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ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between ARID mutations, molecular features, and clinical outcomes in melanoma patients. Cutaneous melanoma samples (n = 1577) were analyzed by next-generation sequencing. Samples were stratified by pathogenic/likely pathogenic mutation in ARID genes (ARID1A/2/1B/5B). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Tumor mutation burden (TMB)-high was defined as ≥ 10 mutations/Mb. Transcriptomic signatures predictive of response to immune checkpoint inhibitors-interferon gamma and T-cell inflamed score were calculated. Real-world overall survival (OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from time of tissue collection until last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p values adjusted for multiple comparisons. ARID2 mutations were more prevalent in cutaneous melanoma compared to ARID1A (11.0%: n = 451 vs 2.8%: n = 113), with concurrent ARID1A/ARID2 mutation in 1.1% (n = 46) of samples. ARID mutations were associated with a high prevalence of RAS pathway mutations-NF1 (ARID1A, 52.6%; ARID2, 48.5%; ARID1A/2, 63.6%; and ARID-WT, 13.3%; p

Abstract Arthritis often results in unmet healthcare needs for older adults with cognitive decline, who may struggle to communicate pain or recall symptoms. However, the risk factors for arthritis in this group remain underexplored. We addressed this gap by identifying and comparing arthritis risk factors among older adults with varying cognitive statuses. Data from 334 participants with cognitive decline and 808 participants with normal cognition were analysed using the Korean Longitudinal Study of Aging, tracking arthritis diagnoses over 12 years with Kaplan–Meier curves and Cox proportional hazards regression. Results showed 47.6% of older adults with cognitive decline developed arthritis, compared with 30.1% with normal cognition. Key risk factors for the cognitive decline group included depressive symptoms (hazard ratio [HR]: 1.87), living alone (HR: 1.66), infrequent social interactions (HR: 1.42), and greater dependency in daily activities (HR: 1.41). In the normal cognition group, additional chronic illnesses (HR: 1.41) and higher body mass index (HR: 1.09) were significant risk factors. Understanding these distinct risk factors is crucial for preventing and managing arthritis among at risk groups. Moreover, these findings can assist in developing comprehensive public health strategies integrating mental health and social support to improve health outcomes for older adults with cognitive decline.

We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.

In type 1 endometrial cancer, unopposed estrogen stimulation is thought to lead to endometrial hyperplasia which precedes malignant progression. Recent data from our group and others suggest that ALDH activity mediates stemness in endometrial cancer, but while aldehyde dehydrogenase 1 (ALDH1) has been suggested as a putative cancer stem cell marker in several cancer types, its clinical and prognostic value in endometrial cancer remains debated. The aim of this study was to investigate the clinical value of ALDH1 expression in endometrial hyperplasia and to determine its ability to predict progression to endometrial cancer. Interrogation of the TCGA database revealed upregulation of several isoforms in endometrial cancer, of which the ALDH1 isoforms collectively constituted the largest group. To translate its expression, a tissue microarray was previously constructed which contained a wide sampling of benign and malignant endometrial samples. The array contained a metachronous cohort of samples from individuals who either developed or did not develop endometrial cancer. Immunohistochemical staining was used to determine the intensity and frequency of ALDH1 expression. While benign proliferative and secretory endometrium showed very low levels of ALDH1, slightly higher expression was observed within the stratum basalis. In disease progression, cytoplasmic ALDH1 expression showed a step-wise increase between endometrial hyperplasia, atypical hyperplasia, and endometrial cancer. ALDH1 was also shown to be an early predictor of EC development, suggesting that it can serve as an independent prognostic indicator of patients with endometrial hyperplasia with or without atypia who would progress to cancer (p = 0.012).

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10-8 and 4.42 × 10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

In recent clinical practice, a biomarker of vagal neuroimmunomodulation (NIM), namely the ratio of vagally-mediated heart rate variability (vmHRV) and CRP, was proposed to index the functionality of the cholinergic anti-inflammatory pathway. This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N = 1255 and Whitehall II wave 5: N = 7870) with complete data from a total of N = 3860 participants (36.1% females; average age = 56.3 years; 11.1% deaths, last exit 18.1 years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIMCRP) or IL-6 (NIMIL6). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIMIL6 the lowest quartile was 45% more likely to die during the observed period (max. 18 years follow-up) compared to the highest quartile (HR = 0.55 CI 0.41-0.73; p

70-90% of low-grade gliomas and secondary glioblastomas are characterized by mutations in isocitrate dehydrogenase 1 (IDHmut). IDHmut produces the oncometabolite 2-hydroxyglutarate (2HG), which drives tumorigenesis in these tumors. The phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway represents an attractive therapeutic target for IDHmut gliomas, but noninvasive indicators of drug target modulation are lacking. The goal of this study was therefore to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers associated with IDHmut glioma response to the dual PI3K/(mTOR) inhibitor XL765. 1H-MRS of two cell lines genetically modified to express IDHmut showed that XL765 induced a significant reduction in several intracellular metabolites including 2HG. Importantly, examination of an orthotopic IDHmut tumor model showed that enhanced animal survival following XL765 treatment was associated with a significant in vivo 1H-MRS detectable reduction in 2HG but not with significant inhibition in tumor growth. Further validation is required, but our results indicate that 2HG could serve as a potential noninvasive MRS-detectable metabolic biomarker of IDHmut glioma response to PI3K/mTOR inhibition.

de novo fatty acid biosynthesis (DNFA) is a hallmark adaptation of many cancers that supports survival, proliferation, and metastasis. Here we elucidate previously unexplored aspects of transcription regulation and clinical relevance of DNFA in cancers. We show that elevated expression of DNFA genes is characteristic of many tumor types and correlates with poor prognosis, especially in melanomas. Elevated DNFA gene expression depends on the SREBP1 transcription factor in multiple melanoma cell lines. SREBP1 predominantly binds to the transcription start sites of DNFA genes, regulating their expression by recruiting RNA polymerase II to promoters for productive transcription elongation. We find that SREBP1-regulated DNFA represents a survival trait in melanoma cells, regardless of proliferative state and oncogenic mutation status. Indeed, malignant melanoma cells exhibit elevated DNFA gene expression after the BRAF/MEK signaling pathway is blocked (e.g. by BRAF inhibitors), and DNFA expression remains higher in melanoma cells resistant to vemurafenib treatment than in untreated cells. Accordingly, DNFA pathway inhibition, whether by direct targeting of SREBP1 with antisense oligonucleotides, or through combinatorial effects of multiple DNFA enzyme inhibitors, exerts potent cytotoxic effects on both BRAFi-sensitive and -resistant melanoma cells. Altogether, these results implicate SREBP1 and DNFA enzymes as enticing therapeutic targets in melanomas.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Dysregulation of glucose metabolism and inflammation are key factors in the development of atherosclerosis. The glucose-to-lymphocyte ratio (GLR) is a comprehensive marker for assessing glucose metabolism and inflammation. This study aims to evaluate the association between GLR and all-cause as well as cardiovascular disease (CVD) mortality in patients with ASCVD within the U.S. population. This retrospective cohort study recruited 1,753 ASCVD patients from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) with a median follow-up of 6.25 years. Mortality outcomes were determined by linkage to the National Death Index (NDI) records up to December 31, 2019. Weighted Cox proportional hazard models were used to assess the independent association between GLR and mortality risk. Restricted cubic spline (RCS) curves were used to display the relationship between GLR and all-cause mortality visually, and two-segment Cox proportional hazards models were constructed on either side of the inflection points. Kaplan-Meier survival curves were further used to assess the relationship between GLR and mortality, and further subgroup analyses were performed. Receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive ability of GLR for survival. During a median follow-up of 6.25 years, 624 deaths from various causes were observed, with 254 deaths from CVD. Cox regression analysis revealed a positive association between GLR and both all-cause and CVD mortality. Based on RCS, a J-shaped nonlinear relationship was observed between GLR and all-cause mortality in ASCVD patients, with an inflection point at 3.13. When the GLR < 3.13, it showed a significant negative association with all-cause mortality (HR 0.65, 95% CI 0.47-0.89). When GLR ≥ 3.13 for all-cause mortality, there was a significant positive correlation with all-cause mortality (HR 1.13, 95% CI 1.09-1.17). Subgroup analysis revealed a positive association between GLR and CVD mortality across most subgroups, but the correlation between GLR and CVD mortality was weaker compared to its association with all-cause mortality. In addition, an interaction was detected between GLR and age in relation to all-cause mortality. Moreover, the predictive performance of GLR on all-cause and CVD mortality seemed superior to that of glucose or lymphocytes. Our findings indicate that elevated GLR was closely associated with an increased risk of all-cause mortality and CVD mortality in ASCVD patients. Notably, the relationship between GLR and all-cause mortality exhibited a J-shaped nonlinear pattern, with an inflection point at 3.13., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the NCHS Research Ethics Review Board (ERB). All participants provided written informed consent., (© 2025. The Author(s).)

