Cox Regression Research Articles

Novel Adiposity Indices Are Associated With Poor Prognosis in Heart Failure With Preserved Ejection Fraction Without the Obesity Paradox.

There is limited study that illuminates the relationship between obesity indices and prognosis in patients with heart failure with preserved ejection fraction, nor has it been examined whether the obesity paradox persists when using these metrics. This study is a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. A total of 3114 individuals were included in our final analysis, and a total of 481 (15.4%) all-cause deaths, and 389 (12.5%) heart failure hospitalizations were recorded. In a multivariable Cox regression model, compared with patients with a body mass index (BMI) <24.9 kg/m2, those with a BMI of 25.0-29.9, 30.0-34.9, and 35-39.9 kg/m2 were associated with a decreased risk of all-cause death, with hazard ratio (95% CI) of 0.59 (0.45-0.78), 0.61 (0.46-0.82), and 0.66 (0.47-0.92), respectively. Conversely, patients with a BMI ≥40 kg/m2 showed an increased risk of heart failure hospitalization, compared with BMI <24.9 kg/m2. Furthermore, patients in the highest quintile of obesity indices exhibited a significantly elevated hazard ratio for both all-cause death and heart failure hospitalization, compared with the lowest quintile. An elevated BMI over a certain range was associated with a reduced risk of all-cause death in heart failure with preserved ejection fraction, displaying a U-shaped relationship, with no mortality reduction observed in cases of extreme obesity. In contrast, higher values of novel obesity indices were positively correlated with all-cause death and heart failure hospitalization without the obesity paradox.

Association Between Atrial Fibrillation and Long-term Mortality in Acute MI Patients

Background: AF is a common complication of an acute MI (AMI) and goes along with adverse events. Nevertheless, the therapeutical guidelines and pharmacological possibilities have improved over the past years. Therefore, this contemporary study aimed to clarify the effect of AF on long-term mortality in patients with incident AMI. Methods: This study included 2,313 patients aged 25–84 years with initial AMI that occurred from 2009 until 2017, documented within the population-based Augsburg Myocardial Infarction Registry. Patients were monitored from hospital admission, with a median follow-up duration of 4.5 years (interquartile range 4.4 years). Survival analysis and multivariable Cox regression analysis were conducted to explore the relationship between AF and long-term all-cause and cardiovascular disease mortality. Results: Altogether, 156 individuals had AF on their admission ECG, while the remaining 2,157 presented with sinus rhythm (SR). Patients with AF were significantly older, more frequently had arterial hypertension, non-ST-segment elevation MI, worse kidney function, smaller AMIs, and were more often former and non-smokers. An increased long-term all-cause mortality was observed among the AF group. (AF patients 39.1%, SR group 16.7%), Upon multivariable adjustment, a HR of 1.40 (95% CI [1.05–1.87]; p=0.023) was calculated when comparing the AF with SR patients. Conclusion: An independently increased risk of long-term mortality for patients with AF compared with patients with SR in case of incident AMI was identified. Therefore, AF should be considered as a serious risk factor in AMI patients, and must be treated aggressively to reduce mortality risk.

Comprehensive Analysis and Verification of the Prognostic Significance of Cuproptosis-Related Genes in Colon Adenocarcinoma

Colon adenocarcinoma (COAD) is a frequently occurring and lethal cancer. Cuproptosis is an emerging type of cell death, and the underlying pathways involved in this process in COAD remain poorly understood. Transcriptomic and clinical data for COAD patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We investigated alterations in DNA and chromatin of cuproptosis-related genes (CRGs) in COAD. In order to identify predictive differentially expressed genes (DEGs) and various molecular subtypes, we used consensus cluster analysis. Through univariate, multivariate, and Lasso Cox regression analyses, four CRGs were identified. A risk prognostic model for cuproptosis characteristics was constructed based on four CRGs. This study also examined the association between the risk score and the tumor microenvironment (TME), the immune landscape, and drug sensitivity. We distinguished two unique molecular subtypes using consensus clustering analysis. We discovered that the clinical characteristics, prognosis, and TME cell infiltration characteristics of patients with multilayer CRG subtypes were all connected. The internal and external evaluations of the predicted accuracy of the prognostic model built using data derived from a cuproptosis risk score were completed at the same time. A nomogram and a clinical pathological analysis make it more useful in the field of medicine. A significant rise in immunosuppressive cells was observed in the high cuproptosis risk score group, with a correlation identified between the cuproptosis risk score and immune cell infiltration. Despite generally poor prognoses, the patients with a high cuproptosis risk but low tumor mutation burden (TMB), cancer stem cell (CSC) index, or microsatellite instability (MSI) may still benefit from immunotherapy. Furthermore, the cuproptosis risk score positively correlated with immune checkpoint gene expression. Analyzing the potential sensitivity to medications could aid in the development of clinical chemotherapy regimens and decision-making. CRGs are the subject of our in-depth study, which exposed an array of regulatory mechanisms impacting TME. In addition, we performed additional data mining into clinical features, prognosis effectiveness, and possible treatment medications. COAD’s molecular pathways will be better understood, leading to more precise treatment options.

