Independent Indicator Research Articles

Tissue Eosinophils Threshold and its Association with Adult-Onset Asthma in Chronic Rhinosinusitis.

Tissue eosinophil counts (TEC) might serve as a biomarker linking chronic rhinosinusitis (CRS) and the presence of adult-onset asthma. This study aimed to determine if TEC in sinus mucosa/polyps in CRS patients is an independent indicator of asthma and to identify its optimal cut-off point. This cross-sectional study was conducted on primary CRS patients scheduled for surgery. All patients were assessed by a pulmonologist for asthma diagnosis. Tissues were collected during surgery and evaluated for TEC. Logistic regression and receiver operating characteristic analysis were used to determine significant factors and the optimal cut-off points of TEC associated with asthma. A total of 103 CRS patients were included. Ten patients (9.7%) had underlying asthma, while 13 (12.6%) were first diagnosed by the pulmonologist. TEC ≥40 cells per high-powered field (HPF) exhibited a significant correlation with asthma (area under the curve=0.71, p<0.001). The sensitivity of this cut-off point was 0.70 (95% confidence interval [CI]=0.47-0.87), and specificity was 0.66 (95% CI=0.55-0.76). Positive predictive value and negative predictive value were 0.37 and 0.88, respectively. The cut-off point significantly associated with the presence of asthma, with an adjusted odds ratio of 3.13 (95% CI=1.05-9.35, p=0.04), controlling for polyps, allergic rhinitis, and computerized tomography (CT) score. TEC in CRS patients can help determine the presence of adult-onset asthma, with an optimal threshold of ≥40 cells/HPF. This threshold is significantly associated with asthma independent of polyps, allergy, and CT score.

Regulator of G protein signaling-1 facilitates ovarian cancer development by modulating NF-kB signal pathway

Regulator of G protein signaling 1 (RGS1) is known to be highly expressed in various tumors, but its specific effects and regulatory mechanism in ovarian cancer (OC) progression are not well understood. To delve into the tumor biology, a predictive risk model for OC was developed, incorporating RGS1, PRKG2, CD24, and ABCB1, with RGS1 exhibiting the strongest correlation. The model’s reliability and validity were confirmed through Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and principal component analysis (PCA). The risk score was validated as an independent indicator of overall survival, and a nomogram model was created to predict overall survival. Moreover, RGS1 expression was found to be up-regulated and associated with a poor prognosis in OC. Functional studies revealed that deleting RGS1 inhibited OC cell proliferation both in vitro and in vivo, while overexpression of RGS1 enhanced cell proliferation. Additionally, blocking the NF-kB pathway was shown to impede RGS1-induced proliferation, and overexpression of p65 partially reversed the effects of RGS1 deletion, promoting the tumorigenic properties of OC cells. These findings suggest that RGS1 could be a valuable biomarker for predicting prognosis and a potential novel therapeutic target for OC treatment.

Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.

To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival. Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC. To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model. Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features. Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis. Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

EMPIRICAL INSIGHTS INTO PORTFOLIO MANAGEMENT AND BANK PERFORMANCE IN KOSOVO: A GENERALIZED METHOD OF MOMENTS EXAMINATION

The purpose of this study is to analyze certain banking factors, namely the managing of the investment portfolio in the banking business of Kosovo. The data used are time series on an annual basis for a total of the last 13 years, and these data were tested using the Generalized Method of Moments. The findings of the study on the return on assets show that investments in the production sector have a negative influence, whereas, investments in the trade sector, and investments in short-term securities have a statistically important positive influence on return on assets. With the same level of importance investment in the production sector negatively influences the return on equity, whereas investment in the trade sector and investment in short securities positively affect the return on equity. The surprising result has turned out to be in the rankings in the service sector since it has a non-significant statistical value. From the aspect of innovation and originality, during the investigation of the empirical literature, we did not notice that these independent indicators were included.

