a standardized ECG stress test. We then compared these results with a group of 50 patients who had no hepatic cirrhosis or other significant known pathologies and were not on any medical treatment. At rest, cirrhotic patients had a reduced Valsalva index compared to the control group, but no statistical differences were noted in comparing resting heart rate (HR) values. At Holter monitoring, although there was a trend toward increased corrected QT (QTc) intervals in cirrhotic patients, it did not reach statistical significance, indicating no difference between the two groups. Reduced standard deviation of normal-to-normal (NN) intervals (SDNN) values, statistically significant, were noted in cirrhotic patients compared to the control group, indicating autonomic dysfunction. At stress test, there was no statistically significant difference in the results obtained for maximum HR during exercise between the two groups. Also, the results showed that cirrhotic patients had statistically significantly higher HR values after exercise compared to the control group. In conclusion, cirrhotic patients presented an increased grade of autonomic dysfunction compared to healthy patients, but no differences were noted regarding QT interval abnormalities.

Corresponding author: George Alin Stoica, Lecturer, MD, PhD; e-mail: alin.stoica76@gmail.com

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5. Stroke as the first manifestation of an atrial myxoma. Review of the literature

Mihai-Marius Botezat, Anca-Maria Istrate-Ofiţeru, Larisa Iovan, Elena Cristina Andrei, Cristian Militaru, Emanuel Botezat, Marian Valentin Zorilă, Sebastian Militaru, Ilona Mihaela Liliac

Cardiac myxoma (CM) is the most common benign tumor of the heart and an important etiology of stroke in young adults. The study aimed to provide the latest literature data on CMs and, in particular, on the association between CM and cardioembolic ischemic stroke. It also discussed a specific instance of atrial myxoma (AM) in a young patient who suffered an ischemic stroke linked with familial cavernomatosis. The case presentation focuses on a 43-year-old woman showed up at the hospital’s Emergency Room for transient speech disorders lasting about 15 minutes. The physical examination revealed a preserved mental and cognitive status. Cranial magnetic resonance imaging (MRI) showed three areas of microvascular ischemia (frontal, parietal, and left occipital), in addition to multiple cavernomatous lesions. Because this microvascular ischemias were located in different vascular territories, we considered the cause to be embolic and completed the investigation with a transesophageal cardiac ultrasound that revealed a mobile and heterogeneous tumor mass in the left atrium. Histopathological investigation with immunohistochemistry proved the tumor to be a CM. The patient therapy included a multidisciplinary approach, which led to surgical excision of the tumor. The co-existence of cerebral cavernous malformations (CCMs) and AM might thus be coincidental or induced by a common genetic component. More cases are needed to verify or disprove the concept of a shared genetic basis for CCMs and myxoma.

Corresponding author: Sebastian Militaru, MD; e-mail: sebastian.militaru@umfcv.ro

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6. Lipoprotein (a) in the context of atherosclerosis: pathological implications and therapeutic perspectives in myocardial infarction. A narrative review

Ionut Cezar Buciu, Eugen Nicolae Tieranu, Andreea Stefania Pircalabu, Ovidiu Mircea Zlatian, Ionut Donoiu, Ramona Cioboata, Constantin Militaru, Sebastian Militaru, Mihai-Marius Botezat, Cristian Militaru