Thyroid Malignancies With Thymic Differentiation: Outcomes of Rare SETTLE and CASTLE Tumors.

Spindle epithelial tumors with thymus-like differentiation (SETTLE) and carcinomas showing thymus-like differentiation (CASTLE) are rare intrathyroid tumors. This retrospective cohort study included patients diagnosed with SETTLE, CASTLE, and papillary thyroid carcinoma (PTC) from 2004 to 2020 within the National Cancer Database (NCDB). Demographic, tumor, and treatment characteristics were compared. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox regression models. This study identified 19 patients with CASTLE, 11 with SETTLE, and 483 474 with PTC. CASTLE and SETTLE patients had larger tumors, lymphovascular invasion, and positive surgical margins. They were rarely treated with radioactive iodine treatment but frequently received external beam radiation and chemotherapy. Five-year OS was significantly lower for CASTLE and SETTLE compared to PTC. SETTLE was associated with an increased risk of death. SETTLE and CASTLE are rare intrathyroid tumors with worse survival compared to PTC, often managed with radiation, chemotherapy, and surgery.

Prevalence and Prognostic Significance of Right Ventricular Dysfunction in Patients With Severe Low-Flow, Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Whether the presence of right ventricular (RV) dysfunction may influence the clinical outcome of patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR) has not yet been established. This study included consecutive patients with LFLG-AS undergoing TAVR at 2 high-volume Italian centers. RV dysfunction before TAVR procedure was defined as tricuspid annular plane systolic excursion assessed by transthoracic echocardiography lower than <17 mm. The primary outcome was all-cause death at 1 year. The propensity score weighting technique was implemented to account for potential selection bias between patients with and without RV dysfunction. A prespecified subgroup analysis was conducted to evaluate the consistency of the results in patients with classical and paradoxical LFLG-AS forms. This study included 392 patients; of them, 97 (24.7%) patients showed RV dysfunction before TAVR. At propensity score-weighted adjusted Cox regression analysis, RV dysfunction, according to dichotomous definition, was associated with an increased risk for the primary outcome (adjusted hazard ratio [HR], 3.11 [95% CI, 1.58-6.13]), cardiovascular death (adjusted HR, 3.26 [95% CI, 1.58-6.72]), and major adverse cardiovascular and cerebrovascular events (adjusted HR, 3.39 [95% CI, 1.76-6.53]). Conversely, no difference was detected for the risk of stroke and of permanent pacemaker implantation. No significant interaction of the classical and paradoxical LFLG-AS subgroups was detected for all the outcomes of interest. This study suggests that RV dysfunction echocardiographically assessed by tricuspid annular plane systolic excursion may improve the prognostic stratification of patients with LFLG-AS undergoing TAVR.

Association of dietary anthocyanidins intake with all-cause mortality and cardiovascular diseases mortality in USA adults: a prospective cohort study

