Multivariate Cox Proportional Hazards Analysis Research Articles

Butyrate-producing Faecalibacterium prausnitzii suppresses natural killer/T-cell lymphoma by dampening the JAK-STAT pathway

BackgroundNatural killer/T-cell lymphoma (NKTCL) is a highly aggressive malignancy with a dismal prognosis, and gaps remain in understanding the determinants influencing disease outcomes.ObjectiveTo characterise the gut microbiota feature and identify...

Tumor budding is an independent adverse prognostic factor of pancreatic ductal adenocarcinoma patients treated by resection after preoperative chemoradiotherapy.

To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT). Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor. OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs. 27.5 months, P = 0.014. DSS: 63.3 vs. 33.0 months, P = 0.014. RFS: 20.3 vs. 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS. This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.

Combined healthy lifestyle behaviors and all-cause mortality risk in middle-aged and older US adults: A Longitudinal Cohort Study

BackgroundWhile various lifestyle behaviors separately or partly have been shown to be associated with health outcomes, including a multitude of diseases and death, none of the earlier research has comprehensively investigated the combined impact of modified lifestyle behaviors. This longitudinal study investigated the association between a composite of healthy lifestyle behaviors and all-cause mortality in middle-aged and older Americans. MethodsWe utilized data from the National Health and Nutrition Examination Survey from 2007 to 2018, as well as relevant mortality data, applying the Healthy Lifestyle Score11HLS: Healthy Lifestyle Score. (HLS) index to assess healthy lifestyle behaviors, defined by no smoking, moderate alcohol, appropriate sleep, a balanced diet, adequate physical activity, and limited sedentary time. Weighted multivariate Cox proportional hazards analyses were applied to investigate the associations between these lifestyle practices and overall mortality, followed by stratified analyses to explore potential effect modifications by subgroups. ResultsThis study included 5448 participants, categorized into unfavorable (28%), intermediate (56%), and favorable (16%) HLS groups. During a median 103-month follow-up, 388 participants died. Cox regression revealed that individuals with favorable lifestyles had a reduced likelihood of death than those with unfavorable lifestyles (HR = 0.49, 95% CI: 0.34-0.70). There was a linear negative relationship established between HLS and the likelihood of all-cause death (p for non-linearity = 0.0512). ConclusionAdherence to a composite of healthy habits is linearly and substantially related to decreasing the likelihood of all-cause mortality among the elderly in the U.S., highlighting the substantial benefits of maintaining these behaviors for longevity and health.

Serum potassium levels as an independent predictor of unplanned enteral nutrition discontinuation in older adults with gastroesophageal reflux disease

Background & AimsEnteral nutrition in older adults is often associated with intolerance, a phenomenon not well-understood in the context of gastroesophageal reflux disease (GERD). This observational study aimed to evaluate serum potassium levels as an independent prognostic factor for unplanned enteral nutrition discontinuation in older adults with GERD. MethodsWe conducted a retrospective analysis of 213 consecutive patients with GERD who received enteral nutrition at our institution from April 2018 to March 2023. The dietary assessment involved extracting relevant nutritional information from the patients' medical records. The incidence of enteral nutrition discontinuation due to complications was monitored over a 30-day period after initiation. ResultsPatients were categorized into three groups based on initial serum potassium levels: low (<4.0 mmol/L), intermediate (4.0–4.5 mmol/L), and high (≥4.5 mmol/L). During the follow-up, 35% of patients experienced events leading to the discontinuation of enteral nutrition. Higher potassium levels correlated with an increased risk of unplanned discontinuation of enteral nutrition (log-rank P=0.002). Multivariate Cox proportional hazards analysis identified serum potassium level as an independent predictor of unplanned discontinuation (hazard ratio: 1.700 [95% confidence interval: 1.100-2.627] per 1 mmol/L, P=0.017). ConclusionsSerum potassium level is a robust independent predictor of unplanned enteral nutrition discontinuation in older adults with GERD. Our findings suggest that monitoring and adjusting potassium levels may be essential for improving outcomes in this vulnerable population.

