Bosnian Journal of Basic Medical Sciences (BJBMS)
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Iliac vein stenting outcomes in non-thrombotic and thrombotic diseases: A systematic review and meta-analysis
Get PDFIliac vein stenting (IVS) is an endovascular revascularization procedure for iliac venous outflow obstruction. We aimed to synthesize the efficacy and safety of IVS across iliac vein disease phenotypes and follow-up horizons. Following a pre-registered protocol (PROSPERO CRD42024606701), we systematically searched Embase, Scopus, PubMed, Web of Science, and Cochrane Library on October 5, 2024. Without restricting study design, we included English-language reports with at least 10 patients that reported at least one prespecified outcome (or convertible data) and excluded studies with additional core therapies or duplicated cohorts. Diseases were classified as non-thrombotic iliac vein compression syndrome (NIVCS), post iliac vein thrombotic syndrome (PIVTS), chronic iliac vein obstruction (CIVO, that is, NIVCS or PIVTS), and acute thrombotic iliac vein obstruction (ATIVO, that is, a CIVO patient with acute ipsilateral thrombosis). The primary outcome was cumulative primary patency (CPP); secondary outcomes comprised ulcer healing, edema and pain relief, quality-of-life improvement, revised Venous Clinical Severity Score change, and adverse events. CPPs at prespecified intervals were extracted for each disease category and pooled in separate meta-analyses. Twenty-seven studies (4,782 patients) were included; demographic, intraoperative, and outcome data were systematically abstracted. Pooled CPPs were consistently high, particularly for NIVCS, and were lower when thrombotic components were present (PIVTS and ATIVO), while other efficacy outcomes generally improved and serious complications were uncommon. In conclusion, across diverse iliac vein diseases and follow-up periods, IVS demonstrates good efficacy and safety; this unfunded study supports IVS as a prominent treatment option
Braden score at ICU admission predicts 30-day mortality in acute pancreatitis
Get PDFThe Braden score, a bedside assessment tool for evaluating the risk of pressure ulcers and frailty, may identify vulnerabilities pertinent to outcomes in acute pancreatitis (AP). However, its prognostic significance in this context remains uncertain. This study aimed to determine whether the Braden score at admission predicts all-cause mortality in intensive care unit (ICU) patients with AP and whether it provides additional value to existing clinical models. In a retrospective single-center cohort study utilizing data from MIMIC-IV v3.1 (2008–2022), we included 1,985 adults diagnosed with AP. We analyzed the Braden score as both a continuous variable and a dichotomous variable (high-risk: ≤15 vs. low-risk: >15), with 30-day mortality as the primary endpoint (with secondary endpoints at 90, 180, and 360 days). Our methodology encompassed Kaplan–Meier analysis, multivariable Cox regression, restricted cubic splines, receiver operating characteristic curves, and calibration assessments. By the 30-day mark, a total of 230 deaths were recorded (11.6%). Each 1-point increase in the Braden score correlated with a 7.7% reduction in mortality risk (HR 0.923, 95% CI 0.873–0.976; p=0.005). Furthermore, patients categorized as low-risk experienced lower mortality rates compared to high-risk patients (HR 0.688, 95% CI 0.501–0.945; p=0.021). The discrimination capability at 30 days was moderate (AUC 0.67, 95% CI 0.63–0.71), with an optimal cutoff score of 15 (sensitivity 61%, specificity 65%) and good calibration; however, performance diminished over longer durations. Incorporating the Braden score into a baseline clinical model enhanced predictive accuracy (AUC 0.712 vs. 0.647; NRI 0.235; IDI 0.040; all p<0.001). The Braden score at ICU admission is independently associated with 30-day mortality in patients with AP, providing moderate, well-calibrated predictions and significant incremental value. This supports its application as an early and straightforward tool for risk stratification, pending prospective validation
Mitochondrial dysfunction, reactive oxygen species, and diabetes mellitus – A triangular relationship: A review