Early reduction in total cholesterol to high-density lipoprotein cholesterol ratio predicts hydroxychloroquine efficacy in treating IgA nephropathy

Background Hydroxychloroquine (HCQ) effectively improves lipid levels in patients with autoimmune diseases. This study aimed to examine the effect of HCQ on lipid profiles in patients with immunoglobulin A (IgA) nephropathy (IgAN) and determine whether alterations in lipid profiles can predict the efficacy of HCQ. Methods This study retrospectively analyzed 77 patients, and the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) decline rate after 3 months of HCQ treatment was selected as a predictor based on receiver operating curve analysis. Patients were then divided into low and high TC/HDL-C decline rate groups based on the optimal cutoff value. The Cox proportional hazard model and Kaplan–Meier curve were used to evaluate the value of the TC/HDL-C decline rate in predicting the efficacy of HCQ in patients with IgAN. Results Patients in the high TC/HDL-C decline rate group with ≥50% decrease in proteinuria from baseline experienced a significant improvement during the follow-up. Kaplan–Meier analysis revealed that a high TC/HDL-C decline rate was strongly associated with a higher proteinuria reduction rate in patients with IgAN. Furthermore, multivariate Cox analysis indicated that a higher reduction in the TC/HDL-C ratio (hazard ratio: 2.314; 95% confidence interval: 1.234–4.340; p = 0.009) was an independent predictive indicator for achieving ≥50% reduction in proteinuria with HCQ therapy in IgAN. Conclusion HCQ effectively improves lipid profiles in patients with IgAN, and an early decrease in the TC/HDL-C ratio serves as a predictor of better outcomes in patients treated with HCQ.

Perioperative management of patients with infective endocarditis complicated by acute heart failure

Annotation. The article presents the results of a retrospective analysis, which included clinical data from 311 patients with infective endocarditis over the period from January 1, 2019, to October 22, 2021, at the “M.M. Amosov National Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine”. Clinical and laboratory data, as well as echocardiographic examination results, were recorded and statistically processed using STATISTICA 12.6. An algorithm for diagnostic and therapeutic measures was developed for patients with infective endocarditis presenting signs of acute heart failure during the perioperative period. The presence of vegetations on left heart valves on echocardiography, an end-diastolic index greater than 94.3 ml/m², an end-systolic index greater than 40.5 ml/m², a pulmonary artery pressure above 50 mm Hg, and a baseline NT-proBNP level over 7473.7 pg/ml were identified as independent indicators for admission to the intensive care unit and the need for urgent cardiac surgical intervention. Intraoperative hemosorption demonstrated that in-hospital mortality in the group without hemosorption was higher than in the group where hemosorption was used, with 4 (5.3%) and 1 (3.9%) patients, respectively. The results of the developed perioperative protocol for treating patients with infective endocarditis complicated by acute heart failure suggest it may be recommended for implementation in healthcare facilities.

Distributed Composite Drought Index Based on Principal Component Analysis and Temporal Dependence Assessment

A variety of drought indices were developed to monitor different types of drought, a significant natural hazard with multidimensional impacts. However, no single drought index can capture all dimensions of drought, necessitating a composite drought index (CDI) that integrates a range of indicators. This study proposes a CDI using principal component analysis (PCA) and a temporal dependence assessment (TDA) applied to time series of drought indices in a spatially distributed approach at the basin level. The indices considered include the Simplified Standardized Precipitation Index (SSPI), Simplified Standardized Precipitation-Evapotranspiration Index (SSPEI), soil moisture (SM), Normalized Difference Vegetation Index (NDVI), and streamflow (SF) from two climatically distinct small-sized basins in Portugal. Lag correlation analyses revealed a high contemporaneous correlation between SSPI and SSPEI (r &gt; 0.8) and weaker but significant lagged correlations with SF (r &gt; 0.5) and SM (r &gt; 0.4). NDVI showed lagged and negligible correlations with the other indices. PCA was iteratively applied to the lag correlation-removed matrix of drought indices for all grid points, repeating the procedure for several SSPI/SSPEI time scales. The first principal component (PC1), capturing the majority of the matrix’s variability, was extracted and represented as the CDI for each grid point. Alternatively, the CDI was computed by combining the first and second PCs, using their variances as contribution weights. As PC1 shows its highest loadings on SSPI and SSPEI, with median loading values above 0.52 in all grid points, the proposed CDI demonstrated the highest agreement with SSPI and SSPEI across all grid cells, followed by SM, SF, and NDVI. Comparing the CDI’s performance with an independent indicator such as PDSI, which is not involved in the CDI’s construction, validated the CDI’s ability to comprehensively monitor drought in the studied basins with different hydroclimatological characteristics. Further validation is suggested by including other drought indicators/variables such as crop yield, soil moisture from different layers, and/or groundwater levels.

