Balkan Medical Journal最新文献

Background: Acute ischemic stroke (AIS) remains a leading cause of disability worldwide, placing a significant burden on patients' quality of life and healthcare systems. Pentraxin-3 (PTX-3), an inflammatory biomarker, may be associated with AIS prognosis; however, existing evidence is inconclusive.

Aims: To examine whether serum PTX-3 levels at admission are linked to the likelihood of poor functional outcomes in AIS patients.

Study design: Systematic review and meta-analysis.

Methods: A comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases was conducted to identify studies evaluating PTX-3 levels in AIS patients. Eligible studies included those that measured PTX-3 within 48 h of admission and evaluated outcomes using the modified Rankin Scale, with scores > 2 defined as poor outcomes. A random-effects model was used to calculate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

Results: Ten cohort studies involving1202 AIS patients were included. Higher PTX-3 levels at admission were significantly associated with an increased risk of poor functional outcomes (OR, 2.06; 95% CI, 1.72-2.47; p < 0.001), with no significant heterogeneity (I² = 0%). Meta-regression showed that using higher PTX-3 cutoff values reported stronger associations (p < 0.05). Subgroup analyses confirmed consistent associations across study designs, patient characteristics, and timing of outcome assessment. The association was more pronounced in studies using a PTX-3 cutoff ≥ 3.3 ng/mL compared to those with a cutoff < 3.3 ng/mL.

Conclusion: Elevated serum PTX-3 levels at admission may serve as a prognostic biomarker for poor functional outcomes in AIS. Differences in PTX-3 cutoff values and potential residual confounding should also be considered. Further multicenter studies involving diverse populations are necessary to confirm these results and establish PTX-3 as a reliable prognostic indicator in clinical practice.

Background: Parvovirus B19 (B19V) infection occurs worldwide seasonally, especially in school-age children. Due to limited surveillance, clinicians report an increase of cases to identify outbreaks, while labs determine seropositivity rates. In 2024, B19V outbreak occurred in Türkiye and many other countries.

Aims: To estimate incidences of B19V infection in Türkiye from 2020 to 2024 using National Infectious Disease Surveillance and Early Warning System (IZCI) and to determine case fatality rate (CFR) during the 2024 outbreak period.

Study design: Retrospective descriptive study.

Methods: The number of cases was obtained from the syndromic surveillance of rash diseases in national database. All notifications with International Classification of Diseases, 10th Revision diagnosis code "erythema infectiosum" within the syndromic surveillance were included in the study. All age groups were included in the study and no specific group was excluded. Annual estimated incidences were calculated for past 5 years. The distribution of cumulative incidence for the outbreak by age group and geographical regions was analysed. CFR was calculated for the outbreak period by using the proportion of people who have been diagnosed with B19V. Disease indicators were calculated as crude rates.

Results: The estimated incidence in 2024 was 15.24 per 100,000. The peak of the outbreak was in May. The regions with the highest cumulative incidences during the outbreak period were the Black Sea, Marmara, and Central Anatolia. The highest cumulative incidence was 102.64 per 100,000 in 5-9 age group. The CFR was calculated as 0.0184% in the outbreak with 2 deaths out of 10,898 cases.

Conclusion: Türkiye has experienced the largest B19V outbreak between February and June 2024. This study showed the unusual scale of B19V post-pandemic, suggesting that such outbreaks can be expected after pandemics. The establishment of syndromic surveillance has proved critical for early outbreak detection and response.

Background: Targeted therapies directed at tumor immune checkpoint, like programmed death-ligand (PD-L)1/programmed death (PD)-1, have shown remarkable progress. Nevertheless, treatment efficacy in hepatocellular carcinoma (HCC) is notably compromised due to the intricate immune microenvironment. Exploring alternative checkpoints beyond PD-L1/PD-1, including those not located on the cell surface, may improve our understanding of their roles in areas like diagnostic potential and immune tolerance in HCC.

Aims: To explore the roles of serum exosomal CD155 (exo-CD155) in HCC.

Study design: Experimental study.

Methods: We separated and analyzed serum exosomes from HCC patients. We quantified the concentrations of serum soluble CD155 (sCD155) and serum exo-CD155, and examined their association with disease progression, hepatitis B surface antigen (HBsAg) presence, and the concentrations of α-fetoprotein fraction L3 (AFP-L3) or alpha-fetoprotein (AFP). Additionally, we assessed the diagnostic effect through the receiver operating characteristic (ROC) curve, and the immune suppressive effect on natural killer (NK) cells of exo-CD155.

Results: This study reveal elevated exo-CD155 levels in all HCC patients, with a significant increase in early-stage patients, exhibiting normal AFP/AFP-L3 or HBsAg-positive status. Exo-CD155 is linked to the progression of HCC and shows significant diagnostic effectiveness for the disease. Furthermore, the incubation of NK-92MI with exosomes derived from HCC patients leads to a substantial reduction in immune function, which can be partially counteracted with an antibody that blocks T cell immune receptor immunoglobulin and ITIM domains, (TIGIT)-blocking antibody.