Stomach adenocarcinoma (STAD) is a common malignancy with high heterogeneity and a lack of highly precise treatment options. We downloaded the multiomics data of STAD patients in The Cancer Genome Atlas (TCGA)-STAD cohort, which included mRNA, microRNA, long non-coding RNA, somatic mutation, and DNA methylation data, from the sxdyc website. We synthesized the multiomics data of patients with STAD using 10 clustering methods, construct a consensus machine learning-driven signature (CMLS)-related prognostic models by combining 10 machine learning methods, and evaluated the prognosis models using the C-index. The prognostic relationship between CMLS and STAD was assessed using Kaplan-Meier curves, and the independent prognostic value of CMLS was determined by univariate and multivariate regression analyses. we also evaluated the immune characteristics, immunotherapy response, and drug sensitivity of different CMLS groups. The results of the multiomics analysis classified STAD into three subtypes, with CS1 resulting in the best survival outcome. In total, 10 hub genes (CES3, AHCYL2, APOD, EFEMP1, CYP1B1, ASPN, CPE, CLIP3, MAP1B, and DKK1) were screened and constructed the CMLS was significantly correlated with prognosis in patients with STAD and was an independent prognostic factor for patients with STAD. Using the CMLS risk score, all patients were divided into a high CMLS group and a low CMLS group. Patients in the low-CMLS group had better survival, more enriched immune cells, and higher tumor mutation load scores, suggesting better immunotherapy responsiveness and a possible "hot tumor" phenotype. Patients in the high-CMLS group had a significantly poorer prognosis and were less sensitive to immunotherapy but were likely to benefit more from chemotherapy and targeted therapy. In this study, 10 clustering methods and 10 machine learning methods were combined to analyze the multiomics of STAD, classify STAD into three subtypes, and constructed CMLS-related prognostic model features, which are important for accurate management and effective treatment of STAD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent to publish: All authors agree to publication., (© 2025. The Author(s).)

This study aimed to identify clinical characteristics and develop a prognostic model for non-neutropenic patients with invasive pulmonary aspergillosis (IPA). A retrospective analysis of 151 IPA patients was conducted, with patients categorized into survival (n = 117) and death (n = 34) groups. Clinical data, including demographics, laboratory tests, and imaging, were collected. Multivariate Cox regression analysis identified glucocorticoid use (odds ratio [OR] = 30.223, 95% confidence interval [CI]: 2.676-341.306), intensive care unit admission (OR = 0.133, 95% CI: 0.023-0.758), and the arterial oxygen partial pressure/fractional inspired oxygen ratio (OR = 0.994, 95% CI: 0.990-0.999) as significant predictors of 28-day mortality. A prognostic model was developed based on these factors, showing high predictive accuracy (receiver operating characteristic curve area of 0.918). The model's clinical applicability was validated through calibration curves, bootstrap internal validation, decision curve analysis, and clinical impact curves. Kaplan-Meier analysis further confirmed its utility, indicating a worse prognosis for high-risk patients within 50 days and the highest survival rate at 14 days. This novel model offers valuable insights for predicting survival in non-neutropenic IPA patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study adhered to the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of the General Hospital of Ningxia Medical University (Approval No. KYLL-2024-0954). All methods were carried out in accordance with relevant guidelines and regulations. The written informed consent to participate was obtained from all the patients., (© 2025. The Author(s).)

No consensus exists on the optimal therapy for resectable gastric cancer (GC) and gastroesophageal junction (GEJ) tumors, including the effectiveness of chemoradiotherapy versus perioperative chemotherapy (PC). Our study aimed to compare overall survival (OS) outcomes associated with the recommended treatment modalities for GC and GEJ tumors and evaluate treatment trends from 2010 to 2020. A national registry cohort identified patients with ≥ cT2 nonmetastatic GC and GEJ cancer. Treatment modalities were classified as neoadjuvant chemotherapy (NC), neoadjuvant chemoradiotherapy (NCR), PC, adjuvant chemotherapy (AC), and adjuvant chemoradiation (ACR). Kaplan-Meier curve and multivariable Cox regression models evaluated factors associated with OS. A cohort of 7665 patients were included. Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant settings had worse OS than PC and NC (NCR median 47.15 months, 95% CI 44.58-52.27, and ACR median 52.67 months, 95%CI 42.78-63.93). The Cox proportional hazards model showed that NCR and NC had worse survival than PC (HR 1.74, 95% CI 1.50-2.02, p < 0.001 and HR 1.26, 95% CI 1.10-1.44, p = 0.0008, respectively). Additionally, the most utilized modality during 2020 was NC (35.8%), followed by PC (28.0%) and NCR (24.9%). The utilization of PC and NC had the most substantial rise between 2010 and 2020, increasing by 11.0%. The study demonstrates the association of PC with improved OS outcomes for nonmetastatic GC and GEJ tumors. Therapies combining radiation with chemotherapy and extended lymph node dissection correlated with a worse prognosis compared to PC and NC. Despite the association with improved outcomes, national data reveals low utilization rates for PC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Studies have demonstrated overall prognostic benefits of ICD implantation in patients at increased risk of sudden cardiac death. However, results are inconsistent in certain subgroups. This study aims to evaluate the prognostic implications of comorbidities on ICD outcomes and compare trends in patient selection and outcomes over a decade-long inclusion period. This study analysed 422 patients undergoing ICD implantation between 2011 and 2020. The study endpoint "no-benefit" was characterized by death from any cause occurring without prior appropriate ICD therapy. Benefit of ICD implantation was defined as either receiving appropriate ICD therapy before death or surviving until the end of the observation period. During a mean follow-up of 4.2 ± 3.0 years, no-benefit of ICD implantation was observed in 84 patients (20%). Independent risk factors for no-benefit were age ≥ 68 years (HR 4.599, p < 0.001), anemia (HR 2.549, p < 0.001), peripheral artery disease (HR 2.066, p = 0.007), and chronic obstructive pulmonary disease (HR 1.939, p = 0.014). Subgroup analysis by age < 68 years and ≥ 68 years demonstrated that the risk of no-benefit increases with age and comorbidities. When comparing patients with ICD implantation in 2011-2015 with those in 2016-2020, there were no significant differences in one-, two- and three-year-no-benefit rates. Different comorbidities were associated with no-benefit in the early and late implantation groups. Risk factors such as older age and specific comorbidities are associated with a higher likelihood of no-benefit from ICD implantation. A careful patient selection and consideration of individual risk factors besides advanced age is important., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was received from the local ethics committee of Ruhr University Bochum (Number 21-7439-BR). Informed consent: Patients gave informed consent., (© 2025. The Author(s).)

This study aimed to establish and validate prognostic nomogram models for patients who underwent 131 I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first 131 I administrated activity, and lesion 131 I uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first 131 I administrated activity, 131 I uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first 131 I treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics declarations: The Ethics Committee of Zhejiang Cancer Hospital provided ethical approval for this study (IRB-2024-53) and waived the requirement for individual written informed consent for this retrospective analysis. The study was conducted in accordance with the principles of the Declaration of Helsinki., (© 2025. The Author(s).)

The benefit of adjuvant chemotherapy (CT) for hormone receptor-negative T1a and T1bN0M0 breast cancer remains uncertain. Our study was to explore prognostic value and identify candidates of adjuvant CT for these patients. The data of hormone receptor-negative T1a and T1bN0M0 breast cancer patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were divided into two groups according to the history of adjuvant CT namely the CT group and the no CT (No CT) group. Univariate and multivariate Cox regression analysis were utilized to identify factors linked with cancer specific survival (CSS) and overall survival (OS) for the patients. Kaplan-Meier method was employed to determine survival benefit of adjuvant CT. A total of 3889 patients were included. After propensity score-matching, 1217 patients were assigned to the CT group and 1217 patients were assigned to the No CT group respectively. Based on multivariate Cox regression analysis of OS, older age, single, T1b stage, triple-negative tumor and absence of adjuvant CT were identified as risk factors related to OS. Besides, multivariable Cox regression analysis of CSS showed significant association between grade III+IV, T1b stage, triple-negative tumor and absence of adjuvant CT and CSS. The results from Kaplan-Meier curves revealed that adjuvant CT could bring OS benefit for these patients with more than two risk factors and could improve CSS for the patients with more than one risk factor. Our study supports the implementation of individualized strategies for hormone receptor-negative T1a and T1bN0M0 breast cancer patients. Adjuvant CT was recommended for potential beneficial patients after undertaking a risk-benefit discussion., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical statement: The data are publicly available, the informed consent of patients and ethical approval were waived by the Ethics Committee of the First Affiliated Hospital of Nanchang University., (© 2025. The Author(s).)

Nutrition and inflammation are closely related to prognosis in breast cancer patients. However, current nutritional and inflammatory measures predict disease free survival (DFS) of breast cancer are still different, and the most predictive measures remain unknown. This study aimed to compare the predictive effects of commonly used nutritional and inflammatory measures on DFS and to improve existing nutritional or inflammatory measures in order to develop a new model that is more effective for predicting postoperative recurrence and metastasis in breast cancer patients. The clinical data of 536 female breast cancer patients with invasive ductal carcinoma who underwent surgery at Shaoxing People's Hospital from January 2012 to December 2018 were retrospectively evaluated. The predictive effects of nutritional and inflammatory indicators on DFS were evaluated. Machine learning was used to evaluate and rank laboratory indicators, select relatively important variables to modify nutritional or inflammatory indicators with the best predictive power, and evaluate their predictive role in patients' postoperative recurrence and metastasis. Among various metrics predicting DFS, the CONUT score emerged paramount with an area under the curve (AUC) of 0.667. Interestingly, the combination of the erythrocyte levels with the CONUT score (ECONUT) achieved the highest AUC (0.722). The Kaplan-Meier survival analysis showed that the group exhibiting high ECONUT scores experiencing a notably poorer DFS. ECONUT was identified as an independent risk factor for postoperative DFS (P < 0.001). The ECONUT model could provide an effective assessment tool for predicting DFS in breast cancer patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Shaoxing People’s Hospital (064-Y-01). Due to the retrospective nature of the study, Ethics Committee of Shaoxing People’s Hospital waived the need of obtaining informed consent., (© 2025. The Author(s).)