Anthocyanins, as a type of polyphenolic compound, have been discovered to offer multiple health benefits to humans, including anti-aging and anti-inflammatory properties. This prospective cohort study aims to examine the relationship of dietary intake of anthocyanin with all-cause mortality and cardiovascular diseases mortality in the US. The aim of this research was to explore the possible correlation between anthocyanin consumption and the mortality rate from all causes as well as from cardiovascular disease. Based on the Public Access NHANES-linked National Death Index files up to December 31, 2019, we identified mortality status and heart disease-specific causes of death. A multivariate Cox regression analysis was employed to evaluate the effects of anthocyanin intake on mortality outcomes, generating hazard ratios and 95% confidence intervals, adjusting for various demographic characteristics, lifestyle factors, and comorbid conditions. Additionally, we utilized Kaplan-Meier survival curves, subgroup analyses. In different scenarios, dietary anthocyanin intake was assessed using restricted cubic spline models. A total of 11,959 participants completed the final cohort, averaging 47.12 years of age (SD ± 0.35). Following adjustments for multiple variables, an inverse relationship was identified between anthocyanin intake in the highest quartile and all causes mortality, yielding a hazard ratio (HR) of 0.68 (95% CI: 0.52–0.89). Similarly, elevated anthocyanin consumption was linked to a reduction in heart disease mortality, with HR of 0.61 (95% CI: 0.38–0.97). Additionally, dose–response curve revealed a consistent decrease in both all-cause and cardiovascular mortality with increasing anthocyanin intake. Further subgroup analyses revealed that elevated intake of anthocyanins was linked to decreased all-cause mortality in White individuals and males. Moreover, high anthocyanin intake was significantly correlated with reduced all-cause mortality irrespective of hypertension or hyperlipidemia status. Our research indicates that an appropriate dietary intake of anthocyanins is associated with a reduction in overall mortality rates. Furthermore, the findings reveal a substantial association between anthocyanin intake and decreased mortality from cardiovascular diseases, suggesting that anthocyanins may effectively lower the risk of cardiovascular-related deaths.

Clinical Characteristics and Treatment of Patients Diagnosed with Pulmonary Arterial Hypertension: A Real-World Study in the USA, Europe and Japan.

This study aimed to describe the clinical characteristics of patients with pulmonary arterial hypertension, treatment received, and factors predicting initial or earlier combination therapy. The Adelphi Real World Pulmonary Arterial Hypertension (PAH) Disease Specific Programme™ is a cross-sectional survey with retrospective data collection conducted in the USA, Europe (France, Germany, Italy, Spain, and the UK), and Japan from March to August 2022. Physicians reported patient characteristics, treatment history, and reasons for treatment selection. Descriptive statistics were grouped by country and World Health Organization functional classification. A multivariable Cox regression analysis investigated factors predicting initial or earlier combination therapy use. Data for 1173 patients was provided by 293 physicians. Patients' mean (standard deviation) age was 58.7 (13.8) years and 54.6% were female. Overall, 91.2% of patients were receiving, or had previously received, PAH-specific treatment. About three-quarters of the cohort were still taking the initial treatment strategy: for this group, 54% were prescribed monotherapy and 32% combination therapy; 15% of patients received supportive therapy alone. The proportion of patients receiving PAH-specific treatment was lowest in the USA (82.0%) and highest in France (94.6%). The proportion of patients receiving PAH on combination therapy was lowest in the USA (23.8%) and highest in Germany (36.5%). Treatment was prescribed for PAH in 87.6%, 89.8%, 89.3%, and 75.0% of patients who were functional classI, II, III, and IV, respectively, and combination therapy usage was more likely for those with more advanced functional class. Higher risk status, care by a pulmonologist, Japanese residence, more complete assessments, and hospitalization in the past 12months were statistically associated with decreased time to combination therapy for PAH. Older age was statistically associated with increased time to combination therapy. In this real-world, geographically diverse sample, monotherapy treatment was common, even among patients with advanced disease.

Prediction of recurrence-free survival and risk factors of sinonasal inverted papilloma after surgery by machine learning models

ObjectivesOur research aims to construct machine learning prediction models to identify patients proned to recurrence after inverted papilloma (IP) surgery and guide their follow-up treatment.MethodsThis study collected 210 patients underwent IP resection surgery at a university hospital from January 2010 to December 2023. Six machine learning algorithms including ExtraSurvivalTrees (EST), GradientBoostingSurvivalAnalysis (GBSA), RandomSurvivalForest (RSF), SurvivalSVM, Coxnet and Coxph, were used to construct the prediction models. Shapley Additive Explanations (SHAP) values were used to explain the importance of various features in predicting IP recurrence.ResultsWe found that the recurrence rate of IP patients is 20.00%, with a median recurrence time of 35.5 months. Multivariate Cox regression analysis identified mild or moderate dysplasia as an independent risk factor for recurrence. The EST model performs the best in predicting postoperative recurrence of IP, with C-index of 0.968 and 0.878 in the training and testing sets. SHAP emphasizes five important predictive factors for recurrence, including bone defects, orbital involvement, smoking, no processing of tumor attachment sites and drinking.ConclusionsTo our knowledge, this is the first study to use multiple ML models to predict postoperative recurrence of IP. The EST model has the best predictive performance, with SHAP emphasizing several key predictive factors for IP recurrence. This study emphasizes the practicality of machine learning algorithms in predicting IP clinical outcomes, providing valuable insights into the potential for improving clinical decision-making.

Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients.

Kidney transplantation (KT) is the best kidney replacementtreatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identifyprognostic factors influencing outcomes in ADPKD. Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

Prognostic role of prostate specific antigen kinetics in primary high volume metastatic hormonal sensitive prostate cancer treated with novel hormonal therapy agents

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting.

Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study

BackgroundGestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.MethodsWe conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.ResultsOf 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83–1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.ConclusionsThis large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.

Clinical significance and potential mechanism of hsa_circ_0006892 in acute respiratory distress syndrome complicated with pulmonary fibrosis.

Acute respiratory distress syndrome (ARDS) is a serious acute lung injury, and can develop into pulmonary fibrosis (PLF). Circular RNAs (circRNAs) regulatory network in ARDS is important. The study explored the role of hsa_circ_0006892 in the occurrence of ARDS and the development of PLF. Hsa_circ_0006892 levels were verified in serum samples of 203 ARDS patients with or without PLF, and the diagnostic value was evaluated through ROC. Cox regression analysis was performed to identify PLF-related factors. The downstream target genes were predicted online. The function and pathway of key genes were annotated through GO and KEGG pathway analysis. Protein-protein interaction (PPI) analysis was performed for the examination of protein interactions. qRT-PCR determined the downregulation of hsa_circ_0006892 in the serum of both ARDS and PLF patients. Hsa_circ_0006892 can differentiate ARDS from controls, and independently related to the development of PLF. Nine targeted related miRNAs were integrated with dysregulated miRNAs from GSE27430 dataset. Clinically, miR-486-3p was the only miRNA that was significantly different in both ARDS and PLF groups, and was determined to be the target of hsa_circ_0006892. 180 target genes of miR-486-3p were predicted, which were integrated with ARDS and PLF-related GSE84439 and GSE38958 datasets. Go and KEGG pathway analysis identified Ras signaling pathway as the most commonly enriched pathway in the overlapped genes. The present results identified the differentially expressed hsa_circ_0006892 in ARDS and PLF, and suggested a possible molecular mechanism of hsa_circ_0006892/miR-486-3p axis.

Lymph Node Yield and Long-Term Mortality Risk in Patients with Colon Cancer: A 20-Year Follow-Up National Study.

Lymph node status is a well-established prognostic factor for colon cancer, but the optimal number of nodes for accurate staging remains unclear. This study explored the relationship between lymph node yield (LNY) and 5-year mortality rates in colon cancer patients in New Zealand. Data from the New Zealand Cancer Registry were retrospectively analyzed for patients with TNM stage I, II, and III colon cancer between August 2003 and December 2021, with follow-up until January 2024. The primary outcome was the 5-year all-cause mortality rate, with LNY, age, sex, ethnicity, tumor site, district health board (DHB), and the number of positive nodes as covariates. Statistical analyses included univariate analysis, Cox regression modeling, and chi-squared tests. LNY was a significant predictor of 5-year mortality risk (hazard ratio 0.985, p < 0.0001), adjusted for age, sex, ethnicity, tumor site, and DHB. The strongest association between LNY and mortality rate was observed at 12 nodes. Further increases in LNY beyond 22 nodes did not lead to statistically significant differences in mortality rates. Lymph node ratio (LNR) was strongly associated with survival in stage III colon cancer, independent of LNY and the number of positive nodes. Higher LNY is significantly associated with reduced 5-year mortality rates in stage I-III colon cancer up to the 22-node mark. The strong correlation between LNR and mortality highlights its potential value for improving treatment planning in future clinical practice.