A novel potential measurement indicator with objective and quantitative effect for trigeminal neuralgia: fractional anisotropy in MR-DTI.

To investigate the effect of diffusivity metrics of magnetic resonance diffusion tensor imaging (MR-DTI) in the assessment of treatment effects. MR-DTI examination for trigeminal neuralgia (TN) patients and the diffusivity metrics of the trigeminal ganglion (TG) were analyzed. Before and after the percutaneous stereotactic radiofrequency rhizotomy (PSR) operation, the treatment effect was assessed using pain scores and MR-DTI. The correlation between the diffusivity metrics of cranial nerve five (CNV) and visual analog scale (VAS) pain scores before and after treatment in TN patients was explored. In PSR patients, the fractional anisotropy (FA) of the affected TG is a significantly lower than that of the unaffected side (p < 0.01). After PSR, the diffusivity metrics on the bilateral TGs are not significantly different (p > 0.05). Following PSR treatment, both of the diffusivity metrics (FA) in the lowest area of the CNV and the VAS scores of TN patients show changes. Furthermore, diffusivity metric (FA) on the lowest area of the CNV preoperative is significantly negatively correlated with the VAS scores (p < 0.05). MR-DTI is capable of investigating the longitudinal changes of FA before and after radiofrequency treatment, and diffusivity metrics could be an independent reliable efficacy indicator for TN. The alteration of the diffusivity on TG may be correlated with the effect of radiofrequency treatment.

Pengaruh Pendapatan Asli Daerah dan Pajak Daerah dan Kemiskinan pada Pertumbuhan Ekonomi di Gorontalo

This study aims to analyze the influence of Local Own-Source Revenue (Pendapatan Asli Daerah, PAD), regional taxes, and poverty levels on economic growth in Gorontalo Province during the 2013– 2024 period. PAD and regional taxes are essential indicators of a region's fiscal independence in funding development, while poverty acts as an impediment that can reduce productivity and consumer purchasing power. The research employs quantitative analysis using secondary data obtained from the Central Bureau of Statistics (BPS) and regional financial reports. The results indicate that PAD and regional taxes have a significant positive impact on economic growth, while poverty levels have a significant negative effect. Increased PAD and regional tax revenues contribute to public investment, infrastructure development, and social services, supporting economic activities. On the other hand, high poverty levels slow down economic growth due to limited purchasing power and reduced participation in productive activities. In conclusion, optimizing PAD and regional tax management, along with effective poverty alleviation policies, is crucial to fostering inclusive and sustainable economic growth in Gorontalo. This study is expected to serve as a reference for local governments in formulating more targeted economic development strategies.

Development of differential diagnostic models for distinguishing between limb-girdle muscular dystrophy and idiopathic inflammatory myopathy

