Epidemiological and histopathological aspects of ocular melanomas in Northeastern Romania.

Ocular melanoma is a rare but complex disease in current medical practice. Our retrospective study spans over a period of 28 years and analyzed uveal and conjunctival melanomas that were consecutively admitted, diagnosed, and treated in the 2nd Ophthalmology Clinic of Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania. The patients were selected from the records of the Department of Pathology of our Hospital, being diagnosed by standard histopathological techniques. The aim of this study was to summarize the epidemiological and pathological aspects of uveal and conjunctival melanomas in Northeastern region of Romania. In our study, we did not notice a predilection of uveal and conjunctival melanoma to one particular gender. The most common histological subtypes of ocular melanomas were the heavily pigmented spindle cell subtype, followed by the epithelioid subtype. Our patients sought medical help in a timely manner, before the systemic invasion of the disease could develop.

Cerebellar Abscess Secondary to Cholesteatomatous Otomastoiditis-An Old Enemy in New Times.

Chronic otitis with cholesteatoma is a potentially dangerous disease that can lead to the development of intracranial abscesses. Although cerebellar abscess is half as common as cerebral abscess, it is known for its particularly difficult diagnosis, which requires the visualization of the pathological process continuity from the mastoid to the posterior fossa. In this article, we present an extremely rare case from the literature of cholesteatomatous otomastoiditis complicated with meningitis and cerebellar abscess, along with the description of technical surgical details for the plugging of the bony defect between the mastoid and posterior fossa with muscle and surgical glue. The particularity of this case lies in the late presentation to the doctor of an immunocompetent patient, through a dramatic symptomatology of life-threatening complications. We emphasize the importance of responsibly treating any episode of middle ear infection and considering the existence of underlying pathologies. In such cases, we recommend additional neuroimaging explorations, which can prevent potentially lethal complications. The treatment of such intracranial complications must be carried out promptly and requires collaboration between a neurosurgeon and an ENT surgeon.

Predictor factors for recurrence in atypical meningiomas.

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 cm³ 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 cm³, 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.

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

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.

The Evolution of Pituitary Gland Surgery from the Ancients to the Millennials.

Located at the base of the skull, the pituitary gland has a long and controversial history, not only in terms of its anatomy, but especially in the functions it performs and in the attempt to approach it surgically. Considered by Galen of Pergamon to have a role in releasing waste products of the brain, a theory accepted until the 17th century, the pituitary gland became a separate entity once with the anatomical descriptions of the famous Andreas Vesalius. At the beginning of the 18th century, researches of the time began to be more and more interested in this gland, trying to identify its functions, and at the same time correcting the traditional theories that were wrong or incomplete. Later, they turned their attention to experimental animal studies that represented the germinal nucleus for the transcranial and endoscopic pituitary surgery. In this review, an attempt has been made to record the entire history of anatomy, physiology and surgery of the pituitary gland, from antiquity to the current day's surgical techniques.

Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications.

Type 2 diabetes mellitus (T2DM) still holds the title as one of the most debilitating chronic diseases with rising prevalence and incidence, including its complications such as retinal, renal, and peripheral nerve disease. In order to develop novel molecules for diagnosis and treatment, a deep understanding of the complex molecular pathways is imperative. Currently, the existing agents for T2DM treatment target only blood glucose levels. Over the past decades, specific building blocks of proteins-branched-chain amino acids (BCAAs) including leucine, isoleucine, and valine-have gained attention because they are linked with insulin resistance, pre-diabetes, and diabetes development. In this review, we discuss the hypothetical link between BCAA metabolism, insulin resistance, T2DM, and its microvascular complications including diabetic retinopathy and diabetic nephropathy. Further research on these amino acids and their derivates may eventually pave the way to novel biomarkers or therapeutic concepts for the treatment of diabetes and its accompanied complications.

Brain Tuberculosis: An Odyssey through Time to Understand This Pathology.

