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This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

Objectives: Peritoneal dialysis (PD) serves as a vital renal replacement therapy for patients with end-stage kidney disease (ESKD). γ-Gamma-glutamyl transferase (γ-GGT) is a recognized predictor of oxidative stress and mortality. This study aimed to assess the prognostic significance of γ-GGT in predicting all-cause and cardiovascular mortality among PD patients., Methods: A retrospective study was conducted, enrolling 640 PD patients from a single center. The one-year, three-year, and five-year mortality rates for all causes and cardiovascular causes were evaluated. Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed., Results: Within five years of initiating PD, the observed all-cause mortality rates at one, three, and five years were 11.72%, 16.09%, and 23.44%, while cardiovascular mortality rates were 2.97%, 7.34%, and 11.09%, respectively. Lower γ-GGT levels were associated with decreased all-cause mortality during one-, three-, and five-year follow-ups, along with reduced cardiovascular mortality in the first and third years, as indicated by Kaplan-Meier analysis on median γ-GGT groupings. Multivariate Cox regression analysis showed significantly decreased hazard ratios (HRs) for one- to five-year all-cause mortality and cardiovascular mortality in the lower γ-GGT group compared to higher groups. However, when sex differences were eliminated using separate tertile groupings for males and females, only the one- and three-year all-cause mortality rates demonstrated significantly reduced hazard ratios (HRs) in the lower γ-GGT groups., Conclusion: This retrospective study suggests that γ-GGT levels have prognostic significance in predicting one- and three-year all-cause mortality among PD patients when accounting for sex differences.

Background: Immune and inflammatory factors are considered the basic underlying mechanisms of IgA nephropathy (IgAN). The systemic immune inflammation index (SII) is a new inflammatory biomarker and has been identified as a prognostic indicator for various diseases. However, limited studies have been conducted on the prognostic value of the SII in patients with IgAN, and we aimed to address this gap., Methods: A total of 374 patients with IgAN confirmed by renal biopsy performed from 1 January 2015 to 1 April 2019, were retrospectively included. The follow-up period of all patients was at least 12 months after diagnosis, and the endpoint was defined as end-stage kidney disease (ESKD). Patients were further divided into a high-risk group (SII ≥ 456.21) and a low-risk group (SII < 456.21) based on the optimal cutoff value of the SII determined by receiver operating characteristic (ROC) curve analysis. Baseline clinicopathological parameters were compared between the groups, and Cox proportional hazards analyses and Kaplan-Meier analysis were performed to assess renal survival in IgAN patients., Results: After a median follow-up period of 32.5 months, a total of 53 patients eventually reached ESKD. Patients in the high-SII group tended to have a lower hemoglobin level ( p  = 0.032) and eGFR ( p  < 0.001), a higher serum creatinine level ( p  = 0.023) and 24-hour total protein level ( p  = 0.004), more severe tubular atrophy and interstitial fibrosis ( p  = 0.002) and more crescents ( p  = 0.030) than did those in the low-SII group. Univariate and multivariate Cox regression analyses demonstrated that an SII ≥456.21 was an independent risk factor for poor renal survival in IgAN patients (HR 3.028; 95% CI 1.486-6.170; p  = 0.002). Kaplan-Meier analysis revealed that a high SII was significantly associated with poor renal prognosis ( p  < 0.001) and consistently exhibited remarkable discriminatory ability across different subgroups in terms of renal survival., Conclusion: A high SII was associated with more severe baseline clinical and pathological features, and an SII ≥456.21 was an independent risk factor for progression to ESKD in IgAN patients.

Objective: The impact of sex upon outcomes in acute limb ischemia (ALI) remains disputed. We aim to quantify the effect of sex upon amputation-free survival (AFS) after a percutaneous-first approach for ALI., Methods: This was a two-center retrospective review of ALI managed via a percutaneous-first approach. Demographics, comorbidities, and clinical characteristics were analyzed. The Kaplan-Meier and Cox regression were used to estimate AFS, limb salvage, and overall survival., Results: Over 9 years, 170 patients (n = 87, 51% males; median age, 67 [interquartile range (IQR), 59-77 years) presented with ALI. Rutherford classification was I in 56 (33%); IIa in 85 (50%); IIb in 20 (12%), and III in 9 (5%). Thirty-day mortality, major amputation rate, and fasciotomy rates were 8% (n = 13); 6.5% (n = 11), and 4.7% (n = 8), respectively. Among revascularized limbs, 92% were patent at 30 days. Length of stay was 7 days (IQR, 3-11 days). Complications included 13 bleeding episodes (8%), four cases of atrial fibrillation (2%), and three re-thrombosis/clot extension events (1.7%). No differences were noted in complication rates when stratified by sex. Females were older than males (median age, 70 [IQR, 62-79] vs 65 [IQR, 56-76 years]; P = .02) and more likely to present with atrial fibrillation (20.5% vs 8%; P = .02) and hyperlipidemia (72% vs 57%; P = .04). Females also more frequently presented with multi-level thrombotic/embolic burden compared with males (56% vs 43%; P = .03) and required both aspiration thrombectomy and thrombolysis (27% vs 14%; P = .02). Kaplan-Meier estimated median AFS, limb salvage, and overall survival were 425 days (IQR, 140-824 days); 314 days (IQR, 72-727 days); and 342 days (IQR, 112-762 days). When stratified by sex, females had worse survival (median, 270 days [IQR, 92-636 days] vs 406 days [IQR, 140-937 days]; P = .005) and limb salvage (median, 241 days [IQR, 88-636 days] vs 363 days [IQR, 49-822 days]; P = .04) compared with males. Univariate Cox regression showed female sex (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04-2.05; P = .03), multi-level thrombotic/embolic burden (HR, 1.64; 95% CI, 1.17-2.31; P = .004), and Rutherford class (HR, 1.37; 95% CI, 1.08-1.73; P = .009) predicted major amputation/death. By multivariable Cox regression, multi-level thrombotic/embolic burden (HR, 1.54; 95% CI, 1.09-2.17; P = .01), Rutherford class (HR, 1.34; 95% CI, 1.07-1.69; P = .01), and female sex (HR, 1.45; 95% CI, 1.03-2.05; P = .03) were each independently predictive of major amputation/death., Conclusions: A percutaneous-first strategy is safe and efficacious in the overall ALI population. Similar to prior works, female vs male patients with ALI in our cohort have higher rates of mortality and major amputation. In our multivariable model, multi-level thrombotic/embolic burden was independently associated with a greater than 45% increased hazard of major amputation/death at last follow-up. Further prospective analysis is warranted to elucidate the underlying factors contributing to the higher prevalence of multi-level thrombotic/embolic burden in female patients with ALI, and to further define the optimal percutaneous-first approach for ALI in consideration of patient sex and extent of clot burden., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI)., Methods: A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis., Results: A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients ( p  < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI ( p  < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group ( p  < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone ( p  < 0.001)., Conclusion: High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

Purpose: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date., Methods: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model., Results: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42)., Conclusion: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy., Trial Registry: The clinical trial registration number: ChiCTR2300076883., Competing Interests: Declarations Conflict of interest The authors declare no commercial or financial conflict of interest. Ethical approval This study was approved by Guangdong Provincial Hospital of Chinese Medicine (Ethical Approval No. ZE2022-163). Consent to participate Written informed consents were exempted because of retrospective analysis. Consent for publication All authors declare the fnal manuscript and the submission to this journal., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background The stress hyperglycemia ratio (SHR) indicates relative hyperglycemia levels. Research on the impact of SHR on mortality in coronary heart disease (CHD) patients in intensive care is limited. This study explores the predictive accuracy of SHR for the prognosis of CHD patients in the ICU. Methods This study included 2,059 CHD patients from the American Medical Information Mart for Intensive Care (MIMIC-IV) database. SHR was determined using the formula: SHR = (admission glucose) (mmol/L) / (1.59 * HbA1c [%] - 2.59). Subjects were stratified into quartiles based on SHR levels to examine the correlation between SHR and in-hospital mortality. The restricted cubic splines and Cox proportional hazards models were employed to assess this association, while Kaplan-Meier survival analysis was executed to ascertain the mortality rates across the SHR quartiles. Results Among the 2059 participants (1358 men), the rates of in-hospital and ICU mortality were 8.5% and 5.25%, respectively. Analysis showed SHR as a significant predictor of increased risk for both in-hospital (HR,1.16, 95% CI: 1.02-1.32, P = 0.022) and ICU mortality (HR, 1.16, 95% CI: 1.01-1.35, P = 0.040) after adjustments. A J-shaped relationship was noted between SHR and mortality risks (p for non-linearity = 0.002, respectively). Kaplan-Meier analysis confirmed substantial differences in in-hospital and ICU mortality across SHR quartiles. Conclusions SHR significantly predicts in-hospital and ICU mortality in critically ill CHD patients, indicating that higher SHR levels correlate with longer ICU stays and increased mortality. This underscores the potential of SHR as a prognostic marker for ICU CHD patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Not applicable., (© 2024. The Author(s).)