Lipoprotein(a) [Lp(a)] is a lipoprotein with potent atherogenic and thrombogenic potential. Its role in patients with acute coronary syndrome (ACS) combined with three-vessel disease (TVD) remains unclear. This study aimed to investigate the correlation between Lp(a) levels and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS combined with TVD. Patients who underwent coronary angiography and were diagnosed with ACS combined with TVD were selected for the study. Patients were divided into three groups based on their Lp(a) levels. The correlation between Lp(a) and MACE was evaluated using univariate and multivariate Cox regression analysis, subgroup analysis, sensitivity analysis, Kaplan-Meier survival curve, receiver operating characteristic curve (ROC), and restricted cubic spline plot (RCS). A total of 1504 patients were included, with a median follow-up time of 38 months. Univariate Cox regression analysis showed that patients with higher Lp(a) levels had a significantly increased incidence of MACE (P < 0.001). After adjusting for confounding factors, multivariate Cox regression analysis indicated that high Lp(a) levels remained an independent predictor of MACE (P < 0.05). Subgroup analysis revealed that higher Lp(a) levels were significantly associated with a higher risk of MACE in subgroups including patients aged ≥ 60 years, males, those with hypertension, CKD, without diabetes, without hyperlipidemia, and without stroke (P < 0.05). Sensitivity analysis further confirmed the close correlation between Lp(a) and MACE (P < 0.05). Kaplan-Meier survival curve showed that the cumulative incidence of MACE in the high Lp(a) group was significantly higher than in the low-level group (P < 0.001). The ROC curve analysis indicated that Lp(a) had some predictive value for the occurrence of MACE (AUC: 0.623, 95% CI: 0.593-0.653, P < 0.001). The RCS plot demonstrated that after transforming Lp(a) to a normal distribution as Log10Lp(a), there was an approximately U-shaped nonlinear association between Log10Lp(a) and the risk of MACE (P nonlinear < 0.001). Lp(a) levels were significantly associated with the risk of MACE in patients with ACS combined with TVD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and informed consent: This study was approved by the Ethics Committee of Zhongda Hospital affiliated to Southeast University (Approval number: 2023ZDSYLL141-P01). This study adhered to the principles of the Declaration of Helsinki. Since this was a retrospective study involving existing medical records, direct patient contact was not required, and informed consent was waived by the Ethics Committee of Zhongda Hospital affiliated to Southeast University., (© 2025. The Author(s).)

Identifying dependable prognostic indicators is essential for the efficient management of metabolic dysfunction-associated steatotic liver disease (MASLD). The index of hemoglobin glycation (HGI) has been demonstrated to be closely linked to the onset and advancement of MASLD. Currently, no studies have investigated the relationship between HGI and mortality rates among MASLD patients. This study analyzed data from the National Health and Nutrition Examination Surveys (NHANES) covering 1999 to 2018, involving 8,257 adult patients diagnosed with MASLD. The HGI was determined using a linear regression model that correlated hemoglobin A1c (HbA1c) with fasting plasma glucose (FPG). The study employed Kaplan-Meier survival curves and weighted Cox proportional hazards models to evaluate the independent association between HGI and mortality risk. The study utilized restricted cubic splines (RCS) to visually depict the relationship between HGI and mortality risk. Over a median follow-up duration of 97.0 months, there were 1,352 recorded deaths, among which 386 were attributed to cardiovascular disease (CVD). Participants were classified into two groups based on their HGI values: the high HGI group (≥ 0.4605) and the low HGI group (< 0.4605). The results from the weighted Cox proportional hazards model indicated that individuals in the high HGI group faced a significantly higher risk of all-cause mortality (HR 1.47, 95% CI 1.19-1.82, P < 0.001). However, no significant increase in CVD mortality risk was observed (HR 1.38, 95% CI 0.95-1.99, P = 0.090). The RCS analysis identified a U-shaped association between HGI and both all-cause mortality and CVD mortality, with critical points at -0.0564 and - 0.0573, respectively. Below the critical points, HGI was negatively correlated with all-cause mortality (HR 0.82, 95% CI: 0.72-0.92, P < 0.001) and not significantly associated with CVD mortality (HR 0.78, 95% CI: 0.57-1.07, P = 0.126). Above the critical points, HGI was significantly positively correlated with both all-cause mortality (HR 1.36, 95% CI: 1.20-1.53, P < 0.001) and CVD mortality (HR 1.44, 95% CI: 1.11-1.88, P = 0.007). Further subgroup and interaction analyses corroborated the reliability of these findings. HGI could potentially function as a useful and dependable marker for evaluating all-cause mortality and cardiovascular mortality in MASLD patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The research received clearance from the National Center for Health Statistics (NCHS) Research Ethics Review Committee. Each participant provided written consent prior to engagement in the study., (© 2024. The Author(s).)

Uterine Corpus Endometrial Carcinoma (UCEC) represents a common malignant neoplasm in women, with its prognosis being intricately associated with available therapeutic interventions. In the past few decades, there has been a burgeoning interest in the role of mitochondria within the context of UCEC. Nevertheless, the development and application of prognostic models predicated on mitochondrial-related genes (MRGs) in UCEC remains in the exploratory stages. This study utilized RNA sequencing data and clinical information from the TCGA database to identify differentially expressed MRGs (DEMRGs) between UCEC and normal groups that are associated with overall survival (OS). Patients were randomly assigned to training and testing cohorts in a 1:1 ratio. In the training cohort, a risk model based on DEMRGs was developed using Lasso Cox regression analysis. Subsequently, patients in both cohorts were stratified into high-risk and low-risk groups based on their median risk scores. The prognostic performance of the model was validated through Kaplan-Meier survival analysis, ROC curves, and nomograms. Additionally, further analyses including functional enrichment, immune landscape assessment, prediction of response to ICB therapy, mutation profiling, and drug sensitivity analysis elucidated biological distinctions between the identified risk groups. We established a risk model incorporating eight MRGs. Patients classified within he high-risk group exhibited significantly poorer prognoses relative to those in the low-risk group. Functional enrichment analysis identified substantial differences in biological processes and signaling pathways between the high-risk and low-risk cohorts. Immune landscape analysis showed that patients with elevated risk scores exhibited significant immunosuppressive and immune evasion mechanisms. Conversely, low-risk patients exhibited higher expression of human leukocyte antigen (HLA) family members and immune checkpoint genes (ICGs) compared to their high-risk counterparts.Consequently, low-risk patients showed greater responsiveness to immunotherapy and potential small molecule drugs, whereas high-risk patients were more susceptible to chemotherapy. The mitochondrial-related risk model formulated in this study demonstrates efficacy in predicting both prognosis and response to immunotherapy in patients with UCEC, thereby providing a scientific basis for personalized treatment strategies. Future research endeavors should focus on further validating the clinical utility of this model and investigate the specific mechanisms of the identified MRGs in UCEC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Ethical approval for this study was granted by the Ethics Review Committee of the Cancer Hospital of Shantou University Medical College., (© 2025. The Author(s).)

Cancer is a fatal disease with a high global prevalence and is associated with an increased incidence of metabolic disorders. This study aimed to develop a novel metabolic prognostic system to evaluate the overall metabolic disorder burden in cancer patients and its relationship with their prognosis. The patients in this study were enrolled from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. The least absolute shrinkage and selection operator (LASSO) analysis was used to screen for indicators of metabolic disorders. Cox regression analysis was used to evaluate the independent association between indicators of metabolic disorders and mortality in patients. The Kaplan-Meier method was used to evaluate the survival of patients with varying burdens of metabolic disorders. Finally, nomogram prognostic models and corresponding calculators were constructed and evaluated using the areas under the receiver operating characteristic curves (AUC), decision curve analysis (DCA), and calibration curves. Five of the 19 hematological indexes, including hemoglobin, neutrophils, direct bilirubin, albumin, and globulin, were selected as the evaluation indicators of metabolic disorder burden and independent risk factors for prognosis in cancer patients. Patients with a higher metabolic disorder burden had poorer survival rates. The AUC of the 1-year, 3-year, and 5-year overall survival of the prognostic nomogram was 0.678, 0.664, and 0.650, respectively. DCA and calibration curves indicated that the clinical benefit rate of metabolic disorder burden prognostic markers was high. Patients with a higher metabolic disorder burden had poorer survival rates. The nomogram and corresponding calculator can accurately evaluate the metabolic disorder burden and predict the prognosis of patients with cancer., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study followed the Helsinki declaration. All participants signed an informed consent form, and this study was approved by the Institutional Review Board of each hospital (Anhui Provincial Cancer Hospital, Affiliated Cancer Hospital of Harbin Medical University, Affiliated Cancer Hospital of Zunyi Medical College, Guizhou Province, Beijing Shijitan Hospital, Beijing Cancer Hospital, Cancer Hospital of Chinese Academy of Medical Sciences, Chongqing Daping Hospital, Chongqing Third People’s Hospital, Chongqing Cancer Hospital, First Hospital of Jilin University, Foshan First People’s Hospital, Fujian Provincial Cancer Hospital, First Affiliated Hospital of Guangxi Medical University, First Hospital of Shanxi Medical University, Guangxi Zhuang Autonomous Region People’s Hospital, Guangdong Provincial People’s Hospital, Guigang People’s Hospital of Guangxi Province, Hebei province people’s Hospital, Huizhou Central People’s Hospital, Liaoning Provincial Cancer Hospital, Sichuan Provincial Cancer Hospital, Shanghai Ruijin Hospital, Shanghai Tenth People’s Hospital, The Affiliated Hospital of Chengde Medical College, Tangdu Hospital of the Fourth Military Medical University, The Fourth Affiliated Hospital of Harbin Medical University, The First Hospital of Hebei Medical University, The Third Affiliated Hospital of Kunming Medical University, Tianjin Medical University Cancer Hospital, The First Affiliated Hospital of Zhejiang University, The Second Affiliated Hospital of Zhejiang University, The First Affiliated Hospital of Sun Yat-sen University, The Second Hospital of Hebei Medical University, The Fourth Hospital of Hebei Medical University, The First Affiliated Hospital of Kunming Medical University, West China Hospital of Sichuan University, Wuhan Tongji Hospital, Xijing Hospital, Xinjiang Kashgar First People’s Hospital, Xingtai People’s Hospital, Yunnan Cancer Hospital, Yuncheng Central Hospital, Zhejiang First Hospital, Zhejiang People’s Hospital, and Zhejiang Cancer Hospital) (Registration number: ChiCTR1800020329). Consent for publication: All authors approved the publication., (© 2025. The Author(s).)