ObjectiveLimb-girdle muscular dystrophy (LGMD) is usually confused with idiopathic inflammatory myopathy (IIM) in clinical practice. Our study aimed to establish convenient and reliable diagnostic models for distinguishing between LGMD and IIM.MethodsA total of 71 IIM patients, 24 LGMDR2 patients and 22 LGMDR1 patients diagnosed at our neuromuscular center were enrolled. Differences in clinical, laboratory and histopathological characteristics were comprehensively compared. A nomogram and a decision tree were developed to distinguish between LGMD and IIM patients.ResultsCompared to patients with LGMD, IIM patients exhibited a significantly older age of onset, a higher prevalence of cervical flexor weakness and a more commonly diffuse MHC-I expression on muscle pathology. The ratio of synchronous serum myoglobin (Mb, ng/ml) to creatine kinase (CK, U/L) before immunotherapy was significantly higher in IIM patients than in LGMD patients. Receiver operating characteristic analysis indicated a high differential diagnostic efficiency of synchronous Mb/CK with a cutoff value of 0.18. A nomogram prediction model and a decision tree were developed based on four independent indicators (age of onset, cervical flexor weakness, synchronous Mb/CK and diffuse MHC-I expression). Five-fold cross-validation and bootstrapping techniques substantiated the discriminate efficacy of the nomograph and decision tree.ConclusionWe developed two practical differential diagnosis models for LGMD and IIM based on the analysis of four accessible indicators, including the age of onset, cervical flexor weakness, the ratio of synchronous Mb/CK values and diffuse MHC-I expression. Further studies with larger samples are needed to refine the predictive efficiency of the differential diagnostic models.

Prognostic impact of tumor‑associated stroma in triple-negative breast cancer.

To establish the histological categorization of tumor‑associated stroma (TAS) that reflects the biological behavior of triple-negative breast cancer (TNBC). One-hundred-and-twenty surgically resected cases of TNBC were examined. We histologically categorized the TAS in the invasive frontal region into two groups: mature stroma (MS) and immature stroma (IS). The designation of IS was applied for tumors in which the largest myxoid stroma filled a high-power magnification field. When there were no myxoid stroma that meet the criteria for IS, TAS was categorized as MS. The tumors with type MS were observed in 103 (85.8%) of patients, whereas 17 (14.2%) of patients had tumors with IS. In total, 72 out of 120 patients with TNBC exhibited high tumor-infiltrating lymphocytes (TILs) representing 60% of the cohort. The incidences of high TILs were 66% (68 out of 103) in the MS group but only 23.5% (4 of 17) in the IS group (p = 0.001). Progression-free survival (PFS) and overall survival (OS) curves were different between IS and MS groups (p < 0.001 each), and Cox multivariate regression analysis revealed that IS was an independent indicator for lower PFS and OS rates (p < 0.001; p = 0.008). Our findings suggest that TAS characteristics, particularly the distinction between IS and MS, play a significant role in the prognosis of TNBC. The presence of IS, associated with poor prognosis and low TILs, contrasts with the favorable outcomes observed in cases with MS. Understanding these TAS dynamics could aid in identifying patients with varying prognostic outcomes in TNBC, necessitating further research into the mechanisms behind these observations.

SELF-REGULATED LEARING DESIGN AS AN APPLICATION OF STUDENT'S SELF-ASSESSMENT IN MATHEMATICS LEARNING

Self-regulated learning is one of the important factors in learning to control oneself in thinking and acting. The purpose of this research is to analyze how much students have achieved their independence in learning. Student learning independence includes all matters of student learning independently without the help of others, student learning motivation or things that affect student independence in learning, especially in learning mathematics. This analysis study will be continued as an effort to improve self-regulated learning. The scope of self-regulated learning was analyzed by descriptive quantitative method through data collection techniques in the form of questionnaires on the object of research taken from a population of 25 students. Data collection was carried out with a questionnaire consisting of 20 statements from indicators of students' self-regulated learning ability. In learning mathematics, students who have initiative and instrinsic learning motivation, apply learning targets, and set a learning schedule in the percentage of almost half of the students do according to these indicators of independence. Almost all students diagnose learning needs, view difficulties as challenges, utilize and seek relevant sources. However, a small proportion of students lack self-efficacy or confidence in their abilities and are still low in evaluating the learning process and results. So that as an educator this needs to be considered to be able to improve students' self-regulated learning abilities (learning independence) in order to improve student achievement.

