Bosnian Journal of Basic Medical Sciences (BJBMS)
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Prediction of mortality in patients with secondary pulmonary embolism based on primary admission indication: A short communication
We evaluated the prediction of mortality in patients admitted to the intensive care unit (ICU) who subsequently developed a pulmonary embolism (PE) (i.e., secondary PE) using three PE-specific scores, the Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI), and modified sPESI (ICU-sPESI) and compared them to the gold standard for the assessment of ICU all-cause mortality, the Acute Physiology and Chronic Health Evaluation-IV (APACHE-IV). All critical care admission indications were grouped into four major categories: post-operative, cardiovascular, infectious (sepsis), and other. The APACHE-IV displayed better discriminative ability to predict in-hospital mortality than the PESI and ICU-sPESI, but these two scores still performed fair for the ICU admissions related to postoperative, cardiovascular, and other admission types. Meanwhile, the sPESI displayed poor predictive performance across all four admission categories. Notably, discriminatory performance for patients with an infection-related admission was consistently low regardless of which score was used
Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients
A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity
lncRNA CASC7 contributes to the progression of LPS-induced liver injury by targeting miRNA-217/TLR4 axis
It has been reported that long non-coding RNAs (lncRNAs) are involved in sepsis-induced liver injury, while the role of cancer susceptibility candidate 7 (CASC7) in liver injury induced by sepsis remains elusive. In our study, 62 patients and 55 healthy controls were enrolled from our hospital, from whom CASC7 and microRNA-217 (miR-217) in serum samples were detected by quantitative real-time PCR (qRT-PCR). Then the sepsis-induced liver injury mice model was established by lipopolysaccharide (LPS). The effect of CASC7 on liver injury induced by sepsis was confirmed by hematoxylin and eosin (HE) staining, ELISA assay, TUNEL assay, Annexin V-FITC apoptosis assay and cell counting kit-8 (CCK-8) assay, respectively. Besides, RNA pull-down, luciferase reporter gene assay, qRT-PCR, and western blot were used to evaluate the underlying mechanisms. In this study, lncRNA CASC7 was significantly increased while miR-217 was significantly decreased in patients with sepsis-induced liver injury compared with that in healthy controls. There was a negative association of CASC7 and miR-217 in serum samples from patients with sepsis-induced liver injury and healthy controls. CASC7 was upregulated in a time-dependent manner in liver tissues of LPS-treated mice. It was found that knockdown of CASC7 reduced the liver injury induced by LPS in mice. In vitro, LPS treatment enhanced cell apoptosis, while knockdown of CASC7 inhibited the role of LPS in cell apoptosis. Moreover, knockdown of CASC7 suppressed the LPS-enhanced tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) expression. In addition, miR-217 was found to be a target of CASC7, and miR-217 mimic could reverse CASC7-promoted liver injury. Furthermore, toll-like receptor 4 (TLR4) was identified as the target of miR-217, and both CASC7 and miR-217 could downregulate the mRNA and protein level of TLR4. Additionally, TLR4 overexpression could reverse miR-217-inhibited or CASC7-promoted liver injury. Taken together, CASC7 contributes to the progression of LPS-induced liver injury via the miR-217/TLR4 axis.
Analysis of prognostic factors and construction of prognostic models for invasive lobular carcinoma of the breast
Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling
Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers
The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients
Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach
The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography-assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from ten cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein–protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan–Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real-time-polymerase chain reaction (RT-PCR). Out of 5714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors, such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival (OS). Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management
PD-L1 expression in testicular germ cell tumors undergoing spontaneous regression
Spontaneous regression of testicular germ cell tumors is a well-known phenomenon; however, the precise mechanisms of spontaneous regression are still unknown. Our study aimed to investigate programmed death-ligand 1 (PD-L1) expression in spontaneously regressed testicular germ cell tumors, exploring the link between the immune response and spontaneous regression. From a sample of 356 testicular germ cell tumors, we singled out 5 completely regressed and 6 partially regressed tumors. In four out of six cases with partial regression, a residual seminoma component was found, while in the remaining two cases, an embryonal carcinoma component was found. Comparisons were made with 20 pure seminomas and 20 mixed germ cell tumors (MGCTs). A semiquantitative immunohistochemical analysis of PD-L1 expression in tumor cells and intra/peritumoral lymphocytes was performed. There was no PD-L1 expression in tumors with complete regression. All partially regressed tumors showed expression in intra/peritumoral lymphocytes within the tumor remnants. Expression was significantly more frequent in pure seminomas compared to MGCTs (P = 0.004). A positive correlation was demonstrated between the seminoma component and the proportion of PD-L1 positive lymphocytes, with a Kendall\u27s Tau-b coefficient of 0.626 (P < 0.001). Tumor cells showed PD-L1 expression in three MGCTs within the embryonal carcinoma component. Our results support an immunological mechanism of spontaneous tumor regression, with the strongest potential in testicular tumors containing seminoma components. However, further research is necessary to determine the role of PD-L1 ligand more precisely in the microenvironment of spontaneously regressed tumors
Analysis of the correlation between the Systemic Inflammatory Response Index and the severity of coronary vasculopathy
This study aims to analyze the correlation between Systemic Inflammatory Response Index (SIRI) and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). It also aims to assess the predictive value of SIRI for the severity of coronary artery stenosis. A total of 2990 patients who underwent coronary angiography were included in this study. The Gensini score was used to estimate the severity of coronary vascular lesions. The predictive ability of SIRI for CHD was evaluated using receiver operating characteristic (ROC) curves. Binary multivariate logistic regression analysis was used to predict the likelihood of CHD based on the SIRI index. The results showed that people with higher SIRI were more likely to have CHD (P < 0.001). After controlling for other risk factors, the highest quartile had a significantly higher incidence of coronary artery disease compared to the lowest quartile (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.73-3.92, P < 0.001). Furthermore, the Gensini score was significantly higher in the fourth quartile group (T4) compared to the first (T1) and second (T2) quartile groups (P < 0.001). Additionally, the SIRI was significantly higher in the group with severe coronary artery lesions compared to the mild and moderate groups (P < 0.001). The SIRI also showed a higher predictive ability for the extent of coronary lesions under the ROC curve compared to other commonly used markers, including platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001). Therefore, SIRI positively correlates with coronary artery stenosis in CHD patients, serving as an effective early screening marker for assessing stenosis severity.