Lipoprotein (a) [Lp(a)] is a recognized independent cardiovascular (CV) risk factor with significant implications in the morphopathology of atherosclerotic plaques, particularly in the context of myocardial infarction (MI). Structurally, Lp(a) consists of a low-density lipoprotein (LDL) particle covalently bound to apolipoprotein A (ApoA), and its resemblance to plasminogen (PLG) underpins its dual proatherogenic and prothrombotic effects. Elevated Lp(a) levels disrupt endothelial repair mechanisms, enhance the deposition of oxidized LDL, and promote foam cell formation, which are critical for the initiation and progression of atherosclerosis. Pathologically, atherosclerotic plaques associated with Lp(a) display hallmark features of instability, including thin fibrous caps, increased macrophage infiltration, calcification, and fragile neovascularization. These features contribute to plaque ruptures and thrombotic complications. Additionally, the structural similarity of Lp(a) to PLG interferes with fibrinolysis, creating a prothrombotic environment that exacerbates the risk of acute ischemic events. Genetic and non-genetic factors influence plasma Lp(a) concentrations, with significant inter-individual and ethnic variability contributing to varying CV risk profiles. Despite advancements in the understanding of the pathophysiological role of Lp(a), effective therapeutic options remain limited. Current management focuses on mitigating traditional CV risk factors, while emerging therapies, such as antisense oligonucleotides and short interfering ribonucleic acid (siRNA) targeting hepatic ApoA production, offer promising avenues for reducing Lp(a) levels. Further clinical validation of these therapies is warranted. This review underscores the importance of incorporating Lp(a) measurement into routine CV risk assessment and emphasizes the need for continued research on its morphopathological impacts and therapeutic modulation, with the aim of reducing the burden of atherosclerosis and MI.

Corresponding author: Mihai-Marius Botezat, Assistant, MD, PhD; e-mail: mihaibotezat@yahoo.com

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7. The intriguing perineurial cells - an updated overview of their origin, structure, functions and implication in pathology

Anne-Marie Constantin, Adina Bianca Bosca, Carmen Bianca Crivii, Andreea Crintea, Rada Teodora Sufletel, Bogdan Catalin Alexandru, Alina Simona Sovrea

The paper overviews the uniquely intricate and distinct perineurium that envelops nerve fibers in bundles. It consists of perineurial cells (PCs), connective tissue, and blood vessels. The perineurium creates a microenvironment for efficient signal transmission, protects and maintains neuronal structure and function, and facilitates neuronal repair. PCs are a unique type of myofibroblasts essential for maintaining nerve homeostasis. They act as an effective blood-nerve barrier (BNB), protecting against toxins, infections, and mechanical trauma. Despite their crucial function, the origin, ultrastructure, molecular structure, and functional roles of PCs remain a mystery, making them a fascinating area of study.

Corresponding author: Adina Bianca Bosca, Associate Professor, DMD, PhD; e-mail: biancabosca@yahoo.com

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8. Immunoexpression of E-cadherin, beta-catenin and Ezrin in non-small cell lung carcinomas

Daniela Florentina Grecu, Bianca Catalina Andreiana, Claudiu Margaritescu, Alexandru Florian Grecu, Marian Valentin Zorila, Daniela Marinescu, Alex Emilian Stepan

Lung cancer continues to have the highest mortality rate in the world, non-small cell lung carcinoma (NSCLC) representing the most common tumor form. The therapeutic interference of the tumor intercellular adhesion disruption mechanisms can provide therapeutic targets to improve the patients prognosis. The study included 52 cases diagnosed with NSCLC, for which the immunohistochemical expressions of E-cadherin, beta-catenin and Ezrin were analyzed in relation to the epidemiological and histological prognostic parameters. The histopathological analysis indicated the predominance of high-grade acinar adenocarcinoma (ADK) and non-keratinizing squamous cell carcinoma (SCC), with frequent vascular invasion and in stages II-IV. Final staining scores (FSS) of E-cadherin were superior in the case of acinar, lepidic and papillary ADK, with a high degree of differentiation, without vascular invasion and in initial tumor stages. The same aspect was also observed in the case of beta-catenin reactions, which were present only at the membrane level, increased FSS being also present in the case of mucinous carcinomas. The membrane/cytoplasmic immunoexpression of Ezrin was superior in the case of cribriform, solid, micropapillary, lepidic and non-keratinized squamous carcinomas, with vascular invasion and in advanced tumor stages. Membrane reactions of Ezrin prevailed only in the case of acinar, lepidic and papillary ADK. The negative linear correlation of E-cadherin and beta-catenin with Ezrin and the relationships of the markers with the histological parameters of NSCLC indicate their utility potential for the identification of aggressive malignant lung tumors.