Integration of the systemic inflammatory response index with pulse pressure enhances prognostication of cardiovascular mortality in the general population of the United States: insights from the NHANES database.

The prognostic significance of utilizing both the systemic inflammatory response index (SIRI) and pulse pressure (PP) collectively in assessing cardiovascular mortality (CVM) across populations remains to be elucidated. Multivariate Cox proportional hazards analysis investigated the SIRI, PP, and CVM association. Receiver operating characteristic (ROC) curves evaluated the predictive performance of the combined SIRI and PP for CVM in the broader demographic. Subsequently, the area under the ROC curve (AUC) was compared using the Z-test, and a novel nomogram was developed to assess its accuracy in predicting CVM. Restricted cubic spline (RCS) was used to evaluate the association between SIRI and PP. The study involved 19,086 NHANES database individuals, with 9,531 males (49.94%). During the follow-up period, 456 CVM instances (2.39%) occurred. Multivariate Cox proportional hazards analysis revealed both the SIRI [adjusted hazard ratio (HR) 1.16, P < 0.001] and PP (HR = 1.01, P = 0.004) as independent CVM predictors. A 0.1-unit SIRI increase and 10 mmHg PP escalation correlated with 2% (adjusted HR = 1.02, P < 0.001) and 7% (adjusted HR = 1.07, P = 0.004) CVM enhancements, respectively. The combined SIRI and PP area under the curve was 0.77, ranging from 0.77 to 0.79 in female cohorts, non-smokers, and non-pathological contexts. High SIRI and PP, either high SIRI or PP, were associated with 3 and 2 times the CVM risk compared to low SIRI and PP. Adding the SIRI and PP to general risk factors improved CVM predictive efficacy (Z = 4.17, P < 0.001). The novel nomogram's concordance index was 0.90, indicating excellent discrimination. The predicted probabilities' calibration plot aligned with actual CVM rates at 1, 5, and 10 years. RCS showed an S-shaped relationship between SIRI and PP. Integrating the SIRI with PP demonstrates substantial predictive efficacy for CVM within the broader United States community, notably in female cohorts, non-smokers, and non-pathological contexts.

Association Between Wound Healing and the Japanese Below-the-Knee Chronic Total Occlusion Score in Patients With Chronic Limb-Threatening Ischemia After Endovascular Therapy.

In the current study, we hypothesized that the Japanese below-the-knee chronic total occlusion score could be used to stratify the lesion difficulty of endovascular therapy for below-the-knee chronic total occlusion through angiographic evaluation. We thus aimed to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion score in patients with chronic limb-threatening ischemia after successful endovascular therapy for below-the-knee chronic total occlusion. This was a retrospective, single-center observational study. We enrolled 139 consecutive patients with chronic limb-threatening ischemia (149 limbs), who underwent successful endovascular therapy for chronic total occlusion between February 2008 and December 2017. The Japanese below-the-knee chronic total occlusion score was assessed based on the definition of the target arterial path. The evaluation items were the rate of amputation-free survival and wound healing at 1 year, and the association between wound healing at 1 year and the Japanese below-the-knee chronic total occlusion score. The rates of amputation-free survival and wound healing at 1 year were 88.0 and 56.4%, respectively. Multivariate Cox proportional hazard analysis identified direct flow to the wound (hazard ratio: 2.34, 95% confidence interval: 1.28-4.66; p<0.01); Wound, Ischemia, and foot Infection stages 1-3 (hazard ratio: 2.81, 95% confidence interval: 1.63-5.18; p<0.01); and a Japanese below-the-knee chronic total occlusion score ≤1 (hazard ratio: 1.70, 95% confidence interval: 1.02-2.98; p=0.04) to be predictors of wound healing. A Japanese below-the-knee chronic total occlusion score ≤1, direct flow to the wound, and Wound, Ischemia, and foot Infection stages 1-3 were found to be associated with wound healing after successful endovascular therapy for below-the-knee chronic total occlusion in patients with chronic limb-threatening ischemia. This study was conducted to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion (J-BTK CTO) score in patients with chronic limb-threatening ischemia (CLTI) after successful endovascular treatment (EVT). The results showed that the J-BTK CTO score not only evaluates the difficulty of EVT but also can predict limb prognosis. Using the J-BTK CTO score, it seems possible to predict the limb prognosis and make it useful in clinical practice.

