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9 result(s) for "Gliga, Maximilian Cosma"
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Immunohistochemical analysis of filamin a expression in acromegaly and its correlation with tumor characteristics and treatment response
Acromegaly, caused by growth hormone-secreting pituitary tumors, often causes significant challenges in its management due to poor surgical outcomes and resistance to pharmacological treatment. The present study aims to explore the expression of Filamin A (FLNA), a cytoskeletal protein involved in somatostatin receptor signaling, and its clinical relevance in acromegaly. We conducted immunohistochemical (IHC) study on 34 GH-secreting pituitary tumors to evaluate FLNA expression intensity and its associations with somatostatin receptors (SSTR2, SSTR5), E-Cadherin, tumor characteristics obtained through imaging studies, and pharmacological treatment responses. Our findings revealed a 100% FLNA positivity rate, with moderate to strong FLNA expression correlating significantly with SSTR5 expression and the presence of suprasellar tumor extension, indicating a potential role in tumor invasiveness. Moreover, patients with macrodenomas presented significantly higher FLNA intensity compared to the ones with microadenomas. FLNA expression showed no significant association with SSTR2, E-Cadherin, surgical cure rate or first-generation somatostatin receptor ligand (fgSRL) responses. However, the series of patients treated with Pasireotide ( n  = 4) demonstrated a trend suggesting better biochemical control with higher FLNA expression. In conclusion, our results suggest that FLNA may be associated with tumor invasiveness in GH-secreting pituitary tumors. While data on Pasireotide-treated patients are exploratory, further studies are needed to assess FLNA’s potential as a treatment response marker in acromegaly.
PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts.
Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin
Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = −0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.
Successful Pregnancy in a Patient with Long-Standing Acromegaly – a Case Report
Introduction: Acromegaly is a rare endocrine disorder of the growth hormone (GH)-insulin-like growth factor 1 (IGF1) metabolism that can affect women of fertile age. Although uncommon, pregnancies in acromegalic women can occur, with data regarding the management of these cases being very limited, mostly consisting of case reports.Case Presentation: We present the case of an acromegalic woman, first diagnosed at the age of 22, after the surgical resection of a pituitary mass. Throughout the evolution, she received conventional radiotherapy and has been treated with somatostatin receptor ligands (SRLs), dopamine agonists (DAs), and GH-blockers. At the age of 37, the patient decided to become pregnant while she was on Pegvisomant and DA therapy. The treatment was stopped, and the patient became pregnant at the age of 38. Tumor size and IGF-1 values have remained stable throughout the pregnancy, and no complications occurred. A healthy child with normal birth weight was delivered on term through Cesarean section.Conclusions: Managing pregnant women with acromegaly is challenging because of the little available data regarding the safety of medical treatment and a high interindividual variability of GH-IGF-1 evolution during this period. The particularity of our case was a patient with a long history of acromegaly, who had an uneventful pregnancy despite stopping all medical treatment.
Clinical Implications of Molecular and Genetic Biomarkers in Cushing’s Disease: A Literature Review
Cushing’s disease (CD) is a rare disorder caused by adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumors, which lead to chronic hypercortisolism and significant complications with increased mortality. These tumors are characterized by a substantial heterogeneity in their biological behavior, prognosis, and therapeutic response, making their management challenging. While transsphenoidal surgery remains the first-line treatment, recurrence rates remain high, and alternative therapeutic approaches, such as pharmacological therapy and radiotherapy, have a variable efficacy and are frequently limited due to side effects. Increasing evidence suggests that molecular biomarkers, both immunohistochemical and genetic, may play an important role in predicting a tumor’s aggressiveness, recurrence risk, and response to targeted therapies. The immunohistochemical evaluation of its granulation pattern, Ki-67 proliferation index, and E-cadherin expressions have been linked to a tumor’s invasiveness and surgical outcomes, while somatostatin and dopamine receptor expressions may influence its response to Pasireotide and cabergoline therapy. Genetic alterations such as USP8 mutations impact tumor growth and its response to targeted therapies, whereas CABLES1 and TP53 alterations may contribute to more aggressive tumor behavior. Despite these findings, the clinical applicability of many of these markers remains limited by inconsistent validation and lack of standardized cutoff values. This narrative review provides an update on the latest evidence regarding the roles of molecular biomarkers in corticotropinomas, emphasizing their role in prognosis, recurrence risk, and the response to different treatment options. A better understanding and integration of these biomarkers into clinical practice could lead to a better patient stratification, more efficient therapeutic strategies, and personalized treatment approaches for patients with CD.