Get PDFDiabetes mellitus (DM) disrupts cellular homeostasis and is characterized by mitochondrial structural and functional impairments similar to those found in other metabolic disorders. Mitochondrial dysfunction (MD) leads to the excessive production of reactive oxygen species (ROS), which are central to the progression of cardiovascular (CV) disease—the leading cause of mortality associated with DM. ROS-driven oxidative stress (OS) is implicated in cardiac injury in both clinical and experimental contexts. This review synthesizes recent literature on the role of MD in the development and progression of DM and its associated CV complications, highlighting disrupted pathways that regulate the balance between ROS production and antioxidant defenses. We summarize alterations in mitochondrial dynamics—including fusion, fission, and mitophagy—mtDNA damage, and impaired oxidative phosphorylation characterized by dysregulated mitochondrial membrane potential (ΔΨm), electron transport chain (ETC) defects, uncoupling, and substrate overload. Additionally, we discuss hyperglycemia-activated pathways such as polyol flux, AGE–RAGE interactions, protein kinase C/nicotinamide adenine dinucleotide phosphate (PKC/NADPH) oxidase activation, and poly(ADP-ribose) polymerase 1 (PARP-1)-mediated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibition, which contribute to inflammation, endothelial dysfunction, β-cell failure, insulin resistance, and micro/macrovascular injury. Diagnostic and biomarker strategies encompass mtDNA analysis, bioenergetic assays, metabolomics, proteomics, and imaging techniques including PET, MRI, and NIRS. Therapeutic approaches aimed at restoring mitochondrial function and mitigating OS include mitochondria-targeted antioxidants (such as MitoQ, CoQ10, SkQ1, SS-31, and Mito-TEMPO), metabolic drugs (including metformin and SGLT2 inhibitors), lifestyle modifications, and emerging gene-editing technologies. The interplay between mitochondria, ROS, and DM reflects a tightly regulated aspect of cellular physiology; while targeted and personalized strategies hold promise, they necessitate rigorous evaluation
Immune-related gene expression in severe periodontitis assessed by NanoString technology: A preliminary study
Get PDFPeriodontitis is an inflammatory disease characterized by the destruction of the periodontal attachment apparatus, which includes alveolar bone, periodontal ligament, and cementum. This destruction is driven by a dysregulated host immune response to pathogenic subgingival biofilm. The present preliminary study aimed to evaluate immune-related gene expression patterns in patients with stage III/IV periodontitis utilizing the NanoString nCounter® platform. Unstimulated saliva samples were collected from twelve individuals: ten with severe periodontitis (stage III/IV) and two periodontally healthy controls. Total RNA was isolated and analyzed using the nCounter® Human Inflammation Panel, which profiles 249 inflammation-associated human genes. Data normalization and differential expression analysis were performed with nSolver™ software. Following quality control, genes with low expression (mean normalized counts < 20) were excluded, resulting in 89 genes available for comparison. Among these, 26 genes (29.2%) met a predefined effect-size threshold (|log2FC| ≥ 1), comprising 23 upregulated and 3 downregulated transcripts in the periodontitis group. Notably, the upregulated genes HLA-DRB1 (p = 0.003; FDR = 0.267) and CCR1 (p = 0.007; FDR = 0.312) exhibited relatively large log2 fold changes and the lowest unadjusted p-values; however, neither retained significance after FDR correction. These findings underscore the feasibility of salivary gene expression profiling as a method for identifying molecular markers associated with disease severity. Given their roles in immune activation and leukocyte recruitment, HLA-DRB1 and CCR1 emerge as potential biomarker candidates for detection, risk stratification, and therapeutic monitoring in periodontitis, necessitating validation in larger, well-characterized cohorts
Preoperative predictors of mortality in intestinal perforation
Get PDFBowel perforation represents a prevalent and life-threatening emergency within general surgical pathology. This study aims to evaluate clinical and biochemical parameters that predict mortality in cases of bowel perforation. A retrospective analysis was performed on 144 patients who underwent surgical intervention for bowel perforation between 2019 and 2024. Key variables assessed included the albumin/creatinine ratio, age, serum albumin levels, CRP, and history of COVID-19. Mortality-associated variables were analyzed using univariate and multivariate logistic regression, as well as receiver operating characteristic (ROC) analysis. The mean age of the patients was 60 years, with 84 patients (58.3%) being male. The overall mortality rate was 25%. Independent predictors of mortality identified in the study included an albumin/creatinine ratio <3.38 (odds ratio [OR]: 12.666, p<0.001), age >66 years (OR: 3.273, p=0.036), and serum albumin levels <3 g/dL (OR: 5.653, p=0.002). ROC analysis indicated that the area under the curve (AUC) for the albumin/creatinine ratio was 0.879, establishing it as the parameter with the highest predictive accuracy for mortality. Among patients with a history of COVID-19, ischemia was the predominant cause of perforation (87.5%), while malignancy was the leading cause (41.4%) in those without a COVID-19 history. This difference in etiology was statistically significant (p<0.001). In conclusion, the albumin/creatinine ratio, age, and serum albumin levels are robust parameters for predicting mortality in bowel perforation cases. Furthermore, a history of COVID-19 significantly increases the risk of bowel perforation due to ischemia
