Cox Regression Research Articles

Prevalence and Risk Factors for Malignant Nodal Involvement in Early esophago-gastric Adenocarcinoma: Results from the Multicenter Retrospective Congress Study (endosCopic resectiON, esophaGectomy or Gastrectomy For Early Esophagogastric Cancers).

The aim of this study was to quantify LNM risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma. The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of lymph node metastasis (LNM). Current models to select organ-preserving vs. surgical treatment are inconsistent. CONGRESS is a UK-based multicentre retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015-2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival. 1,601 patients from 26 centres were included, with median follow-up 32 months(IQR 14-53). 1285/1612(80.3%) underwent ER, 497/1601(31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs. T1a 7.1%), lymphovascular invasion (17.2% vs. 12.6%), or signet cells (28.6% vs. 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33(0.15-0.77),P=0.010. This large multicentre dataset suggests that early EG adenocarcinoma is associated with significant risk of LNM. This data is representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving vs. surgical treatment is urgently required.

Socioeconomic factors associated with the presence of and outcomes in metabolic dysfunction-associated steatotic liver disease.

The association between socioeconomic factors and disease severity is not well studied in people living with metabolic dysfunction-associated steatotic liver disease (MASLD). We thus examined if socioeconomic factors influence the presence of, or risk for future, major adverse liver outcomes (MALOs) in people living with MASLD. We conducted a register-based cohort study that included all individuals with a MASLD diagnosis between 1987 and 2020 in Sweden. Logistic and Cox regression were used to examine the association between socioeconomic factors (country of birth, educational level, and marital status) and the presence of MALOs before or upon MASLD diagnosis or during follow-up, respectively. In total, 14 026 people living with MASLD were identified, among whom the median age was 55 years, 50% were male and 775 (5.5%) had MALOs before or upon diagnosis. The adjusted odds ratio (aOR) for pre-existing MALOs was higher in divorced (aOR = 1.29, 95% confidence interval [CI] = 1.06-1.57) compared to married individuals. The aOR for pre-existing MALOs was lower among those with >12 years of education (aOR = .76, 95% CI = .62-.93) compared to individuals with an education level of 10-12 years. During a 5.2-year median follow-up, several socioeconomic factors were associated with increased rates of developing MALOs in a crude model; however, none were independently associated with incident MALOs after adjustment for confounders. Socioeconomic factors were associated with somewhat higher odds for prevalent, but not incident, MALOs in people living with MASLD, after adjustments. This suggests primarily that risk factors for fibrosis progression are differently distributed across socioeconomic subgroups.

Occupational Exposure to Silica Dust and Silicosis Risk in Chinese Noncoal Mines: Qualitative and Quantitative Risk Assessment.

Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.

Association between alcohol consumption and incidence of type 2 diabetes in middle-aged Japanese from Panasonic cohort study 12

AbstractThis retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan’s medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3–13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were negatively associated with developing type 2 diabetes compared to complete alcohol abstainers. Alcohol consumption at levels of 39 to < 66 g/day and at levels of ≥ 66 g/day were positively associated with developing type 2 diabetes in participants with BMI < 25 kg/m2. All levels of alcohol consumption were negatively associated with developing type 2 diabetes in participants with BMI ≥ 25 kg/m2. Moderate-to-heavy alcohol consumption were positively associated with developing type 2 diabetes for participants with BMI < 25 kg/m2, whereas alcohol intake was negatively associated with developing type 2 diabetes among participants with BMI ≥ 25 kg/m2.

Comparison of Ticagrelor with Clopidogrel on Coronary Microvascular Dysfunction Following Acute Myocardial Infarction Using Angiography-Derived Index of Microcirculatory Resistance.

This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool. In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90mg twice daily, n = 184) or clopidogrel (75mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up. Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039). The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www. gov (NCT05978726).

Comparison of disease and risk classifications of AML before and after incorporation of NGS analysis of bone marrow samples.

