Multivariate Cox Proportional Hazards Analysis Research Articles

Elevated levels of plasma inactive stromal cell derived factor-1a predict long-term adverse outcomes in diabetic patients with coronary artery disease

Abstract Background Because of the significantly increased cardiovascular risk by complicating type 2 diabetes (T2D) in patients with coronary artery disease (CAD), the appropriate risk estimation is crucial in patients with T2D following percutaneous coronary intervention (PCI). Nevertheless, there is no established biomarker which can precisely predict outcomes in this particular population. Although stromal cell derived factor-1α (SDF-1α) has been suggested to play a key role in the pathogenesis of T2D, the prognostic impact of SDF-1α in the secondary prevention of CAD is yet to be elucidated. In particular, the ability of SDF-1α isoforms in outcome prediction in this population has not been assessed. Purpose The aim of present study was to investigate the prognostic implication of three isoforms of SDF-1α, such as total, active, and inactive forms of SDF-1α in diabetic patients following PCI. Methods This single-center retrospective analysis involved consecutive patients with T2D who underwent PCI for the first time between 2008 and 2018 (n=849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. Participants were divided into two groups according to the median of three forms of plasma SDF-1α levels (total SDF-1α: 2270 pg/mL, active SDF-1α: 686 pg/mL, inactive SDF-1α: 1537 pg/mL) at PCI procedure and the incidence and risk of subsequent endpoints following PCI were assessed. Results Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α (Figure 1). Constantly, multivariate Cox hazard analyses adjusted by age, sex, body mass index (>25), acute coronary syndrome, and chronic kidney disease (≥ stage 3) repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.05–4.67, p=0.04) and 3P-MACE (HR: 2.30, 95% CI: 1.01–5.09, p=0.04). However, neither of total and active SDF-1α reached statistical significance (Figure 2). Furthermore, the addition of inactive SDF-1α to baseline models in multivariate Cox proportional hazard analysis significantly enhanced both the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for all-cause death (NRI 0.29, p=0.009; IDI 0.007, p=0.03) and 3P-MACE (NRI 0.38, p=0.001; IDI 0.007, p=0.01) while adding total and active SDF-1α did not improve them. Conclusion In diabetic patients following PCI, elevated levels of plasma inactive SDF-1α, not total and active isoforms, might be a useful indicator of adverse outcomes.

Impact of extracorporeal cardiopulmonary resuscitation with ECPELLA on improvement of short-term survival in patients with refractory cardiac arrest

Abstract Background Extracorporeal cardiopulmonary resuscitation (E-CPR) is considered for cardiac arrest (CA) patients when conventional CPR is ineffective. While veno-arterial extracorporeal membrane oxygenation (VA-ECMO) robustly maintains systemic perfusion, it also increases left ventricular (LV) afterload. Recently, the transcatheter LV assist device Impella has been introduced, and the potential benefits of its combined use with VA-ECMO (ECPELLA) are anticipated. However, the utility and effective management of ECPELLA remain unclear. Purpose This single-site cohort study aimed to assess the impact of ECPELLA compared to VA-ECMO with or without intra-aortic balloon pump (IABP) in patients with refractory CA who received E-CPR. Methods We retrospectively reviewed 207 consecutive patients who underwent E-CPR between January 2012 and September 2023 at our institute. The patients were divided into two groups, ECEPLLA (n = 65) and VA-ECMO with or without IABP (n = 141). A propensity score analysis was conducted, utilizing 1:1 score matching based on variables including age, the rate of male gender, acute coronary syndrome, out-of-hospital CA (OHCA), in-hospital CA, shockable rhythm, and the time from collapse to VA-ECMO initiation, known as low flow time (LFT). We evaluated 180-day survival rates, hemodynamic data, and safety profiles. Result After propensity score matching, 57 ECPELLA patients and 57 VA-ECMO patients were included for analysis. No significant differences in the adjusted factors and comorbidities were found between the two groups. In the VA-ECMO group, 42 patients (74%) received concomitant use of IABP. During the first 72 hours following the initiation of VA-ECMO, the ECPELLA group received significantly higher total mechanical circulatory support flow compared to the VA-ECMO group, correspondingly received less catecholamine administration, and had more patients started on vasodilators and cardioprotective medications. There were no statistical differences in safety profiles, except for hemolysis and embolic cerebral infarction, between the two groups. Kaplan-Meier analysis demonstrated that the 180-day survival rates were significantly higher in the ECPELLA group than in the VA-ECMO group. In a multivariate Cox proportional hazard analysis that included age, shockable rhythm, OHCA, initial lactate levels, LFT, and ECPELLA, it was found that age (hazard ratio [HR], 1.28 [for 10-year increase]; 95% confidence interval [CI], 1.09–1.51; p = 0.002), initial lactate level (HR, 1.06; 95% CI, 1.01-1.11; p = 0.04), and ECPELLA (HR, 0.55; 95% CI, 0.36–0.85; p = 0.007) were significantly associated with 180-day mortality. Conclusion ECPELLA was associated with improvement of 180-day mortality in patient who received E-CPR. The results suggest that not only the choice of ECPELLA but also sufficient circulatory support during the acute phase, along with modulating catecholamines and vasodilators, may have influenced the prognosis.