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was obtained from the Ethics Committee of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Approval Number: UHCT21803). The Ethics Committee of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China has waived informed consent to our study for minimal ethical implications and issues was involved in this study since this is a retrospective study. Clinical trial number: not applicable for this is an investigator-initiated, retrospective, non-registered clinical study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: SLC35F6 negatively regulates outer mitochondrial membrane permeability and positively regulates apoptotic signaling pathways and cell population proliferation. The biological function of SLC35F6 in bladder cancer (BC) remains inadequately established. This study evaluates the expression and clinical significance of SLC35F6 in BC, assesses its prognostic value and explores its relationship with key immune-related molecules in the tumor microenvironment., Methods: Combining bioinformatics tools and immunohistochemistry (IHC) analysis, the expression of SLC35F6 was analyzed through IHC in the tissues of 145 BC patients treated at the Affiliated Hospital of Nantong University from 2004 to 2009. The relationship between SLC35F6 expression levels and significant clinicopathological factors was examined using the chi-square test. Prognostic values were analyzed using the COX regression model and the Kaplan-Meier survival curve. Analysis of the receiver operating characteristic curve was conducted to assess the predictive performance of SLC35F6 in BC patients., Results: The expression levels of both SLC35F6 mRNA and protein were elevated in BC tissue relative to benign tissue. Kaplan-Meier analysis indicated that patients exhibiting elevated SLC35F6 protein expression had a worse prognosis. Multivariate Cox regression analysis confirmed that SLC35F6, TNM stage and grade are independent risk factors for bladder cancer. SLC35F6, when analyzed alongside clinical pathological factors, enhances the accuracy of survival predictions for Bladder Urothelial Carcinoma (BLCA) patients., Conclusion: SLC35F6 is upregulated in BC patients compared to normal individuals and is linked to a worse prognosis. SLC35F6 analyzed alongside clinical pathological factors can enhance the accuracy of survival predictions for BLCA patients, suggesting its potential value as a prognostic and predictive biomarker., Competing Interests: Declarations. Ethics approval and consent to participate: The informed consent of all patients was obtained before the study. The Ethics Committee of the Affiliated Hospital of Nantong University approved this research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Oral cavity cancer (OCC) represents a significant public health burden in South Asia, ranking as the most prevalent cancer affecting males in Pakistan and contributing considerably to morbidity and mortality. The objective of this study was to evaluate the survival rates in patients diagnosed with OCC in the Pakistani population and identify the factors influencing survival., Methods: This was a retrospective cohort study conducted at the Aga Khan University Hospital Karachi, Pakistan. A total of 2238 cases diagnosed with OCC from May 2011 through December 2020, who met the inclusion criteria, were included. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Adjusted hazard ratios (HR) and their 95% confidence intervals (CIs) were estimated using a Cox regression model to identify the factors significantly influencing survival., Results: Among all cases, 54.0% were diagnosed in individuals 50 years of age and below and 73.0% were tobacco users. Overall survival, 1-year, 3-year, and 5-year survival rates were 54.9%, 88.9%, 81.6%, and 75.9% respectively. After adjustment for all the significant confounding and prognostic factors, age was an important factor showing that adults > 50 years had poorer survival compared to ≤ 50 years (HR = 1.43, 95% CI = 1.11-1.83). Poorly differentiated grade of OCC compared to well-differentiated grade (HR = 2.49, 95% CI = 1.61-3.84) and stage IV compared to earlier stages (HR = 3.56, 95% CI = 2.13-5.94) were also associated with poor survival., Conclusion: Notably, there was a high occurrence of late stage (III and IV) OCC in individuals aged ≤ 50 years, with the buccal mucosa being the most common site involved. Moreover, a large proportion of our patients had a history of tobacco use. Patients with advanced-stage disease and poorly differentiated grade showed poor survival. Therefore, public awareness about tobacco control for OCC prevention and earlier diagnosis of OCC is urgently needed in our Pakistani population., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for this study was obtained from the Ethical Review Committee (ERC) of The Aga Khan University, Karachi, Pakistan (ERC AKU ID #8381). Since this study was based on data retrospectively obtained from the cancer registry, informed consent was not required as all the data were anonymized. Hence, the Ethical Review Committee (ERC) of the Aga Khan University waived the requirement for informed consent for this study. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: The aim of this study was to evaluate the association between living alone and mortality among older patients with and without diabetes., Methods: Electronic patient records were used to identify patients at least 65 years of age with a diagnosis of diabetes and two age- and sex-matched controls without diabetes for each patient with diabetes in 2015. The study population in this analysis consisted of 429 patients with diabetes and 650 controls who returned a questionnaire that contained questions about their diseases, symptoms, and functions. The mortality (2015-2019) data were based on the national registry of Statistics Finland. Cumulative mortality was estimated with Kaplan-Meier's method and compared with the log-rank test. Cox proportional hazards regression was used to estimate the adjusted hazard ratios (HR) and their 95% confidence intervals (CI)., Results: The median follow-up time was 4.3 years. 208 of the controls (32%) and 156 (36%) of the patients with diabetes lived alone. Of the controls, 8.1% (95% CI 5.9-11.1) of those not living alone and 20.2% (95% CI 15.3-26.3) living alone died. The corresponding numbers for patients with diabetes were 15.1% (95% CI 11.3-19.8) and 28.8% (95% CI 22.4-36.7). Among all patients, living alone was associated with increased mortality (HR = 1.84; 95% Cl 1.30-2.61), whereas the diagnosis of diabetes was not (HR = 1.31; 95% Cl 0.94-1.81)., Conclusions: The results of this study show that living alone had a significant impact on the mortality of older patients, regardless of whether they had diabetes or not. Diabetes was not clearly associated with the increased mortality among these older home-dwelling patients., Competing Interests: Declarations. Ethics approval and consent to participate: The survey was conducted in accordance with the ethical principles set by the National Advisory Board on Research Ethics of Finland (15). The study protocol was reviewed and approved by the Research Ethics Committee of the Northern Savo Hospital District, Kuopio, Finland (256/2015) and approved by the Inner Savo Health Care Federation of Municipalities (61 A/2015). By filling out and returning the survey, all participants gave their informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