Mutation profiling by next-generation sequencing (NGS) has facilitated understanding of the molecular pathogenesis of acute myeloid leukemia (AML), and has been incorporated into the new disease classification (International Consensus Classification; ICC) and risk classification (European LeukemiaNet [ELN] 2022; ELN2022). We compared disease subtypes between the previous disease classification (4th edition of the WHO classification; WHO-4) and the ICC in 91 patients with AML diagnosed at our institution. We also compared disease risk classifications using the previous risk classification (ELN2017) and the ELN2022. Targeted sequencing of bone marrow samples was conducted at Kyoto University. We found that entities under AML with recurrent genetic abnormalities were well-established, with almost no change from the WHO-4 to the ICC. In contrast, 16.7% of cases of AML, not otherwise specified in the WHO-4 were reclassified into AML with mutated TP53, and 36.7% were reclassified into AML with myelodysplasia-related gene mutations or cytogenetic abnormalities per the ICC. Meanwhile, the ELN2017 and ELN2022 showed no difference in concordance indexes in multivariate Cox regression analysis for progression-free and overall survival. The superiority of the ELN2022 over the ELN2017 could not be confirmed in our single-center retrospective study, and further investigation including multicenter prospective studies is needed.

Competing risk analysis to estimate amputation incidence and risk in lower-extremity peripheral artery disease.

Background: Patients with peripheral artery disease face high amputation and mortality risk. When assessing vascular outcomes, consideration of mortality as a competing risk is not routine. We hypothesize standard time-to-event methods will overestimate major amputation risk in chronic limb-threatening ischemia (CLTI) and non-CLTI. Methods: Patients undergoing peripheral vascular intervention from 2017 to 2018 were abstracted from the Vascular Quality Initiative registry and stratified by mean age (⩾ 75 vs < 75 years). Mortality and amputation data were obtained from Medicare claims. The 2-year cumulative incidence function (CIF) and risk of major amputation from standard time-to-event analysis (1 - Kaplan-Meier and Cox regression) were compared with competing risk analysis (Aalen-Johansen and Fine-Gray model) in CLTI and non-CLTI. Results: A total of 7273 patients with CLTI and 5095 with non-CLTI were included. At 2-year follow up, 13.1% of patients underwent major amputation and 33.4% died without major amputation in the CLTI cohort; 1.3% and 10.7%, respectively, in the non-CLTI cohort. In CLTI, standard time-to-event analysis overestimated the 2-year CIF of major amputation by 20.5% and 13.7%, respectively, in patients ⩾ 75 and < 75 years old compared with competing risk analysis. The standard Cox regression overestimated adjusted 2-year major amputation risk in patients ⩾ 75 versus < 75 years old by 7.0%. In non-CLTI, the CIF was overestimated by 7.1% in patients ⩾ 75 years, and the adjusted risk was overestimated by 5.1% compared with competing risk analysis. Conclusions: Standard time-to-event analysis overestimates the incidence and risk of major amputation, especially in CLTI. Competing risk analyses are alternative approaches to estimate accurately amputation risk in vascular outcomes research.

Neutrophil to lymphocyte ratio and five-year mortality in patients with acute ischemic stroke

BackgroundPrevious studies linked neutrophil to lymphocyte ratio (NLR) with short-term mortality after acute ischemic stroke (AIS), but its relationship with long-term mortality remains unclear. This study investigates the association between NLR and five-year mortality in AIS patients. MethodWe analyzed 416 AIS patients from April 2012 to January 2016 at Zhangjiagang TCM Hospital. Admission NLR was divided into quartiles: Q1 (<2.00), Q2 (2.00–3.05), Q3 (3.06–5.46), and Q4 (≥5.46). We assessed 5-year all-cause and vascular mortality using Kaplan-Meier, Cox regression, and receiver operating characteristic (ROC) curve analyses. ResultsOver five years, 134 (32.2%) all-cause deaths and 114 (27.4%) vascular deaths occurred. Elevated NLR was significantly associated with increased risks of all-cause and vascular mortality. Multivariate Cox analysis identified stroke history (HR: 1.57, 95% CI 1.08–2.30), baseline National Institutes of Health Stroke Scale (NIHSS) score (HR: 1.09, 95% CI 1.05–1.12), and NLR (HR: 1.09, 95% CI 1.05–1.12) as independent risk factors for all-cause mortality. These factors also predicted 5-year vascular mortality: stroke history (HR: 1.65, 95% CI 1.10–2.49), NIHSS score (HR: 1.10, 95% CI 1.06–1.13), and NLR (HR: 1.08, 95% CI 1.05–1.10). NLR quartiles were significantly linked to both outcomes: all-cause mortality HRs were Q2 (1.87, 95% CI 1.00–3.51), Q3 (2.40, 95% CI 1.31–4.39), Q4 (2.77, 95% CI 1.47–5.24), P for trend = 0.001; vascular mortality HRs were Q2 (1.76, 95% CI 0.88–3.55), Q3 (2.34, 95% CI 1.14–4.40), Q4 (2.57, 95% CI 1.28–5.16), P for trend = 0.002. Kaplan-Meier survival analysis revealed significantly higher mortality rates in higher NLR quartiles (log-rank p < 0.001). ROC analysis identified optimal NLR cutoff values of 3.42 for predicting 5-year all-cause mortality (AUC 0.689) and 3.51 for vascular-cause mortality (AUC 0.700), with moderate sensitivity and specificity. ConclusionsHigher NLR at admission was linked with five-year all-cause mortality and mortality attributed explicitly to vascular causes in AIS patients.