Temporal trends in mitral valve surgery in Denmark: changes in patient characteristics and outcomes from 1996 to 2021

Abstract Background Mitral valve regurgitation (MR) is associated with increased morbidity and mortality. Mitral valve surgery (MVS) is recommended in severe MR, which is the second most common cause of heart valve surgery in the Western world. Data on national practice patterns are lacking and are essential for the continuous epidemiologic surveillance of the disease. Purpose To investigate temporal trends in patient characteristics, incidence and mortality in patients undergoing MVS for MR in Denmark from 1996 to 2021. Methods Using Danish nationwide registries, we identified all patients ≥18 years undergoing MVS for MR. Patients operated due to infective endocarditis were excluded. The study population was grouped into one 6-year and four 5-year calendar bands and type of MVS (mitral valve repair, mechanical or biological valve replacement and transcatheter-edge-to-edge repair (TEER)). Temporal trends in patient characteristics were computed. Annual incidence rates were calculated while considering the total Danish population ≥18 years at risk. For one-year postoperative mortality analysis, the reverse Kaplan-Meier estimator and a multivariable Cox proportional hazard analysis were used. Results We identified 7,813 patients (median age 67.3 years, 65.6% males) undergoing MVS. Over calendar time, burden of comorbidities decreased while median age increased, Table 1. From 1996 to 2021, a stepwise increase was seen in the overall incidence rate for MVS from 3.87 [95% CI 3.32-4.51] to 7.06 [95% CI 6.34-7.58] per 100,000 person-years (p<0.001). The incidence of mechanical valve replacement statistically significantly decreased (p<0.001), while the incidence of mitral valve repair (p=0.004), biological replacement (p≤0.001) and TEER statistically increased (p=0.015), Figure 1. For the overall study period, one-year mortality was 5.0% for mitral valve repair, 12.7% for mechanical valve replacement, 15.7% for biological valve replacement and 19.0% for TEER. Demographics and one-year mortality stratified by calendar period are shown in Table 1. In the mitral valve repair group, adjusted analysis showed a stepwise statistically significant decrease in one-year mortality with HR 0.30 (95% CI 0.17-0.53, p≤0.001) in 2017-2021 as compared to 1996-2001. In the remaining surgical groups, trends were towards decreasing one-year mortality over calendar periods but did not reach statistical significance. Conclusion(s) In this Danish nationwide cohort study, we observed an increase in the incidence of overall mitral valve surgery from 1996 to 2021. The incidence of mechanical valve replacement decreased, while the incidence of mitral valve repair, biological replacement and TEER increased. Mortality rates significantly improved for mitral valve repair patients over calendar time. Continuous epidemiological surveillance of this patient group is required in an era of development in treatment guidelines, surgical methods and patient demographics.Table 1Figure 1