Corresponding author: Alexandru Florian Grecu, Lecturer, MD, PhD; e-mail: alexandru.grecu@umfcv.ro; Marian Valentin Zorila, Lecturer, MD, PhD; e-mail: valentin.zorila@umfcv.ro

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9. Late open conversion: a reliable solution for endoleak management after endovascular aortic aneurysm repair - a single center experience and literature review

Horatiu Flaviu Coman, Octavian Aurel Andercou, Bogdan Stancu, Razvan Alexandru Ciocan, Claudia Diana Gherman, Ana Trif, Moustafa Farran, Peter Lukas Haldenwang, Claudiu George Rascanu

Background/Objectives: Despite the efficacy of endovascular approaches for most secondary interventions post-endovascular aortic aneurysm repair (EVAR), a small proportion of patients need open conversion (OC) procedures. We shared our experience regarding patient outcomes after late OCs post-EVAR. We also performed a literature review of data published on this topic. Patients, Materials and Methods: Medical records of patients who underwent late OCs post-EVAR at a Public Hospital in Germany (2017-2019) were retrospectively analyzed. OC involved total or partial endograft removal followed by aortic reconstruction. Preoperative patients characteristics, indications for OC, and intra-/post-operative outcomes were assessed. Studies published in English (2014-2024) on OCs post-EVAR complications were descriptively analyzed. Results: Six patients underwent late OCs throughout the study (males: 66.67%; age [mean+/-standard deviation]: 66.50+/-2.89 years). Grafts were excised after a median of 72 months (range: 24-132 months), with 2/6 (33.33%) urgent removals and 4/6 (66.67%) elective. 4/6 (66.67%) patients underwent complete removal, and 2/6 (33.33%) were partial. Clamping site was suprarenal in 3/6 (50.00%) patients, supraceliac in 2/6 (33.33%), and infrarenal in 1/6 (16.67%). Technical success was 100%, with 32 minutes mean clamping time and 1.67 L blood loss. Median follow-up was 13 months. No aneurysm growth was observed, and implanted grafts functioned well. 1/6 (16.67%) patients died during the postoperative intensive care unit stay. Seven studies were included in our review. The 30-day mortality post-OCs was 6.2-10.0% in elective setting and up to 40% in urgent. Conclusions: Late OC can be a reliable procedure for managing endoleak post-EVAR. Its success relies on accurate preoperative assessment and surgical expertise.

Corresponding author: Octavian Aurel Andercou, Associate Professor, MD, PhD; e-mail: andercou@yahoo.com

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10. Toxic epidermal necrolysis - clinicopathological aspects and therapeutic management

Eliza-Maria Bordeanu-Diaconescu, Sabina Grama, Andreea Grosu-Bularda, Adrian Frunza, Catalina-Stefania Dumitru, Mihaela-Cristina Andrei, Cosmin-Antoniu Creanga, Tiberiu-Paul Neagu, Ioan Lascar

Toxic epidermal necrolysis (TEN) is a serious dermatological condition often triggered by different drugs or medications or, less commonly, by infections, leading to extensive epidermal detachment and multisystemic complications, resembling the severity and systemic impact of burn injuries. This case report portrays a 26-year-old female patient with a history of psychiatric treatment and recreational drug use, presenting with typical prodromal symptoms and characteristic manifestations on the integument and mucosae. Clinical management involved an interdisciplinary team in a burn center, administering immunoglobulins, systemic steroids, and supportive therapies to prevent complications including infection and to support skin re-epithelization. Histopathological findings confirmed the diagnosis. Despite the extensive lesions, prompt treatment facilitated a positive outcome. The report emphasizes the necessity of referral to specialized centers and the complex, multidisciplinary management required for TEN patients to optimize survival and minimize long-term sequelae.