Conclusion: These results disclose exo-CD155 shows promise for serving as a biomarker for HCC, especially in early-stage patients or those with normal AFP/AFP-L3 levels. Moreover, serum exosomes from HCC patients suppress NK cell immune functions through the TIGIT/CD155 pathway, contributing to immune tolerance in HCC.

Background: Endocrine resistance remains a significant therapeutic challenge in estrogen receptor-positive (ER+) breast cancer, the most common subtype, contributing to increased morbidity and mortality. The interaction between ER and HER family receptors, particularly HER2 and epidermal growth factor receptor (EGFR), drives resistance to standard therapies such as tamoxifen and trastuzumab by activating key signaling pathways, including PI3K/AKT and RAS/MAPK. Dysregulated miRNAs, which are non-coding gene expression regulators, have been linked to therapy response.

Aims: To investigate the role of miR-99b-5p in ER-HER2/EGFR crosstalk in BT-474 cells.

Study design: Experimental study.

Methods: The expression profile and prognostic significance of miR- 99b-5p in breast cancer were analyzed using The Cancer Genome Atlas (TCGA) database. BT-474 cells were transfected with miR-99b-5p mimics and inhibitors, followed by treatment with tamoxifen and trastuzumab to assess their impact on cell proliferation and ER-HER2/EGFR crosstalk. Western blotting was performed to quantify EGFR, HER2, and ESR1 protein levels. Real-time proliferation analysis evaluated changes in cell growth following miRNA transfection and drug treatment.

Results: The study revealed that miR-99b-5p is significantly overexpressed in tumors compared to normal tissues and is associated with poor patient survival and enhanced ER signaling. Transfection with miR-99b-5p mimics increased ESR1 expression and cell proliferation, even in the presence of tamoxifen or trastuzumab, indicating that miR-99b-5p contributes to therapy resistance through receptor crosstalk. Conversely, miR-99b-5p inhibition significantly restored drug sensitivity, reducing proliferation and enhancing the effectiveness of tamoxifen and trastuzumab.

Conclusion: These findings establish miR-99b-5p as a key regulator of endocrine and HER2-targeted therapy resistance. Targeting miR-99b-5p could represent a potential therapeutic strategy to improve treatment outcomes in ER+/HER2+ breast cancer. Further research is needed to clarify the underlying molecular mechanisms and validate the therapeutic potential of miR-99b-5p inhibition in clinical applications.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly impacted global mortality, albeit Türkiye has been largely excluded from mortality studies owing to delayed data release and a lack of nationwide analyses.

Aims: To identify the excess mortality rates in Türkiye between 2020 and 2022, analyze the temporal trends and regional differences, and determine factors associated with excess deaths at the regional level.

Study design: A cross-sectional ecological analysis.

Methods: We analyzed all-cause mortality data from the Turkish Statistical Institute from January 2015 to December 2022. The projected deaths during 2020-2022 were derived from Quasi-Poisson Regression models applied to the 2015-2019 provincial mortality data, adjusting for seasonal trends, population offsets, and overdispersion. The results were aggregated to national and socioeconomic levels for comparative analyses. Excess deaths were calculated as the difference between observed and projected deaths. P-scores and excess mortality per 100,000 inhabitants were utilized as standardized metrics. Socioeconomic disparities were examined using the Socioeconomic Development Ranking of Provinces and Regions (SEGE-2017). We assessed the associations between excess mortality and vaccination coverage, elderly population ratio, intensive care unit beds per 100,000 population, and population per family physician.

Results: Türkiye experienced 247,640 excess deaths [95% confidence interval (CI): 176,405-315,204] from 2020 to 2022. Excess mortality peaked in 2021 with 121,426 excess deaths (27.2% P-score, 143.5 per 100,000 population). Lower vaccination coverage [estimate: -0.51, 95% CI: (-0.81, -0.20), p = 0.001] and higher population per family physician [estimate: 0.01, 95% CI: (0.00, 0.02), p = 0.005] were significantly associated with higher excess mortality. A higher elderly population ratio was positively associated with excess deaths [estimate: 1.41, 95% CI: (0.50, 2.32), p = 0.003]. Socioeconomically less developed regions (SEGE 5 and SEGE 6) exhibited higher P-scores (21.3% and 20.2%, respectively), indicating greater relative increases in mortality when compared with the relatively more developed regions.

Conclusion: Excess mortality in Türkiye during the COVID-19 pandemic was substantial, particularly in 2021, and was influenced by regional socioeconomic disparities, vaccination coverage, and healthcare access. These findings underscore the importance of addressing sociodemographic factors and strengthening primary healthcare services in pandemic responses.