India's high tuberculosis (TB) burden is exacerbated by concurrent silicosis, which increases TB susceptibility and worsens treatment outcomes. Limited studies on TB patients with silicosis highlight the need to address this vulnerable group's specific challenges, particularly to improve diagnosis and management. This retrospective cohort study analyzed survival data from 137 silico-tuberculosis and 2,605 TB-only patients in Khambhat, India, using Kaplan-Meier curves, log-rank tests, and comparisons between Cox proportional hazards and accelerated failure time (AFT) models. The lognormal AFT model, selected for its lowest Akaike Information Criterion (AIC), estimated survival times based on age, gender, HIV status, and prior TB treatment. Among the 2,742 patients, 309 (11%) died within 27 months. Median time from diagnosis to outcome was shorter for deceased patients (1.7 months) than for censored patients (5.6 months, p < 0.001, median test). Kaplan-Meier analysis showed a significantly steeper survival decline for silico-tuberculosis patients (p < 0.001, log-rank test). Silico-tuberculosis was associated with a two-fold increased mortality risk (HR = 2.0, 95% CI: 1.4-3.0, p < 0.001, Cox-proportional hazards regression). The lognormal AFT model indicated silico-tuberculosis patients had 36% of the median survival time compared to TB-only patients (16 vs. 44 months). These findings highlight significantly earlier mortality in silico-tuberculosis patients, underscoring the need for targeted, employer-led care models and TB-silicosis collaborative screening within India's TB program for high-risk occupational groups., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by both the Scientific Advisory Committee and the Institutional Human Ethics Committee at the National Institute of Occupational Health (NIOH), under the Indian Council of Medical Research (ICMR). Access to national tuberculosis (TB) program data was granted by the Gujarat TB Operations Research Committee. Data confidentiality was upheld using anonymized identifiers, such as Nikshay IDs, ensuring participant privacy. The study adhered to the ethical principles of the Declaration of Helsinki. Individual informed consent was waived by the Institutional Human Ethics Committee of NIOH, based on the retrospective nature of the study and the use of anonymized secondary data. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Research has identified a link between the triglyceride-glucose index (TyG-i) and the risk of mortality in severely ill patients. However, it remains uncertain if the TyG-i affects mortality by influencing heart rate (HR)., Methods: This study enrolled 3,509 severely ill participants from the Medical Information Mart for Intensive Care (MIMIC-IV) database who had triglyceride, glucose, and HR data upon entering the ICU. Cox regression models were applied to estimate the effect of the TyG-i and HR on 28-day all-cause mortality (ACM) and 28-day in-hospital mortality (IHM). Additionally, Kaplan-Meier (K-M) survival analysis was employed to explore outcome variations among different patient groups. The association of the TyG-i with HR, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) II was explored through linear regression analysis. Subgroup analysis explored potential interactions among patient characteristics, while sensitivity analysis gauged the robustness of the findings. Additionally, mediation analysis was conducted to assess whether elevated HR acts as an intermediary factor linking the TyG-i to both 28-day ACM and 28-day IHM., Results: During the 28-day follow-up, 586 cases (16.7%) died from all causes, and 439 cases (12.5%) died during hospitalisation. Cox results showed that individuals with a heightened TyG-i and elevated HR had the highest 28-day ACM (Hazard Ratio 1.70, P-value below 0.001) and 28-day IHM (Hazard Ratio 1.72, P-value below 0.001) compared to those with a reduced TyG-i and HR. The K-M curves showed that individuals with low TyG-i and low HR had the lowest incidence of 28-day ACM and 28-day IHM. The linear analysis results evidenced that the TyG-i was independently connected to HR (beta = 3.05, P-value below 0.001), and the TyG-i was also independently associated with SOFA score (beta = 0.39, P-value below 0.001) and SAPS II (beta = 1.79, P-value below 0.001). Subgroup analysis revealed a significant association in participants without hypertension, the interaction of an elevated TyG-i and HR strongly correlated with a higher 28-day death risk (interaction P-value below 0.05). Furthermore, HR mediated 29.5% of the connection between the TyG-i and 28-day ACM (P-value = 0.002), as well as 20.4% of the connection between the TyG-i and 28-day IHM (P-value = 0.002)., Conclusion: For severely ill patients, the TyG-i is distinctly correlated with HR, and elevated levels of both are strongly connected to greater 28-day ACM and 28-day IHM risks, especially in patients without hypertension. Furthermore, elevated HR mediates the connection between the TyG-i and 28-day mortality., Competing Interests: Declarations. Ethics approval and consent to participate: This research was conducted in compliance with the Helsinki Declaration’s guidelines. Approval for using the MIMIC-IV database was obtained from the IRBs of both MIT and BIDMC. The ethical approval previously granted for the MIMIC database covers the data used in this study, obviating the need for further ethical approval or informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: The positive expression of Cyclin D1 in immunohistochemical (IHC) staining serves as the cornerstone for diagnosing mantle cell lymphoma (MCL). However, existing literature does not conclusively establish whether the expression ratio and staining intensity significantly influence diagnostic outcomes or patient prognosis. In this retrospective study, the correlation between comprehensive Cyclin D1 quantification and the prognosis of MCL patients was studied., Methods: The Cyclin D1 protein level was assessed in 120 formalin-fixed paraffin-embedded samples from MCL patients using the quantitative dot blot (QDB) analysis technique. R language software was employed for statistical analysis to determine the optimal threshold with statistical significance. Additionally, Kaplan-Meier method was utilized to evaluate the relationship between the absolute level of Cyclin D1 protein and overall survival (OS) of patients. Furthermore, the Chi-square test was applied to analyze the causes of single and multiple fractures, with a significance level of p < 0.05. Finally, the Log-rank test was used to compare two survival curves, where a significance level of p < 0.05 was considered statistically significant., Results: At the optimized cutoff of 0.46 nmol/g, univariate analysis revealed a positive correlation between Cyclin D1 protein level and patient survival (OS). Specifically, in the subgroup with complete quantification of Cyclin D1 higher than the cutoff, the 5-year OS was 18%, whereas in the subgroup with complete quantification of Cyclin D1 lower than the cutoff, the 5-year OS was 4.8% (Log-rank test, P = 0.017). This indicates that patients with Cyclin D1 levels above the cutoff had significantly better overall survival compared to those below the cutoff. Additionally, in the Pearson distribution test, Ki-67 emerged as an independent prognostic factor for the complete quantification of Cyclin D1. Notably, Cyclin D1 complete quantification results remained unaffected by factors such as gender, age, LDH (Lactate Dehydrogenase) level, Ann Arbor stage(AAS), Ki-67, IPI(International prognostic index), MIPI(Mantle International prognostic index), and MIPI-c (MIPI Combined with Ki-67 Proliferation Index Chi-square test, p > 0.05)., Conclusions: Comprehensive Cyclin D1 quantification, especially above a threshold, significantly correlates with better overall survival in MCL. This highlights its prognostic importance in MCL management. Full quantification of CyclinD1 aids MCL prognosis, while QDB technology for biomarker quantification supports precise clinical prognostic stratification., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Femoral bone metastases (FBM) or lesions (FBL) can lead to loss of mobility and independence due to skeletal-related events (SRE), e.g. pain, deformity and pathological fractures. Aim of this study was to analyze effects of radiotherapy and surgery, different surgical techniques and complications on disease-specific survival (DSS)., Methods: Patients who underwent palliative therapy for FBM or FBL between 2014 and 2020 were retrospectively analyzed. Chi-square test was used to detect intergroup differences. Survival was calculated using Kaplan-Meier method, Cox regression and compared using log-rank test. Complications were evaluated using Chi-Square test., Results: 145 patients were treated for proximal femoral BM/BL or pathologic fractures (10 bilaterally). Three groups were classified: surgery only (S, n = 53), surgery with adjuvant radiation (S + RT, n = 58), and primary radiation only (RT, n = 44). Most common primary tumors were breast (n = 31), prostate (n = 27), and non-small cell lung cancer (n = 27). 47 patients underwent surgery for an impending, 61 for a manifest pathological fracture. There were no significant differences in DSS between the 3 groups (S = 29.8, S + RT = 32.2, RT = 27.1 months), with the S + RT group having the longest one-year survival. Local complications occurred in 25 of 145 patients after a mean interval of 9.9 months., Conclusion: Due to the steadily increasing incidence and survival of patients with FBM/FBL, indication for prevention and treatment of painful and immobilizing SREs should be critically assessed. Surgical treatment should always be performed with maximum stability and, whenever possible, adjuvant RT., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Technische Universität of Dresden (protocol code BO-EK-73022021; date of approval: 25.03.2021). Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) ranks among the most lethal malignancies around the world. However, the current management strategies for predicting prognosis in HCC patients remain unreliable. Our study developed a robust prognostic model based on glutamine metabolism associated-genes (GMAGs), utilizing data from The Cancer Genome Atlas database. The prognostic values of model were validated through the databases of the Gene Expression Omnibus and International Cancer Genome Consortium via Kaplan‒Meier curves and receiver operating characteristic (ROC). The potential biological pathways associated with prognostic risk were investigated through different enrichment analysis, and Gene variation analysis. The correlation between prognostic model and therapeutic responses were analyzed. Quantitative real-time PCR (qRT-PCR) and cellular experiments were measured to analyze the GMAGs. Consequently, a prognostic model was constructed of 4 GMAGs (RRM1, RRM2, G6PD, and GPX7) through least absolute shrinkage and selection operator (LASSO) regression analysis. The Kaplan‒Meier curves and ROC curves showed a reliable predictive capacity of prognosis for HCC patients (p < 0.05). The enrichment analyses revealed a multitude of biological pathways that are significantly associated with cancer. Patients with high prognostic risk might be sensitive to immunotherapy (p < 0.05). The results of qRT-PCR revealed that all 4 GMAGs exhibited significantly higher expression levels in HCC samples compared to normal samples (p < 0.05). Moreover, the knockdown of RRM1 suppresses the progression of HCC cells. In this study, we developed a robust prognostic model for predicting the prognosis of HCC patients based on GMAGs, and identified RRM1 as a potential therapeutic target for HCC., Competing Interests: Declarations Ethical approval This research was approved by the Ethics Committee of Dalian medical university. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: There is controversy about the benefit of administering adjuvant therapy to esophageal cancer (EC) patients after preoperative neoadjuvant therapy and surgical treatment. This study aims to investigate the clinical benefit of postoperative adjuvant therapy in EC patients with neoadjuvant therapy and surgery., Materials and Methods: The study included EC patients diagnosed from 2007 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received neoadjuvant therapy (NCRT) were defined as those who underwent neoadjuvant chemotherapy or neoadjuvant radiotherapy before surgery, while patients who received adjuvant therapy (ACRT) were defined as those who underwent adjuvant chemotherapy or adjuvant radiotherapy after surgery. Propensity score matching (PSM) method was employed to establish matched cohorts, and Kaplan-Meier analysis, COX regression model, and Fine-Gray model were used for survival analysis., Results: The study included a total of 5805 EC patients, with 837 (14.4%) in the ACRT group and 4968 (85.4%) in the no-ACRT group. After PSM, a cohort of 1660 patients who received NCRT was enrolled for analysis, with 830 patients in each group. Kaplan-Meier analysis revealed no significant differences between the two groups in terms of median overall survival (OS) (34.0 vs. 36.0 months, p = 0.89) or cancer-specific survival (CSS) (40.0 vs. 49.0 months, p = 0.16). Multivariate Cox models and Fine-Gray models indicated that ACRT was not a predictive factor for OS or CSS (p > 0.05). Subgroup analysis for CSS suggested a protective effect of ACRT in the N2 (Cox model: HR = 0.640, p = 0.090; Fine-Gray model: HR = 0.636, p = 0.081) and the N3 subgroup (Cox model: HR = 0.302, p = 0.018; Fine-Gray model: HR = 0.306, p = 0.034)., Conclusions: Only for esophageal cancer patients with a more advanced N stage, postoperative adjuvant therapy after completing neoadjuvant therapy and curative surgical treatment may be beneficial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Melanoma is a highly aggressive tumor, predominantly found in the skin, recognized as skin cutaneous melanoma (SKCM). Lymph node metastasis is commonly used as the route of metastasis in SKCM, necessitating the discovery of prognostic genes associated with this process for improved prognosis., Methods: The prognostic significance of lymph node metastasis in SKCM was assessed through Kaplan-Meier analysis in SEER and TCGA-SKCM datasets. Prognostic genes were identified and a prognostic risk model was constructed Enrichment analysis and immune cell infiltration analysis were also carried out.Moreover, a validation in vitro and in vivo were conducted by CCK8,flow cytometry, transwell and animal study., Results: The Kaplan-Meier survival curve revealed that patients with lymph node metastasis had a worse prognosis compared to those without. FCGR3B and PRF1 were screened by TCGA analysis.Additionally, significant differences in nine immune cell types were observed between the two risk groups. Notably, a strong positive association with CD8 T cells and a negative relationship with M2 macrophages were exhibited by PRF1. The validation of our nomogram were conducted in vitro and in vivo, and the results showed the correlations between CD8 + T cell and PRF1., Conclusion: In summary, two prognostic genes (FCGR3B and PRF1) were identified, and a prognostic risk model was developed for SKCM. These findings provide a novel approach for the diagnosis and treatment of SKCM., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Colonoscopy as a common screening practice to prevent colorectal cancer lacks strong evidence. NordICC, the first randomized trial of colonoscopy screening, reported no clear clinical benefit for colonoscopy in the intention-to-screen population with suggested benefit in the risk of colorectal incidence and cancer-specific mortality in the per-protocol analyses. However, although the study was designed to perform survival analysis, no survival outcomes were reported since the underlying assumption for hazard ratio was not valid. We aimed to assess whether colonoscopy screening is associated with improved survival outcomes compared with usual care., Methods: We reconstructed patient-level data from the Kaplan-Meier estimator of the primary endpoints reported in NordICC for the intention-to-screen and adjusted per-protocol populations. The restricted-mean survival time difference (RMST-D) and restricted-mean time loss ratio (RMTL-R), which are robust alternatives to the hazard ratio without specific model assumptions, were calculated for colorectal cancer incidence and death., Results: In this study, no significant difference in colorectal cancer incidence over 10 years was found in the intention-to-screen population (RMST-D: -0.68 days, 95% CI -3.9-2.6; RMTL-R: 1.04, 95% CI 0.88-1.22) or in the per-protocol analysis population (RMST-D: -2.9 days, 95% CI -6.5-0.67; RMTL-R: 1.15, 95% CI 0.97-1.35). In the intention-to-screen population, inviting individuals to colonoscopy did not improve colorectal-cancer death (RMST-D: -0.29 days, 95% CI -1.6-1.0; RMTL-R: 1.07, 95% CI 0.78-1.48). Over 10 years, in the per-protocol analysis, individuals who underwent colonoscopy survived an average of 1.1 more days free of colorectal cancer, but this difference was not statistically significant (RMST-D: 95% CI -0.13-2.3; RMTL-R: 0.72, 95% CI 0.49-1.07)., Conclusions: In this reanalysis of the NordICC data, no evidence of improvement in survival outcomes for participants invited to undergo colonoscopy compared to usual care was identified, even when assuming that all invited participants did undergo colonoscopy. Thus, our results do not support the use of colonoscopy as a population-wide screening test as a mean to decrease colorectal cancer incidence or death., Registry: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Sarcopenia is closely linked to inflammation; however, the association between the systemic inflammatory response index (SIRI) and mortality in patients with sarcopenia remains unclear. This study aims to explore the relationship between SIRI and mortality in sarcopenia patients., Methods: We analyzed data from ten cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, selecting 3,141 sarcopenia patients. Mortality data were obtained from the National Death Index up to December 31, 2019. Participants were divided into three groups based on the ranking of their SIRI values. The association between SIRI and mortality was assessed using Cox proportional hazards models, with smooth curve fitting employed to test the correlation. Sensitivity analyses, subgroup analyses, and interaction tests were conducted to validate the stability of the findings., Results: A total of 101,316 individuals were included in this study. During a median follow-up of 10.4 years (minimum follow-up time of approximately 0.08 years, maximum follow-up time of 20.75 years), 667 participants died. Kaplan-Meier (KM) analysis indicated a higher risk of mortality in the SIRI Q3 group. Cox regression analysis showed a significant association between the SIRI Q3 group and all-cause mortality [HR 1.24 (95% CI: 1.05, 1.47)] and cardiovascular disease mortality [HR 1.46 (95% CI: 1.04, 2.04)]. Subgroup analysis revealed that SIRI was significantly associated with all-cause mortality across various demographic characteristics (e.g., gender, diabetes, hypertension, cardiovascular disease). Sensitivity analysis, excluding participants with cardiovascular disease, those who died within two years of follow-up, and those under 50 years old, indicated higher hazard ratios (HRs) for all-cause and cardiovascular mortality in the SIRI Q3 group., Conclusion: This study demonstrates a significant association between SIRI and an increased risk of mortality in sarcopenia patients aged 20 years and older., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This retrospective study evaluated the association between preoperative topical glaucoma medication containing preservatives and long-term trabeculectomy outcomes in 309 eyes from 201 patients with primary open-angle glaucoma, followed for over 10 years. The Glaucoma Medication Intensity Index (GMII) was calculated to quantify the cumulative preoperative exposure to these medications. Kaplan-Meier analysis revealed cumulative success rates of 89.3%, 59.2%, and 46% at 1, 10, and 20 years postoperatively. At 20 years, the success group had a significantly lower GMII (3.28 vs. 8.74, p = 0.004). A GMII threshold of ≥ 4.35 was associated with poorer long-term intraocular pressure (IOP) control and shorter surgical success duration. Cox regression analysis identified advanced age at surgery, higher GMII, and subsequent cataract surgery as significant risk factors for trabeculectomy failure. These findings underscore the adverse impact of prolonged preoperative use of glaucoma medications on long-term surgical outcomes, highlighting GMII as a valuable predictor for guiding preoperative management strategies., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval and consent to participate This study was approved by the Institutional Review Board (IRB) of the Yeungnam University Hospital (approval number: 2024-07-021) and adhered to the tenets of the Declaration of Helsinki throughout all research procedures. The requirement for written informed consent was waived by the IRB due to the retrospective nature of the study., (© 2024. The Author(s).)