Corresponding author: Andreea Grosu-Bularda, Lecturer, MD, PhD; e-mail: andreea.grosu-bularda@umfcd.ro

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11. The impact of matrix metalloproteinases and their tissue inhibitors in patients with chronic glaucoma - a literature review

Teodor Cerbulescu, Andrei Anghel, Diduta Alina Brie, Flavia Medana Petrascu, Madalina Casiana Salavat, Adina Iuliana Ardelean, Ileana Ramona Barac, Ovidiu Boruga

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in the pathophysiology of chronic glaucoma, as they are involved in extracellular matrix (ECM) remodeling in the trabecular meshwork (TM), affecting its ability to efficiently regulate intraocular pressure (IOP). Ensuring the balance between MMPs and TIMPs helps to maintain homeostasis in ocular tissues, which is essential to avoid glaucomatous lesions. Elevated levels of MMPs and increased degradation of the ECM, ultimately affecting aqueous humor outflow and increasing IOP, characterize glaucoma. In the current literature review, the impact and interactions of MMPs and TIMPs in chronic glaucoma have been emphasized, with multiple but still unelucidated roles in the mentioned pathology including their clinical implications, future research directions, and therapeutic approaches. Research to date indicates that the expression of TIMPs is altered in patients with chronic glaucoma, suggesting a compensatory response to increased MMPs activity. Certain drugs can influence the expression levels of MMPs and TIMPs, therefore therapeutic strategies can be developed to restore the balance between tissue enzymes and their inhibitors. Therefore, understanding the relationship between MMPs and TIMPs is a key factor in the pathogenesis of chronic glaucoma. Understanding the interplay between the two provides interesting insights into ECM remodeling in ocular tissues, highlighting the potential of targeted therapies to restore the balance between proteolytic enzymes and their inhibitors.

Corresponding author: Flavia Medana Petrascu, Assistant, MD, PhD; e-mail: flavia.petrascu@umft.ro

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12. 10 Years of experience in the evaluation and management of pediatric neck masses

Dan Iovanescu, Ionut Tanase, Karina Cristina Marin, Daniela Roxana Vintila, Mihaela Negrea, Carmen Aurelia Mogoanta, Gheorghe Iovanescu, Alina-Maria Georgescu, Ion Cristian Mot

The discovery of a cervical mass in children is a situation quite frequently encountered and often represents a diagnostic or therapeutic challenge for the practicing physician. Although approximately 12% to 15% of all neck masses (NMs) in children may be malignant, most commonly these masses are benign. This study included 137 patients aged between 14 months and 18 years old, with the majority (54.01%) of patients being less than five years old. A total of 83 (60.58%) patients were presented with a single NM, with 64 (59.12%) patients having mass located on the midline of the neck. Preoperatively, in addition to laboratory tests, imaging examinations played an important role in diagnostic orientation and determining the therapeutic plan. Among the imaging examinations, ultrasound was the most commonly used, performed in 87 (63.5%) of the patients. The definitive diagnosis was established based on the histopathological examination of the excised specimens. Midline NMs were most frequently thyroglossal duct cysts or dermoid cysts, while lateral NMs were often lymphadenitis or branchial cysts. The aim of this study was to present the experience of 10 years in evaluating cervical masses in the neck area that appeared in children, their possible causes, the methods of investigation (considering the contribution and limitations of each diagnostic method), and the therapeutic approach (since there is no clear standardization of treatment in the literature).

