Journal of European Internal Medicine Professionals

Exploring The Role of Circulating Biomarkers in Glioblastoma Multiforme: Bridging The Gap Between Laboratory and Clinic

Taylan Turan, Meliha Nur Türken — Tue, 25 Mar 2025 00:00:00 +0300

Glioblastoma multiforme is the most prevalent and aggressive primary malignant brain tumor in adults, characterized by significant intratumoral heterogeneity and resistance to conventional therapies. Despite improvements in surgical resection, radiotherapy, and chemotherapy with temozolomide, GBM remains incurable, with a median survival of 10–15 months. Current diagnostic modalities include magnetic resonance imaging and tissue biopsies, face early detection, real-time monitoring, and comprehensive tumor profiling limitations. These challenges underscore the urgent need for minimally invasive, highly specific, and sensitive diagnostic tools. Liquid biopsy has emerged as a promising alternative, enabling the detection of circulating biomarkers, including circulating tumor cells, cell-free nucleic acids, extracellular vesicles, and proteins from biofluids such as blood and cerebrospinal fluid. These biomarkers offer insights into tumor heterogeneity, therapeutic resistance, and progression while facilitating dynamic treatment response monitoring. This review explores the potential of circulating biomarkers in revolutionizing GBM diagnosis and management, focusing on their molecular characteristics, clinical utility, and limitations. By integrating these innovative approaches into clinical practice, liquid biopsy has the potential to significantly improve patient outcomes, heralding a new era in the diagnosis, prognosis, and therapeutic monitoring of GBM.

What’s Missing In Diabetes Treatment? A Novel Agent Finerenone?

İlyas Öztürk, Saliha Yıldırım, Melike Polat — Tue, 25 Mar 2025 00:00:00 +0300

Diabetic kidney disease represents a leading cause of chronic kidney disease and end-stage renal disease worldwide. The pathogenesis is primarily driven by persistent hyperglycemia, which induces oxidative stress, low-grade chronic inflammation, and activation of profibrotic signaling pathways. These mechanisms promote mesangial expansion, podocyte injury, and tubular epithelial-to-mesenchymal transition, culminating in glomerulosclerosis and tubulointerstitial fibrosis. Fibrosis is a hallmark of progressive diabetic kidney disease, characterized by excessive deposition of extracellular matrix components, leading to structural distortion and progressive decline in glomerular filtration rate.

Proteinuria, a key clinical manifestation of diabetic kidney disease, reflects dysfunction of the glomerular filtration barrier and serves as both a marker and mediator of disease progression. Filtered proteins exert direct cytotoxic effects on proximal tubular epithelial cells, inducing proinflammatory and profibrotic responses that exacerbate tubulointerstitial injury and accelerate fibrosis.
Despite standard-of-care therapy with renin-angiotensin-aldosterone system blockade, a significant proportion of patients exhibit residual proteinuria and progressive renal fibrosis, underscoring the need for additional therapeutic interventions. Mineralocorticoid receptor overactivation has emerged as a critical driver of renal inflammation and fibrosis in diabetic kidney disease. Finerenone, a novel non-steroidal, selective mineralocorticoid receptor antagonist, has demonstrated potent antifibrotic and antiproteinuric effects by attenuating the transcription of proinflammatory and profibrotic mediators, including transforming growth factor-beta and connective tissue growth factor. Finerenone reduces macrophage infiltration, extracellular matrix accumulation, and fibrosis in glomerular and tubulointerstitial compartments.

The landmark FIDELIO-DKD and FIGARO-DKD trials established the efficacy of finerenone in reducing albuminuria and slowing the progression of kidney disease in patients with type 2 diabetes and chronic kidney disease. By directly targeting key pathophysiological mechanisms of renal fibrosis and proteinuria, finerenone offers a novel and evidence-based therapeutic strategy to mitigate kidney disease progression in this high-risk population.

Comment On: Pregnancy and The Kidneys: A Brief Systematic Review

Hayal Uzelli Şimşek — Sun, 23 Mar 2025 00:00:00 +0300

Comment on: “Pregnancy and The Kidneys: A Brief Systematic Review”

Abstract: Not Available

Pain-related Factors in Hemodialysis Patients

Tue, 25 Mar 2025 00:00:00 +0300

Background: Pain is a prevalent issue among patients undergoing hemodialysis (HD). This study aimed to evaluate the prevalence of pain and identify factors associated with pain in HD patients.

Methods: Two hundred two HD patients participated in the study. Demographic and clinical data, pain characteristics, and sleep quality were recorded. Symptom burden and pain severity were assessed using the Edmonton Symptom Assessment Scale (ESAS) and the McGill-Melzack Pain (MGP) questionnaire.