CD8+ T cell‑related KCTD5 contributes to malignant progression and unfavorable clinical outcome of patients with triple‑negative breast cancer.

Triple‑negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer that lacks expression of estrogen receptor, progesterone receptor, and HER2, making it more challenging to treat with targeted therapies. The present study aimed to identify CD8+ T cell‑associated genes, which could provide insight into the mechanisms underlying TNBC to facilitate developing novel immunotherapies. TNBC datasets were downloaded from public databases including The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium, and Gene Expression Omnibus. Candidate genes were identified integrating weighted gene co‑expression network analysis (WGCNA), differential gene expression, protein‑protein‑interaction network construction and univariate Cox regression analysis. Kaplan‑Meier survival, multivariate Cox regression and receiver operating characteristic analysis were performed to evaluate the prognostic value of hub genes. Knockdown experiments, alongside wound healing, Cell Counting Kit‑8 and Transwell migration and invasion assays were performed. In total, seven gene modules were associated with CD8+ T cells using WGCNA, among which potassium channel tetramerization domain 5 (KCTD5) was significantly upregulated in TNBC samples and was associated with poor prognosis. KCTD5 expression inversely associated with infiltration ratios of 'Macrophages M1', 'Plasma cells', and 'γδ T cells', but positively with 'activated Mast cells', 'Macrophages M0', and 'Macrophages M2'. As an independent prognostic indicator for TNBC, KCTD5 was also associated with drug sensitivity and the expression of programmed cell death protein 1, Cytotoxic T‑Lymphocyte‑Associated Protein 4 (CTLA4), CD274), Cluster of Differentiation 86 (CD86), Lymphocyte‑Activation Gene 3 (LAG3), T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT). Knockdown of KCTD5 significantly inhibited viability, migration and invasion of TNBC cells in vitro. KCTD5 was suggested to impact the tumor immune microenvironment by influencing the infiltration of immune cells and may serve as a potential therapeutic target for TNBC.

Energy Intake and Dietary Glycemic Load in Late Morning and Risk of Type 2 Diabetes: The Hispanic Community Health Study/Study of Latinos-A Multicenter Prospective Cohort Study.

To evaluate the association between meal timing and type 2 diabetes risk in U.S. Hispanic/Latino adults. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, community-based, prospective cohort study. This study included 8,868 HCHS/SOL adults without diabetes at baseline (2008-2011) and attending the visit 2 examination (2014-2017). Energy intake and glycemic load (GL) in each meal timing were assessed at baseline using two 24-h dietary recalls. Incident diabetes was identified through annual follow-up calls or at visit 2. Hazard ratios (HRs) for incident diabetes were estimated using Cox models, accounting for the complex survey design. The study population (50.9% female) had a baseline mean age of 39.0 (95% CI, 38.4-39.5) years. Over a median (range) follow-up of 5.8 (0.8-9.6) years, 1,262 incident diabetes cases were documented. Greater energy intake and GL in late morning (9:00-11:59 a.m.) were associated with a lower diabetes risk, whereas greater energy intake and GL in other meal timings were not. After accounting for diet quantity and quality, sociodemographic characteristics, lifestyle factors, and chronic conditions, the HRs were 0.94 (95% CI, 0.91-0.97) per 100-kcal energy intake increment and 0.93 (0.89-0.97) per 10-unit GL increment in late morning. Replacing energy intake or GL from early morning (6:00-8:59 a.m.), afternoon (12:00-5:59 p.m.), or evening (6:00-11:59 p.m.) with late-morning equivalents was associated with a comparably lower diabetes risk. This study identified late morning as a favorable meal timing in Hispanic/Latino adults, providing a novel perspective on type 2 diabetes prevention that warrants confirmation.