We aimed to investigate the correlation between the serum D-dimer (D-D) to albumin (ALB) ratio (DAR) and 28-day all-cause mortality in patients with sepsis. Data from sepsis patients admitted to the intensive care unit (ICU) of Wuhan Fourth Hospital from October 2021 to January 2024 were collected. Univariate cox analysis was performed for mortality factors in sepsis patients, and multiple cox regression models were used to analyze independent mortality risk factors. The receiver operating characteristics (ROC) curve was used to analyze the value of DAR in predicting sepsis mortality, and the Kaplan-Meier method was used to plot the survival curve. A total of 833 patients with sepsis in the ICU of our hospital were selected and divided into alive group (n = 574) and death group (n = 171) according to their 28-day survival. In the death group, D-D and DAR levels were higher, while ALB levels was lower than in the alive group. Spearman analysis found that DAR level were positively correlated with APACHE II and SOFA scores. Multivariate cox regression analysis showed that DAR was an independent predictor of all-cause mortality within 28 days of admission for sepsis patients (HR = 17.956, 95% CI 3.435-93.851, p < 0.001). The ROC curve results showed that the cut-off value of DAR was 0.068, with a sensitivity of 78.4% and a Youden index of 0.375, predicting mortality in sepsis patients, with an area under curve (AUC) of 0.767 (95% CI 0.744-0.790, P < 0.001). Further analysis divided patients into low DAR (DAR < 0.068) and high DAR (DA ≥ 0.068) groups based on the optimal cut-off value. Kaplan-Meier analysis found higher mortality in the high DAR group. DAR is an independent predictor of all-cause mortality within 28 days of admission in sepsis patients. Combining these two indicators can improve clinical treatment guidance and reduce the risk of death., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are currently 2 major diagnostic biomarkers for gastric cancer (GC). The aims of study were to detect the expression of long intergenic nonprotein coding RNA 1133 (LINC01133), and to evaluate its diagnostic and prognostic value in GC. Furthermore, the clinical performance of the joint detection of LINC01133, CEA and CA19-9 was also evaluate in GC., Methods: The data were collected from 156 GC, 96 chronic superficial gastritis, 77 chronic atrophic gastritis patients and 89 healthy controls. LINC01133 expression was determined by quantitative real-time PCR. Receiver operating characteristics analysis was used to evaluate the diagnostic value of LINC01133, CEA, CA19-9 individually and jointly. Kaplan-Meier method and log-rank test were used to conduct survival comparison analysis. Cox regression was used to screen the independent prognostic factors for GC., Results: Serum LINC01133 expression was decreased in GC patients compared with chronic superficial gastritis, chronic atrophic gastritis and healthy controls, and had considerable diagnostic potential, and notably, the joint detection of LINC01133, CEA, and CA19-9 showed the highest diagnostic accuracy in distinguishing GC patients from healthy or gastritis patients. LINC01133 expression was associated with GC patients' CEA and CA19-9 levels, tumor size, differentiation, lymph node metastasis and tumor node metastasis stage. Low LINC01133 was associated with poor GC survival, and was an independent prognostic factor for GC., Conclusion: Decreased serum LINC01133 had considerable diagnostic potential, and the joint detection of LINC01133, CEA, and CA19-9 might be a more efficient diagnostic strategy for GC patients. Reduced LINC01133 served as a prognostic biomarker to predict poor GC survival., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies., (© 2024 UICC.)