Tuberculosis is a contagious disease that has been a concern for humanity throughout history, being recognized and referred to as the white plague. Since ancient times, starting with Hippocrates and Galen of Pergamon, doctors and scientists have attempted to understand the pathogenesis of tuberculosis and its manifestations in the brain. If, in the medieval period, it was believed that only the touch of a king could cure the disease, it was only in the early 17th and 18th centuries that the first descriptions of tuberculous meningitis and the first clinico-pathological correlations began to emerge. While the understanding of neurotuberculosis progressed slowly, it was only after the discovery of the pathogenic agent in the late 19th century that there was an upward curve in the occurrence of treatment methods. This review aims to embark on an odyssey through the centuries, from ancient Egypt to the modern era, and explore the key moments that have contributed to the emergence of a new era of hope in the history of neurotuberculosis. Understanding the history of treatment methods against this disease, from empirical and primitive ones to the emergence of new drugs used in multi-drug-resistant tuberculosis, leads us, once again, to realize the significant contribution of science and medicine in treating a disease that was considered incurable not long ago.

Epidemiological and pathological characteristics of spinal metastases from gastrointestinal cancers - a series of 40 cases.

Spinal metastases from gastrointestinal (GI) cancer are rare and as a result there are only case reports or small series in the literature. The aim of our work was to identify the demographic aspects, the location, and the histopathological aspects of spinal metastases from GI cancers diagnosed and treated in a reference Hospital in Romania over a period of nine years, and comparing the data obtained with those from the recent literature. This is a retrospective case series study on spinal metastases from GI cancers, developed in patients older than 18 years that were surgically treated between January 2013 and December 2021 within three Neurosurgery Clinics from Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, which is a tertiary Hospital in Romania regarding the surgical treatment of spinal metastases. We included in our study the patient's demographic data (age and gender), clinical data (location of spinal metastases), radiological investigations and pathological features of the lesions. Regarding the immunohistochemical stainings, the following antibodies were used: anti-cytokeratin (CK)7, anti-CK20, anti-CK19, anti-caudal-type homeobox 2 (CDX2), anti-human epidermal growth factor receptor 2 (HER2), and anti-Ki67. Our series included 40 adult patients (≥18 years old) with a male:female ratio of 3:1, in favor of male patients. The mean age of all patients was 66.42 years. The primary sites of spinal metastases from GI cancers were from all segments of the GI system: the most frequent, however, was from the colorectal level (40%) and the least from the oral cavity level (2.5%). The most common site of spinal metastases from GI cancer was predominantly lumbar region (47.5%), and the most frequent histological type was adenocarcinoma (57.5%), followed by hepatocellular carcinoma (27.5%), pancreatic ductal carcinoma (5%) and squamous cell carcinoma (2.5%). Our results have important clinical implications because they suggest that there are certain subsets of patients with certain types of GI cancers that cause metastases in certain regions of the spine.

Clinicopathological characteristics and prognostic factors of atypical meningiomas with bone invasion: a retrospective analysis of nine cases and literature review.

BACKGROUND: Meningiomas are the most common primary neoplasms of the central nervous system in adults, arising from the arachnoid cap cells. Thus, grade 2 meningiomas are situated on the border between benignity and malignancy. Among the many prognostic factors that have been investigated in these tumors, bone invasion is one of them. OBJECTIVE: The aim of our study was to identify whether bone invasion influences tumor recurrence and progression-free survival (PFS) in patients with atypical meningiomas (AMs). PATIENTS, MATERIALS AND METHODS: Out of 81 patients with AMs followed over a period of five years, we identified nine patients with bone invasion. We analyzed their demographic, clinical, imaging, and pathological characteristics, such as age, gender, radiological aspects, morphological features, extent of resection, recurrence rate, and PFS over a follow-up period of 60 months. Bone invasion was determined based on preoperative, surgical, and pathological reports. RESULTS: Out of the nine patients with bone invasion, four had convexity meningiomas, four had parasagittal meningiomas and one had a falcine meningioma. Regarding tumor recurrence∕progression, most patients (n=6) recurred within the first 24 months after surgery. Our study showed that the early recurrence/progression of tumor (at 12 months) correlated with extensive presence of malignancy criteria, especially with the presence of 15-18 mitoses∕10 high-power fields, as well as with large foci of spontaneous necrosis, but also with tumor bone infiltration, extensive bone lamellae destruction, and tumor infiltration of adjacent muscle with its atrophy due to tumor compression. Patients with bone invasion had a PFS of 29.3 months, compared to patients without invasion who had a higher PFS (49.3 months). Significant statistical associations were observed between bone invasion and tumor recurrence (p=0.002) and PFS (p=0.004). CONCLUSIONS: Our study emphasizes the importance of a thorough histopathological examination of the surgical specimen, which can provide significant data for the assessment of the progression of an AM [World Health Organization (WHO) grade 2] with bone invasion. AM infiltration in adjacent bone and muscle increases the rate of tumor recurrence and decreases PFS over a follow-up period of 60 months.