Associations between paraclinical parameters, symptoms and quality of life in patients with acromegaly: a cross sectional study
Introduction Acromegaly is a rare chronic endocrine disorder that can lead to significant quality of life (QoL) impairment and persistent symptomatology in both biochemically uncontrolled as well as in cured or controlled patients. We aimed to conduct an observational cross-sectional study investigating the associations between biochemical disease control, associated comorbidities, and symptoms severity on QoL in a cohort of acromegalic patients. Methods Thirty-one patients with acromegaly were enrolled in our study. AcroQoL and PASQ (Pain assessed acromegaly symptoms questionnaire) questionnaires were applied to all patients. Information about disease status, associated comorbidities, and other relevant clinical and paraclinical data were gathered. Results Patients with uncontrolled acromegaly presented worse QoL and symptoms scores than controlled patients, but the difference was not statistically significant (AcroQoL 57.22 vs 64.04, p  > 0.05; PASQ 12 vs 16.47, p  > 0.05). Worse symptoms were significantly associated with impaired QoL (overall symptoms score on PASQ was negatively correlated with AcroQoL total score, r  = − 0.61, p  < 0.05). Cardiovascular complications were associated with lower QoL scores, but not with worse symptoms (AcroQoL total score in patients with- versus patients without cardiovascular complications: 54.89 vs 70.14, p  < 0.05). Conclusions Achieving biochemical control of acromegaly might not be enough to reverse the QoL impairment and improve symptomatology in acromegalic patients. While symptoms severity and the presence of cardiovascular complications seem to play an important role in reducing patients QoL, the roles of disease control, diabetes, and pituitary insufficiency are less clear.
The Pathophysiology and Management of Diabetic Ketoacidosis in COVID-19 Patients: A Literature Review
Diabetic individuals are considered a vulnerable population during the COVID-19 Pandemic, and several studies noted worse outcomes, including death, among those who get infected. Diabetic emergencies, such as ketoacidosis (DKA), are common and potentially life-threatening conditions in uncontrolled patients. While the pathophysiological background of the relationship between COVID-19 and DKA is not fully understood, early reports available so far indicate that patients with pre-existing diabetes who get infected with the SARS-CoV 2 virus are at higher risk of DKA. It was also suggested that DKA is a poor prognostic sign for infected patients, these being at higher risk of developing worse forms of COVID-19 disease and having high mortality. Therefore, healthcare personnel dealing with such patients face a considerable challenge, as the correct and safe emergency management of such cases is far from established. This article aimed to conduct a study that reviews the current published data available about patients with DKA and COVID-19.
A Prospective Study about the Influence of Selenium Based Supplements on the Autoimmune Process Evolution and the Health-Related Quality of Life in Patients with Chronic Autoimmune Thyroiditis
: The purpose of this study was to investigate the benefits of two different Selenium based supplements on patients with chronic autoimmune thyroiditis. : We conducted a prospective study on 50 patients with chronic autoimmune thyroiditis, who were divided into three different treatment groups, one group taking Selenium 100 μg, one Procor T (a combination of Selenium 100 μg and other elements like copper, Zinc and Q10 Conenzyme) and one control group taking Placebo pills. We measured on two follow up visits the antibody levels (anti-thyroidperoxidase- TPO Ab) and offered each patient a standardised questionnaire regarding the thyroid-related quality of life (THYPROro). : At the 6 months follow up visit there was a statistically significant decrease in the antibody levels for each treatment group compared to the base levels. The THYPROro questionnaire scores showed an improvement in most aspects regarding the quality of life as well, but there was no significant difference between the placebo and the treated groups in the magnitude of this improvement. : Based on our results, we could not identify a certain benefit in improving quality of life with the supplementation of Selenium, as the improvements were at a similar level for the patients who took Placebo pills. Further studies with more patients, as well as taking the Selenium defficiency in consideration (by measuring the basal serum level of Selenium for each patient) would be required to find the target group of patients who could have most benefits of Selenium-based supplementation.