Prognostic value of the neutrophil-to-lymphocyte ratio and prognostic nutritional index in unresectable hepatocellular carcinoma patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors

ABSTRACT This study aimed to investigate the role of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in unresectable hepatocellular carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). The optical cutoff values of the NLR and PNI were determined via time-dependent receiver operating characteristic curve analysis. The associations between overall survival (OS) and various potential risk factors were analyzed. Forty-nine HCC patients were enrolled in this retrospective study. The optimal pretreatment NLR and PNI cutoff values were 2.4 and 41, respectively. The median follow-up was 8 (range 3–36) months. The median OS in the high NLR subgroup was lower than that in the low NLR subgroup (7 vs. 9 months, p < .05). However, the high PNI group had better OS than the low PNI group did (12 vs. 7 months, p < .05). Univariate analysis revealed that tumor distribution (p = .003), PNI < 41 (p = .013), and NLR ≥ 2.4 (p = .010) were associated with unfavorable OS in HCC patients. The multivariate analysis revealed that the PNI (HR = 0.353, 95% CI 0.150–0.831; p = .017) and tumor distribution (HR = 0.336, 95% CI 0.137–0.826; p = .017) were independent indicators of poor prognosis. A pretreatment NLR ≥ 2.4 and PNI < 41 are related to poor survival in unresectable HCC patients receiving TKI and ICI treatment. Moreover, a lower PNI is an independent indicator of poor prognosis when ICIs are combined with TKIs.

FINANCIAL ECONOMY OF THE SELECTED COMMUNE IN 2020-2022

The aim of the article is to analyze and assess the financial condition of the Jelcz-Laskowice commune. The financial management of the commune reflects effective budget management and shows its ability to function independently and develop further. The analysis of the commune’s budget is a tool for assessing its condition and the effectiveness of the actions taken, while the indicator analysis is the starting point for local government units in planning and implementing future budget expenditures. The assessment of the Jelcz-Laskowice commune was carried out in 2020-2022. The analysis used indicators to assess the financial condition of local government units, i.e.: budget indicators, per capita indicators, liabilities indicators by debt titles and indicators assessing the development potential of the commune. The obtained results indicate an improvement in the financial condition of the Jelcz-Laskowice commune. The increase in the income and expenditure independence indicator of the commune suggests that the unit is becoming more financially independent, which indicates the increased ability of the commune to manage its finances independently. The share of own revenues and operating surplus in total budget revenues showed an upward trend, remaining at a stable level. The Jelcz-Laskowice commune demonstrated stable financial development and effective budget management in the analysed period.

Impact Analysis of the Digital Entrepreneurial Ecosystem to Improve the Tourism Industry and Social Sustainability

Digitalisation is a key enabler of sustainable tourism in an industry that has recently been transformed by new sustainable innovations and digital solutions. In this study, we analysed the effects of the digital entrepreneurial ecosystem (DEE) on the tourism industry and social sustainability of 27 EU countries. The study underlines the key independent indicators representing the impact of the DEE’s elements. Also, a quantitative and comparative approach was considered using the panel data method and clustering analysis for data from 2014 to 2021. Our findings show significant positive impacts of DEE elements that have significantly contributed to tourism and social sustainability growth. Furthermore, hierarchical clustering analysis (HCA) revealed that eight countries (cluster A), including Germany, the UK, France, Spain, and Italy, had the highest average digitalisation levels, affecting their tourism growth and social sustainability. Ultimately, we indicate different digital user levels and marketplace, such as networks designed to produce cloud infrastructure, digital platforms, and digital tourist-based devices and applications, as having the capability to enhance tourism and social sustainability.

Hematoma surface irregularity predicts postoperative rebleeding and poor drainage in patients with spontaneous intracerebral hemorrhage following minimally invasive surgery: a retrospective cohort study at a high-volume stroke center.