Purpose: Uveal melanoma (UM), although a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiation therapy. This study sought to elucidate the significance of the prescription dose by employing time-dose-response models for patients with UM receiving photon-based stereotactic radiosurgery (SRS)., Methods and Materials: The analysis included patients with UM treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into 3 dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose-response models for LC were created at 2, 4, and 7 years after SRS using maximum-likelihood fitted logistic models., Results: Outcomes from 594 patients with 594 UMs were used to create time-dose-response models. The prescribed doses and the number of patients were as follows: 17 to 19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose-response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For 4 years and a LC of 90%, a dose of approximately 21 Gy was required. After 7 years, the 21 Gy prescription dose was predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy., Conclusions: In contrast to prior findings, the time-dose-response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To identify the impact of surgical compliance on survival in patients with kidney cancer and to explore the factors that influence surgical compliance., Methods: Clinical date of kidney cancer patients were identified from the SEER databases, and the patients were divided into surgical compliance group and surgical noncompliance group. Cox survival analysis and Kaplan-Meier curves were used to evaluate the effect of surgical compliance on overall survival (OS) and cancer-specific survival (CSS). A diagnostic nomogram was constructed to quantify individual differences in compliance, and receiver operating characteristics (ROC) curves and calibration curves were used to assess the accuracy of the nomogram. Propensity score matching (PSM) was performed to balance potential baseline confounding factors., Results: Of the 133,950 patients eligible for surgical resection, 2,814 (2.1%) patients did not opt for surgery ultimately. Surgical noncompliance was associated with poor prognosis. In all patients, Cox regression analysis showed that surgical noncompliance was an independent predictor for OS [before: HR = 2.490, 95% CI 2.374-2.612, p < 0.001; after: HR = 2.380, 95% CI 2.202-2.573, p < 0.001] and CSS [before: HR = 2.490, 95% CI 2.318-2.675, p < 0.001; after: HR = 2.035, 95% CI 1.813-2.285, p < 0.001] of kidney cancer patients before and after PSM. Multivariable logistic regression revealed that older age, afro-american origin, lower household income, and advanced tumor grade were associated with surgical noncompliance. The ROC and calibration curves showed that the diagnostic nomogram had high predictive accuracy., Conclusion: Surgical compliance was an independent prognostic factor for OS and CSS in patients with kidney cancer, and surgical noncompliance was associated with poor survival., Competing Interests: Declarations Ethical approval The data was derived from the SEER database, it was unnecessary to obtain patient consent again. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer (BRCA) is among the most prevalent cancers and is responsible for numerous patient fatalities. Immunotherapy has emerged as a promising approach to cancer treatment. Recent studies have identified Siglec-15 as a novel immune target that plays a crucial role in tumor immune evasion, suggesting its potential significance in BRCA. We utilized databases such as TCGA to investigate the relevance of SIGLEC15 in BRCA. The expression of the Siglec-15 protein in 74 breast cancer patients was detected using immunohistochemistry, and its association with clinicopathological features and overall survival was evaluated. The co-expression of Siglec-15, CD68, CK, and CD8 in BRCA tissues was identified through multiplex immunofluorescence staining. Our study revealed that SIGLEC15 expression in BRCA was significantly elevated compared to adjacent normal tissues. Kaplan-Meier analysis identified SIGLEC15 as a prognostic protective factor. According to the receiver operating characteristic curve analysis, SIGLEC15 could predict the luminal subtype of BRCA. Enrichment analysis demonstrated that SIGLEC15 involves various biological pathways, including immunity, metabolism, tumors, and infectious diseases. Correlation analysis revealed an association between SIGLEC15 expression and immune infiltration in BRCA. We also confirmed that the Siglec-15 protein is expressed in cancer cells, tumor-infiltrating T cells, and macrophages in BRCA tissues, significantly higher levels than in normal breast tissues. Consequently, SIGLEC15 correlates with tumor immune infiltration, molecular subtypes, and BRCA progression and prognosis. However, further research is required to elucidate the role of SIGLEC15 in breast cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone., Methods: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life., Results: A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups., Conclusions: The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes., Methods: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point., Results: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group., Conclusions: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population., Methods: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure., Results: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001)., Conclusions: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain., Methods: We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status)., Results: A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%)., Conclusions: Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.)., (Copyright © 2024 Massachusetts Medical Society.)