Overexpression of H2AFX gene in neuroblastoma is associated with worse prognosis.

Neuroblastoma (NB) is the most common solid tumour in childhood, and rises in the sympathetic nervous system. Here, we addressed the in silico analysis of the association between the expression of H2AFX gene involved in DNA damage response, and the survival of a cohort of 786 NB patients. In silico gene expression was retrieved from the publicly available dataset summarised by Cangelosi etal., including 13,696 gene expression profiles of 786 NB tumours at onset of disease. The prognostic value of H2AFX (H2A histone family member X) gene expression for event-free survival (EFS) and overall survival (OS) was evaluated by Kaplan-Meier and Cox regression analysis. The main results were validated on another openly accessible in silico database (NRC-283) containing 13,489 gene expressions in 283 NB patients. The expression of H2AFX protein was then tested by immunofluorescence on 48 primary NB samples of different tumour stages. H2AFX activity as an oncogene has been further validated in vitro by silencing the molecule in two NB cell lines, characterised by MYCN amplified or not, and performing cell growth and migration assays. A strong inverse association between H2AFX expression and patients' survival was observed and confirmed by immunofluorescence results on primary NB tissue sections. Cox regression analysis also disclosed H2AFX as an independent predictor of EFS and OS. The gene-silencing experiments strongly suggested an oncogenic role for H2AFX on NB cells, regardless of MYCN amplification. H2AFX is a prognostic marker for unfavourable NB and could be considered a target for therapeutic interventions.

Identification of Biomarkers for Endometrial Cancer Based on Natural Killer Cell-Related Genes

Endometrial cancer (EC) is a malignant tumor. Natural killer (NK) cells play a crucial role in various cancers, but their role in EC is unclear. To this purpose, in this paper, differential expression analysis was performed on transcriptome data from the TCGA database, and the obtained DEGs and the collected NRGs were intersected, and single-factor Cox regression analysis and Lasso-Cox regression analysis were performed on the intersected genes to obtain prognosis-related genes and risk model, respectively. These genes and models were validated by Kaplan-Meier (KM) survival curve analysis and ROC analysis on the internal and external test sets. In addition, nomogram models were constructed based on prognosis-associated genes, sample risk scores, and clinical factors. Finally, we explored the immune landscape of high- and low-risk groups of EC. The results showed that the risk models constructed in this paper exhibited excellent predictive effects, which will facilitate research on the precision treatment of EC. There were significant differences in prognosis, immune cell infiltration abundance, immune checkpoint-associated genes, and HLA gene expression between high- and low-risk groups of EC. The risk model in this paper can provide a reference for the personalized treatment of EC. In addition, we performed RT-qPCR to validate the levels of genes significantly associated with prognosis.

Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study

BackgroundHypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited. ObjectivesThe purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients. MethodsWomen with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes. ResultsBC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy (P for interaction = 0.01). ConclusionsWomen with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status.

Risk predictive model for the development of hepatocellular carcinoma before initiating long-term antiviral therapy in patients with chronic hepatitis B virus infection.

It is generally acknowledged that antiviral therapy can reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), there remains a subset of patients with chronic HBV infection who develop HCC despite receiving antiviral treatment. This study aimed to develop a model capable of predicting the long-term occurrence of HCC in patients with chronic HBV infection before initiating antiviral therapy. A total of 1450 patients with chronic HBV infection, who received initial antiviral therapy between April 2006 and March 2023 and completed long-term follow-ups, were nonselectively enrolled in this study. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis was used to construct the model. The results were validated in an external cohort (n = 210) and compared with existing models. The median follow-up time for all patients was 60 months, with a maximum follow-up time of 144 months, during which, 32 cases of HCC occurred. The nomogram model for predicting HCC based on GGT, AFP, cirrhosis, gender, age, and hepatitis B e antibody (TARGET-HCC) was constructed, demonstrating a good predictive performance. In the derivation cohort, the C-index was 0.906 (95% CI = 0.869-0.944), and in the validation cohort, it was 0.780 (95% CI = 0.673-0.886). Compared with existing models, TARGET-HCC showed promising predictive performance. Additionally, the time-dependent feature importance curve indicated that gender consistently remained the most stable predictor for HCC throughout the initial decade of antiviral therapy. This simple predictive model based on noninvasive clinical features can assist clinicians in identifying high-risk patients with chronic HBV infection for HCC before the initiation of antiviral therapy.