The surface regularity index (SRI) reflects hematoma surface regularity in patients with intracerebral hemorrhage (ICH). Studies had reported an association between hematoma surface irregularity and hematoma expansion (HE). However, research on the correlation between the SRI and clinical outcomes in ICH patients following minimally invasive surgery (MIS) is limited. This study aimed to investigate the ability of the SRI to predict rebleeding and poor drainage in patients with spontaneous ICH following MIS. The data of patients with ICH who underwent MIS between January 2021 to September 2022 at Beijing Tiantan Hospital, a high-volume stroke center, were retrospectively analyzed. The clinical, radiological, and surgical characteristics of the patients were systematically reviewed. The hematoma were segmented and constructed, and the SRI scores were estimated using image-processing software [three-dimensional (3D) Slicer] based on preoperative computed tomography (CT) scans. Univariate and logistic regression analyses were conducted to identify potential predictors for post-MIS rebleeding and poor drainage (defined as a residual hematoma >15 mL). A total of 151 ICH patients were included in the study, of whom 28 (18.5%) experienced post-MIS rebleeding, and 75 (49.7%) had poor drainage. The SRI was found to be independently associated with rebleeding [odds ratio (OR): 0.926, 95% confidence interval (CI): 0.891-0.963; P<0.001] and poor drainage (OR: 0.912, 95% CI: 0.882-0.944; P<0.001) after adjusting for confounders in the logistic regression. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the SRI in predicting postoperative rebleeding was 0.765 (the cut-off point, sensitivity, and specificity were 44.980, 66.7%, and 82.1%, respectively), and that for poor drainage was 0.809 (the cut-off point, sensitivity, and specificity were 53.462, 61.8%, and 89.3%, respectively). The hematoma SRI is an independent indicator of postoperative rebleeding and poor drainage in ICH patients following MIS.

Up-to-Date Snapshot of Current and Emerging Medical Therapies in Primary Biliary Cholangitis.

Background/Objectives: Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic disease of the liver that symptomatically can present with pruritus and fatigue. Its established first- and second-line therapies are ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) although they provide limited symptom management. Liver transplantation offers a potentially curative therapeutic option in refractory cases progressing to cirrhosis. Novel research published after the current guidelines highlights the importance of providing an up-to-date analysis of treatment options available. Methods: In this study, we conducted a literature search using Pubmed, Ovid Medline, and SCOPUS to provide a narrative review of first-line, second-line, and emerging therapies in PBC. Results: UDCA has been well established as a long-term, safe therapy within the literature although it is possible that treatment dosage can be further optimised in refractory patients. It has a favourable side effect profile. Despite improving biochemical markers, histopathological profile, and overall outcomes, up to 30-40% of patients are refractory to it. Age and sex are highlighted as independent indicators of non-responsiveness. This necessitates effective second-line therapies. Future trials could aim to investigate UDCA as a co-first-line therapy. Further supporting results for OCA were found in the interim extension trial of the seminal POISE study. The long-term phase 4 COBOLT trial is still awaiting results to further assess the complications, adherence, and potential adverse effects. It is a viable option in UDCA-refractory patients. The high incidence rate of dose-related pruritis indicates that alternative second-line options are needed. Bezafibrate is an off-label antilipemic agent that shows promise as a prospective second-line therapy option. The landmark BEZURSO trial alleviated some efficacy and safety concerns, but it remains associated with elevated serum creatinine; thus, it should be considered with caution. Other prospective second-line therapies are budesonide, triple therapy, and novel agents such as seladelpar and elafibranor. Conclusions: UDCA should remain the treatment of choice for PBC, though perhaps not as monotherapy. With further investigation, BF shows promise as a new second-line therapy alongside OCA, which it may outperform.

Association of albumin to urea nitrogen ratio with 30-day mortality in adult hemophagocytic lymphohistiocytosis: a retrospective cohort study.

Hemophagocytic lymphohistiocytosis (HLH) is a severe disease with a grim prognosis. This study aims to investigate the potential role of albumin to urea nitrogen ratio (AUR) as a predictor of 30-day mortality in adult HLH patients. This retrospective analysis involved patients admitted to the hospital with a first-time diagnosis of HLH between January 2015 and September 2021. The primary outcome was defined as 30-day all-cause mortality. Patients were categorized as survivors and non-survivors, as well as test and validation cohorts. Clinical signs and laboratory biomarkers on admission were picked up. A total of 467 patients were included in the study, with a 30-day mortality rate of 31.0% (n = 145). There were no significant differences observed between the test and validation cohorts. Surviving patients exhibited significantly higher levels of AUR. Multivariate analysis indicated that an AUR < 3.40 was deemed to be an independent risk factor (test cohort: HR: 3.663, P < 0.001; validation cohort: 2.475, P = 0.013; total cohort: 2.976, P < 0.001). The area under the receiver operating characteristic curve (AUC) values were 0.734 in the test cohort, 0.690 in the validation cohort, and 0.711 in the total cohort. AUR emerged as an independent and reliable risk indicator for 30-day mortality in adults with HLH, offering clinicians a tool to identify high-risk patients efficiently.