Results: The majority of participants were male (59.9%), with a mean age of 59.6±12.7 years. Pain was reported by 80.2% of the patients and was significantly more prevalent among females (p=0.001) and individuals with lower educational levels (p=0.005). Median ESAS and MGP scores were 20 (range: 4-84) and 47 (range: 22-84), respectively. Patients reporting pain had significantly higher levels of CRP (p=0.044), parathyroid hormone (p=0.005), and higher ESAS scores (p=0.001). Sleep quality was impaired in 37% of patients. ESAS scores were significantly higher among females (p=0.003), those with impaired sleep quality (p<0.001), and regular analgesic users (p=0.002). MGP scores were significantly elevated in patients with diabetes (p=0.002), lower educational attainment (p=0.022), daily pain occurrence (p<0.001), and poor sleep quality (p<0.001). Additionally, patients with pain in multiple body regions reported higher MGP scores (p<0.001). There was a significant correlation between MGP scores, age (p=0.001), and ESAS scores (p<0.001).

Conclusion: Pain is highly prevalent among HD patients and is associated with female gender, lower educational level, elevated CRP, and higher parathyroid hormone levels. The severity of pain is particularly influenced by diabetes, low education level, and the number of painful body regions. Moreover, pain significantly impacts symptom burden and sleep quality.

Mortality Rates and Predictors in Hospitalized COVID-19 Patients Receiving Hemodialysis for Different Conditions

Mehmet Gurdal Savsar, Emre Yaşar, Ebru Gok Oguz, Mehmet Deniz Ayli — Tue, 25 Mar 2025 00:00:00 +0300

Background: To determine the mortality rates and predictors in patients hospitalized and treated for COVID-19 infection, who are also receiving hemodialysis (HD).

Method: This retrospective study included 104 patients who received HD and were hospitalized due to COVID-19 between March 2020 and 2021. Hospitalized patients who received HD were categorized into three groups: maintenance HD (MHD) patients, those receiving HD due to acute kidney injury (AKI) or chronic kidney disease (CKD), and those receiving HD due to AKI without CKD.

Results: Sixty-four (62%) of the patients were male. The mean age of the patients was 68±13 years. 37 were receiving MHD, 41 were receiving HD due to AKI on CKD, and 26 received HD due to AKI without CKD. 12(32%) of MHD patients and 29(71%) of patients receiving HD due to AKI on CKD died (p=0.002). Of the patients receiving HD due to AKI without CKD, 26(100%) died. Patients receiving HD due to AKI without CKD had the highest mortality rate compared to both MHD and AKI in CKD groups (p<0.001). Factors predicting mortality included lymphopenia, HD due to AKI on CKD, a more than two-fold increase in AST, the requirement of mechanical ventilation, and elevated d-dimer levels.

Conclusions: We showed high mortality in all patients receiving HD for different clinical conditions. These findings highlight the necessity of close monitoring and early intervention in COVID-19 patients who received HD.

Progestin Repairs the Mitochondria Membrane Potential by Preventing Membrane Hyperpolarization in Mitochondria Transferred Endometrial Stromal Cells

Hayal Uzelli Şimşek — Tue, 25 Mar 2025 00:00:00 +0300

Background: The regenerative capacity of the endometrium is attributed to stem/progenitor cells. Despite their remarkable regenerative capacity, in some cases, impairments in regeneration can be observed. Endometrial mitochondria transplantation into the uterine cavity improves the uterine environment in Asherman’s syndrome. Mitochondria transfer shows therapeutic advantages by supporting tissue metabolism and viability. However, the disruptive environment of the endometrium could affect mitochondrial health adversely. Increasing mitochondrial activity with progestin protects against apoptosis. The aim was to investigate the effect of progestin supplementation during exogenous mitochondrial transplantation. The study was designed as an in vitro cell culture of endometrial stromal cells. Mitochondria were isolated from the same cell line, representing autologous mitochondria transplantation.

Material and Method: The transplantation of mitochondria was detected by fluorescence labeling of mitochondria. Viability was assessed by CCK8, and apoptosis was detected by AnnexinV/PI staining. Gene expression analysis was performed for Ki67, p38, and Erk1/2.

Results: Mitochondria were successfully transferred into endometrial stromal cells. The viability was not significantly altered due to the exogenous mitochondria, despite the increase in the reactive oxygen level. The addition of progestin is also well tolerated. The combined application of both mitochondria and progestin further supports the viability of cells without inducing the level of reactive oxygen species. Apoptotic levels were decreased in the presence of progestin even in the co-transfection group of mitochondria and progestin. The mitochondrial cell membrane was evaluated with JC-1 showing that the disrupted membrane potential was recovered by progestin, improving the damaged membrane potential of the mitochondria.

Conclusion: The damaged membrane potential improved in the presence of progestin, helping to improve the overall output of the mitochondrial transplantation.