Lactylation in ischemic brain injury—metabolic mechanisms, neuroinflammation, and therapeutic targets: A review
Get PDFCerebral ischemic injury, a major cause of mortality and disability, results from reduced or interrupted blood flow to the brain, most commonly in ischemic stroke. Insufficient oxygen and nutrient supply disrupts cellular metabolism, leading to neuronal death, neurological dysfunction, and lasting impairments. Current therapeutic strategies, including thrombolysis, mechanical thrombectomy, and anticoagulation, primarily aim to restore perfusion and provide neuroprotection by preserving the ischemic penumbra. While these interventions can partially rescue viable tissue in the acute phase, their effectiveness is constrained by narrow therapeutic windows, low recanalization rates, and contraindications, leaving significant unmet clinical needs. Consequently, the search for novel, targeted approaches has become a central focus of ischemic stroke research. Recent discoveries have identified lactylation, a newly recognized post-translational modification derived from lactate, as a key regulator of gene expression, protein function, and metabolic reprogramming. Once regarded as a simple glycolytic byproduct, lactate is now known to act as both an alternative energy substrate and a signaling molecule, influencing neuronal metabolism, antioxidant defense, and inflammatory responses. In ischemic brain injury, lactylation modifications of histone and non-histone proteins may either protect neurons—by supporting energy homeostasis, regulating stress-responsive genes, and suppressing apoptosis—or exacerbate injury through neuroinflammation, excitotoxicity, and immune evasion. Evidence indicates that the outcomes of lactylation depend on lactate concentration, timing of accumulation, cell type, and the balance between “writer” and “eraser” enzymes. Therefore, lactylation emerges as a promising yet complex therapeutic target in cerebral ischemia. Modulating lactate metabolism and its downstream modifications offers new opportunities to expand the therapeutic window, attenuate neuronal injury, and improve recovery. This review summarizes the molecular mechanisms linking lactate and lactylation to ischemic injury, highlights current contradictions in experimental findings, and explores the potential of targeting lactylation pathways for innovative treatment strategies
Mitochondrial dysfunction triggers Zbp1-mediated necroptosis and inflammation in acute lung injury
Get PDFAcute lung injury (ALI) is driven by dysregulated inflammation, but how mitochondrial damage engages necroptosis in alveolar macrophages remains unclear. We aimed to define the mechanistic link between mitochondrial impairment and Zinc finger protein 1 (Zbp1)–mediated necroptosis in the murine alveolar macrophage–like cell line (MH-S). MH-S cells were stimulated with lipopolysaccharide (LPS) and profiled by RNA sequencing; necroptotic death was quantified by Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release, Zbp1 localization was examined by immunofluorescence microscopy, and Zbp1, receptor-interacting protein kinase 3 (RIPK3)/phospho-RIPK3 (p-RIPK3) and mixed lineage kinase domain-like protein (MLKL)/phospho-MLKL (p-MLKL) were measured by Western blotting. Mitochondrial status was assessed by mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (ΔΨm; JC-1), mitochondrial permeability transition pore (MPTP) opening, adenosine triphosphate (ATP) content, and the markers ATP synthase F1 subunit alpha (ATP5a1), mitochondrial transcription factor A (TFAM), and translocase of outer mitochondrial membrane 20 (TOMM20); inflammatory responses were quantified by flow cytometry and qPCR. The mitochondria-targeted antioxidant Mito-TEMPO was used to interrogate the role of oxidative stress. LPS markedly increased Zbp1 transcription, coincident with upregulation of pro-inflammatory genes and activation of necroptosis; mitochondrial damage and elevated mtROS were critical upstream events for Zbp1 induction, driving RIPK3 and MLKL phosphorylation, necroptosis, and cytokine release. Mito-TEMPO restored mitochondrial function, lowered mtROS, downregulated Zbp1 and its necroptotic effectors (p-RIPK3, p-MLKL), and significantly reduced both necroptotic injury and inflammatory output. Collectively, mitochondrial dysfunction–driven mtROS initiates the Zbp1/RIPK3/MLKL necroptotic axis in alveolar macrophages, thereby amplifying pulmonary inflammation in ALI; targeting mtROS may mitigate necroptosis and protect against lung injury
