Multivariate Cox Proportional Hazards Model Research Articles

Revisiting the Relationship Between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

Introduction: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer, yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathological features, and survival in well-differentiated thyroid cancer and to evaluate the significance of 4 cm as a cutoff for management decisions. Methods: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2015) and categorized by tumor size (i.e., small [≤4 cm] or large [>4 cm]) and presence of high-risk histopathological features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small versus large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrates conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). Results: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p < 0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p < 0.001) or other high-risk features alone (MMD: 0.49, p < 0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. Conclusions: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of well-differentiated thyroid cancer.

Association of R-loop binding proteins with prognosis and anti-neoplastic drug sensitivity in lung adenocarcinoma: a bioinformatic study.

OBJECT: To investigate the association of R-loop binding proteins with prognosis and chemotherapy efficacy in lung adenocarcinoma. METHODS: The data related to R-loop regulatory genes were obtained from literature of R-loop proteomics and relevant databases. We used 403 lung adenocarcinoma cases in the Cancer Genome Atlas as training set, and two datasets GSE14814 and GSE31210 in Gene Expression Omnibus as validation sets. The weighted gene co-expression network analysis (WGCNA) was employed to identify R-loop genes with a significant impact on the clinical phenotype of lung adenocarcinoma. Least absolute shrinkage and selection operator (LASSO) regression was utilized to eliminate genes exhibiting multicollinearity. A multivariate Cox proportional hazards model was employed to scrutinize clinical variables and R-loop characteristic genes that exert independent prognostic effects on patient survival. Subsequently, a risk score model was constructed. The predictive capacity of this model for the prognosis of patients was analyzed and validated. Additionally, the performance of risk model on the anti-neoplastic drug sensitivity was assessed. The mutations of R-loop gene were analyzed by maftools. The effect of PLEC expression on anti-tumor drug sensitivity was tested on non-small cell lung adenocarcinoma H1299 and A549 cells in vitro. RESULTS: A collection of 1551 R-loop genes were obtained, and 78 genes exhibited significant effects on the clinical phenotype shown on WGCNA. The LASSO regression analysis retained 14 R-loop genes. A multivariate Cox analysis further identified 3 R-loop genes (HEXIM1, GLI2, PLEC) and a clinical variable (tumor grading) that were associated with patient prognosis. Risk prediction model was established according to the regression coefficients of each parameter. Kaplan-Meier survival analysis showed that the prognosis of high-risk group patients was significantly worse than that of low-risk group (P<0.01). The time-dependent ROC curve showed that the risk model had good predictive ability in both training and validation sets. Predictive analyses of anti-neoplastic drug sensitivity indicated a diminished responsiveness to both chemotherapy and targeted treatment drugs among high-risk patients. The expression of PLEC was strongly correlated with the sensitivity of gefitinib, a classical EGFR inhibitor. CONCLUSIONS: R-loop binding proteins have been identified as significant determinants in the prognosis and therapeutic strategies for lung adenocarcinoma. The results indicates that therapeutic interventions targeting these specific R-loop binding proteins might contribute to a better survival in lung cancer patients.

Evaluation of patients with severe pulmonary hypertension and a range of comorbidities prescribed inhaled treprostinil

PurposePatients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with PH secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. MethodsPatients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group, and included patients with Group 1, Group 2, Group 3, combined Group 2 & 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation or transition to intravenous prostacyclin, was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and REVEAL Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. ResultsThe cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Group 2 & 3; and 15.9% with either Group 4 or 5 PH. At 3-months and 6-months of follow-up, 24.8% and 38.9% of patients respectively were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted HR: 5.02, 95% CI: 3.44 – 7.31). There was no significant difference in disease worsening among WSPH Groups. ConclusionIn a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.

The Utility of Sentinel Lymph Node Biopsy in Elderly Patients with Melanoma.