The association between the recently updated cardiovascular health (CVH) assessment algorithm, the Life's Essential 8 (LE8), and all-cause mortality among adults with depression remains unknown. From the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018, a cohort of 2,935 individuals diagnosed with depression was identified. Their CVH was evaluated through the LE8 score system. The investigation of mortality status utilized connections with the National Death Index up to December 31, 2019. To assess the impact of CVH on mortality risk, Kaplan-Meier survival analysis and Cox proportional hazards models, adjusting for variables related to demographics and socioeconomic status, were applied. Among 2,935 participants, those with higher CVH levels had significantly lower all-cause mortality compared to those with lower CVH levels. Cox regression analyses demonstrated that each 1-point increase in CVH score was associated with a lower risk of all-cause mortality [HR = 0.97, 95%CI:0.96-0.98]. The inverse association between CVH and mortality persisted across different demographic and socioeconomic subgroups. Higher CVH levels were associated with a significantly lower risk of all-cause mortality in individuals with depression. These findings underscore the importance of comprehensive CVH management as part of healthcare strategies for people with depression, suggesting that improving CVH may contribute to longer life expectancy in this vulnerable population., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: All human subjects involved in this study were treated in accordance with the ethical principles outlined in the Declaration of Helsinki, and the study was approved by the Research Ethics Review Board of the National Center for Health Statistics (NCHS). The patients/participants provided their written informed consent to participate in this study. Consent for publication: Not applicable., (© 2025. The Author(s).)

This study aims to explore the relationship between the albumin-corrected anion gap (ACAG) and short- and long-term all-cause mortality (ACM) in patients with acute pancreatitis (AP) managed in the intensive care unit (ICU). We conducted a retrospective analysis utilizing data extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. This study sought to investigate the correlation between ACAG and ACM among patients diagnosed with AP across various disease stages. R statistical software was used to identify the optimal thresholds for ACAG. Kaplan-Meier survival curves and multivariate Cox proportional hazards regression models were employed to assess the association between ACAG and short- and long-term ACM of AP. The predictive ability, sensitivity, specificity, and area under the curve (AUC) of ACAG for short- and long-term ACM in AP were investigated using receiver operating characteristic analysis. Subgroup analyses were also conducted. A cohort comprising 605 participants was included in this study. The ideal threshold for ACAG identified by R statistical software was 21.5. Cox proportional hazards modeling revealed that there was an independent association between patients with AP with ACAG ≥ 21.5 and ACM at 3, 7, 10, 14, 28, 90, and 180 days and 1 year before and after adjustment for confounders. Survival curves demonstrated that patients with ACAG ≥ 21.5 had lower survival rates at 3, 7, 10, 14, 28, 90, and 180 days and 1 year. In addition, ACAG showed superior performance, with a larger AUC than the anion gap, albumin, and Systemic Inflammatory Response Syndrome score and Sequential Organ Failure Assessment at 3, 7, 10, 14, 28, 90, and 180 days and 1 year. Subgroup analysis revealed no significant interaction between ACAG and any subgroups Elevated levels of ACAG were found to be associated with increased short- and long-term ACM in patients with AP, and ACAG may be an independent predictor of ACM at different disease stages., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethic Statement: In order to safeguard patient confidentiality, all personal data underwent de-identification, with random numerical identifiers assigned in place of individual identification. Consequently, the Beth Israel Deaconess Medical Center ethics committee exempted the necessity for informed consent., (© 2025. The Author(s).)

Bcl-2, a key regulator of cellular apoptosis, is typically linked to adverse prognosis in solid tumors due to its inhibition of apoptotic cell death and promotion of cellular proliferation, leading to tumor progression. However, studies on Bcl-2 in breast cancer have shown inconsistent results, with some indicating favorable outcomes. This study aims to determine the subtype-specific role of Bcl-2 in breast cancer. Female breast cancer patients who completed primary treatment at Wonju Severance Hospital, Korea, from 2004 to 2018 were included. Clinicopathological characteristics, including Bcl-2 expression, were collected, and patients were classified based on Bcl-2 expression in more than or less than 10% of tumor cells. Kaplan-Meier curves compared recurrence-free interval (RFI) and overall survival (OS). The final cohort of 617 patients, with a mean age of 54.79 ± 11.2 years, showed no overall survival difference by Bcl-2 status (p = 0.616). In HER2-overexpressed patients, high Bcl-2 expression was linked to poor prognosis (p = 0.0021). This trend appeared in ER-positive (p = 0.297) and ER-negative (p = 0.029) subgroups. Conversely, in HER2-negative patients, Bcl-2 overexpression indicated better survival (p = 0.009), consistent in ER-positive (p = 0.259) and ER-negative (p = 0.010) subgroups. Bcl-2's impact on survival varies with HER2 status, showing poor prognosis in HER2-overexpressed and better prognosis in HER2-negative patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of of Wonju Severance Christian Hospital, Wonju, Korea (CR323024). Informed consent: Patient consent was waived due to retrospective nature of the study., (© 2025. The Author(s).)

The Systemic Inflammation Response Index (SIRI), a marker used to assess systemic inflammation, is associated with lower patient survival rates in various cancer types. Factors contributing to the recurrence of colorectal cancer (CRC) have been examined previously using the preoperative SIRI. Herein, we investigated the association between the preoperative SIRI level and both the recurrence-free survival (RFS) and overall survival (OS) in patients diagnosed with CRC. We retrospectively analyzed the case of 406 patients who underwent curative surgery for Stage I-III CRC at a single institution during 2012- 2017. Based on their SIRI levels, we categorized the patients into a low-SIRI group (≤ 1700) and a high-SIRI group (> 1700). Multivariable analyses revealed that a high-SIRI level was an independent risk factor for 5-year RFS (p = 0.045) and OS (p = 0.048) in CRC patients. A Kaplan-Meier analysis demonstrated significantly poorer 5-year RFS and OS outcomes in the high-SIRI group compared to the low-SIRI group (p = 0.0001, p = 0.017 respectively). These findings suggest that the high-SIRI level is significantly associated with a poorer prognosis in patients diagnosed with CRC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics: This study was approved by the Teikyo University Ethics Committee (No. 19-127)., (© 2024. The Author(s).)

