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- Woldmar, N., et al.
(author)
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Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases
- 2023
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 8:1
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Journal article (peer-reviewed)abstract
- Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259. Results: Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases. Conclusions: This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
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- Sovic, J., et al.
(author)
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Patterns of Antibiotic Prescription in Endodontic Therapy in the Republic of Croatia
- 2024
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In: Antibiotics. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2079-6382. ; 13:7
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Journal article (peer-reviewed)abstract
- In response to the global trend of decreasing antibiotic usage, this study aimed to evaluate the nature and frequency of antibiotic prescriptions in conjunction with endodontic therapy in Croatia and to assess the attitudes of Croatian dental practitioners towards the endodontic treatment of patients susceptible to bacterial endocarditis. A survey questionnaire was sent to all dental practitioners in Croatia, achieving a response rate of 27%. The most frequently prescribed antibiotic was penicillin with clavulanic acid (63.4%), while standalone penicillin was less prevalent (18.6%). For patients exhibiting penicillin allergies, 90% of respondents indicated clindamycin as their preferred alternative. Antibiotics were mostly prescribed for localized acute apical abscesses without fever, followed by prophylaxis for infectious endocarditis and cellulitis. Only 1.3% of the respondents reported frequent antibiotic prescriptions without accompanying local treatment. While a substantial proportion of surveyed practitioners professed familiarity with the latest guidelines for antibiotic prophylaxis, their choice of antibiotics did not consistently reflect this claim. Most respondents conducted endodontic procedures on patients at risk of bacterial endocarditis. The findings highlight a need for targeted continuing education for dental practitioners in the Republic of Croatia, ensuring their practices align with current guidelines and global trends in antibiotic prescription.
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