Differential effects of apelin-13 on lipid peroxidation and DNA oxidation in doxorubicin-treated rats: A preliminary study
Get PDFDoxorubicin-induced cardiotoxicity is closely associated with oxidative stress (OS), and apelin-13 has been proposed as a potential cardioprotective peptide. However, its effects on specific oxidative stress (OS) markers remain poorly understood. This preliminary study aimed to evaluate the impact of apelin-13 on oxidative stress markers in rats chronically treated with doxorubicin (DOX). Male rats received DOX with or without apelin-13 (40 µg/kg body weight/day). The levels of 8-hydroxy-2\u27-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. The DOX treatment resulted in increased MDA levels, which were unaffected by apelin-13. Conversely, 8-OHdG levels decreased with DOX alone but returned to baseline levels in the presence of DOX and apelin-13. In conclusion, while apelin-13 did not mitigate DOX-induced lipid oxidative damage, it may selectively influence nuclear OS markers. This suggests a complex and context-dependent role of apelin-13 in modulating oxidative stress associated with DOX treatment
Endothelial activation and stress index predicts 28-day mortality in patients undergoing CRRT
Get PDFThe endothelial activation and stress index (EASIX) is recognized as a prognostic indicator across various diseases; however, its utility in patients undergoing continuous renal replacement therapy (CRRT) is limited. This study aimed to investigate the relationship between EASIX and prognosis in individuals receiving CRRT. Data from patients receiving CRRT were extracted from the Medical Information Mart for Intensive Care IV database. EASIX was calculated and log2-transformed. Kaplan–Meier survival analysis was conducted based on log2(EASIX) quartiles. Cox proportional hazards regression was utilized to estimate the relationship between EASIX and 28-day all-cause mortality. Potential nonlinear associations were evaluated through restricted cubic splines (RCS) analysis, and subgroup analyses were performed to assess the robustness of EASIX\u27s impact on all-cause mortality. A total of 2,873 ICU patients treated with CRRT were enrolled. Kaplan-Meier analysis revealed that higher EASIX scores were significantly associated with lower 28-day survival (log-rank p < 0.001). After adjusting for confounding factors, EASIX remained significantly associated with the risk of 28-day all-cause mortality among CRRT patients (HR: 1.066; 95% CI: 1.026–1.107; p = 0.001). The area under the curve (AUC) of the SOFA+EASIX model was 0.694 (95% CI: 0.673–0.714; p < 0.001), slightly higher than that of the SOFA scores alone. These results suggest that EASIX may enhance the predictive performance of SOFA scores. RCS analysis indicated a linear association between log2(EASIX) and 28-day all-cause mortality (p for overall = 0.001; p for nonlinear = 0.224). Subgroup analyses confirmed the robustness of this association across various patient groups. In conclusion, EASIX is independently associated with mortality in patients undergoing CRRT. Prospective studies are warranted to further explore its therapeutic and prognostic significance
Unveiling the synergistic power of 3-hydrazinoquinoxaline-2-thiol and vancomycin against MRSA: An in vitro and in silico evaluation
Get PDFMethicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing infections ranging from skin disorders to severe conditions like infective endocarditis. Its evolving resistance, including resistance to β-lactams and last-resort antibiotics, such as vancomycin, daptomycin, and linezolid, necessitates alternative therapies. This study investigates the synergistic efficacy of vancomycin and 3-hydrazinoquinoxaline-2-thiol (3HL) against 23 clinical MRSA isolates. Susceptibility testing was performed using broth microdilution and checkerboard assays, while in silico analyses assessed interactions between vancomycin and 3HL. Vancomycin exhibited minimum inhibitory concentrations (MICs) ranging from 0.25 to 1 µg/mL, whereas 3HL showed higher MICs of 16–32 µg/mL. Synergistic interactions were confirmed via checkerboard assays, with fractional inhibitory concentration index (FICI) values between 0.236 and 0.5, indicating enhanced vancomycin efficacy. Notably, vancomycin MICs decreased significantly when combined with 3HL. In silico docking revealed interactions with penicillin-binding protein 2a (PBP2a), suggesting promising therapeutic potential. Vancomycin exhibited superior docking scores (−8.9 kcal/mol) and stabilizing hydrogen bonds, effectively targeting key protein grooves. Both compounds demonstrated potential for overcoming PBP2a’s structural occlusions, suggesting their role in combating β-lactam-resistant strains through targeted protein inhibition and structural stabilization