The Cardiometabolic Index (CMI) is a well-recognized risk factor for a range of cardiovascular diseases and diabetes mellitus. However, the population-level characteristics of CMI and its potential association with mortality risk among individuals over 40 years of age have not been investigated. This study aims to assess the association between CMI and both all-cause and cardiovascular mortality among the middle-aged and elderly population. This cohort study utilized data from 3752 American adults extracted from the Sleep Heart Health Study (SHHS) conducted from 1995 to 2011. The CMI was calculated using the waist-to-height ratio, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). The primary outcomes were all-cause mortality and cardiovascular mortality, with mortality data sourced from the SHHS Linked Mortality File. Kaplan-Meier survival curves and Cox regression models were employed to assess the prognostic value of the CMI. Among the 3752 American adults, the mean (SD) age was 65.9 (10.1) years, and 1969 (52.5%) were women. The mean (SD) CMI was 0.914 ± 0.939. Over an average follow-up period of 10.7 years, there were 926 all-cause deaths and 289 cardiovascular deaths. Participants were categorized into three groups based on their CMI levels: tertile (T) 1: 0.315 ± 0.0994; T2: 0.680 ± 0.128; T3: 1.75 ± 1.23. Multivariate Cox proportional hazards analysis showed that elevated CMI was significantly associated with all-cause mortality (HR 1.215, 95% CI 1.032-1.43 for T2; HR 1.309, 95% CI 1.115-1.537 for T3) and cardiovascular mortality (HR 1.305, 95% CI 0.971-1.755 for T2; HR 1.457, 95% CI 1.091-1.947 for T3). After adjusting for confounders, elevated CMI remained significantly associated with all-cause mortality (HR 1.315, 95% CI 1.098-1.575 for T3) and cardiovascular mortality (HR 1.562, 95% CI 1.124-2.17 for T3). Kaplan-Meier survival curves indicated significantly worse outcomes for participants in the higher CMI tertiles for both all-cause mortality (log-rank p = 0.0035) and cardiovascular mortality (log-rank p = 0.035). This national cohort study found that CMI is significantly associated with both all-cause and cardiovascular mortality among American adults aged over 40. These findings suggest that CMI could be a valuable tool for identifying high-risk individuals, thereby aiding in the implementation of targeted preventive strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Although it is a leading cause of cancer-related mortality among women globally, breast cancer (BC) has drawn increased attention owing to its poor prognosis and the challenges associated with limited treatment options. SLC35A2 was shown to be dysregulated in a number of tumor types according to multiple investigations. However, its function in BC was rarely reported. This study aims to investigate the expression of SLC35A2 in BC and its impact on the functionality and prognosis of BC cells. We collected 11 pairs of BC tissues and normal specimens, obtaining clinical information from 1,118 BC patients through RNA sequencing analysis. Different BC cell lines were used in experiments, and the roles of SLC35A2 in cell proliferation, invasion, and migration was assessed through gene silencing and functional assays. Additionally, a prognostic model, including SLC35A2 expression levels, age, T-stage, M-stage, N-stage, and clinical stage, was constructed, and its predictive performance in overall survival was validated using time-dependent receiver operating characteristic curves. High SLC35A2 expression was correlated positively with patient age and T-stage. Kaplan-Meier survival curves and Cox regression analysis confirmed the independent and significant prognostic value of SLC35A2 in overall survival. Functional experiments demonstrated that SLC35A2 silencing inhibited the proliferation, migration, and invasion of BC cells, affecting their metastatic potential through modulation of the Wnt/β-catenin/EMT signaling pathway. In conclusion, our study reveals the crucial role of SLC35A2 in BC, providing a novel biomarker for clinical management and valuable insights into the underlying mechanisms of BC pathogenesis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study has been approved by the ethics committee institution of Shenzhen Hospital of Union Medical College of Huazhong University of Science and Technology (2022-No.056). Research involving human research participants has been done in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Red blood cell distribution width (RDW) is considered to be associated with the prognosis of patients with severe infections. This study aims to investigate the relationship between RDW and prognosis in osteomyelitis patients admitted to the ICU. Through a retrospective cohort study, relevant records of severe osteomyelitis patients were collected from the Medical Information Mart for Intensive Care (MIMIC-IV) database. Patients were divided into low-level and high-level groups based on the median RDW. The primary outcome was the one-year mortality rate of ICU patients. Univariate and multivariate Cox models were used to determine the relationship between RDW and mortality rate in osteomyelitis patients, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. Kaplan-Meier survival curves were used to analyze patient survival status. Restricted Cubic Spline (RCS) was used to detect the nonlinear relationship between RDW and mortality rate. Stratified analysis was performed to explore the interaction between different subgroups. The study included a total of 1109 patients, among which 134 (12.08%) died within one year. Results from both univariate and multivariate Cox regression analyses indicated a significant association between elevated RDW levels (HR = 2.128, 95% CI 1.324-3.420) and an increased risk of mortality in patients with osteomyelitis. Kaplan-Meier survival curves demonstrated that the survival time of patients in the low RDW group was greater than that of those in the high RDW group (p < 0.0001). RCS analysis revealed a non-linear increase in the strength of the correlation between patient mortality rate and continuous changes in RDW. Subgroup analysis also observed a relationship between RDW levels and mortality rates in patients with osteomyelitis. Elevated RDW levels are correlated with an increased risk of mortality in osteomyelitis patients admitted to the ICU., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The establishment of MIMIC-IV (v2.0) was approved by the institutional review boards of the Beth Israel Deaconess Medical Center (Boston, MA) and Massachusetts Institute of Technology (Cambridge, MA). Thus, this study was granted a waiver of informed consent., (© 2024. The Author(s).)

This retrospective cohort study aimed to evaluate the association between pre-existing heart failure and both mortality and the recurrence of sepsis. A total of 16,092 sepsis patients without a history of heart failure and 841 sepsis patients with pre-existing heart failure were identified from the Medical Information Mart for Intensive Care version IV (MIMIC-IV ) database. All patients were adults admitted to intensive care units, and no specific interventions were applied. After matching, Kaplan-Meier survival analysis showed significantly poorer long-term survival rates in patients with heart failure, both in the original (p < 0.0001) and the matched cohort (p = 0.00059). Mortality rates were tracked over different time periods, revealing that the mortality disparity became evident after the first year (p = 0.029). Besides, the cumulative incidence of sepsis recurrence was substantially higher in patients with a history of heart failure (p < 0.001) when deaths without recurrence were treated as competing events. Moreover, there was no statistically significant difference observed in the deaths without recurrence between the two groups (p = 0.251). In conclusion, pre-existing heart failure is associated with an increased risk of long-term mortality, which may be partly explained by a higher incidence of recurrent sepsis in this population., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The utilization of these databases was authorized by the Institutional Review Boards of Beth Israel Deaconess Medical Center (BIDMC) and the Massachusetts Institute of Technology. The requirement for patient consent was waived by Institutional Review Boards of BIDMC and Massachusetts Institute of Technology, given that all patient identifiers had been removed from databases. One of the authors (Xiu-Ping Hu) has completed the requisite training and was granted access to these databases, holding a record ID of 52,834,169., (© 2024. The Author(s).)

The purpose of this study was to analyze the efficacy of treatment and survival after administration of immune checkpoint inhibitor (ICI) in Japanese patients and had endocrine-related and/or other immune-related adverse events (irAEs), as well as irAEs in multiple organs. This is a single-center, retrospective, observational study of 571 Japanese patients treated with ICI at our hospital. We evaluated the occurrence of Grade 3 or higher irAEs and the life expectancy and treatment efficacy after ICI administration. Endocrine-related irAE (E-irAE), other irAE (O-irAE), endocrine-related and other irAE (EO-irAE), and multiple endocrine-related irAE (ME-irAE) were evaluated in groups. 80.8% of patients had an irAE, with the highest incidence of irAE with ipilimumab plus PD-1 inhibitor, followed by atezolizumab 59.0%, pembrolizumab 53.7%, avelumab 50.0%, and nivolumab 47.3%, Durvamumab 26.7% followed; Kaplan-Meier survival curves showed higher survival rates in patients with irAE compared to non-irAE, and higher survival rates in EO-irAE and ME-irAE compared to E-irAE and O-irAE (p < 0.001). The COX proportional hazard ratios for overall survival were E-irAE 0.611 (0.480-0.772), O-irAE 0.758 (0.597-0.957), EO-irAE 0.622 (0.466-0.819) and ME-irAE 0.463 when non-irAE was set at 1.000 (0.257-0.775). When grade 3 or higher irAEs appeared, regardless of their type, there was a trend toward higher survival and post-treatment remission rates after ICI administration. In addition to this, patients with irAEs in multiple endocrine tissues and patients with irAEs in both endocrine and other organs had a better response to treatment after ICI administration., Competing Interests: Declarations. Competing interests: H.K. has received honoraria for lectures, received scholarship grants, and received research grant from Novo Nordisk Pharma, Sanofi, Eli Lilly, Boehringer Ingelheim, Taisho Pharma, Sumitomo Pharma, Takeda Pharma, Ono Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Kissei Pharma, MSD, AstraZeneca, Astellas, Novartis, Kowa, Abbott. K.K. has been an advisor to, received honoraria for lectures from, and received scholarship grants from Novo Nordisk Pharma, Sanwa Kagaku, Taisho Pharma, Kowa, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Astellas, Boehringer Ingelheim. S.N. has received honoraria for lectures from Novo Nordisk Pharma and Daiichi Sankyo. All other authors have no conflict of interests., (© 2024. The Author(s).)

The aim of this study was to explore the high-risk factors for recurrence in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy or radiotherapy (dCRT or dRT). Conditional survival (CS) was used to evaluate the dynamic survival and recurrence risk of patients after treatment, and individualized monitoring strategies were developed for patients. Logistic regression analysis was performed to determine independent recurrence risk factors. Calibration curves and receiver operating characteristic (ROC) curve were used to evaluate nomogram models. Kaplan-Meier curves were used to compare survival rates in different groups and to calculate CS rate. A total of 677 patients were included. Multivariate logistic analyses demonstrated that chemotherapy cycles, tumor length, body mass index (BMI), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were independent recurrence risk factors (p < 0.05). Subsequently, we constructed nomogram models to predict recurrence and risk stratification. Kaplan-Meier curves showed that conditional locoregional recurrence-free survival and distant metastasis-free survival of patients in different risk groups and clinical stages progressively increased with survival time, whereas local recurrence and distant metastasis annual recurrence rates decreased yearly with increasing survival time. Finally, we developed an individualized follow-up strategy based on CS at different frequencies. Individualized follow-up strategies developed on the basis of CS can better monitor the changes in patients' conditions and contribute to timely salvage treatment and rational allocation of healthcare resources., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was sanctioned by Fujian Cancer Hospital’s Ethics Committee (SQ2022-185). All patients provided written informed consent., (© 2024. The Author(s).)

The latest World Health Organization Classification of Tumors, Fifth Edition, recognizes the invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC) as a distinct malignant entity rather than a subtype of papillary thyroid carcinoma (PTC). This reclassification highlights the need to explore potential prognostic differences between IEFVPTC and classic PTC. This study utilized the Surveillance, Epidemiology, and End Results (SEER) database to compare prognoses of patients diagnosed with IEFVPTC and classic PTC between 2004 and 2019. Propensity score matching (PSM) was employed to adjust for confounding variables and reduce selection bias. Kaplan-Meier survival curves and Cox regression models were used to evaluate overall survival (OS) between the two groups. A total of 1,530 IEFVPTC and 81,508 classic PTC patients were analyzed. Before PSM, significant differences were noted in race, T-stage, N-stage, M-stage, laterality, radiotherapy, surgical modality, tumor size, and income. Post-PSM, these differences were not statistically significant (p > 0.05). Kaplan-Meier curves and Cox regression models showed no significant differences in OS between IEFVPTC and classic PTC both before and after PSM. This PSM analysis revealed no significant differences in overall survival between patients with IEFVPTC and classic PTC, suggesting that the reclassification of IEFVPTC does not translate into distinct prognostic outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: The SEER database is publicly available and does not contain patient information; consequently, ethical review and approval was waived., (© 2024. The Author(s).)