Supplemental oxygen prescriptions after hospitalization for coronavirus disease 2019

BackgroundThe role of home oxygen therapy for patients recovering from Coronavirus Disease 2019 (COVID-19) pneumonia, characterized by impaired gas exchange, is not well-defined. ObjectivesTo compare the characteristics, duration, odds of receiving, and continuing to receive home oxygen prescriptions between patients discharged home after COVID-19 pneumonia hospitalization and those discharged after non-COVID-19 pneumonia. MethodsFrom April 2020 to March 2021, 52,951 patients with COVID-19 pneumonia (53.6 % women, 64 % White) were identified, and from January 2019 to December 2019, 26,701 patients with non-COVID pneumonia (53.9 % women, 76.7 % White) were identified, using the Optum Clinformatics Data Mart Database. New oxygen prescriptions were identified through Healthcare Common Procedure Coding Systems codes. Propensity score matching adjusted for confounders, and Cox regression analysis was conducted to compare post-discharge oxygen use. ResultsFollowing hospitalization, oxygen was prescribed to 52,951 patients with COVID-19 pneumonia and 26,701 patients with non-COVID pneumonia in the United States. The COVID-19 pneumonia group were four times more likely to be prescribed supplemental oxygen compared to the non-COVID-19 pneumonia group (OR 4.22; 95 % confidence interval [CI] 3.76–4.74). This trend persisted in sensitivity analyses: ICU patients (OR 4.05; 95 % CI 3.36–4.88) and those who received both ICU admission and mechanical ventilation (OR 3.84; 95 % CI 2.32–6.37). Hispanic patients had the highest likelihood of receiving a supplemental oxygen prescription after discharge (OR 6.75; 95 % CI 5.03–9.05). ConclusionsPost-hospitalization, one in five patients with COVID-19 received prescriptions for supplemental oxygen, which was significantly higher than the proportion of patients with non-COVID-19 pneumonia.

The proteinuria selectivity index value predicts the remission of IgA nephropathy: a retrospective cohort study

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n = 39) and high-PSI groups (PSI ≥0.243, n = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02–3.85 and HR 1.75; 95% CI 1.01–3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01–0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

The neutrophil–lymphocyte ratio is associated with all-cause and cardiovascular mortality in cardiovascular patients

This study investigates the relationship of neutrophil–lymphocyte ratio (NLR) with the risk of all-cause and cardiovascular mortality in patients with cardiovascular disease. The data for this analysis came from 2239 participants with cardiovascular disease of the National Health and Nutrition Examination Survey conducted between 1999–2018. The optimal cutoff point for NLR was determined using maximally selected rank statistics. Survival analysis was performed using Cox regression models to assess the impact of NLR on the risk of all-cause mortality and cardiovascular mortality. Restricted cubic spline was used to visualize the association of NLR with mortality risk. Subgroup analysis was performed to examine the relationship between NLR and mortality within subgroups based on age, sex, diabetes and hypertension. During a median follow-up period of 6.7 (IQR, 3.3–10.9) years, 992 all-cause deaths occurred, including 381 cardiovascular deaths. Our study revealed that NLR is a risk factor for all-cause mortality (HR: 1.15 95%Cl: 1.11 ~ 1.19) and cardiovascular mortality (HR: 1.14 95%Cl: 1.08 ~ 1.2) among patients with cardiovascular disease. The restricted cubic spline regression analysis showed a non-linear association between NLR and all-cause mortality (p < 0.05 for nonlinearity) in cardiovascular patients. This association remained robust in subgroup analyses stratified by age, sex, diabetes, and hypertension. Conclusion NLR stands as a significant risk factor for both all-cause and cardiovascular mortality among patients with cardiovascular disease.

Characterisation of incident interstitial lung disease in late systemic sclerosis.