Disparities in the access to atrial fibrillation ablation in Denmark

Abstract Background Atrial fibrillation (AF) is a common arrhythmia that can lead to serious complications such as stroke, heart failure, as well as reduced quality of life. Radiofrequency and cryoablation are safe and effective treatments for AF, but they are not offered equally to all patients. Purpose The study aims to identify the demographic groups more or less likely to undergo AF ablation. Methods Using nationwide National Registries, all Danish patients with newly diagnosed AF between the 1st of January 2005, and the 31st of December 2018 were identified. The association between patients, stratified by gender, age, level of education and attachment to the job market, and the likelihood of receiving AF ablation was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidence of AF ablation among these groups was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 176,248 patients were included in the study. Men were more likely to receive ablation than women (7% vs 3%). When analysing age, patients aged 25-44 and 45-64 were most likely to receive ablation, while only 0.7% of patients aged 80 or above received ablation. The rate of ablation significantly decreased with decreasing level of education. Patients with a Ph.D. or doctorate degree were more likely to receive ablation than patients with only basic school education (22% vs 2%). Finally full-time employed patients were most likely to receive ablation, followed by self-employed, unemployed, on sick leave, undergoing education, and early retired patients. Retired patients were the least likely to receive ablation (3%). Conclusion This study found that women, older patients, patients with lower levels of education, and patients who are not employed or who are retired are less likely to receive AF ablation. These findings suggest that there are significant social and economic disparities in AF ablation treatment in Denmark.Ablation by educationForest plot: Cox analysis

Prior fecal immunochemical test positivity is associated with adverse prognosis in patients with acute ST-segment elevation myocardial infarction

Abstract Backgrounds While fecal immunochemical testing (FIT) is commonly used for disease screening, its significance in other conditions, particularly in patients with ST-segment elevation myocardial infarction (STEMI), is not extensively researched. Purpose This study aimed to investigate the impact of prior positive FIT results on the clinical prognosis of patients with STEMI. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients discharged from 72 hospitals from 2010 to 2023. A total of 76,157 patients with acute STEMI patients were enrolled. Positive FIT was defined as "+-" or higher on the fecal occult blood test. Propensity score matching (PSM) was employed to balance differences between the two groups. Kaplan-Meier analysis with log-rank tests compared endpoint risks between groups, and a multivariable Cox regression model adjusted for potential confounders. The primary endpoint was Net Adverse Clinical Event (NACE), including cardiac death, recurrent myocardial infarction, revascularization, stroke, cerebral hemorrhage, and gastrointestinal bleeding. Results After 1:3 PSM,2,148acute STEMI patients were included, with 537 having prior positive FIT and 1,611 without. Patients with prior positive FIT were more likely to have comorbidities such as hyperlipidemia, prior malignancy, post-coronary artery bypass grafting, renal insufficiency, and prior cerebral hemorrhage. The prior positive FIT group had a higher proportion of prior clopidogrel and indobufen usage, while aspirin use during follow-up was lower. Kaplan-Meier analysis demonstrated a significantly higher risk of NACE in acute STEMI patients with prior positive FIT (before PSM: log-rank P = 0.001, after PSM: log-rank P = 0.005, Figure 1）, as well as increased rates of Major Adverse Cardiac and Cerebral Events (MACCE), all-cause death, and gastrointestinal bleeding (log-rank P < 0.05 for all). Multivariate Cox-proportional hazard analysis adjusted for age, sex, percutaneous coronary intervention during hospitalization, diabetes, hypertension, ischemic stroke, atrial fibrillation, medication during hospitalization, and follow-up showed similar results (Figure 2). Conclusions This study reveals a significant association between prior positive FIT and higher rates of NACE, MACCE, all-cause death, and gastrointestinal bleeding in STEMI patients within 1 year. A history of positive FIT results could serve as a prognostic indicator in this specific patient population.

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score < 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA < 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Frailty and its association with readmissions in patients with rheumatoid arthritis: A national readmissions database study.

