Bosnian Journal of Basic Medical Sciences (BJBMS)
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Identifying patients at risk of prolonged hospital length of stay after total knee arthroplasty: A real-world study on the creation and validation of a cloud estimator
Get PDFAccurate prediction of the length of stay for patients undergoing total knee arthroplasty (TKA) is critical for efficient medical resource allocation. This study aimed to create a user-friendly model to assist this estimation process. A secondary analysis was conducted on 2676 patients who underwent elective primary TKA at a tertiary academic medical center in Singapore from January 2013 to June 2014. The eligible patients (n = 2600) were randomly divided into a training cohort (n = 2081) and a validation cohort (n = 519), at a ratio of 4:1. A prolonged hospital stay was defined as exceeding six days. Multivariable logistic regression was used to develop a prediction model, and an online calculator was created to facilitate its application. The model\u27s discrimination power, goodness-of-fit, and clinical applicability were evaluated. Additionally, models using other statistical methods were developed for performance comparison. The model includes predictors such as age, operation duration, history of cerebrovascular accidents, creatinine levels, procedure site, the American Society of Anesthesiologists Physical status, hemoglobin levels, and primary anesthesia type. The model demonstrated robust discrimination power with a C statistic of 0.70 (95% confidence interval, 0.64 to 0.75), satisfactory goodness-of-fit (Hosmer–Lemeshow test, P=0.286), and was applicable when thresholds were between 0.08 and 0.52, based on decision curve analysis. A predictive model was developed that can be used to identify patients who are likely to require an extended stay following TKA. This could assist in planning bed availability and guiding therapeutic decisions
Potential susceptibility genes in patients with stage III and IV periodontitis: A whole-exome sequencing pilot study
Get PDFThe aim of this study was to screen potential susceptibility genes using whole-exome sequencing (WES) in 15 Han Chinese patients with stage III or IV periodontitis and to evaluate the quantity and quality of genomic DNA extracted from saliva. DNA was extracted from saliva epithelial cells, quality-tested, and then subjected to WES and bioinformatics analyses. All variation loci were analyzed and interpreted following the American College of Medical Genetics and Genomics (ACMG) criteria. Candidate pathogenic variation loci were identified and verified using Sanger sequencing. Correlation and functional analyses of the candidate genes were used to identify potential susceptibility genes in patients with severe periodontitis. LFNG, LENG8, NPHS1, HFE, ILDR1, and DMXL2 genes were identified in over two cases each with shared mutations. Following these analyses, the DMXL2 gene was identified as being associated with stage III and IV periodontitis. These results suggest a potential pathophysiological risk mechanism for periodontitis, but need to be verified through larger clinical studies and mechanistic experiments to determine the pathogenicity of these gene mutations and their generalizability to a wider population of periodontitis patients. By screening candidate pathogenic variation loci using WES in 15 Han Chinese patients with stage III or IV periodontitis, our study could provide a pipeline and feasibility support for the identification of susceptibility genes in patients with stage III and IV periodontitis
Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study
Get PDFPostoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects
CAR-macrophage versus CAR-T for solid tumors: The race between a rising star and a superstar
Get PDFAdoptive cell therapy (ACT) has been demonstrated to be one of the most promising cancer immunotherapy strategies due to its active antitumor capabilities in vivo. Engineering T cells to overexpress chimeric antigen receptors (CARs), for example, has shown potent efficacy in the therapy of some hematologic malignancies. However, the efficacy of chimeric antigen receptor T cell (CAR-T) therapy against solid tumors is still limited due to the immunosuppressive tumor microenvironment (TME) of solid tumors, difficulty in infiltrating tumor sites, lack of tumor-specific antigens, antigen escape, and severe side effects. In contrast, macrophages expressing CARs (CAR-macrophages) have emerged as another promising candidate in immunotherapy, particularly for solid tumors. Now at its nascent stage (with only one clinical trial progressing), CAR-macrophage still shows inspiring potential advantages over CAR-T in treating solid tumors, including more abundant antitumor mechanisms and better infiltration into tumors. In this review, we discuss the relationships and differences between CAR-T and CAR-macrophage therapies in terms of their CAR structures, antitumor mechanisms, challenges faced in treating solid tumors, and insights gleaned from clinical trials and practice for solid tumors. We especially highlight the potential advantages of CAR-macrophage therapy over CAR-T for solid tumors. Understanding these relationships and differences provides new insight into possible optimization strategies of both these two therapies in solid tumor treatment
The protective effect of DNase I in retinal vein occlusion