Sentinel lymph node biopsy (SLNB) is performed less often for older patients with melanoma. We investigated the association of SLNB and melanoma-specific survival (MSS) in the elderly. We retrospectively reviewed the Surveillance, Epidemiology, and End Results (SEER: 2010-2019) for patients ≥70 years with cT2-4N0M0 melanoma. We used multivariable Cox proportional hazard models to evaluate the impact of SLNB performance and SLN status on MSS at increasing age cutoffs. In addition, we evaluated the association of different factors with SLNB performance using multivariable logistic regression. We identified 11,548 patients. Sentinel lymph node biopsy occurred in 6754 (58.5%) patients, 1050 (15.5%) of whom had a positive SLN. On adjusted SEER analysis, a negative SLN was independently associated with improved MSS (overall hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.63-0.67) for patients up to 87 years old. Positive SLNB was independently associated with inferior MSS (HR 1.71, 95% CI 1.93-1.98). Increasing age groups were significantly associated with decreased SLNB performance. Sentinel lymph node biopsy is associated with cancer-specific survival and adds prognostic information for elderly patients with melanoma. Sentinel lymph node biopsy performance should not be eliminated in elderly patients based on age alone, unless justified by poor performance status, patient preference, or other surgical contraindications. Decreased SLNB performance with increasing age in our cohort may indicate a missed therapeutic opportunity in the care of elderly patients with melanoma.

NLR, MLR, and PLR are adverse prognostic variables for sleeve lobectomy within non-small cell lung cancer.

The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central-type non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan-Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. The disease-free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan-Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs. <2.196, p = 0.0009), MLR (≥0.2763 vs. <0.2763, p = 0.0018), and PLR (≥126.11 vs. <126.11, p = 0.0354). Similarly, significant differences in DFS were observed for NLR (≥3.010 vs. <3.010, p = 0.0005), MLR (≥0.2708 vs. <0.2708, p = 0.0046), and PLR (≥126.11 vs. <126.11, p = 0.0028). Univariate Cox analysis showed that NLR (hazard ratio [HR]: 2.469; 95% confidence interval [CI]: 1.416-4.306, p < 0.001), MLR (HR: 2.192, 95% CI: 1.319-3.643, p = 0.002) and PLR (HR: 1.696, 95% CI: 1.029-2.795, p = 0.038) were correlated alongside OS. Multivariate Cox analysis showed that NLR (HR: 2.036, 95% CI: 1.072-3.864, p = 0.030) was a separate OS risk variable. Additionally, the pN stage (HR: 3.163, 95% CI: 1.660-6.027, p < 0.001), NLR (HR: 2.530, 95% CI: 1.468-4.360, p < 0.001), MLR (HR: 2.229, 95% CI: 1.260-3.944, p = 0.006) and PLR (HR: 2.249, 95% CI: 1.300-3.889, p = 0.004) were connected to DFS. Multivariate Cox analysis showed that pN stage (HR: 3.098, 95% CI: 1.619-5.928, p < 0.001) was a separate DFS risk variable. The study demonstrates that NLR, MLR, and PLR play a convenient and cost-effective role in predicting survival and recurrence among individuals alongside central-type NSCLC having SL.

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD). We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study. This study included 1,231 adult participants (62% female) with biopsy-proven MASLD who had VCTEs at least one year apart. LSM progression and regression were defined by a ≥ 20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n=680) versus no T2DM (n=551) at baseline. The mean (±SD) age and BMI were 51.8 (±12.0) years and 34.0 (±6.5) kg/m2, respectively. The median (IQR) time between the first and last VCTE measurements was 4.1(2.5-6.5) years. Participants with T2DM had higher LSM progression at 4-years (12% vs. 10%), 6-years (23% vs. 16%), and 8-years (50% vs. 39%), p=0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR 1.35, 95% CI 1.01-1.81, p=0.04). T2DM was not associated with LSM regression (p=0.71). Mean HbA1c was significantly associated with LSM progression (p=0.003) and regression (p=0.02). Utilizing serial VCTE data from a multicenter study of participants with biopsy-proven MASLD, we demonstrate that T2DM and HbA1c are associated with LSM progression.