It remains unknown whether frailty status confers an increased risk of readmission in patients with rheumatoid arthritis (RA). From the 2018 Nationwide Readmissions Database (NRD), we identified adult patients (age ≥ 18years) admitted with a diagnosis of RA between January to June 2018. Utilizing validated Hospital Frailty Score, patients' frailty risk score was calculated at the time of index admission and categorized into frail (score ≥ 5) and non-frail (score < 5) groups. Our primary outcomes of interest were (1) 180- day readmission rate (2) inpatient mortality; secondary outcomes included prolonged length of stay, LOS (LOS ≥ 7days), and costs of hospitalization. Multivariable Cox proportional hazard analysis was performed to evaluate the independent effect of frailty adjusting for confounding variables. 133,187 patients met inclusion criteria, with mean age 67.7years, of whom 64,131 (48.1%) patients were categorized as frail. The rate of readmission was significantly higher in the frail (56.60%) compared to the non-frail group (30.61%). At index hospitalization, frail patients also had significantly higher inpatient mortality compared to non-frail patients (3.36% vs 0.39%, p < 0.005), longer LOS (26.24% vs 7.82%, p < 0.005). On multivariate analysis frailty was independently associated with a 9% increased risk of readmission (adjusted hazard ratio, 1.09; 95% confidence interval, 1.08 - 1.11). People with RA who are frail have higher rates of readmission than those who are not frail. These findings are crucial in identifying at-risk patients with RA and in discharge planning after hospitalization. Key Points • People with RA who are frail have higher rates of readmission than those who are not frail. • Frail RA patients are also at higher risk of hospitalization-related adverse outcomes, including inpatient mortality and longer hospital stay. • Sepsis is the most common cause for readmission identified in frail patients with RA. • These findings suggest that frailty may be a useful metric in identifying patients with RA at an increased risk of adverse health outcomes.

Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study.

Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer. This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups. Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5months vs 6.9months, p<0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8months vs 7.7months, p=0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group. The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.

Incidence and risk factors of post-stroke seizure among ischemic stroke patients

BackgroundPost-stroke seizure (PSS) increases morbidity and mortality after ischemic stroke, but a comprehensive understanding of its incidence and risk factors is lacking. We report the rate and risk factors of PSS at a single institution. MethodsA retrospective cohort study of adult acute ischemic stroke patients between 2018 and 2022 at a comprehensive stroke center was conducted. Patients with a history of seizures, additional stroke during index admission, or death within 7 days of stroke onset were excluded. Early PSS was defined as a new seizure occurring ≤7 days after stroke onset, while late PSS occurred >7 days after stroke onset. Multivariable logistic regression and cox proportional hazard analysis was conducted. Results1211 participants met inclusion criteria. Patients were a mean age of 67.82 and were primarily male (58.7 %), white (72.6 %), and non-Hispanic (91.9 %). Incidence of PSS was 8.8 % (n = 106), of which 53.8 % (n = 57) were early and 46.2 % (n = 49) were late. Bivariate analysis identified younger age, diabetes, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early Computed Tomography Score ≤5, cortical involvement, and hemorrhagic transformation as significant in the development of PSS. Multivariable cox proportional hazard analysis identified cortical involvement (hazard ratio [HR]: 2.31, 95 % confidence interval [CI] [1,29, 4.14]), NIHSS ≥ 21 (HR: 1.82, 95 % CI [1.02, 3.22]),and younger age (HR: 0.97, 95 % CI [0.96, 0.98]) as significant PSS predictors. ConclusionPSS occurred in 8.8 % of patients presenting with ischemic stroke. Hemorrhagic transformation, cortical involvement, high NIHSS, and younger age were significant predictors of PSS.

Arterial Stiffness Associated with Long-Term Major Adverse Cardiac Events in Patients of Primary Aldosteronism.

As a novel parameter for risk prediction, artery stifiness may hold promise in refining risk assessment strategies, guiding therapeutic interventions, and ultimately improving cardiovascular outcomes in patients with primary aldosteronism (PA). To investigate the correlation between brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, and the occurrence of major adverse cardiovascular events (MACEs) in patients with PA under a primary prevention design. Among the 830 patients included in the final analysis, 113 (13.6%) developed inciden t MACEs over a median follow-up period of 5.8 years, with a crude rate of 23.2 per 1000 person-years. Multivariable Cox proportional hazards analyses revealed that baPWV was an independent risk factor for incident MACEs, with an adjusted hazard ratio of 1.01 (P = 0.028). The generalized additive model identified a cut-off value of 2000 cm/s for baPWV, which was independently associated with incident MACEs, with a hazard ratio of 1.72 (P = 0.045). Subgroup analyses revealed that PA patients who were mineralocorticoid receptor antagonist (MRA) users and had high baPWV had a significantly higher risk of incident MACEs (HR = 3.34; P < 0.001), while the risk was not significant in patients who underwent adrenalectomy (P = 0.062). Furthermore, the addition of baPWV to the cardiovascular Framingham risk score significantly improved the category-free net reclassification index (0.308, P < 0.001). Our study found that 13.6% of patients with PA developed MACEs after a median follow-up of 5.8 years. Our findings highlight the potential utility of baPWV as a tool for risk stratification in PA patients in primary prevention, whereas adrenalectomy appears to mitigate this risk irrespective of baPWV. The measurement of baPWV could be a valuable addition to hypertension screening programs for primary prevention, providing additional predictive information for the potential occurrence of MACEs.