Visceral leishmaniasis (VL) is a neglected tropical disease that mostly affects the working-class and impoverished segments of society, having a significant negative effect on the economic development of the affected nation. While anti-leishmanial medications lower mortality among VL patients, patients may still die or require more time to recover (TTR) while receiving treatment. In this regard, there are limited studies in Ethiopia. This study aims to determine the time to recovery and its associated predictors among adult VL patients at Metema Hospital. A hospital-based cross-sectional study design was employed, and the data were collected in patient's charts from September 2017 to September 2021. Data were entered and analyzed using Epi-data, STATA version 14.2, and R 3.4.0 statistical software. The Kaplan-Meier survival curve and log-rank tests were used to compare the survival time. The Cox proportional hazard model assumption and model fitness were checked and used to identify statistical association predictors in VL patients. The Cox proportional hazard (Cox-PH) model was fitted. The overall medium recovery time was 7 days (minimum 4, maximum 14 days). The variables nasal bleeding (adjusted hazard ratio/AHR: 0.44; 95% CI: 0.19-0.89), no comorbidity (AHR: 2.29; 95% CI: 1.27-4.11), relapse VL (AHR: 0.33; 95% CI: 0.15-0.75),low parasite load (AHR: 2.58; 95% CI: 1.48-4.51), and ambulatory (AHR: 3.26; 95% CI: 2.45-6.53) were significantly associated with TTR in VL patients. Patients with comorbidities, nasal bleeding, relapse VL, bedridden, and high parasite load should be treated and monitored carefully to recover quickly from their illness., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous cancer with limited therapeutic options. Using publicly available datasets, we identified the WD repeat domain 54 (WDR54) gene as a potential therapeutic target in HNSCC. Gene expression profiling interactive analysis version 2 (GEPIA2) was used to identify genes differentially overexpressed in HNSCC. Our results showed that WDR54, a member of the WD40 repeat domain family, was overexpressed in HNSCC tumor samples. Analysis of three gene expression omnibus datasets showed that WDR54 was overexpressed in tumor samples. Using the UALCAN database, we showed that WDR54 expression in patients with HNSCC at different tumor stages gradually increased with disease progression. We confirmed the association between WDR54 and metastasis using TNMplot.com. WDR54 was overexpressed in metastatic samples compared to that in normal and tumor samples. Kaplan-Meier analysis showed that patients with high WDR54 levels had a poorer prognosis. Additionally, WDR54 expression was correlated with the epidermal growth factor receptor, which is frequently overexpressed in HNSCC. Our findings suggest that WDR54 is a promising biomarker and therapeutic target in HNSCC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The Platelet-to-Lymphocyte Ratio (PLR) has emerged as a cost-effective biomarker for systemic inflammation and adverse cardiovascular outcomes, yet its prognostic value in critically ill patients with heart failure (HF) remains unclear. Leveraging the MIMIC-IV database, this study investigates the association between PLR and 1-year all-cause mortality in 7,217 ICU patients with HF. Patients were stratified into tertiles (0-126.45, 126.45-252.40, and 252.40-1000), and mortality risk was analyzed using Kaplan-Meier survival curves and Cox proportional hazards models. Elevated PLR was independently associated with higher mortality, with the highest tertile showing a 36% increased risk compared to the lowest (HR 1.36, 95% CI: 1.23-1.50, P < 0.001). Each tertile increment corresponded to a 17% rise in risk. Subgroup analyses revealed stronger associations in hypertensive patients and identified renal dysfunction and red cell distribution width as key modifiers. Integrating PLR with SOFA and APS III scores significantly enhanced predictive accuracy. By reflecting systemic inflammation and immune dysregulation, PLR offers a robust tool for long-term risk stratification and personalized management of ICU patients with HF. These findings highlight the potential of PLR to refine prognostic models, guide clinical decision-making, and improve critical care outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: All data used in this study were sourced from the MIMIC-IV database, which is approved by the Institutional Review Boards of the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center. As the study did not involve any direct patient intervention and all health information was anonymized, the need for individual patient consent was waived., (© 2024. The Author(s).)

Metabolic syndrome, a cluster of conditions including obesity, hyperglycemia, hypertension, and dyslipidemia, is increasingly recognized for its association with kidney disease. However, the impact of metabolic syndrome on the long-term prognosis of IgA nephropathy(IgAN) remains understudied. From August 2009 to December 2018, we conducted a retrospective cohort study at the Department of Nephrology, General Hospital of Ningxia Medical University, involving 698 patients with primary IgAN identified by the initial renal biopsy. Patients were divided into five groups based on the number of metabolic syndrome components they exhibited, including metabolic syndrome with hyperuricemia: Group A (no components), Group B (one component), Group C (two components), Group D (three components), and Group E (four or more components). We compared and analyzed the effect of metabolic components on the prognosis of IgAN. The mean age was 35.83 years, and 51.86% male. The prevalence of metabolic syndrome was 25.07%. The 24-h urine protein quantification correlated positively with metabolic components (P < 0.05), while eGFR correlated negatively (P < 0.05). Kaplan--Meier analysis showed decreased renal survival with more metabolic components, especially with four or more (P < 0.001). Blood pressure was the most important factor influencing the occurrence of endpoint events in IgAN patients, according to a random forest technique analysis. The incidence of metabolic abnormalities in patients with IgA nephropathy is closely related to the severity of clinical manifestations and poor renal prognosis, with blood pressure being the most critical factor., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki guidelines and approved by institutional review board of General Hospital of Ningxia Medical University. The ethical approval number is KYLL-2024-0950.All patients were provided with the option to opt out of the study. The need for informed consent was waived using our hospital’s opt-out method., (© 2024. The Author(s).)

Solute transport family 7A member 7 (SLC7A7) mutations contribute to lysinuric protein intolerance (LPI), which is the mechanism of action that has been extensively studied. In colorectal cancer (CRC), SLC7A7 appears to play a role, but the features and mechanisms are not yet well understood. Survival was analyzed using the Kaplan-Meier analysis. Enrichment analysis was performed to characterize, immune infiltration, methylation, genetic instability, and crucial pathways of SLC7A7. Afterward, functional experiments were conducted in vitro to investigate how SLC7A7 affects tumor metastasis. Mechanistically, quantitative real-time PCR (qRT-PCR), western blot (WB), and methylated RNA immunoprecipitation (me-RIP) were carried out to confirm the methylation modification of SLC7A7 and related functions. High levels of expression of SLC7A7 are predictive of a worse prognosis for CRC patients. Enrichment analysis showed that SLC7A7 was significantly enriched during EMT and could be enriched in the Wnt/β-catenin signaling pathway, immune infiltration analysis of pan-cancer showed that SLC7A7 was significantly enriched in macrophages, and methylation analysis showed that SLC7A7 methylation modification affected the prognosis of specific cancers. SLC7A7 was indicated to promote the migration and invasion of CRC cells in in vitro functional experiments. Mechanistically, SLC7A7 was observed to potentially interact with the Wnt/β-catenin signaling pathway, possibly by influencing adenomatous polyposis coli (APC) expression. Furthermore, we identified that SLC7A7 undergoes N7-methylguanosine (m7G) modification, which may regulate SLC7A7 mRNA stability, with Quaking (QKI) potentially playing a role in this process by recognizing the m7G modification. Our results indicate that SLC7A7 may promote CRC metastasis through the SLC7A7/APC/Wnt/β-catenin signaling pathway. Moreover, m7G modification might be involved in regulating SLC7A7 mRNA stability, highlighting a novel layer of regulation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval was confirmed by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (2019-KY-423). All mouse procedures were approved by the Institutional Animal Care and Use Committee of Zhengzhou University., (© 2024. The Author(s).)

Polyomavirus enhancer activator 3 (PEA3), an ETS transcription factor, has been documented to regulate the development and metastasis of human cancers. Nonetheless, a thorough analysis examining the relationship between the PEA3 subfamily members and tumour development, prognosis, and the tumour microenvironment (TME) across various cancer types has not yet been conducted. The expression profiles and prognostic significance of the PEA3 subfamily were evaluated using data from the GEO, TCGA, and PrognoScan databases, in conjunction with COX regression analyses and the Kaplan-Meier Plotter. Furthermore, the relationships between PEA3 subfamily expression, stemness scores, tumor microenvironments, immune subtypes, and drug susceptibility across multiple cancer types were explored. We found that ETV1, ETV4 and ETV5 are highly expressed in cancer, and their biological functions are synergistic. In the prognostic analysis of the Cancer Genome Atlas, the PEA3 subfamily genes were found to be associated with the prognosis of multiple cancers such as Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), etc., and marked a worse prognosis at different endpoints. In addition, it was significantly correlated with the stromal and immune scores of pan-cancer, and also significantly associated with the RNA stemness score and DNA stemness score of pan-cancer. Expression levels of the PEA3 subfamily genes correlate with immune subtypes of LIHC, LUAD, and Lung squamous cell carcinoma. We also found a variety of drugs with positive and negative associations of ETV1, ETV4 and ETV5. These findings elucidate the role of the PEA3 subfamily gene as a biomarker for carcinogenesis and cancer progression, offering valuable insights for future research into the PEA3 subfamily gene as a potential therapeutic target across various cancer types., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval: The analysis utilized publicly available GWAS summary statistics, and no new data collection was conducted, obviating the need for additional ethical approval or consent to participate., (© 2024. The Author(s).)