Abstract 4137249: Left atrial functional reserve predicts recurrence of atrial arrhythmia following catheter ablation in patients with persistent atrial fibrillation

Background: Left atrial (LA) functional remodeling plays an essential role in the pathophysiological mechanisms of atrial fibrillation (AF). LA reservoir strain (LARS) measured by speckle-tracking echocardiography (STE) exhibits acceptable predictive value for recurrent atrial arrhythmia in patients with paroxysmal AF, while its performance in persistent AF remains inconclusive. Recently, LA functional reserve, a novel concept of LA mechanics in response to acute-volume overload, is drawing attention. Research Questions: Are LARS and LA functional reserve associated with recurrent atrial arrhythmia after catheter ablation in patients with persistent AF? Methods: Ninety-two patients who underwent first catheter ablation for persistent AF were included in the study. LARS at rest and LA functional reserve were assessed by STE 1-4 days before catheter ablation. LA functional reserve was calculated as change in LARS after passive leg lifting. Recurrence of arrhythmia was defined as atrial arrhythmia of ≥ 30 seconds duration after a 2-month blanking period. Results: The median values of LARS and LA functional reserve were 14.4 % (interquartile range [IQR] 10.9 to 18.2) and 1.0% (IQR -1.2 to 3.6), respectively. During a mean follow-up of 13.2 ± 9.9 months, 29 (31.5%) patients experienced recurrent AF. When we stratified patients into 2 groups according to LARS and LA functional reserve (below vs. above median values), patients with impaired LA functional reserve (&lt; 1.0%) were at higher risk of AF recurrence (log-rank test p value=0.026), but this was not observed for LARS (Figure). In multivariable Cox proportional hazard analysis, impaired LA functional reserve was associated with recurrent atrial arrhythmia independent of AF risk factors, left ventricular ejection fraction and LARS at rest (adjusted hazard ratio 3.99, p=0.004). Conclusions: Evaluation of LA functional reserve may provide valuable information for optimal patient selection as well as follow-up strategy after catheter ablation in patients with persistent AF.

Abstract 4125606: Systolic Blood Pressure During Sleep Determined by Pulse Transit Time Predicts Worsening Heart Failure in Patients with Heart Failure

Introduction: Intensive blood pressure (BP) lowering therapy is associated with lower rates of major adverse cardiac and cerebrovascular events in the general population. On the other hand, lower daytime systolic BP (SBP) is associated with higher mortality in patients with heart failure (HF). However, prognostic impact of SBP during sleep was unclear in patients with HF. Methods and Results: We measured continuous SBP during sleep non-invasively by pulse transit time in 379 patients with HF (median age 71, male 53.6%). Beat-to-beat SBP was calculated based on pulse transit time, which was defined as the travel time from the R-wave of electrocardiogram to the pulse wave at the finger detected by plethysmography. Mean values of SBP during sleep were used in the present study. The primary endpoint was hospitalization for worsening HF. The patients were divided into three groups based on the tertiles of SBP during sleep: High SBP group (median SBP 138 mmHg, n = 127), Middle SBP group (median SBP 117 mmHg, n = 127), and Low SBP group (median SBP 100 mmHg, n = 125). The Low SBP group showed the youngest age (High, Middle, and Low groups; 73, 73, 68 years, P &lt; 0.001). Levels of B-type natriuretic peptide (207.7, 216.7, and 407.2 pg/mL, P = 0.039) and estimated glomerular filtration rate (52.6, 54.0, and 57.1 mL/min/1.73 m 2 , P = 0.041) were the highest in the Low SBP group. During the follow-up period of median 1,083 days after SBP measurement, 66 patients experienced hospitalization for worsening HF. Kaplan-Meier analysis revealed that primary endpoint occurred most frequently in the Low SBP group ( Figure ). Multivariable Cox proportional hazard analysis showed that the lowest SBP tertile was associated with the primary endpoint compared to the highest SBP tertile (hazard ratio 2.546, 95% confidence interval 1.257–5.158, P = 0.009). Conclusion: Low SBP during sleep was associated with hospitalization for HF in patients with HF.