The vasculogenic mimicry, CD146+ and CD105+ microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (p < 0.0001) in cases with unfavourable prognosis. Univariate survival analysis highlighted the significant role of these factors in progression-free survival, while multivariate Cox analysis identified VM and CD146+ vessels as predictive factors. This study demonstrates, for the first time, that VM, CD146, and CD105-positive vessels are involved in EA prognosis, suggesting their potential as independent prognostic indicators and targets for antiangiogenic therapy. However, these findings require further validation through large-scale studies.

The value of D-dimer-albumin ratio as a prognostic biomarker in critically ill patients with sepsis: A retrospective single-center study

BackgroundThis study aimed to examine the potential prognostic significance of the D-dimer-albumin ratio (DAR) in critically ill patients with sepsis. MethodsA retrospective cohort study was carried out at the Affiliated Hospital of Jiangsu University, involving 1123 patients diagnosed with sepsis from January 2015 to November 2023. The patients were categorized into four groups (Q1-Q4) based on their DAR levels. The primary outcomes measured were in-hospital mortality and ICU mortality. Survival analysis was conducted using Kaplan-Meier survival curves and the log-rank test. Additionally, Cox proportional hazards regression models were utilized to investigate the relationship between the DAR and all-cause mortality. ResultsThe study population had a median age of 75 years (interquartile range: 65–84), and the median DAR was 0.15 (interquartile range: 0.08–0.32). The rates of hospital mortality and ICU mortality were 33.7 % and 31.9 % respectively. There was an observed increase in the cumulative incidence of 30-/60-day mortality with higher DAR levels (log-rank test, P < 0.001). After accounting for other variables, the results from multivariable Cox proportional hazards analyses demonstrated that DAR independently predicted hospital death [HR (95%CI): 1.419 (1.205–1.670); P < 0.001] and ICU death [HR (95%CI): 1.437 (1.219–1.693); P < 0.001]. ConclusionsThe DAR was found to be an independent predictor of all-cause mortality in critically ill patients with sepsis.

Epidemiology of chronic pulmonary aspergillosis: A nationwide descriptive study

BackgroundChronic pulmonary aspergillosis (CPA) has recently gained attention owing to its substantial health burden. However, the precise epidemiology and prognosis of the disease are still unclear due to the lack of a nationwide descriptive analysis. This study aimed to elucidate the epidemiology of patients with CPA and to investigate their prognosis. MethodsUsing a national administrative database covering >99% of the population in Japan, we calculated the nationwide incidence and prevalence of CPA from 2016 to 2022. Additionally, we clarified the survival rate of patients diagnosed with CPA and identified independent prognostic factors using multivariate Cox proportional hazard analysis. ResultsDuring the study period, while the prevalence of CPA remained stable at 9.0–9.5 per 100,000 persons, its incidence declined to 2.1 from 3.5 per 100,000 person-years. The 1-, 3-, and 5-year survival rates were 65%, 48%, and 41%, respectively. During the year of CPA onset, approximately 50% of patients received oral corticosteroids (OCS) at least once, while about 30% underwent frequent OCS treatment (≥4 times per year) within the same timeframe. Increased mortality was independently associated with older age (>65 years) (hazard ratio [HR], 2.65; 95% confidence interval (CI), 2.54–2.77), males (1.24; 1.20–1.29), a history of chronic obstructive pulmonary disease (1.05; 1.02–1.09), lung cancer (1.12; 1.06–1.18); and ILD (1.19; 1.14–1.24); and frequent OCS use (1.13; 1.09–1.17). Conversely, decreased mortality was associated with a history of tuberculosis (HR, 0.81; 95% CI, 0.76–0.86), non-tuberculous mycobacteria (0.91; 0.86–0.96), and other chronic pulmonary diseases (0.89; 0.85–0.92). ConclusionsThe incidence of CPA decreased over the past decade, although the prevalence was stable and much higher than that in European countries. Moreover, the patients’ prognosis was poor. Physicians should be vigilant about CPA onset in patients with specific high-risk underlying pulmonary conditions.