Mitochondria are pivotal in cellular energy metabolism and have garnered significant attention for their roles in cancer progression and therapy resistance. Despite this, the functional diversity of mitochondria across various cancer types remains inadequately characterized. This study seeks to fill this knowledge gap by introducing and validating MitoScore-a novel metric designed to quantitatively assess mitochondrial function across a wide array of cancers. Our investigation evaluates the capacity of MitoScore not only to distinguish between tumor and adjacent normal tissues but also to serve as a predictive marker for clinical outcomes. We analyzed gene expression data from 24 cancer types and corresponding normal tissues using the TCGA database. MitoScore was calculated by summing the normalized expression levels of six mitochondrial genes known to be consistently altered across multiple cancers. Differential gene expression was assessed using DESeq2, with a focus on identifying significant changes in mitochondrial function. MitoScore's associations with tumor proliferation, hypoxia, aneuploidy, and clinical outcomes were evaluated using Spearman's correlation, linear regression, and Kaplan-Meier survival analyses. MitoScore was significantly higher in tumor tissues compared to normal tissues across most cancer types (p < 0.001). It positively correlated with tumor proliferation rates (r = 0.46), hypoxia scores (r = 0.61), and aneuploidy (r = 0.44), indicating its potential as a marker of aggressive tumor behavior. High MitoScore was also associated with poorer prognosis in several cancer types, suggesting its utility as a predictive biomarker for clinical outcomes. This study introduces MitoScore, a metric for mitochondrial activity often elevated in tumors and linked to poor prognosis. It correlates positively with hypoxia and negatively with stromal and immune infiltration, highlighting mitochondria's role in the tumor microenvironment. MitoScore's association with genomic instability, such as aneuploidy, suggests mitochondrial dysfunction contributes to cancer progression. Despite challenges in mitochondrial-targeted therapies, MitoScore may identify tumors responsive to such treatments, warranting further research for clinical application., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors reviewed and approved the final version for submission., (© 2024. The Author(s).)

Accurate and timely genetic material replication is essential for preserving genomic integrity. The replication process begins with chromatin licensing and DNA replication factor 1 (CDT1). It has been demonstrated that dysregulated CDT1 expression causes genomic instability, damages DNA, and may even cause cancer. Although this protein is overexpressed in several malignancies, its significance in gastric cancer is still unknown. This work aims to investigate the biological function and molecular mechanism of CDT1 in gastric cancer. Bioinformatics studies were carried out using TCGA database, Kaplan-Meier and GEPIA online data analysis software. The expression of CDT1 in stomach cancer tissues was determined by immunohistochemistry, and its relationship to clinicopathological features was examined. Using siRNA and cell function experiments, the impact of CDT1 expression on the capacity of gastric cancer cell lines to proliferate, migrate, and invade was investigated. In gastric cancer tissues, CDT1 is overexpressed and is linked to a dismal prognosis. Through the up-regulation of M-cyc, MCM5 (microchromosome maintenance protein 5), CyclinD1, N-cadherin, and the down-regulation of E-cadherin, CDT1 facilitated the proliferation and invasion of gastric cancer cells. The study's findings shed insight on the possible molecular processes behind CDT1's function in promoting the start and progression of gastric cancer and demonstrate the potential predictive and diagnostic use of CDT1 expression in gastric cancer., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Glioma, the most prevalent primary intracranial malignancy among adults, is distinguished by its high morbidity and recurrence rates, posing a considerable threat to patients' quality of life and survival prospects. Consequently, the pursuit of efficacious molecular prognostic markers holds paramount importance. The exploration of the role of the KDELR3 kinase family in various neoplastic conditions constitutes an emerging area of research. However, the biological functions of KDELR3 and its prognostic implications in brain tumors remain largely undocumented. This study endeavored to ascertain the potential of KDELR3 as a prognostic indicator for glioma. We integrated a comprehensive dataset encompassing 1127 glioma samples, sourced from our cohort, The Cancer Genome Atlas (TCGA), and the Chinese Glioma Genome Atlas (CGGA), to delve into the expression patterns of KDELR3 in glioma and their associated implications. Notably, KDELR3 was markedly overexpressed in glioma and demonstrated a positive correlation with clinical progression. By utilizing Kaplan-Meier survival analysis and the Cox proportional hazards regression model, we evaluated the prognostic significance of KDELR3, revealing it as an independent predictor of adverse outcomes in glioma patients. Furthermore, gene set enrichment analysis unveiled potential signaling pathways associated with KDELR3 expression in glioma, primarily encompassing Cytokine-cytokine receptor interaction, extracellular matrix (ECM)-receptor interaction, and complement and coagulation cascades. In summation, our findings provide profound insights into the potential role of KDELR3 and its application as a novel and promising prognostic biomarker for glioma., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Recent studies recommend sublobectomy as a surgical approach for non-small cell lung cancer (NSCLC) tumors that are 2 cm or smaller. However, it remains unclear whether NSCLC patients with squamous cell carcinoma (SCC) have comparable outcomes to those with adenocarcinoma (ADC) following sublobectomy. To that end, this study aims to compare the survival outcomes between SCC and ADC in patients with stage IA NSCLC (≤ 2 cm) who have undergone sublobectomy. We identified stage IA (≤ 2 cm) NSCLC patients diagnosed with lung squamous cell carcinoma or adenocarcinoma pathology and underwent sublobectomy from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2020. Overall survival (OS) was determined using the Kaplan-Meier method, and Cox proportional hazards regression was employed to identify risk factors for OS. A total of 9,831 patients diagnosed with stage IA NSCLC (≤ 2 cm) were evaluated. Of these, 2,078 patients met the inclusion criteria, including 1,565 with adenocarcinoma (ADC) and 513 with squamous cell carcinoma (SCC). Notably, SCC was associated with worse overall survival compared to ADC (HR: 2.02, 95% CI: 1.34-3.05, P = 0.03). Subgroup analyses revealed that SCC was comparable to ADC in terms of OS for tumors ≤ 1 cm (HR: 1.22, 95% CI: 0.47-3.18, P = 0.83), while patients with SCC displayed worse OS compared to ADC for tumors > 1 to 2 cm (HR: 2.05, 95% CI: 1.31-3.23, P = 0.002). Cox proportional hazards regression analysis identified female sex (HR: 1.53, 95% CI: 1.08-2.19, P = 0.017), high tumor grade (HR: 1.76, 95% CI: 1.02-3.03, P = 0.011), and SCC (HR: 1.58, 95% CI: 1.08-2.30, P = 0.017) as independent risk factors for OS. In patients with stage IA (≤ 2 cm) NSCLC who underwent sublobectomy, SCC is associated with worse overall survival compared to ADC. Furthermore, being female, having a high tumor grade, and SCC pathology are independent risk factors for OS in these patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There are no studies discussing the significance of neutrophil-to-lymphocyte ratio (NLR), neutrophil-percentage-to-albumin ratio (NPAR), and systemic immune-inflammation index (SII) in predicting poor prognosis in patients with metabolic dysfunction associated steatotic liver disease (MASLD); this study aimed to investigate the relationship between these three inflammatory markers and all-cause mortality and cardiovascular disease (CVD) mortality in patients with MASLD. Survival data for 3970 participants were obtained from National Death Index (NDI) records associated with the National Health and Nutrition Examination Survey (NHANES) dataset, the associations of NPAR, NLR, and SII with all-cause and CVD mortality were analyzed using multivariate COX regression modeling, restricted cubic spline (RCS) was used to explore nonlinear relationships and to determine the inflection point, regrouping was done according to the nonlinear inflection point, using multivariate COX regression modeling, subgroup analysis, and the Kaplan-Meier survival curves to evaluate differences in risk of death between the two groups. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive efficacy of NPAR, NLR, and SII on survival outcomes. Multivariate COX regression and RCS analyses revealed a positive linear correlation between NLR and all-cause and CVD mortality, whereas a nonlinear relationship was found between NPAR and SII and all-cause and CVD mortality. Further reclassified into two groups according to the inflection point, multivariate COX regression analyses showed a significant difference in the risk of death between the two NPAR groups (HR 1.37, 95% CI = (1.01, 1.86) for all-cause mortality and HR 2.03, 95% CI = (1.24, 3.32) for CVD mortality ) and no difference in the risk of death between the two SII groups (HR 1.11, 95% CI = (0.87, 1.42) for all-cause mortality and HR 1.35, 95% CI = (0.86, 2.12) for CVD mortality), and Kaplan-Meier survival curves showed that both all-cause and CVD mortality rates were higher in patients with MASLD above the NPAR inflection point (log-rank P < 0.05). Subgroup analyses showed that the associations between high levels of NPAR and all-cause mortality were generally consistent across populations (P interaction > 0.05). Also, COPD subgroups had a significant effect on the correlation between high levels of NPAR and CVD mortality (P interaction < 0.05). Time-dependent ROC show the predictive value of NPAR, NLR, and SII for all-cause and CVD mortality in MASLD patients. The correlation between NPAR and mortality was nonlinear, and NLR was linearly and positively correlated with mortality, Measuring NPAR and NLR may be useful in assessing risk and predicting prognosis in populations of patients with MASLD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional review board statement: The NHANES survey protocol was approved by the NCHS Ethics Review Committee, and all respondents signed an informed consent form so that secondary analyses of the data were conducted without the need for another ethical review. The approval of the NCHS Research Ethics Review Board can be accessed on the NHANES website ( https://www.cdc.gov/nchs/nhanes/irba98.htm ) (accessed on June 4, 2024)., (© 2024. The Author(s).)