NCMP-10. EFFECT OF EXTENT OF RESECTION ON GLIOMA SEIZURE OUTCOMES BASED ON MOLECULAR GROUPS

Abstract INTRODUCTION Increased extent of resection (EOR) is a known predictor of seizure freedom in glioma patients. However, it is unknown how tumor genomic alterations affect EOR-induced seizure control. OBJECTIVE To evaluate the genotype-specific impact of EOR on post-operative seizure control METHODS Records of 553 glioma patients who underwent tumor resection from 2012-2023 were reviewed. All patient tumors were analyzed with next generation sequencing and FISH analysis. The unsupervised machine learning algorithm non-negative matrix factorization (NMF) was used to cluster the genomic data. Clinical variables including extent of resection of contrast enhancing tumor and non-enhancing tumor, temozolomide therapy, and radiation therapy were analyzed using Cox Proportional Hazards models. RESULTS NMF clustering of tumor sequencing data revealed four molecular groups: Group 1 (n=56): CDKN2a loss, EGFR copy number gain or mutation, TERT promoter (TERTp) mutation, and MGMT methylated; Group 2 (n=27): IDH mutation, TP53 mutation, and MGMT methylated; Group 3 (n=60): TP53 mutation, TERTp mutation and MGMT methylated; Group 4 (n=244): MGMT unmethylated. Thresholds in the post-operative residual non-enhancing tumor volume (NETV) were identified which marked the most difference in seizure control. For patients in Group 1, the NETV threshold that led to improved epilepsy outcomes was &amp;lt;94.7 cc (p=0.047), whereas the threshold for Group 4 was &amp;lt;89.1 cc (p=0.016). When analysis was conducted for Group 2, the threshold of 10.2 cc failed to reach significance (p=0.1). Interestingly, the threshold analysis for Group 3 found that having a NETV of &amp;gt; 10.1 cc showed improved seizure outcomes (p=0.016). A multivariable cox proportional hazard analysis found that twelve-month seizure freedom was predictive of better OS in group 1 (HR 0.02, p=0.05) and group 4 (HR 0.21, p=1.63e-9). CONCLUSION Our study reveals clinically distinct molecular groups of glioma that display different seizure responses. This data suggests a tumor-specific approach to aggressiveness of extent of resection in order to achieve optimal seizure control.

SURG-03. GENE EXPRESSION CHANGES ASSOCIATED WITH RECURRENCE AFTER GROSS TOTAL RESECTION OF NEWLY DIAGNOSED WHO GRADE 1 MENINGIOMA

Abstract Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a “low risk” group, but some low risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. This was a retrospective, international, multi-center cohort study that included WHO grade 1 meningiomas that underwent GTR as first treatment. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low risk meningiomas. 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. Median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence (LFFR) was 90.5%, and median time to recurrence of 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low risk meningiomas with significant differences in LFFR (HR 2.5, 95% CI 1.2-5.1, p=0.016). In conclusion, gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