The number of cancer survivors worldwide is increasing every year, making secondary primary cancers (SPC) is a growing health threat. Studies have been conducted to investigate the risk of occurrence between digestive system tumors (DST) and thyroid cancer (TC). However, existing studies have tended to focus more on the risk of developing SPC and less on the impact of SPC on the survival of cancer survivors. In this study, using the Surveillance, Epidemiology, and End Results database, we aimed to explore the impact of TC on the survival of patients with DST by data between 2000 and 2018. The study employed the standardized incidence ratio to assess the relative risk of SPC, propensity score matching was conducted to mitigate confounding effects, Kaplan-Meier, Cox proportional risk model and competitive risk model were used to analyze the factors affecting the overall survival and cancer-specific survival. We furthermore explored the influence of pathological types and radiotherapy of TC on the survival of DST patients. 518,901 patients with DST only, 801 patients with TC occurring earlier than DST (TC-1st), and 744 patients with DST occurring earlier than TC (DST-1st) were included. The total incidence rate of small intestine cancer after TC was higher than that of the general population, and the incidence of TC after DST was higher than in the general population. DST patients with a history of TC had better overall survival and lower cancer-specific mortality and this difference was particularly significant in patients with DST-1st. In addition, radiotherapy for TC had no effect on cancer-specific mortality in patients with DST., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999-2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259-1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260-1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To analyze the survival status and prognostic factors of patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension (HHT-PAH). Methods: This prospective study included patients diagnosed with HHT-PAH at the Fuwai Hospital of the Chinese Academy of Medical Sciences and Guangdong General Hospital from August 2009 to December 2019. Patients were followed up every 6 months±2 weeks, with all-cause mortality as the study endpoint. Multivariate Cox proportional hazards regression mode was used to further screen and validate the prognostic factors. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the survival time differences between patients with and without hepatic arteriovenous malformations. Results: A total of 18 HHT-PAH patients were included, with 14 females (77.8%) and a median age [ M ( Q 1 , Q 3 )] of 39 (32, 45) years. The median follow-up time was 129 (51, 156) months. During the follow-up period, 12 patients (66.7%) died, with a median survival time of 70 (32, 123) months. The 1-year, 3-year, 5-year, and 10-year survival rates were 100.0%, 70.8%(95% CI : 52.3%-96.0%), 53.1%(95% CI : 34.0%-83.0%), and 26.6%(95% CI : 10.6%-66.4%), respectively. HHT-PAH patients with hepatic arteriovenous malformations had a shorter median survival time than those without hepatic arteriovenous malformations [31.0 months (95% CI : 16.6-45.4 months) vs 84.0 months (95% CI : 54.4-113.6 months), P =0.024]. Cox proportional hazards regression analysis showed that hepatic arteriovenous malformation ( HR =4.493, 95% CI : 1.064-18.978) was a risk factor for all-cause mortality in HHT-PAH patients. Conclusions: The 10-year survival rate of HHT-PAH patients is poor. The presence of hepatic arteriovenous malformations is a risk factor for mortality in HHT-PAH patients.

Background: Predicting chemorefractory disease in advanced epithelial ovarian cancer (EOC) remains challenging. This study aimed to identify clinicopathological factors and hemogram data as predictive markers for chemorefractory EOC and to explore potential therapeutic approaches that may mitigate these unfavorable conditions., Methods: We conducted a retrospective analysis of patients with advanced EOC treated with chemotherapy. Hemogram data and clinicopathological variables were collected. We employed logistic regression to assess factors associated with chemorefractory EOC and used the Kaplan-Meier method for survival analysis., Results: Among the 191 patients analyzed, suboptimal surgery, lymphocyte count < 1440/mm3, systemic immune-inflammation index (SII) ≥ 2350, and lack of bevacizumab therapy were independently associated with chemorefractory EOC (OR 19.30, 95% CI 7.01-53.12; OR 9.07, 95% CI 2.76-29.82; OR 12.45, 95% CI 3.87-40.07; OR 6.61, 95% CI 2.01-21.78, respectively). Elevated SII was also identified as a risk factor for poor progression-free (PFS) and overall survival (OS). Specifically, patients with high SII who did not receive bevacizumab had a significantly higher probability of chemorefractory EOC and poorer survival outcomes compared to those who received bevacizumab., Conclusions: Our findings suggest that hemogram parameters and clinicopathological factors such as suboptimal surgery, lymphocyte count, SII, and bevacizumab therapy status are predictive markers for chemorefractory disease in advanced EOC. Elevated SII emerged as a predictor for poorer PFS and OS outcomes, particularly in the absence of bevacizumab therapy., Competing Interests: Declarations Ethics approval and consent to participate About the ethics approval and consent to participate, the study was approved by the Institutional Review Board (IRB number: 202301253B0) of Chang Gung Memorial Hospital, and according to the Declaration of Helsinki. The requirement for written informed consent was waived due to the retrospective nature of the analysis and individual patients was not affected. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, characterized by high mortality. This study aimed to explore the prognostic value and function of alternative lengthening of telomeres (ALT)-related genes in HCC., Methods: Differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) and then intersected with ALT-related genes to obtain ALTDEGs. Risk score model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression and validated with Gene Expression Omnibus (GEO) datasets. The predictive efficacy of the risk score and ALTs-score was evaluated by Kaplan-Meier curves, time-ROC curves, and the nomogram analyses. The impacts of SMG5 silencing on the HCC cell behaviors were assessed by CCK-8, wound healing, and Transwell assays., Results: A total of 500 ALTDEGs were screened and 13 genes (CDCA8, SMG5, RAD54B, FOXD2, NOL10, RRP12, CCT5, CCT4, HDAC1, DDX1, HRG, HDAC2, and PPP1CB) were identified for constructing a prognostic model. The overall survival (OS) curves, time-ROC curves, and nomograms based on the risk score or ALTs-score were developed to optimally predict the survival of HCC patients. ALTs-score was correlated with immune infiltration and confirmed its value in predicting immunotherapy outcomes. Furthermore, RT-qPCR demonstrated that eight risk signature genes were up-regulated in HCC cells. SMG5 silencing suppressed the proliferation, migration, and invasion of HCC cells. It was also found that SMG5 silencing reduced C-circle level in SNU-387 cells., Conclusion: We identified new ALT-related prognostic biomarkers for HCC. SMG5 knockdown inhibited the HCC progression, which might be a promising target for HCC therapy., Competing Interests: Declarations Ethics approval and consent to participate All animal experiments were approved by The First Affiliated Hospital of Gannan Medical University (No. 22SC-2024-191) in accordance with ARRIVE Guidelines. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

There are few analyses comparing complete nephrectomy with resection of the renal parenchyma only (CN) or radical nephrectomy that includes simultaneous resection of the parenchyma, affected perirenal fascia, perirenal fat, and ureter (RN) relative to partial nephrectomy (PN) for patients with nonmetastatic (M0) renal cell carcinoma (RCC) in terms of overall survival (OS). This study aimed to evaluate the effect of different nephrectomy on the OS of M0 RCC and to identify the main beneficiaries of different nephrectomy. The data was collected from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier plots, and multivariable Cox regression models were used. Propensity score matching (PSM) was performed to reduce the effect of selection bias. A prognostic model for M0 RCC patients after nephrectomy was established using the deep learning framework. Stage I M0 RCC patients who received PN did not have a better prognosis than none surgery in terms of CSS and OS after PSM. Stage I M0 RCC patients who received PN did not have a better prognosis than CN in terms of CSS but had in terms of OS after PSM. Stage I M0 RCC patients who received PN had a better prognosis in terms of CSS and OS after PSM. The test set AUC values for 1/3/5/7/9 year survival prediction of the surgical decision model were 0.844, 0.812, 0.794, 0.79, 0.813. For OS and CSS in M0 RCC patients, PN was superior to CN and RN regardless of grade. But for grade I, PN and none surgery did not show significant differences. In order to further categorize surgical patients and make more precise decisions regarding their treatment, a surgical decision-making model has been established., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval and consent to participate Patient consent was waived due to this article using data from the SEER database, which are publicly available deidentified patient data from the National Cancer Institute (NCI), USA., (© 2024. The Author(s).)