Humps and bumps of head: review of meningiomas of the scalp.

Meningiomas are a type of tumor that arises from meningothelial cells and primarily develops in intracranial space, being some of the most common benign tumors of the central nervous system. However, meningiomas can rarely occur on the scalp and are called primary cutaneous meningiomas. Since the pathogenesis of these lesions is still uncertain, these tumors still pose challenges in terms of histopathological diagnosis. In this review, we will discuss the main cases of scalp meningiomas in the literature, their classification, pathological and immunohistochemical diagnosis, differential diagnosis with other scalp lesions and the most effective treatment. This study highlights the importance of immunohistochemistry in the differential diagnosis of skin lesions located on the scalp.

Current Challenges in the Treatment of the Omphalocele-Experience of a Tertiary Center from Romania.

Omphalocele is a congenital abdominal wall defect with a constant incidence in recent decades, sometimes representing a real burden for neonatal intensive care units due to prolonged hospitalization and the evolution to death. In our study, we aimed to detect the main risk factors of an unfavorable evolution in the case of omphalocele. METHODS: Retrospective cohort study of all neonates with omphalocele treated in our tertiary pediatric hospital during the last three decades; from 158 patients, 139 patients were eligible for the study. We tried to determine the risk of death using logistic regression model. RESULTS: If the neonate develops sepsis, then there is an increased risk (13.03 times) of evolution to death. Similarly, the risk of death is 10.82 times higher in the case of developing acute renal failure, 6.28 times higher in the case of associated abnormalities, 5.54 in the case of developing hemorrhagic disease, and 3.78 in the case of conservative treatment (applied for giant omphalocele or severe chromosomal abnormalities). Prematurity increases by 3.62 times the risk of death. All six independent variables contributed 61.0% to the risk of death. The area under the ROC curve is 0.91, meaning that the diagnostic accuracy of our logistic regression model is very good for predicting the contribution of the six independent variables to the risk of death. CONCLUSION: Although in the past 30 years we witnessed several improvements in the antenatal diagnosis and management of omphalocele, survival rate remained constant, 47.5% overall. Much effort is still needed to eliminate the risk factors for death in this condition.

Contribution of Oxidative Stress (OS) in Calcific Aortic Valve Disease (CAVD): From Pathophysiology to Therapeutic Targets.

Calcific aortic valve disease (CAVD) is a major cause of cardiovascular mortality and morbidity, with increased prevalence and incidence. The underlying mechanisms behind CAVD are complex, and are mainly illustrated by inflammation, mechanical stress (which induces prolonged aortic valve endothelial dysfunction), increased oxidative stress (OS) (which trigger fibrosis), and calcification of valve leaflets. To date, besides aortic valve replacement, there are no specific pharmacological treatments for CAVD. In this review, we describe the mechanisms behind aortic valvular disease, the involvement of OS as a fundamental element in disease progression with predilection in AS, and its two most frequent etiologies (calcific aortic valve disease and bicuspid aortic valve); moreover, we highlight the potential of OS as a future therapeutic target.

Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives.

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through its microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds the quality of life of these patients. Considering DKD is the main cause of end-stage renal disease (ESRD) in developed countries, extensive research is currently investigating the matrix of DKD pathophysiology. Hyperglycemia, inflammation and oxidative stress (OS) are the main mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-ß, NF-κB, MCP-1, VCAM-1, ICAM-1) and the activation of diverse pathways (e.g., PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state with impairment of the antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations in the renal filtration unit. Hitherto, a wide spectrum of pre-clinical and clinical studies shows the beneficial use of NRF2-inducing strategies, such as NRF2 activators (e.g., Bardoxolone methyl, Curcumin, Sulforaphane and their analogues), and other natural compounds with antioxidant properties in DKD treatment. However, limitations regarding the lack of larger clinical trials, solubility or delivery hamper their implementation for clinical use. Therefore, in this review, we will discuss DKD mechanisms, especially oxidative stress (OS) and NRF2/KEAP1/ARE involvement, while highlighting the potential of therapeutic approaches that target DKD via OS.

