PubMed İndeksli Yayınlar Koleksiyonu

Quantitative Iron Measurements in the Basal Ganglia of NBIA Patients Using QSM: Insights From a Tertiary Center

Wed, 01 Jan 2025 00:00:00 GMT

Quantitative Iron Measurements in the Basal Ganglia of NBIA Patients Using QSM: Insights From a Tertiary Center Uygun, Ozge; Ozcan, Alpay; Aras, Fuat Kaan; Bozdemir, Evrim; Ugur Iseri, Sibel; Gueltekin, Murat; Akcakaya, Nihan Hande Objective: Neurodegeneration with brain iron accumulation (NBIA) comprises rare genetic disorders characterized by predominantly extrapyramidal symptoms and iron deposition in the basal ganglia. Conventional magnetic resonance imaging (MRI) detects qualitative changes but cannot accurately quantify iron accumulation. Quantitative susceptibility mapping (QSM) allows precise in vivo quantification of iron, providing insight into the pathophysiology of the disease. Methods: We studied 27 genetically confirmed NBIA patients and 11 age-matched healthy controls using susceptibility-weighted imaging (SWI) on a 3 Tesla MRI scanner. Basal ganglia regions of interest (ROIs) were manually delineated and QSM values were extracted. Results: Sixteen NBIA patients and 11 controls were analyzed. QSM showed significantly higher iron in the globus pallidus (GP) (p = 0.008), with PKAN patients showing a 2.5-fold increase in GP iron (p = 0.001). MPAN patients showed 2.5 times higher iron in both GP and substantia nigra (SN). A GP iron level > 0.1133 ppm increased the likelihood of PKAN 18-fold. Atypical PKAN cases had 2.5 times higher SN iron levels compared to classic cases. Interpretation: QSM is a sensitive and noninvasive tool for detecting and quantifying iron accumulation in NBIA. The GP consistently showed the highest susceptibility values across subtypes, emphasizing its significant role in disease pathology. Distinct patterns of iron deposition in different NBIA subtypes may reflect subtype-specific mechanisms with diagnostic and therapeutic relevance. Age-related susceptibility changes were found to be significant, reinforcing the need to account for age when interpreting QSM data. More importantly, QSM may serve as a candidate biomarker for longitudinal disease monitoring in future clinical trials targeting disease-modifying therapies in NBIA.

Oral Glucocorticoids for Skin Fibrosis in Early Diffuse Systemic Sclerosis: A Target Trial Emulation Study From the European Scleroderma Trials and Research Group Database

Wed, 01 Jan 2025 00:00:00 GMT

Oral Glucocorticoids for Skin Fibrosis in Early Diffuse Systemic Sclerosis: A Target Trial Emulation Study From the European Scleroderma Trials and Research Group Database Mongin, Denis; Matucci-Cerinic, Marco; Walker, Ulrich A.; Distler, Oliver; Becvar, Radim; Siegert, Elise; Ananyeva, Lidia P. ObjectiveThe objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc).MethodsWe performed an emulated randomized trial comparing the changes from baseline to 12 +/- 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (<= 20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups.ResultsWe matched 208 patients (mean age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 +/- 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4-4.0] in treated vs 3.1 [95% CI 1.9-4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (<= 24 months) or with mRSS <= 22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups.ConclusionWe did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.

Absence seizures: Update on signaling mechanisms and networks

Wed, 01 Jan 2025 00:00:00 GMT

Absence seizures: Update on signaling mechanisms and networks Akman, Ozlem; Onat, Filiz Absence seizures (AS) are a hallmark of genetic generalized epilepsies (GGE), characterized by brief episodes of impaired consciousness accompanied by electroencephalographic spike-and-wave discharges (SWDs). Traditionally attributed to cortico-thalamo-cortical (CTC) dysrhythmia, emerging evidence suggests a more intricate pathophysiological framework involving high-order thalamic nuclei, the basal ganglia, limbic structures, and the cerebellum. Rather than arising abruptly from a discrete cortical event, SWDs appear to develop progressively through dynamic network interactions. This paradigm shift underscores the necessity of a network-based approach to comprehensively understand AS pathophysiology. Concurrently, advances in electrophysiology and neuroimaging are refining our understanding of the signaling mechanisms that drive AS generation. This review explores the network dynamics underlying AS, synthesizing recent experimental and clinical findings to provide an integrative framework for future research and the development of novel therapeutic strategies in absence epilepsy.Plain Language SummaryAbsence seizures are brief episodes of staring and unresponsiveness, often beginning in childhood, and are caused by abnormal rhythmic activity in the brain. This review summarizes recent research on how specific brain circuits generate and maintain these seizures. While most studies have focused on the cortex and thalamus, we also highlight the contributions of other regions such as the basal ganglia, cerebellum, and limbic structures. Understanding how these brain networks interact may help explain seizure patterns and guide the development of improved treatments.

Vitamin D Supplementation During Neoadjuvant Chemotherapy for Breast Cancer Improves Pathological Complete Response: A Prospective Randomized Clinical Trial

Wed, 01 Jan 2025 00:00:00 GMT

Vitamin D Supplementation During Neoadjuvant Chemotherapy for Breast Cancer Improves Pathological Complete Response: A Prospective Randomized Clinical Trial Ozkurt, Enver; Ordu, Cetin; Ozmen, Tolga; Ilgun, Ahmet Serkan; Soybir, Gursel; Celebi, Filiz; Koc, Ertan IntroductionAchieving a pCR serves as a biomarker indicating enhanced overall survival for breast cancer patients undergoing NST. Vitamin D enhances the antitumor effect of chemotherapeutics as demonstrated in cancer cells and animal models. In this prospective randomized clinical study, we aim to investigate the effect of oral vitamin D supplementation during neoadjuvant systemic therapy (NST) on pathologic complete response (pCR).MethodsBetween June 2019 and June 2023, an oral form of 50,000 IU vitamin D3 (cholecalciferol) replacement was administered once a week during NST for the study group.ResultsThere were 114 (50.2%) cases in the study group and 113 (49.8%) in the control group (totally 227 cases). Factors that positively influenced pCR were higher clinical T stage, higher AJCC clinical stage, Estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, high Ki-67 expression (>= 20%), hormone negative molecular subtypes, and vitamin D intake in univariate analysis. In the multivariate analysis, factors significantly affecting pCR were vitamin D intake (OR: 2.33, 95% CI 1.20-4.53; p = 0.013), hormone receptor negativity (OR: 2.22, 95% CI 1.11-4.43; p = 0.024), and Ki-67 >= 20% (OR: 3.27, 95% CI 1.03-10.34; p = 0.044).ConclusionsThis is the first and only study to compare the effect of oral vitamin D supplementation on pCR during NST. Vitamin D supplementation during NST has a significant effect on pCR in breast cancer patients. Although this effect is not significant for axillary pCR, there is an almost significant correlation.Trial RegistrationClinicalTrials.gov (Identifier: NCT03986268)