The impact of socioeconomic status on overall survival in patients at a radiation oncology center: A retrospective study.

147 Background: There are few reports examining the impact of socioeconomic status (SES), as indicated by the Area Deprivation Index (ADI), on overall survival (OS) in radiation oncology patients, making this an important area of investigation. This study aims to investigate the influence of ADI on OS in radiation oncology patients, while controlling for stage and other relevant variables. Methods: This retrospective study analyzed data from radiation oncology patients treated at a large multi-site single-institution center from October 2006 to January 2024. Demographic and treatment information, including age, gender, race, insurance status, comorbidity index (CCI), mental health disorders (MHD), treatment intent, cancer type, and stage, were collected. The ADI was used to measure SES and was gathered from the Neighborhood Atlas. Kaplan-Meier curves were generated for all patients, with separate curves for different cancer types. The impact of demographic, clinical, and socioeconomic factors on OS was assessed using a Cox proportional hazards multivariable (MVA) logistic regression analysis. The model was stratified by treatment intent, cancer type, stage, insurance status, and CCI. Results: In this comprehensive analysis of 7343 patients, the median follow-up was 12.00 months (IQR: 1.8–36.82). Most patients were breast cancer (30.2%), over 65 years old (60.5%), and had an ADI below the mean (55.5%), indicating lower socioeconomic disadvantage. Kaplan-Meier analysis showed that 5-year OS rates were significantly lower for the fourth quartile ADI group (85.1%) compared to the first quartile ADI group (94.0%) (p&lt;0.001). Among different cancer types, significant differences in OS were observed for breast cancer (p=0.002) and miscellaneous (uncategorized) cancers (p=0.005), with lung cancer showing a trend towards significance (p=0.053). The MVA revealed that patients in both the third quartile (hazard ratio (HR)=1.343, 95% CI: 1.029–1.752, p=0.030) and fourth quartile (HR=1.403, 95% CI: 1.075–1.829, p=0.013) of ADI had significantly higher likelihood of mortality compared to those in the first ADI quartile. Conclusions: SES, as measured by ADI, significantly impacts OS in radiation oncology patients. Poorer patients, indicated by higher ADI, exhibited worse survival outcomes despite controlling for cancer type, stage, treatment intent, CCI, MHD, and insurance status. These findings underscore the need for targeted interventions to address socioeconomic disparities in cancer care to improve survival outcomes for disadvantaged populations.

Predictors of recurrent restenosis after repeat drug-coated balloon therapy for drug-coated balloon restenosis in femoropopliteal lesions: Results of the RECURRENCE study.

Despite the widespread use of drug-coated balloons (DCBs) for femoropopliteal (FP) lesions, there is still no consensus on treatment strategies for DCB restenosis. This study aimed to determine the risk factors for recurrent restenosis after repeat DCB therapy for DCB restenosis in FP lesions. This multicenter retrospective study assessed 1176 consecutive limbs in 860 patients who successfully received initial DCB therapy for FP lesions at four cardiovascular centers between May 2018 and December 2022. Among these patients, 118 consecutive limbs of 104 patients treated via repeat DCB for primary DCB restenosis were enrolled. The Kaplan-Meier estimate of freedom from recurrent restenosis was 74.6% at 1 year. Cox proportional hazard multivariate analysis revealed that recurrent restenosis was independently associated with the time from initial DCB to primary restenosis (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.79-0.92; p < 0.001), history of ≥2 endovascular therapies (EVTs) (HR, 3.11; 95%CI, 1.36-7.12; p = 0.007), and PACSS grade 3 or 4 (HR, 2.76; 95%CI, 1.15-6.63; p = 0.023). Furthermore, receiver operating characteristic curve analysis showed that the cutoff value of the time from initial DCB to primary restenosis to prevent recurrent restenosis was 12.6 months, with an area under the curve of 0.841 (p < 0.001). Repeat DCB therapy for DCB restenosis might be an acceptable strategy, particularly for restenosis that occurred more than 12.6 months after initial DCB, given the rate of freedom from recurrent restenosis.