Skin Dialogues in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin disorder associated with significant quality-of-life impairment and increased risk for allergic and non-allergic comorbidities. The aim of this review is to elucidate the connection between AD and most common comorbidities, as this requires a holistic and multidisciplinary approach. Advances in understanding these associations could lead to the development of highly effective and targeted treatments.

Diagnosis Difficulties and Minimally Invasive Treatment for Ovarian Masses in Adolescents.

About 1% of childhood tumors can be malignant ovarian tumors and differential diagnosis with benign ones is sometimes difficult before surgery. Concerning the management of such tumors in adolescents for which future fertility is a concern, there is specific interest in their malignant potential and the possible use of ovarian-sparing operative techniques, as well the suitability of chemotherapy. To exemplify the difficulties of preoperative differential diagnosis, personalized approach and the difficulties of deciding to preserve the affected ovary, we report a rare case of a 14-year-old female adolescent with a growing abdominal painless mass and without any other chronic diseases. After physical examination and imaging investigations, laparoscopic surgical procedure is performed, the peritoneal cavity is explored and the well-delimited gigantic tumor is removed. Considering the normally looking pelvis and absence of adenopathy, as well as the patient's age and wish to have children, both ovaries are preserved. Laparoscopy has become the gold standard in the management of this condition, although there are few studies that report this approach in children; the differential diagnosis between a benign and a malignant tumor cannot be established exactly until after the histological examination, which revealed in our case a cystic teratoma with mature tissues. A better understanding of clinical features and evolution of giant ovarian masses in adolescents could help clinicians better diagnose and treat such lesions.

Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives.

Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction-oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.

Unusual Case of Masseter Muscle Hypertrophy in Adolescence-Case Report and Literature Overview.

Unilateral hypertrophy of the masseter muscle is a very rare pathological entity in children. Its etiology is uncertain and it requires a high degree of suspicion, as it must be differentiated from other conditions of the masseter area. As there are few pathological studies to elucidate this condition, we report a rare case of unilateral masseter muscle hypertrophy in a 16-year-old female patient with gradual onset of a painless swelling in the posterior left cheek which caused facial asymmetry with repercussions on the patient's self-image. The diagnosis of unilateral masseter muscle hypertrophy was suggested by clinical examination, ultrasound scanning, and nuclear magnetic resonance, and was confirmed by histologic examination two years later when the patient returned for the surgical correction. The pathological findings report showed fragments of skeletal muscle with hypertrophic fibers associated with normal-sized muscle fibers in both longitudinal and transverse sections. The postoperative evaluation was favorable as both the adolescent and her family were satisfied with her look on the 14th day, 1st year, and 3rd year follow-ups. In conclusion, unilateral masseter muscle hypertrophy in adolescence is a sensitive problem due to the psychological implications of facial appearance. Definite diagnosis and treatment of the hypertrophied muscle is the ideal solution.

Complete oculomotor nerve palsy - first manifestation of gastric adenocarcinoma: clinical experience and literature review.