Interstitial lung disease (ILD) is a common and potentially lethal complication of systemic sclerosis (SSc). Screening by HRCT is recommended in all patients with risk factors, including early disease. Little is known on late presentations of ILD. This study aimed to characterize the incidence, risk factors and outcomes of late-onset SSc-ILD. Subjects enrolled in the Canadian Scleroderma Research Group (CSRG) cohort from 2004 to 2020 without prevalent ILD were included. Incidence and risk factors for ILD (on HRCT) were compared according to disease duration above (late) and below (earlier) 7 years from first non-Raynaud manifestation. Risk of ILD progression was compared using Kaplan-Meier and multivariable Cox models. Overall, 199/969 (21%) patients developed incident ILD over a median of 2.4 [1.2, 4.3] years. The incidence rate in late SSc (3.7/100 person-years) was lower than in earlier SSc (relative risk 0.68, 95%CI:0.51-0.92). Risk factors for incident ILD included male sex, diffuse subtype, myositis, anti-topoisomerase I autoantibodies and higher C-reactive protein levels. Patients with late-onset ILD were also less frequently White and more frequently had arthritis and anti-RNA-polymerase III autoantibodies. Lung disease severity was similar between late- and earlier-onset SSc-ILD (FVC 88% and 87%, DLCO 64% and 62%, respectively). Progression rates were also similar between late- and earlier-onset SSc-ILD (log-rank p=0.8, hazard ratio 1.11, 95% CI: 0.58-2.10). ILD can present in late SSc. Risk factors and progression rates overlapped with earlier-onset SSc-ILD. Surveillance for ILD should continue in longstanding SSc. Frequency and modality of monitoring remain to be defined.

Evaluating the effects of 5-aminosalicylic acid on tofacitinib treatment in ulcerative colitis.

Tofacitinib and aminosalicylic acid (5-ASA) are commonly used to treat ulcerative colitis (UC). However, evidence on the effect of concomitant 5-ASA use in patients receiving tofacitinib is limited. This study investigated the effects of 5-ASA combined with tofacitinib in UC patients. This retrospective cohort study used data from the Medical Data Vision database, including patients with UC treated with tofacitinib from May 2018 to April 2022. Patients were grouped according to tofacitinib dosage and assessed for the efficacy of concomitant 5-ASA use. The primary endpoint was clinical relapse. A total of 1213 patients with UC were included in the analysis, with 416 in the 5mg BID group and 797 in the 10mg BID group. In the 5mg BID group, the cumulative relapse-free rate was significantly higher in patients receiving concomitant 5-ASA (P<0.0001). Multivariate Cox regression analysis confirmed that concomitant 5-ASA use significantly reduced the risk of clinical relapse (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31-0.70). In the 10mg BID group, no significant difference was noted in the cumulative relapse-free rate between patients treated with and without 5-ASA (P=0.445). Similarly, multivariate Cox regression analysis indicated that concomitant 5-ASA use did not significantly affect relapse risk (adjusted HR, 0.97; 95% CI, 0.71-1.32). Concomitant 5-ASA use reduced the risk of relapse in patients on 5mg tofacitinib BID, suggesting benefits at lower doses. However, no significant benefit was observed with 5-ASA use in those 10mg tofacitinib BID.

Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC.

The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.

Integrated machine learning to predict the prognosis of lung adenocarcinoma patients based on SARS-COV-2 and lung adenocarcinoma crosstalk genes.

Viruses are widely recognized to be intricately associated with both solid and hematological malignancies in humans. The primary goal of this research is to elucidate the interplay of genes between SARS-CoV-2 infection and lung adenocarcinoma (LUAD), with a preliminary investigation into their clinical significance and underlying molecular mechanisms. Transcriptome data for SARS-CoV-2 infection and LUAD were sourced from public databases. Differentially expressed genes (DEGs) associated with SARS-CoV-2 infection were identified and subsequently overlapped with TCGA-LUAD DEGs to discern the crosstalk genes (CGs). In addition, CGs pertaining to both diseases were further refined using LUAD TCGA and GEO datasets. Univariate Cox regression was conducted to identify genes associated with LUAD prognosis, and these genes were subsequently incorporated into the construction of a prognosis signature using 10 different machine learning algorithms. Additional investigations, including tumor mutation burden assessment, TME landscape, immunotherapy response assessment, as well as analysis of sensitivity to antitumor drugs, were also undertaken. We discovered the risk stratification based on the prognostic signature revealed that the low-risk group demonstrated superior clinical outcomes (p < 0.001). Gene set enrichment analysis results predominantly exhibited enrichment in pathways related to cell cycle. Our analyses also indicated that the low-risk group displayed elevated levels of infiltration by immunocytes (p < 0.001) and superior immunotherapy response (p < 0.001). In our study, we reveal a close association between CGs and the immune microenvironment of LUAD. This provides preliminary insight for further exploring the mechanism and interaction between the two diseases.