This study aims to analyze the differential expression of METTL14 in pancreatic cancer (PC) tissues and adjacent normal tissues, and its correlation with clinical outcomes. According to the inclusion and exclusion criteria, a total of 80 patients diagnosed in our hospital from January 2021 to January 2023 were chosen as research subjects. RTQ-PCR has detected the mRNA level expression of METTL14 in cancer and para-cancerous tissues. Immunohistochemistry was used to detect the protein expression of METTL14 in cancer and para-cancerous tissues. To compare the relationship between METTL14 expression and clinicopathological parameters in different PC patients. Kaplan-Meier survival analysis of the relationship between METTL14 expression in PC tissues and patient survival prognosis. The Multifactor COX model evaluates factors affecting the prognosis of PC. The expression level of METTL14 mRNA in PC tissues was 5.51 ± 0.35 (kDa), and the positive rate of METTL14 protein expression in PC tissues of all patients was 73.75 (59/80). Tumor location (P = 0.012), tumor differentiation degree (P = 0.028), tumor AJCC stage (P = 0.000), and lymph node metastasis (P = 0.000) were significantly related to the positive rate of METTL14 protein expression in PC tissue. Follow-up results showed that among 80 patients, 63 died. The three-year survival rate of the METTL14 positive group was 13.56% (8/59), and the three-year survival rate of the negative group was 42.86% (9/21). The difference in the three-year survival rate between METTL14 positive and negative expression groups was statistically significant (P = 0.031). Multivariate COX regression analysis results showed that METTL14 was positive (OR 2.797, 95% CI 1.233-5.877), tumor AJCC stage II-III (OR 1.628, 95% CI 1.435-3.859) and lymph node metastasis (OR 1.733, 95% CI 1.122-2.372) were substantive risk factors for poor prognosis in patients with PC. METTL14 expression increases in PC tissue, which is related to tumor AJCC stage, tumor differentiation, and lymph node metastasis, and can be evaluated in the survival prognosis of patients with PC., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical approval and consent to participate This study was approved by the patient’s informed signature and officially recognized by the ethics committee of China Medical University Affiliated Shengjing Hospital Shenbei Campus. This study was conducted in accordance with the declaration of Helsinki., (© 2024. The Author(s).)

Background: The association between the frailty index (FI) and the risk of chronic lung diseases (CLDs) remains unexplored, warranting further research., Methods and Materials: This study investigated the relationship between FI and CLD risk using data from the China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), comprising a combined sample of 9642 individuals. Propensity score weighting was used to ensure similar distribution of covariates across FI groups. The Wilcoxon rank-sum test was used to analyze differences in FI scores between groups with and without CLD. Kaplan-Meier curves and Cox regression analysis were employed to explore the association between frailty status and CLD incidence, with sensitivity analyses conducted for validation., Results: Higher FI scores were significantly associated with increased CLD risk in both cohorts (p < .05). Kaplan-Meier survival and Cox regression analyses indicated that frail individuals have a significantly elevated risk of CLD compared to robust individuals, particularly in certain subgroups (e.g., female) within the CHARLS cohort (p < .05). The ELSA cohort yielded similar results (p < .05), affirming FI as a strong predictor of CLD. Additional risk factors identified included age, smoking, and unmarried status (p < .05). Frail individuals consistently exhibited the highest risk in both cohorts (CHARLS HR = 1.54, p = .003; ELSA HR = 6.64, p < .001). The sensitivity analysis did not substantially alter the significant associations., Conclusion: These findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk., (© 2024. The Author(s).)

Purpose: Early-onset colorectal cancer (CRC) (EOCRC, < 50 years) has distinct clinicopathological features from late-onset CRC (LOCRC, ≥ 50 years). However, evidence on survival outcomes is contradictory. We aimed to analyse the differences in 5-year overall survival (OS) between EOCRC and LOCRC., Methods: A retrospective cohort study was conducted during 2018-2022. Individuals aged ≥ 18 years diagnosed with CRC at two hospitals in Medellín, Colombia were included. Clinicopathological and survival data were retrieved from the medical records and a public government database. Patients were categorized into EOCRC and LOCRC groups. Five-year OS rates were calculated using the Kaplan-Meier method and prognostic factors for OS were identified through Cox regression models., Results: Among 1022 patients, 52.5% were female, and 13.5% (n = 138) had EOCRC. Patients with EOCRC showed higher 5-year OS rates than LOCRC patients (54% vs. 32%). Univariable analyses indicated a 37% lower risk of death for EOCRC compared to LOCRC (HR: 0.633, 95%CI: 0.476-0.840, p = 0.002). After multivariable analyses, advanced staging and higher tumour grading were prognostic factors for worse OS (HR: 2.127, 95% CI:1.405-3.220, p = 0.0001; and HR: 12.896, 95%CI: 6.310-26.355, p = 0.000; respectively), and being in the EOCRC group remained as a prognostic factor for higher OS (HR: 0.482, 95% CI: 0.336-0.690, p = 0.000)., Conclusion: EOCRC is associated with significantly better 5-year OS rates and prognosis compared to LOCRC. Advanced stage and higher tumour grading are predictors of lower OS among all CRC patients. These findings highlight the importance of age-related risk stratification and personalized therapeutic approaches in CRC., (© 2024. The Author(s).)

The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan-Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P < 0.05). The five-year survival of EOCRC patients was significantly better than that of LOCRC patients (P < 0.05). Laparoscopic surgery improved the long-term survival of EOCRC patients. Proficient mismatch repair (pMMR) favored the long-term survival of EOCRC patients. The survival rate of EOCRC patients at TNM stages I and II was higher than that of LOCRC patients at the same stages (P < 0.05). The age cumulative curve showed a substantial increase in the number of CRC patients at 40 years. The long-term prognosis of EOCRC patients is better than that of LOCRC patients, especially among those with pMMR, stages I-II, and who undergo laparoscopic surgery. For people with a high risk of cancer, such as a family history of cancer and poor lifestyle habits, the starting age for CRC screening should be 40 years., (© 2024. The Author(s).)

The role of statins in improving cardiovascular outcomes is well established, but little is known about their impacts on long-term outcomes in persistent tobacco users with stable coronary artery disease (CAD) who receive percutaneous coronary intervention (PCI). A population of persistent smokers with CAD treated by PCI was analyzed. From 2012 through 2019, a cohort of 907 persistent tobacco users with stable CAD undergoing PCI were enrolled from the inpatient department of Taichung Tzu Chi Hospital, Taiwan. We surveyed statin users and non-statin users after index PCI, and general characteristics, major risk factors, angiographic findings, and long-term clinical outcome were compared. Kaplan-Meier curve was used to compare the survival difference and Cox proportional hazard model was used to analyze the predictors for all-cause mortality and major adverse cardiovascular events, including cardiovascular (CV) mortality, myocardial infarction, and repeated PCI procedures. The statin group had a higher average total cholesterol (P < .01) and low-density lipoprotein cholesterol (LDL-C) level (P < .01) and was younger (P < .01) than the non-statin group. Ninety-six point one percent patients in the statin group had a LDL-C level below 100 mg/dL after treatment. They also had a more frequent history of acute coronary syndrome and lower prevalence of chronic kidney disease than the non-statin group (both P < .01). Freedom from all-cause and CV mortality were lower in the non-statin group than the statin group (both P < .01). After adjustment for age and chronic kidney disease, statin treatment no longer reduced the risk of CV mortality (hazard ratio: 0.32, 95% confidence interval = 0.07-1.49), but was still associated with a reduction in all-cause mortality (hazard ratio: 0.27, 95% confidence interval = 0.10-0.75). In persistent tobacco users undergoing PCI, patients treated with statin for LDL-C values above 100 mg/dL had a similar level of cardiovascular protection as those with LDL-C below 100 mg/dL and without statin treatment. Therefore, smoking attenuates pleiotropic effect of statin. Nevertheless, statin therapy was still associated with a reduction of all-cause mortality., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The stress hyperglycemia ratio (SHR) is associated with poor outcomes in critically ill patients. However, the relationship between SHR and mortality in patients with sepsis-associated acute kidney injury (SA-AKI) remains unclear., Methods: The data of patients with SA-AKI, identified based on the KDIGO criteria, were retrospectively collected from the Beth Israel Deaconess Medical Center between 2008 and 2019. SHR was calculated as follows: (glycemia [mmol/L]) / (1.59 × HbA1c [%] - 2.59). Primary outcomes were 30-day and 1-year mortality. The cumulative incidence of all-cause mortality was assessed using Kaplan-Meier survival analysis. Multivariable-adjusted logistic and Cox models and restricted cubic spline curves were used to analyze the correlation between SHR and all-cause mortality. Post-hoc subgroup analysis was performed to compare the effects of SHR across different subgroups., Results: 1161 patients with SA-AKI were identified and categorized into four SHR quartiles as follows: Q1 (0.26, 0.90), Q2 (0.91, 1.08), Q3 (1.09, 1.30), and Q4 (1.31, 5.42). The median age of patients was 69 years, with 42.7% of the patients being women and 20.2% of the patients having chronic kidney disease. The 30-day and 1-year mortality were 22.1% and 35.0% respectively. Kaplan-Meier survival analysis indicated a gradual decrease in survival probability with increasing SHR quartiles. An increased SHR exhibited a strong correlation with 30-day mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.18-1.90; P < 0.001) and 1-year mortality (HR, 1.32; 95% CI, 1.06-1.65; P = 0.014). SHR has a nonlinear relationship with 1-year mortality but not with 30-day mortality (P-nonlinear = 0.048 and 0.114, respectively). The results of subgroup analysis were mostly consistent with these findings., Conclusion: An increased SHR is independently associated with 30-day and 1-year mortality in patients with SA-AKI. Therefore, SHR may serve as an effective tool for risk stratification in patients with SA-AKI., (© 2024. The Author(s).)