Red cell distribution width to albumin ratio and mortality in acute pulmonary thromboembolism
The red cell distribution width (RDW)/albumin ratio (RAR) is an inflammation-based prognostic biomarker. To date, its prognostic value in patients with pulmonary thromboembolism (PTE) has been investigated in only one study. This study aimed to assess the effect of RAR on mortality in patients with PTE. Patients admitted for PTE between 2017 and 2023 were retrospectively reviewed. The data collected included demographic information, comorbidities, clinical findings, RDW, albumin, troponin, D-dimer levels, and in-hospital and 30-day mortality outcomes. RAR was calculated by dividing the RDW by albumin. A total of 190 patients were included in the study, of whom 83 (43.7%) were male. The mean age was 63 years (range: 23–89), and the mean RAR was 4.48% ± 1.68% /g/dL. A positive correlation was observed between RAR and both age and troponin level, whereas inverse correlations were noted with systolic blood pressure (sBP), diastolic blood pressure (dBP), and oxygen saturation (SpO2). Using a cutoff value of 5.294 determined by ROC analysis, patients with RAR ≥ 5.294 had a significantly shorter mean survival time than those with RAR value < 5.294 (16.310 months vs 35.163 months; log-rank test, P < 0.001). Multivariate Cox regression analysis identified malignancy (hazard ratio [HR], 4.213; 95% confidence interval [CI], 1.103–16.090; P = 0.035) and RAR (HR: 1.295, 95% CI: 1.035–1.621, P = 0.024) as independent predictors of survival. In conclusion, an RAR value ≥ 5.294 was associated with significantly shorter survival, underscoring its potential utility as a prognostic marker in clinical practice for non-massive PTE
Enhancing clinical decision-making in closed pelvic fractures with machine learning models
Closed pelvic fractures can lead to severe complications, including hemodynamic instability (HI) and mortality. Accurate prediction of these risks is crucial for effective clinical management. This study aimed to utilize various machine learning (ML) algorithms to predict HI and death in patients with closed pelvic fractures and identify relevant risk factors. The retrospective study included 208 patients diagnosed with pelvic fractures and admitted to Suning Traditional Chinese Medicine Hospital between 2019 and 2023. Among these, 133 cases were identified as closed PFs. Patients with closed fractures were divided into a training set (n = 115) and a test set (n = 18). The training set was further stratified into two groups based on hemodynamic stability: Group A (patients with HI) and Group B (patients with hemodynamic stability). A total of 40 clinical variables were collected, and multiple machine learning algorithms were employed to develop predictive models, including logistic regression (LR), C5.0 Decision Tree (DT), Naive Bayes (NB), support vector machine (SVM), K-nearest neighbors (KNN), random Forest (RF), and artificial neural network (ANN). Additionally, factor analysis was performed to assess the interrelationships between variables. The RF and LR algorithms outperformed traditional methods—such as central venous pressure (CVP) and intra-abdominal pressure (IAP) measurements—in predicting HI. The RF model achieved an average under the ROC (AUC) of 0.92, with an accuracy of 0.86, precision of 0.81, and an F1 score of 0.87. The LR model had an average AUC of 0.82 but shared the same accuracy, precision, and F1 score as the RF model. Key risk factors identified included TILE grade, heart rate (HR), creatinine (CR), white blood cell count (WBC), fibrinogen (FIB), and lactic acid (LAC), with LAC levels >3.7 and an injury severity score (ISS) >13 as significant predictors of HI and mortality. In conclusion, the RF and LR algorithms are effective in predicting HI and mortality risk in patients with closed PFs, enhancing clinical decision-making and improving patient outcomes