Impact of Early Bleeding on Long-Term Mortality Following Left Atrial Appendage Occlusion

BackgroundShort-term antithrombotic therapy is recommended after left atrial appendage occlusion(LAAO) to reduce the risk of device-related thrombosis(DRT). However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. ObjectiveWe aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. MethodsPatients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within three months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio(HR). Multivariable regression analysis was used to identify predictors of early bleeding. ResultsAmong the 592 patients included, 389(66%) were male, and mean age was 75.6 years. Eighty-three patients(14.0%) experienced early bleeding, with the majority having minimal(63.4%) or minor(17.3%) bleeding. At a median follow-up of 14.4 months(IQR 4.2-27.9), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjustedHR, 2.07; 95%CI, 1.15-3.75; P=0.02). A history of intracranial bleeding, non-paroxysmal atrial fibrillation, CHA2DS2VASc score, and early DRT were independent predictors of early bleeding. Anti-thrombotic therapy on discharge was not associated with early non-procedural bleeding. ConclusionsOne in seven patients experience a non-procedural bleeding event within 90 days after LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

Postoperative Radiotherapy in Advanced Stage Squamous Cell Carcinoma Requiring Maxillectomy.

To evaluate whether postoperative radiotherapy (PORT) improves survival among patients who received maxillectomy for pT4aN0 maxillary gingival or hard palate squamous cell carcinoma (SCC) with respect to tumor size. Retrospective analysis. National Cancer Database from 2004 to 2019. Included adult patients who received maxillectomy (partial, subtotal, or total) and neck dissection for treatment-naive margin negative pT4aN0 SCC of the maxillary gingiva or hard palate. Adjusted for age, gender, race, insurance status, income, education, urban/rural, facility type, region, comorbidity index, tumor grade, and tumor extension. Inverse probability weights were incorporated into a multivariable Cox proportional hazards model. A priori post hoc subgroup analysis was performed according to tumor size. We included 416 patients who underwent maxillectomy for pT4aN0 SCC of the maxillary gingiva or hard palate (mean [standard deviation] age, 71.5 [11.3] years; male, 190 [45.7%]; tumor size 2 cm, 362 [87%]). Overall, 49.3% of patients received PORT (205 patients). PORT was associated with a 50% improvement in survival compared to surgery alone (adjusted hazard ratio [aHR], 0.50; 95% confidence interval [95% CI], 0.32-0.81). On subgroup analysis, PORT was associated with improved survival for tumors 2 cm (aHR, 0.47; 95% CI, 0.29-0.77), but not for tumors < 2 cm (aHR, 1.15; 95% CI, 0.33-4.08). The vast majority of patients with pT4aN0 bone-invading SCC of the maxillary gingiva and hard palate benefit from PORT. Patients with tumors < 2 cm did not demonstrate a survival benefit from adjuvant treatment, suggesting that bony invasion alone may not be sufficient criteria for treatment escalation.

Ineffective Cardiac Resynchronization Pacing is Associated with Poor Outcomes in a Nationwide Cohort Analysis

Delivery of cardiac resynchronization therapy (CRT) requires left ventricular myocardial capture to achieve clinical benefits. We sought to determine whether ineffective pacing impacts survival. Ineffective ventricular pacing (VP) was defined as the difference between percent delivered CRT (%VP) and percent EffectivCRTTM in CRT devices. Using the Optum® de-identified Electronic Health Record dataset (Optum® EHR) and Medtronic CareLinkTM data warehouse, we identified patients implanted with applicable devices with at least 30 days follow-up. Kaplan-Meier and Cox proportional hazards models assessed the impact of %VP and % ineffective VP on survival. Among 7,987 patients with 2.1±1.0 years follow up, increasing ineffective VP was associated with decreasing survival: the highest observed survival was in the quartile with <0.08% ineffective VP and the lowest survival was in the quartile with >1.47% ineffective VP (85.1% vs. 75.7% at 3 years, p<0.001). As expected, patients with more than the median %VP of 97.7% had better survival than patients with <97.7% VP (84.2% vs. 77.8%, p < 0.001). However, patients that had >97.7% VP but >2% ineffective VP had similar survival to patients with <97.7% VP but ≤2% ineffective VP (81.6% vs 79.4%, p = 0.54). A multivariable Cox proportional hazards model demonstrated that <97.7% VP (adjusted HR 1.29; 95% CI 1.14-1.46; p <0.001) and >2% ineffective VP (HR 1.35; 95% CI 1.18-1.54; p<0.001) were both significantly associated with decreased survival. Ineffective VP is associated with decreased survival. In addition to maximizing the percentage of delivered CRT pacing, every effort should be made to minimize ineffective VP.