This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small cell lung cancer (NSCLC). Early-stage NSCLC patitents who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary endpoint were the patterns of disease progression, which were divided into local recurrence, regional failure, and distant metastasis. Kaplan-Meier method survival analysis was used to calculate overall survival (OS), progression-free survival (PFS). Cox model was used for univariate analysis and multivariate analysis. A total of 215 patients with 224 lesions were enrolled. After the median follow-up time of 50.8 months (1.0-117.9 months), 76 (35.3%) patients progressed, with regional progression occurring in 4 cases (1.8%), local and local-regional progression in 17 cases (7.9%), various distant metastases developing in 55 cases (25.6%). The OS rates at 1, 3, and 5 years were 97.1%, 80.9%, and 63.8%, respectively, with a median OS of 92.2 months (95%CI, 61.5-122.9 months). The PFS rates at 1, 3, and 5 years were 87.5%, 65.9%, and 50.8%, respectively, with a median PFS of 62.2 months (95% CI, 45.0-59.4 months). There was no significant difference in OS (P = 0.832) and PFS (P = 0.672) between the two groups with or without pathology. Multivariate analysis showed that BED and patient age were independent prognostic factors affecting early-stage lung cancer survival (all P < 0.05). Distant metastasis was the main failure pattern of inoperable early-stage NSCLC after SBRT, and the high-risk population should be selected for further systemic treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study has been approved by the Ethics Committee of Zhejiang Cancer Hospital (IRB-2023-588) with the informed consent of all participants and/or their legal guardians., (© 2024. The Author(s).)

This nationwide population-based retrospective cohort study aims to investigate the association between Moyamoya disease (MMD) and open-angle glaucoma (OAG). In this study using the Korean National Health Insurance Service database, a total of 36,432 patients having diagnostic code with MMD between 2002 and 2022, and their age-, sex-matched non-MMD controls (n = 346,769) were included. We used a Cox proportional hazard model to determine the association between MMD and subsequent OAG after excluding cases with preexisting diagnosis of MMD for the initial 2-year. Kaplan-Meier survival analyses with log-rank test were performed to compare the incidence probability of OAG based on the MMD diagnosis. Cox regression analysis showed that the diagnosis of MMD was associated with increased risk of subsequent diagnosis of OAG (adjusted HR, 1.26; 95% CI, 1.14-1.38; P < 0.001). The cumulative incidence probability of OAG was 3.7% in MMD group and 2.9% in control group at the end of the study period, and was significantly higher among MMD patients than controls consistently during the study period (P < 0.001).In conclusion, the nationwide longitudinal data of Korean population revealed a significant association between MMD and OAG. Presence of MMD may increase the risk of developing OAG., Competing Interests: Declarations. Ethics approval: Institutional Review Board of the Seoul National University Bundang Hospital (No. X-2306-837-903). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Dyskalemia are associated with an increased risk of mortality in patients undergoing maintenance hemodialysis (MHD). However, studies evaluating the impact of serum potassium variability on mortality in MHD patients are scarce. To investigate serum potassium variability and its association with prognosis in MHD patients, we conducted a retrospective study on maintenance hemodialysis patients from three campus of Renji Hospital between June 2018 and December 2022. The exposure of interest was serum potassium variability defined as the coefficient of variation of serum potassium levels (CVSP). Cox regression models and Kaplan-Meier survival analysis were used to assess the prognostic significance of serum potassium variability. In a subgroup analysis, the association between serum potassium variability and prognosis was investigated in patients within normal serum potassium concentration range. Total of 588 maintenance hemodialysis patients were included. During a median follow-up of 45 months (24, 54), 121 patients (20.6%) died. The survival analysis suggested significantly higher survival rates for both all-cause (p < 0.01) and cardiovascular (p < 0.01) death in patients in the highest group of CVSP (H-CVSP) compared with those in the the lowest group (L-CVSP). After adjustment, the all-cause mortality hazard ratio compared to L-CVSP was 2.17 [95% confidence interval (CI) 1.18, 3.97] for H-CVSP (p < 0.05) and was 2.53 [95%CI 1.03, 6.22] for cardiovascular mortality (p < 0.05). In the subgroup analysis, 493 patients (83.8%) presented normokalemia (the mean of serum potassium levels ≥ 3.5mmol/L and ≤ 5.0mmol/L) were included. Similar association was found between serum potassium variability and accumulated survival rates, and higher serum potassium variablity was remained an independent risk factor for cardiovascular mortality (2.69, 95% CI 1.07-6.78, p < 0.05) in patients within normal serum potassium concentration range. In conclusion, a higher serum potassium variability was associated with all-cause and cardiovascular mortality in maintenance haemodialysis patients, even in the normal range., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Adjuvant radiotherapy (RT) in breast cancer (BC) is often used to eradicate remaining tumor cells following surgery with the goal of maximizing local control and increasing overall survival. The current study investigated the impact of age and BC molecular subtype on overall survival after RT using a meta-analysis of the METABRIC and TCGA BC patient cohorts. We found that RT significantly prolonged survival across the whole BC patient population. The survival benefit of RT was predominantly observed in stage II BC patients treated with breast conserving surgery. Patients were then stratified by age and molecular subtype to investigate survival rate associated with RT. An increase in survival for the luminal-A and basal BC molecular subtypes was observed after RT. Stratifying patients based on age revealed that increased survival was restricted to younger patients (≤60 years of age at diagnosis). There was a significant survival benefit of radiotherapy for younger patients with tumors of the luminal A and basal molecular subtypes. Patients with other breast tumor subtypes or older breast cancer patients did not seem to benefit effects of RT. Therefore, alternate local treatment strategies should be considered for older, luminal B, and HER2 driven BC patients.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P

Chondrosarcoma (CS) is a rare cancer, but it is the second most common primary malignant bone tumor and highly resistant to conventional chemotherapy and radiotherapy. Aberrant DNA methylation in the promoter CpG island of Wnt inhibitory factor 1 (WIF1) has been observed in different cancers. However, no studies have shown the relationship between WIF1 methylation and CS. In this study, we found promoter methylated WIF1 in both CS cell lines (CS-1 and SW1353) and tumor tissues. Western blot analysis confirmed loss WIF1 expression and activation of Wnt pathway proteins (Wnt5a/b, LRP6, and Dvl2). We subsequently examined the correlation between levels of WIF1 methylation and overall survival (OS) and progression-free survival (PFS) in CS patient samples with a follow-up spanning 234 months (mean: 57.6 months). Kaplan-Meier survival curves and log-rank tests revealed that high levels of WIF1 methylation were associated with lower OS and PFS rates (p

Hyponatremia has been established as a prognostic indicator of survival in metastatic non-small cell lung cancer (mNSCLC). Conversely, the influence of normal sodium levels remains unexplored. This study aims to investigate the impact of natremia in mNSCLC patients undergoing treatment with immune checkpoint inhibitors (ICIs). Clinical and biochemical data of patients treated with ICIs for mNSCLC were obtained. Availability of baseline sodium values was a study inclusion criterion. Patients were categorized into two groups based on the cut off sodium value, determined using the receiver operating characteristic curve. Subsequently, the influence of sodium levels on response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) was analyzed. PFS and OS were assessed via the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were conducted to evaluate prognostic factors for PFS and OS. The analysis included 88 patients, of whom 73.1% were men, with a median age of 71 years (range, 47-91). A comparison between patients with baseline natremia ≥ 140 mEq/L (n = 43) and those with < 140 mEq/L (n = 45) revealed PFS durations of 7.0 vs. 2.1 months (p < .01) and OS durations of 15.6 vs. 6.8 months, respectively (p = .02). In the univariate survival analysis, pre-ICI serum sodium ≥ 140 mEq/L (p = .01) was associated with improved PFS, while factors associated with OS included brain metastasis (p = .05) and pre-ICI serum sodium ≥ 140 mEq/L (p = .02). In the multivariate analysis, pre-ICI serum sodium ≥ 140 mEq/L maintained a statistically significant association with OS (p = .04)..This study represents the first investigation into the impact of normonatremia in mNSCLC. Our findings suggest that serum sodium levels < 140 mEq/L at baseline and initial assessment are independently associated with poorer PFS and OS in mNSCLC patients undergoing first-line treatment with ICIs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are at increased risk of developing atrial fibrillation (AF). Abnormal P-wave parameters (PWPs) have been identified as independent predictors of AF, however, their prognostic significance in DLBCL patients remains unknown. Newly diagnosed DLBCL patients from January 2015 to August 2022 were retrospectively included in this study. Patients were devided as with abnormal PWPs or without it. Primary outcome was the all-cause mortality. The median duration of follow-up was 16.3 months. The Kaplan‒Meier method and multivariable COX proportional hazards regression models were used to analyze the relationship between PWPs and all-cause mortality. Logistic regression analyses were performed to identify risk factors associated with PWPs. A total of 374 newly diagnosed DLBCL patients were included, of whom 137 patients exhibited abnormalities in PWPs. Compared to the group with normal PWPs, patients with PWPs abnormalities had a higher proportion of males (p = 0.001), elevated levels of blood urea nitrogen (p = 0.038) and blood creatinine (p = 0.005), and a higher rate of all-cause mortality (p = 0.001). PWPs, particularly P-wave duration (p = 0.017) and P-wave terminal force in lead V1 (PTFV1) (p = 0.001), were independently correlated with all-cause mortality in DLBCL patients. Furthermore, male patients exhibited a higher susceptibility to abnormal PWPs (p = 0.001). PWPs, particularly P-wave duration and PTFV1, serve as simple yet effective prognostic indicators for all-cause mortality in DLBCL patients. Consequently, vigilant monitoring of PWPs, particularly in male patients, is warranted to accurately evaluate the prognosis of DLBCL., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study adhered to the tenets of the Helsinki Declaration and was certified by the Medical Ethics Committee of the First Affiliated Hospital of Xi’an JiaoTong University (NO. XJTU1AF2022LSK-410). The informed consent was obtained from all patients and/or their legal guardians to use their clinical data., (© 2024. The Author(s).)