Corresponding author: Ionut Tanase, Lecturer, MD, PhD; e-mail: ionut_tanase1987@yahoo.com; Karina Cristina Marin, MD, PhD; e-mail: marinkrn@yahoo.com

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13. Castleman disease as the great mimicker: the role of complex morpho-pathological evaluation

Ionut Tanase, Caius-Codrut Sarafoleanu, Bogdan Mihail Cobzeanu, Alina-Maria Georgescu, Constantin-Ioan Busuioc, Dan Iovanescu, Florentina-Carmen Badea

Castleman disease (CD) is a group of lymphoproliferative disorders characterized by abnormal enlargement of lymph nodes (LNs) and a wide range of symptoms. Only a few cases are found in the head and neck. Based on clinical presentation and evolution, the disease can be classified into two main subtypes: unicentric CD (UCD), characterized by the enlargement of a single LN or a single LN chain, and multicentric CD (MCD), characterized by the involvement of multiple LNs and regions, with more important systemic symptoms and a poor prognosis. CD is also known as the great mimicker and can be easily misdiagnosed, sharing similar clinical and imaging characteristics with other pathologies, mainly when it is found in the neck. A histopathological (HP) and immunohistochemical (IHC) correlation is essential in these cases to accurately diagnose and establish the proper treatment plan. In light of this, we present a rare case of a 15-year-old young female with a slowly expanding, isolated supraclavicular mass. An excisional biopsy was performed, and the results confirmed the presence of CD, hyaline-vascular type. As of this writing, there was no evidence of recurrence or new enlarged LNs. We also review CD s clinical and HP features and the diagnostic and treatment challenges it poses.

Corresponding author: Alina Maria Georgescu, MD, PhD Student; e-mail: alinamaria.georgescu@gmail.com; Florentina-Carmen Badea, MD; e-mail: carmeen.badea@gmail.com

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14. Comprehensive insights into Pindborg tumor: etiology, advanced diagnostic approaches, and evidence-based management strategies - review of literature

Cristian Niky Cumpata, Maria Cristina Munteanu, Elena Cristina Andrei, Ilona Mihaela Liliac, Cristina Jana Busuioc, Paolo Di Francesco, Madalina Anca Moldovan, Simona Iuliana Enache, Alexandru Burcea, Ciprian Laurentiu Patru, Calin Rares Roman

Pindborg tumor is a calcifying epithelial odontogenic tumor possibly arising from developmental disturbances in dental lamina remnants. It predominantly affects individuals in their third decade of life, with women also experiencing later onset. The tumor exists in two forms, namely intraosseous (central) and extraosseous (peripheral), with the former showing higher post-surgery recurrence rates of about 14%. Despite its rarity, the tumor can be misdiagnosed due to symptoms resembling dental issues and headaches, or it may even be asymptomatic. Radiologically, it presents a mix of radiolucent and radiopaque areas, sometimes unilocular or multilocular. Histopathologically, it is characterized by nests and sheets of polygonal epithelial cells with eosinophilic cytoplasm and prominent nucleoli. The presence of eosinophilic amyloid-like material and calcifications is distinctive, ranging from small concretions to larger aggregates. The exact origin of amyloids is unknown, but they are thought to derive from degraded keratin filaments. Treatment varies by tumor location, with more invasive procedures required for jaw tumors, including bone resection, due to their aggressive growth and invasion of the surrounding tissues. Accurate, individualized treatment is crucial for patient outcomes, particularly in cases where the tumor s calcification is absent, indicating a severe impact on health. Our study included a case report of a 12-year-old patient who presented to the dental clinic complaining of sporadic pain in the area of the lower right front teeth. During a clinical examination of the area, we noticed a deformation of the alveolar bone, with a depressed mucosa. We followed the chronological steps of radiological examination, lesion excision, and histopathological examination to obtain a definitive diagnosis.