Associations of biological age accelerations and genetic risk with incident endometrial cancer: a prospective analysis in UK Biobank.

Endometrial cancer (EC) is one of the gynecologic malignancy cancer with increasing incidence and mortality rates, partly due to aging populations and genetic risks. This study explores the associations between biological age accelerations (BAA) and risk of incident EC and assesses the joint effect of genetic factor and BAA. Based on the UK Biobank cohort, 132,315 women participants were included for primary analysis and 124,119 white participants for genetic risk analysis. Biological age(BA) was calculated using the Klemera-Doubal (KDM) and PhenoAge method based on clinical biomarkers. We calculated two metrics for BAA (including KDM residual and PhenoAge residual) using residual analysis, comparing them against chronological age. The risk of incident EC was evaluated using multivariable Cox proportional-hazards models, adjusting for relevant covariates. Polygenic risk scores (PRS) were computed from known EC-associated SNPs. Both KDM and PhenoAge residual, were significantly associated with increased EC risk. In fully adjusted models, the highest tertile of KDM and PhenoAge residual was significantly associated with incident EC compared with the lowest group, with HRs of 1.278 (P=0.0044) and 1.424 (P<0.0001), repectively. The population-attributable fractions were 7.84% for KDM residual (P=0.0044), 9.78% for PhenoAge residual (P=0.0005), and 8.47% for genetic risk (P=0.0005). Additionally, joint associations of BAA and genetic risk with incident EC was evaluated. Compared with low genetic risk and low BAA, high genetic risk and high BAA was significantly associated with the incidence of EC with HRs of up to 2.172 (95% CI 1.592-2.963) for KDM and 2.226 (95% CI 1.640-3.022) for PhenoAge. Overall, higher levels of PhenoAge residual were consistently associated with an increased risk of incident EC, regardless of genetic risk. BAA and genetics both enhance the risk of incident EC. The effect of the PhenoAge residual is greater than that of the investigated genes, which in turn is greater than that of the KDM residual. These findings highlight the importance of considering both BAA and genetic factors in EC prevention.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

Association of atherogenic index of plasma with cardiovascular disease mortality and all-cause mortality in the general US adult population: results from NHANES 2005–2018

BackgroundThe atherogenic index of plasma (AIP) is a critical metric for predicting cardiovascular outcomes. However, its associations with cardiovascular disease mortality (CVM) and all-cause mortality (ACM) remain unclear. This study aims to elucidate the relationship between baseline AIP levels and CVM and ACM among a broad cohort of US adults.MethodsUtilizing data from the National Health and Nutrition Examination Survey (2005–2018), we analyzed 18,133 adults aged ≥ 18. Baseline triglycerides and high-density lipoprotein cholesterol levels were measured to calculate the AIP. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up through December 31, 2019. Multivariable Cox proportional hazard models examined the associations between baseline AIP and mortality risks. Additionally, restricted cubic splines were utilized to investigate potential non-linear relationships, with subgroup analyses conducted across strata defined by age, gender, body mass index, diabetes, hypertension, and metabolic syndrome to assess variability in these associations.ResultsOver a median 95.0-month follow-up, there were 1870 all-cause deaths and 579 cardiovascular disease-related deaths. Our findings indicate a J-shaped association between the AIP and ACM (threshold = 0.0905); specifically, when baseline AIP exceeded 0.0905, a significant positive association with ACM emerged (hazard ratio, HR (95% confidence interval, CI): 1.61(1.08–2.37)). However, after adjusting for confounders, the relationship between AIP and CVM was not statistically significant (HR 1.31, 95% CI 0.93–1.86). Notably, in the 40–60-year age group, AIP was significantly positively associated with ACM and CVM, with HRs and 95% CIs of 1.51 (1.08v2.10) and 2.63 (1.39–4.98), respectively.ConclusionsA J-shaped relationship was observed between baseline AIP levels and ACM within the general US population, with a threshold of 0.0905. Moreover, AIP could potentially be an effective predictor for future ACM or CVM, particularly among individuals aged 40–60. Further investigation is warranted to corroborate these findings.

Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression

To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Associations Between Dietary Intake of Tomato and Lycopene with All-Cause and Cancer-Specific Mortality in US Adults with Diabetes: Results From a Cohort Study

This study aimed to explore the association between dietary intake of tomatoes and lycopene with all-cause and cancer mortality among US adults with diabetes. We hypothesized that a higher intake of tomato and lycopene is related to a reduced risk of all-cause and cancer mortality among adults with diabetes. This prospective study was conducted among 9213 US adults with diabetes using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Data on dietary intake of tomatoes and lycopene were obtained from two 24-h dietary recalls. Multivariate Cox proportional hazard models determined the associations between tomato/lycopene intake and mortality. A higher intake of tomatoes and lycopene was significantly associated with a lower risk of all-cause mortality (tomato: Q5 vs. Q1: HR = 0.68, 95% CI = 0.54–0.86, p = 0.001, p for trend = 0.001; lycopene: Q5 vs. Q1: HR = 0.78, 95% CI = 0.64–0.95, p = 0.013, p for trend = 0.006) after adjusting for all covariates. Compared with the lowest quintile of tomato and lycopene intake, the highest quintile was associated with a lower risk of cancer mortality (tomato: HR = 0.58, 95% CI = 0.35–0.96, p = 0.035; lycopene: HR = 0.63, 95% CI = 0.40–0.98, p = 0.043). Our study demonstrated that dietary intake of tomatoes and lycopene was significantly associated with a lower risk of all-cause mortality in US adults with diabetes. High consumption of tomatoes and lycopene was also related to reduced cancer mortality in US adults with diabetes.

The impact of discharge letter content on unplanned hospital readmissions within 30 and 90 days in older adults with chronic illness – a mixed methods study

BackgroundCare transitions are high-risk processes, especially for people with complex or chronic illness. Discharge letters are an opportunity to provide written information to improve patients’ self-management after discharge. The aim of this study is to determine the impact of discharge letter content on unplanned hospital readmissions and self-rated quality of care transitions among patients 60 years of age or older with chronic illness.MethodsThe study had a convergent mixed methods design. Patients with chronic obstructive pulmonary disease or congestive heart failure were recruited from two hospitals in Region Stockholm if they were living at home and Swedish-speaking. Patients with dementia or cognitive impairment, or a “do not resuscitate” statement in their medical record were excluded. Discharge letters from 136 patients recruited to a randomised controlled trial were coded using an assessment matrix and deductive content analysis. The assessment matrix was based on a literature review performed to identify key elements in discharge letters that facilitate a safe care transition to home. The coded key elements were transformed into a quantitative variable of “SAFE-D score”. Bivariate correlations between SAFE-D score and quality of care transition as well as unplanned readmissions within 30 and 90 days were calculated. Lastly, a multivariable Cox proportional hazards model was used to investigate associations between SAFE-D score and time to readmission.ResultsAll discharge letters contained at least five of eleven key elements. In less than two per cent of the discharge letters, all eleven key elements were present. Neither SAFE-D score, nor single key elements correlated with 30-day or 90-day readmission rate. SAFE-D score was not associated with time to readmission when adjusted for a range of patient characteristics and self-rated quality of care transitions.ConclusionsWhile written summaries play a role, they may not be sufficient on their own to ensure safe care transitions and effective self-care management post-discharge.Trial registrationClinical Trials. giv, NCT02823795, 01/09/2016.

Endoscopic ultrasound-guided hepaticogastrostomy vs. antegrade metal stent placement keeping an access route in patients with malignant biliary obstruction.