Pre-infection liver function is associated with all-cause mortality among hemodialysis patients with SARS-CoV-2 Omicron variant infection

Background There is ample evidence to suggest that patients infected with SARS-CoV-2 Omicron variant may experience liver dysfunction. However, the impact of pre-infection liver function on postinfection mortality rates remains inadequately researched. Methods Data from 847 hemodialysis (HD) patients, diagnosed with Omicron across six HD centers between December 2022 and February 2023, were analyzed. Initial liver function assessments were conducted, following which patients were monitored for mortality outcomes. The stepwise multivariable Cox regression analysis and receiver operating characteristic (ROC) curves were utilized to identify the predictors of mortality. Results From the total, 98 patients (11.6%) succumbed, with a majority (80/98) within a month postinfection. The deceased patients were observed to be mostly older males with an increased prevalence of diabetes and tumors, signifying higher AST and C-reactive protein levels. These patients also exhibited lower hemoglobin, albumin, and prealbumin levels. An elevated AST [per 1 IU increment; HR 1.04 (95% CI 1–1.04), p = 0.026], AST/ALT ratio [per 1 increment; HR 1.52 (95% CI 1.27–2.36), p = 0.004], and reduced prealbumin [per 10 mg/L increment; HR 0.93 (95% CI 0.9–0.96), p < 0.001] were discovered to be independent indicators of an increased mortality risk. Notably, AST, AST/ALT ratio, and prealbumin proved significant predictors of mortality (AUC values were 0.59, 0.65, and 0.79 respectively). Conclusions This study underscores that pre-infection liver function, specifically AST, AST/ALT ratio, and prealbumin levels, substantially influence the mortality rates in HD patients following Omicron infection. Therefore, careful consideration of these liver function parameters could guide superior patient management strategies and potentially decrease mortality rates within this at-risk population.

IL-13Rα2 Is Involved in Resistance to Doxorubicin and Survival of Osteosarcoma Patients.

Interleukin 13 receptor alpha 2 (IL-13Rα2) is a receptor with a high affinity for IL-13 and is involved in the progression of human cancers. However, studies on the role of IL-13Rα2 in osteosarcoma are limited. Therefore, this study aimed to investigate the expression and roles of IL-13Rα2 in the progression of osteosarcoma. This study evaluated the roles of IL-13Rα2 in osteosarcomas by evaluating tumor tissues from 37 human osteosarcomas and osteosarcoma cells. Immunohistochemical positivity of IL-13Rα2 was an independent indicator of shorter overall survival and relapse-free survival of 37 osteosarcoma patients and 26 subpopulations of patients who received adjuvant chemotherapy with multivariate analysis. In U2OS and KHOS/NP osteosarcoma cells, overexpression of IL-13Rα2 significantly increased proliferation, migration, and invasion of cells, all of which decreased with knockdown of IL-13Rα2. Overexpression of IL-13Rα2 increased expression of TGF-β, snail, cyclin D1, and BCL2 but decreased BAX, and knockdown of IL-13Rα2 caused a decrease in expression of these molecules. In addition, both in vitro and in vivo, proliferation of osteosarcoma cells increased, and apoptosis decreased with overexpression of IL-13Rα2 under treatment with doxorubicin. Knockdown of IL-13Rα2 sensitized osteosarcoma cells to the cytotoxic effect of doxorubicin. The results of this study suggest that the expression of IL13Rα2 might be used as a potential prognostic indicator in osteosarcoma patients. Furthermore, it is observed that IL13Rα2 influences the resistance to the chemotherapeutic agent doxorubicin. Therefore, a therapeutic trial targeting IL13Rα2 might be a new therapeutic strategy for osteosarcoma, especially those highly expressing IL13Rα2.