Observation on the Effect of Sequentially Combined Multi-modal Artificial Liver Treatment on HBV-related Acute-on-chronic Liver Failure.

To observe the short-term effect of sequentially combined multimodal artificial liver treatment (SCMALT) on HBV-related acute-on-chronic liver failure (HBV-ACLF). HBV-ACLF patients 155 cases undergoing artificial liver treatment were analyzed, and they were sorted into the SCMALT group and the conventional-modal artificial liver treatment (CALT) group. The clinical data of all patients were recorded and the serum levels of interleukin-8 (IL-8), chemokine interferon-inducible protein-10 (IP-10), and interleukin-6 (IL-6) were detected. The changes in the 30-day survival rate, cytokine level, model for end-stage liver disease (MELD) score, and complications of artificial liver treatment were analyzed. After being followed up for 30 days, 104 patients survived and 51 died. At the end of the whole-course treatment, the decreases in IL-6, IP-10, and IL-8 levels and MELD scores in the SCMALT group were greater than in the CALT group. Cox regression suggested WBC (OR=1.066 ， 95% CI 1.012-1.123 ， P=0.017), AT-III activity (OR=0.935 ， 95% CI 0.907-0.964 ， P=0.000) at baseline, artificial liver treatment mode (OR=0.362，95% CI 0.164-0.800，P=0.012), number of artificial liver treatments (OR=0.656 ， 95% CI 0.436-0.986 ， P=0.043), spontaneous peritonitis (OR=0.337，95% CI 0.165-0.689，P=0.003), and hepatic encephalopathy (OR=0.104, 95% CI 0.028-0.388 ， P=0.001) were independent influencing factors of 30-day survival rate. SCMALT can significantly prolong the survival period of the patient. No obvious difference was shown in the proportions of bleeding and circulation instability between the two groups (P>0.05). Compared with the CALT, SCMALT can more effectively remove inflammatory mediators and reduce the MELD score in HBV-ACLF patients, which can obviously ameliorate the prognosis, with less effect on the platelet count.

Sex differences in the association of physical functions with hospitalization and mortality events among community-dwelling older adults with disabilities

This study aimed to investigate the role of sex in the association between physical function and the occurrence of hospitalization and mortality among community-dwelling older adults with impairments in activities of daily living (ADL). Participants included community-dwelling older adults aged ≥65 years with ADL disabilities. Physical functions (hand grip strength [HGS], knee extension muscle strength, and comfortable walking speed [CWS]) were measured at baseline and analyzed for association with hospitalization and mortality by sex using Cox regression analysis, adjusted for potential confounders. In this Cox regression analysis, HGS was significantly associated with the occurrence of hospitalization and mortality in women, whereas CWS was significantly associated with the occurrence of hospitalization and HGS with mortality in men. These findings reveal that the predictive ability of adverse events in community-dwelling older adults with disabilities differs by sex, requiring outcome- and sex-specific prognostication.

Prognostic Factors and Overall Survival in Pelvic Ewing's Sarcoma and Chordoma: A Comparative SEER Database Analysis

BackgroundThis study aimed to develop and validate nomograms to predict overall survival (OS) for pelvic Ewing's sarcoma (EWS) and chordoma, identify prognostic factors, and compare outcomes between the two conditions. MethodsWe identified patients diagnosed with pelvic EWS or chordoma from the SEER database (2001-2019). Independent risk factors were identified using univariate and multivariate Cox regression analyses, and these factors were used to construct nomograms predicting 3-, 5-, and 10-year OS. Validation methods included AUC, calibration plots, C-index, and decision curve analysis (DCA). Kaplan-Meier curves and log-rank tests compared survival differences between low- and high-risk groups. ResultsThe study included 1175 patients (EWS: 611, chordoma: 564). Both groups were randomly divided into training (70%) and validation (30%) cohorts. OS was significantly higher for chordoma. Multivariate analysis showed year of diagnosis, income, stage, and surgery were significant for EWS survival, while age, time to treatment, stage, and surgery were significant for chordoma survival. Validation showed the nomograms had strong predictive performance and clinical utility. ConclusionsThe nomograms reliably predict overall survival (OS) in pelvic EWS and chordoma, helping to identify high-risk patients early and guide preventive measures. The study also found that survival rates are significantly higher for chordoma, highlighting different prognostic profiles between EWS and chordoma.