Few studies have compared endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) with EUS-guided antegrade metal stent placement (AGMS). The purpose of this study was to compare times to recurrent biliary obstruction (TRBO) in patients who underwent HGS using metal stents (MS) and those who underwent AGMS keeping access routes with plastic stents (AGMS-AR). This study retrospectively evaluated consecutive patients who underwent HGS or AGMS between September 2016 and December 2022. TRBO, overall survival (OS), and adverse event (AE) rates were compared in the two groups. The risk factors for RBO were determined using a multivariable Cox proportional hazards model. This study included 32 patients in the HGS group and 30 in the AGMS-AR group. Technical success rate was significantly higher in the HGS than in the AGMS-AR group (100 vs. 80%; P = 0.009). The technical success rate without tract dilation was significantly higher in the AGMS-AR than in the HGS group (83 vs. 38%; P < 0.001). RBO rates were significantly higher in the HGS than in the AGMS-AR group (53 vs. 17%; P = 0.024), whereas AE rates did not differ significantly. TRBO differed significantly in the HGS and AGMS-AR groups (159days vs. not reached, P = 0.011), whereas OS did not differ significantly. Multivariable analysis revealed that HGS was an independent risk factor for RBO (hazard ratio, 6.48, P = 0.014). TRBO was significantly longer in patients who underwent AGMS with PS than HGS. AGMS with PS may be effective after the failure of ERCP in patients with malignant biliary obstruction.

Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors

BackgroundTo investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors.MethodsThis nationwide prospective cohort study used data from the US National Health Interview Survey 2009–2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes.ResultsThe mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36–0.69) for all-cause mortality and 0.37 (95% CI, 0.20–0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35–0.77) for all-cause mortality and 0.27 (95% CI, 0.12–0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups.ConclusionThis cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.

A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis.

No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register. Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score-matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan-Meier curves were used to show cumulative probabilities of reaching outcomes. In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59-1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57-2.66; p = 0.60) and 6.0 (0.93, 0.32-2.68; p = 0.89). Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different.

Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study

BackgroundSARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality.MethodsFrom May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction.ResultsWe recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32–12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively.ConclusionThe risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Longitudinal Analysis of Diabetes Mellitus Risk: Smoking Status and Smoking Cessation.

Background/Objectives: Smoking cessation is acknowledged for its health benefits. However, it paradoxically increases diabetes mellitus (DM) risk shortly after quitting due to weight gain. This research aimed to investigate how smoking status could affect the development of DM, focusing on how the risk of acquiring diabetes changed over time after quitting smoking, independent of variables such as weight gain. Methods: The data of 386,558 participants of the Kangbuk Samsung Health Study, excluding those with pre-existing DM, were examined. Smoking status and its long-term effects on DM risk were assessed using multivariate Cox proportional hazards models. Lifestyle factors, including weight change, physical activity levels, and alcohol intake, were adjusted as time-varying covariates throughout the follow-up period. Results: Modified hazard ratios (HRs) indicated no notable disparity in DM risk between individuals who previously smoked and those who had never smoked (HR: 1.04, 95% CI: 0.999-1.08, p-value < 0.001). In contrast, current smokers exhibited a significantly increased DM risk (HR: 1.29, 95% CI: 1.24-1.35, p-value < 0.001). Within the first six years post-cessation, former smokers initially faced a higher DM risk than never smokers (0-2 years, HR: 1.22, 95% CI: 1.15-1.31, p-value < 0.001; 3-5 years, HR: 1.11, 95% CI: 1.04-1.20, p-value < 0.001). After 12 years, they realigned with never smokers (12-46 years, HR: 0.92, 95% CI: 0.86-0.98, p-value = 0.002). Current smokers consistently showed a higher DM risk (0-9 years, HR: 1.29, 95% CI: 1.14-1.46, p-value < 0.001). Adjusting for covariates such as weight change and physical activity did not alter these findings. Conclusions: Our results indicated that former smokers initially experienced an elevated risk of DM relative to never smokers. This increased risk aligned with the risk of never smokers after six years, and the risk continued to improve after 12 years compared to never smokers. This contrasted with current smokers, who maintained a heightened risk of DM, even when adjustments were made for weight change, physical activity, and alcohol intake as time-varying covariates.