A Search for New Biological Pathways in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy by Proteomic Research.

Background/Objectives: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease leading to significant morbidity and mortality. Despite advances in genetic diagnosis, the underlying pathophysiology remains incompletely understood. Proteomic studies offer insights into disease mechanisms by identifying altered protein expression patterns. Here, we conducted a proteomic analysis to elucidate molecular pathways associated with CADASIL. Methods: We enrolled genetically diagnosed CADASIL patients and healthy, genetically related controls. Plasma samples were subjected to proteomic analysis using the Olink platform, measuring 552 proteins across six panels. The data were analyzed from several approaches by using three different statistical methods: Exploratory Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), differential expression with moderated t-test, and gene set enrichment analysis (GSEA). In addition, bioinformatics analysis, including volcano plot, heatmap, and Variable Importance on Projection (VIP) scores from the PLS-DA model were drawn. Results: Significant differences in protein expression were observed between CADASIL patients and controls. RSPO1 and FGF-19 exhibited elevated levels (p < 0.05), while PPY showed downregulation (p < 0.05) in CADASIL patients, suggesting their involvement in disease pathogenesis. Furthermore, MIC-A/B expression varied significantly between patients with mutations in exon 4 versus exon 11 of the NOTCH3 gene (p < 0.05), highlighting potential immunological mechanisms underlying CADASIL. We identified altered pathways using GSEA, applied after ranking the study data. Conclusions: Our study provides novel insights into the proteomic profile of CADASIL, identifying dysregulated proteins associated with vascular pathology, metabolic dysregulation, and immune activation. These findings contribute to a deeper understanding of CADASIL pathophysiology and may inform the development of targeted therapeutic strategies. Further research is warranted to validate these biomarkers and elucidate their functional roles in disease progression.

[Assessment of pulmonary embolism related to active SARS-CoV-2 infection in pregnant women.] / Valoración del tromboembolismo pulmonar relacionado con infección SARS-CoV-2 activa en pacientes embarazadas.

AIM: To analyze the sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out the pulmonary embolism (PE) suspicion during the acute COVID-19 infection hospitalization period in our hospital. MATERIAL AND METHODS: SPECT scintigraphy with a reduced dose (111 MBq) of 99mTc-macroaggregated albumin was performed in all of the patients (n=5). The obtained images were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. RESULTS: Only one of the 5 patients was diagnosed with PE. Two patients obtained pathological findings of the scintigraphy attributable to radiological alterations due to COVID-19 pneumonia, and the other two had normal pulmonary perfussion. CONCLUSION: Given the non-specific features of the clinical manifestations and D-dimer values in COVID-19, as well as their similarity to those of PE, the pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance related to the absence of scientific publications on this group of patients within the context of COVID-19 pandemic exceptional situation.