The diagnosis and management of the alteration of the normal function of the oculomotor nerve (third cranial nerve) varies depending on the characteristics of the paralysis, the age of the patient, and the associated symptoms and signs. Oculomotor nerve palsy may be caused by lesions located anywhere from the oculomotor nucleus to the termination of the third nerve in the extraocular muscles. Although there have been significant advances in neuroimaging to facilitate early diagnosis, the management of a patient presenting with isolated oculomotor palsy is still challenging. This review tackles the case of a 52-year-old patient, with a history of pulmonary tuberculosis (at the age of five), referred to the Department of Ophthalmology, St. Spiridon Emergency Clinical Hospital, Iasi, Romania. The patient had diplopia accompanied by right eyelid ptosis, symptoms that began suddenly 10 days before hospitalization. The clinical examination showed right eye grade II palpebral ptosis, exotropia with limitation of eyeball movements in adduction, supra-∕infraduction. Biomicroscopic examination of the anterior pole revealed the presence of anisocoria and light-near dissociation on the affected side. Numerous investigations were performed to identify the cause, starting with tumoral markers, which were within normal limits. Magnetic resonance angiography (MRA) was performed, and posterior communicating artery aneurysm was ruled out. The endocrinology examination and hormonal laboratory tests were also within normal parameters. Due to suspicions of generalized tuberculosis raised by the infectious disease doctor or presence of secondary lesions, thoraco-abdomino-pelvic computed tomography (CT) scan with contrast agent was done and its findings required gastroenterological exploration. After various explorations, the certainty diagnosis was set by histopathological examination, which revealed gastric adenocarcinoma.

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets.

Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATS) are worldwide known diseases with increased incidence and prevalence. These two are driven and are interconnected by multiple oxidative and metabolic functions such as lipotoxicity. A gamut of evidence suggests that sphingolipids (SL), such as ceramides, account for much of the tissue damage. Although in humans they are proving to be accurate biomarkers of adverse cardiovascular disease outcomes and NAFLD progression, in rodents, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of metabolic driven diseases such as diabetes, ATS, and hepatic steatosis. In this narrative review, we discuss the pathways which generate the ceramide synthesis, the potential use of circulating ceramides as novel biomarkers in the development and progression of ATS and related diseases, and their potential use as therapeutic targets in NAFDL-ATS development which can further provide new clues in this field.

Thymus pathology in myasthenia gravis with anti-acetylcholine receptor antibodies and concomitant Hashimoto's thyroiditis. A four-case series and literature review.

OBJECTIVE: Identifying the morphological features of thymus in patients with myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies and concomitant Hashimoto's thyroiditis (HT), which were recruited from a single surgical unit of a tertiary referral hospital located in the North-Eastern region of Romania, over a period of 11 years. PATIENTS, MATERIALS AND METHODS: We retrospectively reviewed clinical, imaging, laboratory, thymic pathology, and outcome data that were obtained from medical records of patients with MG and concomitant HT, to whom a thymectomy was performed for a suspected thymic lesion. All the surgical interventions were done in the Third Clinic of Surgery, St. Spiridon Emergency County Hospital, Iasi, Romania, for an 11 years' period, i.e., from January 1, 2000 and December 31, 2010. RESULTS: Four patients (three females and one male) were included. The mean age of the patients at the time of their thymectomy was 40.25 years. Of all patients, 75% had moderate or severe MG, 100% had anti-AChR antibodies, and an electromyographic decrement greater than 25%. All patients have been diagnosed with HT in their past medical history by a full thyroid panel [high thyroid-stimulating hormone (TSH) values, low free thyroxine (fT4) values, and the presence of the anti-thyroid antibodies] and all of them have been treated with Euthyrox. Our four patients expressed different MG subtypes, each of them being associated with different thymus pathology. Thoracic computed tomography (CT) scan revealed heterogeneous mediastinal masses and established the correct diagnosis only in 25% of cases. The pathological exams also revealed a heterogeneous pattern of thymic lesions. In contrast with other studies, our patients with MG with anti-AChR antibodies and concomitant HT presented atrophic thymus more frequently (50%), but with particular morphological changes of Hassall's corpuscles. Also, 25% of cases were diagnosed with thymic lympho-follicular hyperplasia (TLFH) associated with thymic epithelial hyperplasia. In B2 thymoma, neoplastic epithelial cells expressed cytokeratin 19 (CK19) immunoreactivity, high Ki67 labeling index and strong p63 immunopositivity. CONCLUSIONS: In our series, MG and HT occurred simultaneously, or one of them was diagnosed before the other, raising some new questions regarding the immune mechanism of these two autoimmune diseases. Due to the heterogeneous morphological changes of the thymus that we found in this study, we can hypothesize that thymus is involved in the pathogenic mechanism of MG with anti-AChR-antibodies and concomitant HT development.