EPID-17. REAL-WORLD OUTCOMES OF BRAIN METASTASES FROM PANCREATIC CANCER: AN ANALYSIS OF 1266 PATIENTS

Abstract BACKGROUND Brain metastases (BMs) from pancreatic cancer (PC) are uncommon. This study examined patterns of care and clinical outcomes for PC BMs. METHODS A retrospective analysis was conducted on PC BMs patients in the US National Cancer Database between 2010-2020, following STROBE guidelines. Treatments were categorized into systemic therapy (Sys) alone, stereotactic radiosurgery (SRS)±Sys, whole brain radiation (WBRT)±Sys, and no brain-specific treatment (NoTx). Primary outcome was median overall survival (mOS), with corresponding hazard ratio for death (HR) and 95% confidence intervals. Prognostic factors were determined using multivariable Cox proportional-hazards analysis including age, sex, race/ethnicity, insurance, Charlson-Deyo score (CDS), concurrent metastases (CMs), and treatment type. RESULTS Of 170,071 metastatic PC patients, 1,266 (0.7%) PC BM patients were included. 45.7% were female and 81.3% were White. Median age was 66.0 years (IQR:58.0-74.0). 34.4% had bone CMs, 45.4% had lung CMs, 60.2% had liver CMs. 48.1% of patients received NoTx, 22.6% Sys, 12.4% WBRT+Sys, 9.8% WBRT, 4.6% SRS+Sys, and 2.5% SRS. mOS (95% CI) was 2.4 months (2.2-2.5) in patients with BMs and 3.9 months (3.8-3.9) in those without BMs (P&amp;lt;0.001). Amongst BM patients, SRS+Sys had a significantly higher mOS of 7.8 months (6.1-14.3) followed by WBRT+Sys: 5.2 months (4.2-6.8), Sys: 4.8 months (4.2-5.8), WBRT: 2.0 months (1.6-2.2), SRS: 1.8 months (1.4-3.7), and NoTx: 1.2 months (1.0-1.3) (P&amp;lt;0.001). Patients treated with SRS alone (HR:2.9, 1.8-4.7, P&amp;lt;0.001), WBRT alone (HR:2.9, 2.0-4.0, P&amp;lt;0.001), and Sys alone (HR:1.5, 1.1-2.1, P=0.009) had significantly lower survival than with SRS+Sys. Patients treated in nonacademic facilities (HR:1.3, 1.1-1.4, P&amp;lt;0.001) and those with CMs (HR:1.4, 1.2-1.6, P&amp;lt;0.001) had poorer survival. CONCLUSIONS BMs in PC are rare and associated with lower survival. SRS+Sys was associated with the best prognosis, but &amp;lt;5% received it. 48% of patients receiving NoTx had mOS of 1.2 months. Future studies exploring care variations are warranted.

Association between serum glucose potassium ratio and mortality in critically ill patients with intracerebral hemorrhage

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality.

Effect of postoperative complications on 5-year survival following laparoscopic surgery for resectable colorectal cancer: a retrospective study

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

Routine Imaging or Symptomatic Follow-Up After Resection of Pancreatic Adenocarcinoma.

International guidelines lack consistency in their recommendations regarding routine imaging in the follow-up after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). Consequently, follow-up strategies differ between centers worldwide. To compare clinical outcomes, including recurrence-focused treatment and survival, in patients with PDAC recurrence who received symptomatic follow-up or routine imaging after pancreatic resection in international centers affiliated with the European-African Hepato-Pancreato-Biliary Association (E-AHPBA). This was a prospective, international, cross-sectional study. Patients from a total of 33 E-AHPBA centers from 13 countries were included between 2020 and 2021. According to the predefined study protocol, patients who underwent PDAC resection and were diagnosed with disease recurrence were prospectively included. Patients were stratified according to postoperative follow-up strategy: symptomatic follow-up (ie, without routine imaging) or routine imaging. Symptomatic follow-up or routine imaging in patients who underwent PDAC resection. Overall survival (OS) was estimated with Kaplan-Meier curves and compared using the log-rank test. To adjust for potential confounders, multivariable logistic regression was used to evaluate the association between follow-up strategy and recurrence-focused treatment. Multivariable Cox proportional hazard analysis was used to study the independent association between follow-up strategy and OS. Overall, 333 patients (mean [SD] age, 65 [11] years; 184 male [55%]) with PDAC recurrence were included. Median (IQR) follow-up at time of analysis 2 years after inclusion of the last patient was 40 (30-58) months. Of the total cohort, 98 patients (29%) received symptomatic follow-up, and 235 patients (71%) received routine imaging. OS was 23 months (95% CI, 19-29 months) vs 28 months (95% CI, 24-30 months) in the groups who received symptomatic follow-up vs routine imaging, respectively (P = .01). Routine imaging was associated with receiving recurrence-focused treatment (adjusted odds ratio, 2.57; 95% CI, 1.22-5.41; P = .01) and prolonged OS (adjusted hazard ratio, 0.75; 95% CI, 0.56-.99; P = .04). In this international, prospective, cross-sectional study, routine follow-up imaging after pancreatic resection for PDAC was independently associated with receiving recurrence-focused treatment and prolonged OS.