Corresponding author: Ilona Mihaela Liliac, Assistant, MD, PhD; e-mail: ilona.mihaela.liliac@gmail.com; Madalina Anca Moldovan, Lecturer, MD, PhD; e-mail: madilazar@elearn.umfcluj.ro

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15. Acute liver damage generates age independent microglia morphology changes in mice

Gabriel Nedelea, Madalina Iuliana Musat, Smaranda Ioana Mitran, Mihai Calin Ciorbagiu, Bogdan Catalin

Non-alcoholic fatty liver disease (NAFLD) has emerged as a silent global epidemic, frequently contributing to systemic inflammation. As the primary immune cells of the central nervous system (CNS), microglia undergo morphological changes that serve as critical indicators of CNS health. In this study, we aimed to quantify alterations in microglial morphology within the cortex of young and aged mice with liver damage. Our results demonstrated that hepatic dysfunction leads to a significant increase in total branch length in both young (285.79+/-68.23 micrometers) and aged animals (268.67+/-69.06 micrometers), compared to their respective controls (164.07+/-33.05 micrometers and 140.96+/-27.18 micrometers) (p<0.0001). Additionally, aged animals with liver damage exhibited a mean branch length of 5.84+/-0.66 micrometers, higher than 2.63+/-0.19 micrometers observed in those without liver injury. The number of primary branches in aged mice with liver damage decreased from 6.6+/-1.2 branches to 3.1+/-1.5 (p<0.0001). In addition, we have shown a decrease in the number of secondary branches in aged animals with liver damage. This suggests that microglia not only respond to CNS-specific injuries but also to chronic systemic pathologies like NAFLD. These findings highlight the importance of better understanding the liver–brain axis in order to better understand the neuroimmune consequences of systemic diseases.

Corresponding author: Mihai Calin Ciorbagiu, Assistant Professor, MD, PhD; e-mail: mihai.ciorbagiu@umfcv.ro

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16. Clinicopathological and molecular landscape in colorectal cancer associated with colorectal polyps and inflammatory bowel disease

Diana Lavinia Pricope, Adriana Grigoras, Constantin Aleodor Costin, Cornelia Amalinei

Although inflammatory bowel disease (IBD) and colorectal polyps are considered as significant risk factors of colorectal cancer (CRC), the molecular mechanism associated with colorectal carcinogenesis is still explored. Unlike sporadic CRC, local persistent inflammation in IBD induces genetic and epigenetic alterations, leading to tumor development. Moreover, cumulative data indicate that colorectal polyps display a significant malignant potential. In this context, our study aimed to investigate the clinicopathological features of CRC associated with IBD and/or colorectal neoplastic polyps in a retrospective group of CRC cases. The clinical data and histopathological features of CRC cases have been collected from our files. Immunohistochemical examination of mismatch repair (MMR) proteins has been performed in a selected case. The study group comprised 40 patients, 72.5% men and 27.5% women, with a median age of 64.73+/-9.09 years. Out of the cases with double association, 62.5% of CRC cases displayed colorectal polyps, while 32.5% of patients were diagnosed with both CRC and IBD, which encompassed both ulcerative colitis (UC) and Crohn s disease (CD). Two patients included in our study group exhibited a triple association of IBD, colorectal polyps, and CRC, one of them showing defective MMR (dMMR) phenotype. Although our results provide significant data on the relationship between IBD, colorectal polyps, and colorectal carcinogenesis, future cohort studies are needed to improve our understanding on the complex mechanism of colorectal carcinogenesis, ultimately guiding improved prevention, diagnosis, and treatment strategies for these patients.

Corresponding author: Adriana Grigoras, Associate Professor, MD, PhD; e-mail: adriana.grigoras@umfiasi.ro, a_grigoras6600@yahoo.com

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17. Significance of inflammation-related markers and histopathological features in mitral valve regurgitation

Elena Carmen Opris, Horatiu Suciu, Alexandra Iulia Puscas, Sanziana Flamand, Marius Mihai Harpa, Cosmin Ioan Opris, Ioan Jung, Cristian Olimpiu Popa, Kimberly-Allisya-Stefanya Neeter, Simona Gurzu

The lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), C-reactive protein (CRP)-to-lymphocyte ratio (CLR) and fibrinogen-to-albumin ratio (FAR) are well-known indicators of the systemic inflammatory response (SIR). Less is known about the association of SIR with the echocardiographic parameters and the histopathological (HP) aspects of the mitral valve in patients who have undergone cardiac surgery to repair or replace the mitral valve. Information on serum parameters, transesophageal echocardiography findings, and HP results was obtained from 166 patients who had undergone cardiac surgery to address mitral valve regurgitation. Among these patients, 30 were diagnosed with mitral valve prolapse, with 15 cases showing mitral valve flail or chordae rupture. The possible association between SIR, echocardiographic aspects of mitral valve flail and the HP aspect was checked. Fibrosis, hyalinization and myxoid degeneration of the valve were scored under microscope. Hyalinization of the mitral valve had a significant positive association with LMR and PLR (p=0.041 and p=0.03, respectively) and with NLR (p=0.093). A higher fibrosis degree was present in the valves without flail compared with those with flail (p=0.000). The monocyte average values of the group without flail were statistically significantly higher than those in the flail group (p=0.029). An increase of one unit in the value of monocytes was found to decrease the chances of flail [odds ratio (OR) 0.017, p=0.068, significant at p<0.1 level]. SIR parameters can be used to appraise inflammation status in mitral valve disease and to establish the risk of chordae rupture/flail in the case of mitral valve prolapse.

Corresponding author: Simona Gurzu, Professor, MD, PhD; e-mail: simonagurzu@yahoo.com, simona.gurzu@umfst.ro

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18. Histopathological parameters and immunoexpression of CD45RO (CLA) and CD68 in chronic rhinosinusitis with nasal polyps

Irina Enache, Alex Emilian Stepan, Florin Anghelina, Ionica Daniel Vilcea, Mioara Desdemona Stepan, Carmen Aurelia Mogoanta, Andrei Osman

Nasal polyps develop as a result of inflammation of the nasal and sinus mucosa. Allergies and nasal infections cause inflammation, and these are the main reasons why these symptoms appear in the first place. This study highlights the involvement of macrophages, as well as T- and B-lymphocytes, in the pathophysiology of nasal polyps. For the evaluation of lymphocyte activity, we analyzed the immunoexpression of cluster of differentiation 45RO [CD45RO; common leukocyte antigen (CLA)] and for macrophages we analyzed the immunoexpression of cluster of differentiation 68 (CD68). Our research, conducted on 110 sinonasal polyps harvested from chronic rhinosinusitis patients with nasal polyps, focused on analyzing both the epithelial and stromal compartments in relation to pre-established composite scores. Additionally, specific histopathological parameters were included in the study. We concluded that the inflammatory cells were more prevalent in the stromal compartment compared to the epithelial compartment. The statistical evaluation of CD45RO (CLA) and CD68 scores in the stromal compartment were also associated with high histological composite scores.

Corresponding author: Carmen Aurelia Mogoanta, Associate Professor, MD, PhD; e-mail: carmen_mogo@yahoo.com

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19. Unveiling the cause of sudden cardiac death: a macroscopic and microscopic analysis at the Institute of Forensic Medicine, Cluj-Napoca (Romania)

Daniela Cristina Pavel, Costel Vasile Siserman, Mihaela Laura Vica, Bogdan-Alexandru Gheban, Ioana-Andreea Gheban-Rosca, Alexandra Maria Sonfalean, Denisa Stefania Jurje, Denisa Lucian, Silvia Stefana Balici, Horea-Vladi Matei