High plasma levels of fortilin are associated with cardiovascular events in patients undergoing coronary angiography.

Excessive apoptosis and its insufficient clearance is characteristic of atherosclerotic plaques. Fortilin has potent antiapoptotic property and is abundantly expressed in atherosclerotic plaques. Fortilin-deficient mice had less atherosclerosis with more macrophage apoptosis. Recently, we reported that plasma fortilin levels were high in patients with coronary artery disease (CAD). However, its prognostic value has not been elucidated. We investigated plasma fortilin levels and major adverse cardiovascular events (MACE) in 404 patients (mean age 68 ± 12 years; 276 males) undergoing coronary angiography for suspected CAD. MACE was defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 404 patients, 218 (54%) had CAD. Plasma fortilin levels were higher in patients with CAD than without CAD (median 74.9 vs. 70.9 pg/mL, p < 0.05). During a mean follow-up of 5.7 ± 4.2 years, MACE was observed in 59 (15%) patients. Notably, patients with MACE had higher fortilin levels (median 83.0 vs. 71.4 pg/mL) and more often had fortilin level > 80.0 pg/mL (54% vs. 36%) than those without MACE (p < 0.025). A Kaplan-Meier analysis showed lower event-free survival in patients with fortilin > 80.0 pg/mL than in those with ≤ 80.0 pg/mL (p < 0.001). In multivariate Cox proportional hazards analysis, fortilin level (> 80.0 pg/mL) was an independent predictor of MACE (hazard ratio: 2.29, 95%CI: 1.36-3.85, p < 0.002). Among the 218 patients with CAD, fortilin level was also a significant predictor of MACE (hazard ratio: 2.48; 95%CI: 1.34-4.61, p < 0.005). Thus, high plasma fortilin levels were found to be associated with cardiovascular events in patients with CAD as well as those undergoing coronary angiography.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy.

The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Preoperative fibrinogen level predicts the risk and prognosis of patients with native valve infective endocarditis undergoing valve surgery.

The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32-0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (<3.28 g/L) had a significantly greater mortality rate (p = 0.034) than did those with high FBG levels (>3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

Type and dimensions can predict ventricular arrhythmias and cardiac death in primary benign cardiac tumors in children

Despite being extremely rare in children, primary benign cardiac tumors can cause malignant ventricular arrhythmias (VA) or even sudden cardiac death. To assess the predictors of cardiovascular death and malignant VAs, we designed a retrospective single-center study enrolling paediatric patients. We defined as primary outcome a composite of cardiovascular death, sustained VT, ventricular fibrillation and rapid, symptomatic non-sustained VT. Our secondary endpoint was to assess the prevalence of clinically significant arrhythmias in our population. Methods and resultsWe fitted a multivariate Cox regression model to assess the predictors of the primary outcome. Over a period of 38 years, a total of 97 children were enrolled in the study. Among them, there were 73 rhabdomyomas, 13 fibromas, 3 myxomas, 3 teratomas, 1 lipoma, 2 haemangiomas and 2 fibroelastomas. Over a median follow up of 10.53 years, 16 patients met the primary outcome. Kaplan Meier unadjusted survival estimates showed that tumor dimensions larger than 2.3 cm and diagnosis of fibroma predicted worse outcomes compared with smaller tumors or other histotypes, (log rank p < 0.0002 and < 0.0001 respectively). In multivariate Cox proportional hazards analysis, diagnosis of fibroma and tumor dimensions were independently associated to the primary endpoint (HR: 5.06, 95 %CI (1.3–19); and 1.26 • (1.05–11), respectively). Clinically significant arrhythmias were reported in 24.5 % of the study population. ConclusionsAmong paediatric primary cardiac tumors, type and dimensions may predict the hazard of malignant VAs and cardiac death.