Association between Lactate dehydrogenase and 28-day all-cause mortality in patients with non-traumatic Intracerebral hemorrhage: A retrospective analysis of the MIMIC-IV database.

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan-Meier (KM) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The KM curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P = 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719-6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211-4.846; P = 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522-6.126; P = 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a non-linear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic intracerebral hemorrhage. Specifically, patients with elevated LDH levels within the first 24 hours of ICU admission are at a higher risk of mortality.

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.

Adjuvant Trastuzumab Plus Pertuzumab Versus Trastuzumab Alone in Patients Achieving Pathologic Complete Response After Chemotherapy With Trastuzumab and Pertuzumab: A Retrospective Cohort Study

BackgroundFor patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab (T) and pertuzumab (P), the benefit of adding P to T remains uncertain. We compared survival outcomes according to the type of adjuvant anti-HER2 therapy in patients with pCR after chemotherapy with TP. MethodPatients who achieved pCR in both the breast and axilla after neoadjuvant chemotherapy with TP were included. Recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) were evaluated. Univariate and multivariate Cox proportional hazards analyses were used to assess the impact of different adjuvant therapies on RFS and DRFS. ResultsIn total, 386 patients were included, with 69 (17.9%) receiving adjuvant TP and 317 (82.1%) receiving adjuvant T alone. At a median follow-up of 49 months, the 3-year RFS rate was 96.1%. There was no significant difference in the 3-year RFS between groups (94.2% in TP and 95.6% in T), with an adjusted hazard ratio (HR) of 1.15 (95% CI, 0.37-3.55, P = .806). In the clinical node-positive group (n = 294), there was no difference in survival between groups (HR 1.64, 95% CI, 0.58-4.65, P = .35). The multivariate analysis showed no significant predictors of recurrence or distant recurrence, including clinical tumor size, nodal status, ER/PR/HER2 status, and adjuvant radiotherapy receipt. Among 11 patients with brain metastasis after pCR, there was no difference according to the type of adjuvant anti-HER2 therapy. ConclusionsIn patients with pCR who responded to chemotherapy and dual HER2 blockade (TP), the 3-year RFS and brain metastasis-free survival did not differ according to the type of adjuvant anti-HER2 therapy.

Optimal Treatment Strategies for Early-Stage Primary Mediastinal Germ Cell Tumors

Data on optimal therapy for patients with primary mediastinal germ cell tumors consist overwhelmingly of single-institution studies with small sample sizes. The objective of this study is to assess the association of survival outcomes with surgery vs non-operative management for patients with early-stage primary mediastinal germ cell tumors. Overall survival of all patients with seminomas and non-seminomatous primary germ cell tumors in the mediastinum who received 1) chemotherapy, or 2) surgery with or without chemotherapy (referred to as 'surgery' for simplicity) for early-stage disease from 2004-2015 in the National Cancer Database was assessed using Kaplan-Meier analysis, propensity score-matched analysis, and multivariable Cox proportional hazards analysis. Among patients with seminomas, chemotherapy alone was used in 120 (80.5%) patients and surgery was used in 29 (19.5%) patients. There was no significant difference in 5-year survival between surgery and chemotherapy in unadjusted and propensity score-matched analysis. Among patients with non-seminomatous tumors, chemotherapy alone was used in 91 (46.7%) patients and surgery was used in 104 (53.3%) patients. Surgery was associated with improved 5-year survival when compared to chemotherapy in unadjusted, and multivariable-adjusted, and propensity score-matched analysis. In this national analysis, multimodality treatment involving surgery was associated with improved survival when compared to chemotherapy alone for early-stage primary mediastinal non-seminomatous germ cell tumors. For seminomas of the mediastinum, chemotherapy was associated with similar long-term outcomes when compared to multimodality treatment involving surgery.

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 (&amp;gt;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.