Objective: To explore the relationship between hypernatremia and 28-day mortality in elderly sepsis patients., Methods: A total of 179 elderly patients (age ≥65 years) with elevated serum sodium admitted to the Department of Critical Care Medicine of Nanjing Hospital affiliated with Nanjing Medical University from September 2021 to September 2022 were included in this retrospective observational study. The clinical data of all patients were collected, and the patients were divided into septic group and nonseptic groups according to the Sepsis 3.0 definition. The clinical features, acute physiological and chronic health II score (APACHE II score), mechanical ventilation time, serum sodium value and duration of serum sodium elevation were compared between the two groups. ROC curves were drawn to evaluate the predictive value of each index on the prognosis of sepsis patients, and Kaplan‒Meier survival analysis was carried out on patients with different serum sodium peaks., Results: (1) The changes in serum sodium within 48 hours after admission in the sepsis group were small and statistically significant compared with those in the nonsepsis group (P = 0.039); however, the serum sodium elevation duration was longer (P = 0.018). (2) Compared with nonseptic patients, the 7-day mortality of septic patients was higher (15.8 vs. 7.7, P<0.001). The 28-day mortality of septic patients was higher than that of nonseptic patients, but there was no significant difference between the two groups (P = 0.086). (3) The serum sodium level in the sepsis group was higher than that in the nonsepsis group on the 1st, 3rd, 5th and 7th days (P<0.001). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (4) The ROC curve analysis showed that the peak value of serum sodium had predictive value for the prognosis severity of elderly patients with sepsis. The area under the curve (AUC) was 0.753, the 95% confidence interval (95% CI) was 0.639~0.867, and the best cut-off value was 154.9 mmol/L. (5) According to the best cut-off value of the serum sodium peak, the septic patients were divided into two groups: the peak value of serum sodium was ≥154.9 mmol/L (group A), and the peak value of serum sodium was <154.9 mmol/L (group B). Among them, the case fatality rate was higher at 7 days and 28 days when the peak value of serum sodium was ≥154.9 mmol/L (group A) (22.0% vs. 8.6%); the χ2 value was 35.379, P<0.05; 75.6% vs. 37.1%, χ2 = 14.21, P = 0.003). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (6) Kaplan‒Meier survival analysis showed that the median survival time of patients with a serum sodium peak ≥154.9 mmol/L (group A) was significantly shorter than that of patients with a serum sodium peak < 154.9 mmol/L (group B) (16.7±1.4 d vs. 24.8±1.2 d, P <0.05)., Conclusions: The serum sodium increase in elderly sepsis patients lasts for a long time, and the serum sodium fluctuation is relatively small. The serum sodium peak value has predictive value for 28-day mortality., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer., Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020., Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien-Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan-Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892-37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076-8.340; p = 0.036) were independent prognostic factors for disease-free survival., Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival., (© 2024. The Author(s).)

Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear., Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis., Results: A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients., Conclusions: In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The 5-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis-free survival than placebo among patients with BRAF V600-mutated stage III melanoma. Longer-term data were needed, including data regarding overall survival., Methods: We randomly assigned 870 patients with resected stage III melanoma with BRAF V600 mutations to receive 12 months of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Here, we report the final results of this trial, including results for overall survival, melanoma-specific survival, relapse-free survival, and distant metastasis-free survival., Results: The median duration of follow-up was 8.33 years for dabrafenib plus trametinib and 6.87 years for placebo. Kaplan-Meier estimates for overall survival favored dabrafenib plus trametinib over placebo, although the benefit was not significant (hazard ratio for death, 0.80; 95% confidence interval [CI], 0.62 to 1.01; P = 0.06 by stratified log-rank test). A consistent survival benefit was seen across several prespecified subgroups, including the 792 patients with melanoma with a BRAF V600E mutation (hazard ratio for death, 0.75; 95% CI, 0.58 to 0.96). Relapse-free survival favored dabrafenib plus trametinib over placebo (hazard ratio for relapse or death, 0.52; 95% CI, 0.43 to 0.63), as did distant metastasis-free survival (hazard ratio for distant metastasis or death, 0.56; 95% CI, 0.44 to 0.71). No new safety signals were reported, a finding consistent with previous trial reports., Conclusions: After nearly 10 years of follow-up, adjuvant therapy with dabrafenib plus trametinib was associated with better relapse-free survival and distant metastasis-free survival than placebo among patients with resected stage III melanoma. The analysis of overall survival showed that the risk of death was 20% lower with combination therapy than with placebo, but the benefit was not significant. Among patients with melanoma with a BRAF V600E mutation, the results suggest that the risk of death was 25% lower with combination therapy. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in the management of CAP in a contemporary real-world setting., Methods: This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017 and 2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan-Meier survival curves were used to analyse these outcomes, considering competing risks., Results: The study population primarily comprised elderly individuals (median age 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders and 17.3% (276/1595) among the rest., Conclusion: Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this ageing population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders., Competing Interests: Conflict of interest: T. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Foundation, Erik and Susanna Olesen's Charitable Fund, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Roche, Novartis and Kancera AB, consultancy fees from GSK and Pfizer, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, AbbVie and AstraZeneca, participation on a data safety monitoring board or advisory board with GSK, Pfizer, Gilead Sciences, MSD, Pentabase, Janssen and AstraZeneca, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Eli Lilly (donation of trial medication (baricitinib)). M. Fally reports leadership roles with the European Respiratory Society (member of the Clinical Practice Guidelines Methodology Network and Secretary of Assembly 10, Group 1 (Bronchiectasis and Respiratory Infections)) and Danish Medical Journal (Associate Editor). The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy., Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival., Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group., Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)., (Copyright © 2024 Massachusetts Medical Society.)

This study aimed to construct and assess a machine-learning algorithm designed to forecast survival rates and risk stratification for patients with gastric neuroendocrine neoplasms (gNENs) after diagnosis. Data on patients with gNENs were extracted and randomly divided into training and validation sets using the Surveillance, Epidemiology, and End Results database. We developed a prediction model using 10 machine learning algorithms across 101 combinations to forecast cancer-related mortality in patients with gNENs, selecting the best model using the highest mean over a sequence of time-dependent area under the receiver operating characteristic (ROC) curve (AUC). The performance of the final model was assessed through time-dependent ROC curves for discrimination and calibration curves for calibration. The maximum selection rank method was used to determine the best prognostic risk score threshold for classifying patients into high- and low-risk groups. Afterward, Kaplan-Meier analysis and log-rank test were used to compare survival rates among these groups. Our study examined 775 patients with gNENs, dividing them into training and validation sets. A training set comprised 543 patients, with a median follow-up of 42 months and cumulative mortality rates of 40.0% at 1 year, 48.6% at 3 years, and 54.0% at 5 years. A validation set comprised 232 patients, with cumulative mortality rates of 29.1% at 1 year, 43.5% at 3 years, and 53.2% at 5 years. The optimal random survival forest (RSF) model (mtry = 4, node size = 5) achieved an AUC of 0.839 for survival prediction in the training set. Comprising 11 variables such as demographics, treatment details, tumor characteristics, T staging, N staging, and M staging, the RSF model revealed high predictive accuracy with AUCs of 0.92, 0.96, and 0.96 for 1-, 3-, and 5-year survival, respectively, which was consistently reflected in the validation set with AUCs of 0.88, 0.92, and 0.89, respectively. Moreover, patients were risk-stratified. Although our RSF model effectively stratified patients into different prognostic groups, it needs external validation to confirm its utility for noninvasive prognostic prediction and risk stratification in gNENs. Further research is required to verify its broader clinical applicability., (© 2024. The Author(s).)