Effect of Sepsis-3 Definition on the Classification of Patients with Sepsis or Septic Shock in South Korea.

Little is known about differences in patient characteristics before and after implementation of the new definition of sepsis (Sepsis-3) and whether the new definition is affecting clinical practice in intensive care units. To examine and compare the clinicoepidemiologic characteristics of patients with sepsis or septic shock before and after implementation of Sepsis-3. In this population-based cohort study, a nationwide registration database in South Korea was used to identify patients with sepsis or septic shock. Patients admitted to hospitals from 2012 to 2015 constituted the Sepsis-2 group, and patients admitted from 2017 to 2020 constituted the Sepsis-3 group. The study involved 443 217 patients, of whom 170 660 (38.5%) were in the Sepsis-2 group and 272 557 (61.5%) were in the Sepsis-3 group. The mean (SD) age was 73.3 (14.5) years in the Sepsis-2 group and 75.5 (14.5) years in the Sepsis-3 group. The intensive care unit admission rate was higher in the Sepsis-2 group (34.6%, 59 081 of 170 660) than in the Sepsis-3 group (21.3%, 57 997 of 272 557). Multivariable Cox regression analysis showed that 1-year all-cause mortality was 21% lower in the Sepsis-3 group than in the Sepsis-2 group (hazard ratio, 0.79; 95% CI, 0.78-0.79; P < .001). Implementation of the Sepsis-3 definition was associated with an increased number of patients with sepsis. Other findings suggested that patients in the Sepsis-2 group had more severe illness, with increased 1-year all-cause mortality, compared with those in the Sepsis-3 group.

Preditores de progressão da doença renal policística autossômica dominante: uma coorte brasileira de centro único

Abstract Introduction: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. Methods: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate &lt;30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. Results: The factors independently associated with the renal outcomes were total kidney length – adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057–1.224), glomerular filtration rate – HR (95% CI): 0.970 (0.949–0.992), and serum uric acid level – HR (95% CI): 1.643 (1.118–2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985–33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919–0.997) were associated with the secondary outcome. Conclusions: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.

Loss of copy numbers of retrotransposons (HERVK) on chromosome 7p11.2 impacts EGFR (Epidermal Growth Factor Receptor)-induced phenotypes for platinum sensitivity and long-term survival in ovarian cancer-A study from the OVCAD consortium.

We analyzed variations in the epidermal growth factor receptor (EGFR) gene and 5'-upstream region to identify potential molecular predictors of treatment response in primary epithelial ovarian cancer. Tumor tissues collected during debulking surgery from the prospective multicenter OVCAD study were investigated. Copy number variations in the human endogenous retrovirus sequence human endogenous retrovirus K9 (HERVK9) and EGFR Exons 7 and 9, as well as repeat length and loss of heterozygosity of polymorphic CA-SSR I and relative EGFR mRNA expression were determined quantitatively. At least one EGFR variation was observed in 94% of the patients. Among the 30 combinations of variations discovered, enhanced platinum sensitivity (n = 151) was found dominantly with HERVK9 haploidy and Exon 7 tetraploidy, overrepresented among patients with survival ≥120 months (24/29, p = .0212). EGFR overexpression (≥80 percentile) was significantly less likely in the responders (17% vs. 32%, p = .044). Multivariate Cox regression analysis, including age, FIGO stage, and grade, indicated that the patients' subgroup was prognostically significant for CA-SSR I repeat length <18 CA for both alleles (HR 0.276, 95% confidence interval 0.109-0.655, p = .001). Although EGFR variations occur in ovarian cancer, the mRNA levels remain low compared to other EGFR-mutated cancers. Notably, the inherited length of the CA-SSR I repeat, HERVK9 haploidy, and Exon 7 tetraploidy conferred three times higher odds ratio to survive for more than 10 years under therapy. This may add value in guiding therapies if determined during follow-up in circulating tumor cells or circulating tumor DNA and offers HERVK9 as a potential therapeutic target.