Sudden cardiac death (SCD) remains a critical public health problem, prompting efforts to understand its underlying causes and identify patients at risk. Despite declining cardiovascular mortality in developed nations, SCD still claims millions of lives annually, disproportionately affecting men and older individuals with a higher prevalence of ischemic heart disease. This study aimed to investigate the potential association between macroscopic and microscopic diagnoses in SCD cases based on a cohort of 3438 medico-legal autopsy reports collected at the Institute of Forensic Medicine, Cluj-Napoca, Romania, between 2014-2018. By analyzing representative heart tissue samples collected during autopsies, particularly from areas exhibiting visible abnormalities, we aimed to establish a link between macroscopic observations and microscopic confirmation. A detailed histopathological analysis on archived tissue samples focused on both ventricles, on areas with potential macroscopic indicators like myocardial ischemia, coronary atherosclerosis, and interstitial fibrosis. Standard techniques were employed to prepare tissue sections for microscopic examination, allowing for the evaluation of various parameters such as the presence and extent of atherosclerosis, necrosis, fibrosis, lipomatosis, edema, and blood stasis. This study investigated the correlation between macroscopic observations of potential SCD risk factors, such as ischemia, atherosclerosis, and fibrosis, and their microscopic confirmation through detailed tissue analysis. Our analysis revealed that circulatory-metabolic lesions of the heart, lung and brain are central and strongly correlated both macroscopically and microscopically with a SCD event, while non-circulatory pathology needs to pass the threshold for macroscopic diagnostics before being able to significantly influence the chances for developing a SCD event. Establishing such associations could improve the accuracy of high-risk SCD factors identification, potentially leading to more effective preventive strategies.

Corresponding author: Mihaela Laura Vica, Associate Professor, MD, PhD; e-mail: mvica@umfcluj.ro

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20. Biological and cytological-morphological assessment of tuberculous pleural effusions

Iancu Emil Plesea, Elena Leocadia Plesea, Razvan Mihail Plesea, Mircea-Sebastian Serbanescu, Marian Olaru, Dragos Nicolosu, Gheorghe Gindrovel Dumitra, Valentin Titus Grigorean, Claudia Lucia Toma

Aim: Tuberculosis (TB) came back in the top of causes for infectious disease-related deaths and its pleural involvement is still in the top two extrapulmonary sites. The authors continued their studies on TB pleural effusions (Pl-Effs) with the assessment of biological and cytological variable of pleural fluid (PF), introducing in the investigation algorithm and testing a new tool, the computer-assisted evaluation of cell populations on PF smears. Patients, Materials and Methods: A series of 85 patients with TB pleurisy (PLTB) were selected from a larger group of 322 patients with different types of Pl-Effs. The algorithm of investigation included. clinical variables, biological assays of PF, gross aspects including imagistic variables and PF cytology on May-Grunwald-Giemsa (MGG)-stained smears. All the data obtained were entered into and processed using Microsoft Excel module of the 2019 Microsoft Office Professional software along with the 2014 XLSTAT add-in program for MS Excel. The PF cellularity was assessed qualitatively by a cytologist and quantitatively with in-house software. Continuous variables were compared using Pearson s correlation test, while categorical variables were compared using chi-squared test. Results: Our analysis showed that patients were usually males, aged between 25 and 44 years with Pl-Eff discovered at clinical imagistic examination, almost always one-sided and free in the pleural cavity. Its extension was either moderate or reduced. The PF had a serous citrine appearance in most of the cases, and biological characteristics pleaded for an exudate [high levels of proteins and lactate dehydrogenase (LDH)], with elevated adenosine deaminase (ADA) values and rich in lymphocytes (Ly). The attempt to identify the pathogen in PF was not of much help. Apart from Ly, neutrophils [polymorphonuclear neutrophils (PMNs)] were a rare presence and their amount had only a trend of direct correlation with Ly. The same situation was encountered in the case of mesothelial cells (MCs). The comparison between the qualitative and the quantitative, computer-assisted evaluations of cytological smears showed that the results of the two methods overlapped in less than one third of the cases, although the sensitivity and specificity values as well as the two calculated predictive values of the qualitative method were encouraging. Conclusions: The assessment of biological variables and cell populations of the PF are basic tools in the diagnosis of pleural TB. The assessment of PF cell population could be improved by the use of computer-assisted quantitative analysis of the PF smears, which is simple to design, easy to introduce and handle and reliable.

Corresponding author: Elena Leocadia Plesea, MD, PhD; e-mail: elena.plesea@umfcv.ro

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