Get PDFRetinal vein occlusion (RVO) ranks as the second most prevalent retinal vascular disease, following diabetic retinopathy. Neutrophil extracellular traps (NETs) play an important role in vascular diseases. This study aimed to elucidate the relationship between NETs and RVO, and to discern the potential role of deoxyribonuclease I (DNase I) in the prevention and treatment of RVO through the modulation of NETs. We analyzed circulating NETs biomarkers, namely cell-free DNA (cf-DNA), myeloperoxidase (MPO)-DNA, and neutrophil elastase (NE), in 30 RVO patients and 30 healthy individuals. We established an RVO mouse model using a retinal laser, and the mice were categorized into two groups: the DNase I group and the control group. Retinal images were taken at predetermined time points, and the state of the retinal vessels was assessed. Both tissue and blood samples were harvested for analysis of NETs expression through methods such as western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our finding indicate an increase in circulating NETs biomarkers in human and mouse RVO cases, while also verifying the presence of NETs in the retinal thrombus of the RVO model. Both in vitro and in vivo tests revealed that DNase I attenuated NETs formation. Moreover, DNase I injections led to diminished NETs biomarker levels and a reduced duration of the thrombus after the RVO model establishment. Consequently, DNase I, a well-established modulator of NETs formation, might exhibit protective properties in the prevention and treatment of RVO
Nomograms for predicting the overall and cancer-specific survival in patients with non-urothelial carcinoma of the bladder: A population-based study
Get PDFNon-urothelial carcinoma of the bladder (NUCB) is a relatively rare condition, with limited comprehensive studies conducted to date. This research aims to establish nomograms for forecasting overall survival (OS) and cancer-specific survival (CSS) in NUCB patients. It utilizes data of 2,522 patients from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. The effectiveness of these nomograms was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Key independent predictors for OS included age, race, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy administration. For CSS, the predictors were similar, encompassing age, sex, marital status, histological variants, grade, T stage, N stage, M stage, radical cystectomy and chemotherapy. The nomograms showed strong predictive accuracy. In the training cohort, the area under the curve (AUC) values were 0.796 (OS) and 0.799 (CSS) at 1-year, 0.807 (OS) and 0.824 (CSS) at 3-year, and 0.807 (OS) and 0.827 (CSS) at 5-year intervals. In the validation cohort, AUC values were 0.798 (OS) and 0.798 (CSS) at 1-year, 0.810 (OS) and 0.826 (CSS) at 3-year, and 0.811 (OS) and 0.825 (CSS) at 5-year intervals, consistently around 0.8. Calibration curves indicated high congruence between predicted and actual probabilities of OS and CSS, while DCA demonstrated the models\u27 substantial clinical utility. Overall, this study successfully developed and validated prognostic nomograms for NUCB, capable of accurately predicting OS and CSS at 1-, 3-, and 5-years, thereby offering valuable support in clinical decision-making and the design of clinical trials
Donor-derived cell-free DNA as a diagnostic marker for kidney-allograft rejection: A systematic review and meta-analysis
Get PDFDonor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72–0.88), 0.80 (95% CI, 0.73–0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR
D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1
Get PDFVascular calcification (VC) is a critical complication in chronic kidney disease (CKD), where transcription factors (TFs) and microRNAs (miRs) could potentially play a pivotal role in its pathogenesis and progression. To explore the potential molecular mechanism by which the TF D-box-binding protein (DBP) regulates the miR-195-5p/cyclin D1 (CCND1) axis and its impact on aortic VC in CKD rats, we established a rat model of CKD with VC through a 5/6 nephrectomy procedure. This model was treated with lentivirus overexpressing DBP or CCND1 to analyze their roles in aortic VC. Additionally, an in vitro cell model of VC was induced by high phosphorus. This model underwent transfection with lentivirus overexpressing DBP or miR-195-5p mimic/inhibitor to confirm their regulatory roles in aortic VC in vitro. We assessed the interactions between DBP and miR-195-5p, as well as between miR-195-5p and CCND1. Our results indicated that the expression of DBP and miR-195-5p was reduced, while CCND1 levels were elevated in both the rat and cell models. Overexpression of miR-195-5p inhibited VC in vascular smooth muscle cells (VSMCs). Bioinformatics prediction and dual luciferase assays confirmed that DBP could act as a TF to enhance miR-195-5p expression, with Ccnd1 identified as a downstream target gene of miR-195-5p. Overexpression of DBP inhibited aortic calcification in CKD rats, whereas overexpression of CCND1 produced the opposite effect. In conclusion, the TF DBP can inhibit CCND1 expression through transcriptional activation of miR-195-5p, thereby preventing VC in rats with CKD
Scientometrics and academia
Get PDFThe social significance and quality of every human activity are proportional to its usefulness to the social community. Science belongs to the very top of the processes and events in the history of humankind that strongly influenced the development of society, which over time transformed it and contributed to the common good. Science produced new knowledge that made it possible for billions of people to rise out of poverty, develop industrialization and mass communication, eradicate many dangerous diseases for humankind, and enable humans to leave their footprints on the moon. Science is a human activity that produces new knowledge presented through innovations, patents, and publications, aimed at solving the problems facing humanity.
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Diabetes-induced peripheral neuropathy: Is prescribing physical exercise the answer?
Get PDFDiabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, has become a global health concern with an increasing prevalence worldwide. The International Diabetes Federation (IDF) estimates that over 537 million adults currently have diabetes, and they project that this figure will likely exceed 780 million by 2045. In addition, a further 541 million adults are thought to exhibit impaired glucose tolerance/prediabetes. Among its many complications, diabetic peripheral neuropathy (DPN) affects up to 50% of sufferers, with some studies showing that its prevalence, even in prediabetes, may be as high as 77%.
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