Cox's Hazards Regression Model Research Articles

The Effect of Botulinum Toxin (Masport) Injection Following Internal Urethrotomy of Bulbar Urethral Stricture: A Pilot Study.

The application of Botulinum toxin (Masport) in urology has a long history. We aimed to assess the effect of local Masport on improvement in patients with urethral stricture by reducing the recurrence of urethral stricture. This pilot study conducted was a double-blind randomized clinical trial with code IRCT20191222045852N1 on patients suffering from urethral stricture. Finally, 28 patients were allocated to intervention and control groups. Twelve patients received intralesional injection with Masport in addition to internal urethrotomy, while 16 patients underwent internal urethrotomy with normal saline. The Cox regression hazard model was used to evaluate the effect of treatment status on recurrence time adjusted for the age, length, and location of the stenosis, cause of the stenosis, and history of previous operations. The effect of treatment type was significant at the .05 level. The past medical history and cause of urethral stricture had a significant impact on relapse-free survival. Also, the improvement in the mean score of the EuroQol Visual Analogue Scale (EQ-VAS), International Prostate Symptom Score (IPSS), and Q-max in the group with Masport was significantly different from the group with normal saline. The internal urethrotomy with intralesional injection of Masport has a better survival prognosis than internal urethrotomy with normal saline group. Therefore, the authors suggest that, given this successful initial clinical trial, consideration be given to future studies involving the use of botox in the management of urethral strictures in conjunction with internal urethrotomy.

Nomogram to Predict the Prognosis of Oligodendroglioma Patients Undergoing Postoperative Adjuvant Chemoradiotherapy

ObjectiveThe aim of this study was to develop a prognostic nomogram for predicting the prognosis of oligodendroglioma patients receiving combined chemoradiotherapy (CRT) after surgery. MethodsThe study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The patients were randomly divided into a development cohort (700 patients) and a validation cohort (244 patients) in a 7:3 ratio. The Cox hazards regression model was used to identify predictors, and a nomogram was constructed to visualize the prognosis. The performance of the prognostic nomogram was evaluated using the consistency index (C-index), clinical net benefit, and calibration. ResultsThe nomogram included five variables: age, marital status, tumor size, site of lesions, and surgery type. The C-index of the training set and validation set were 0.77 and 0.68, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicated that the nomogram had a good clinical net benefit in oligodendroglioma patients receiving CRT after surgery. ConclusionsThis study established and verified a prognostic nomogram for a large cohort of oligodendroglioma patients receiving CRT after surgery based on the SEER database. The nomogram may help clinicians provide personalized treatment services and clinical decisions for patients.

Abstract TP279: Atrial Cardiopathy and Intracerebral Hemorrhage in Patients With Acute Ischemic Stroke

Background and Purpose: Atrial cardiopathy is recognized as a potential contributor to cardiovascular events. Whether atrial cardiopathy is associated with the risk of intracranial hemorrhage in acute ischemic stroke (AIS) remains uncertain. We aimed to investigate the relationship between atrial cardiopathy and intracerebral hemorrhage risk in patients with AIS. Methods: This single-center observational study included 631AIS patients (median age: 70 years [IQR] 61-78; 31.5% female). Atrial cardiopathy was defined as any presence of ≥1: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 (PTFV1) > 5000 μV·ms, or serum NT-proBNP >250 pg/ml. Our primary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH) during follow-up. Our secondary outcome was ischemic stroke recurrence. The association between atrial cardiopathy and outcomes was analyzed using Cox hazards regression models. Results: During a median of 1.57 years follow-up, 67 (10.6%) AIS patients experienced any ICH, and 18 (2.9%) patients developed sICH. In Kaplan-Meier analysis, the rate of any ICH or sICH during follow-up was more frequent in patients with atrial cardiopathy compared to those without (log-rank test, p < 0.001, respectively; Figure 1 ). After adjustment for CHA 2 DS 2 -VAS C , atrial cardiopathy was significantly associated with the risk of any ICH (HR 3.99, 95% CI 2.20-7.22, p < 0.001) or sICH (HR 7.93, 95% CI 1.77-35.51, p = 0.007). There was no significant association of ischemic stroke recurrence with atrial cardiopathy. Conclusions: This investigation suggests a potential link between atrial cardiopathy and an increased risk of intracranial hemorrhage in patients with acute ischemic stroke.

Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). High social vulnerability was associated with increased time to surgery and poor survival after surgery.

Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial

Background and aimsExclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.MethodsThis is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.ResultsOverall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3–19.6) kcal/kg and 0.6 (0.4–0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768–0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770–0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674–0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672–0.962) for protein delivery, respectively), but not in those > 2 mmol/L.ConclusionsDuring the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.Trial registration: ISRCTN12233792, registered on November 24, 2017.

Circulating IL-6 and not its circulating signaling components sIL-6R and sgp130 demonstrate clinical significance in NSCLC patients treated with immune checkpoint inhibitors.

Introduction: Clinical roles of plasma IL-6 levels have been reported in patients with various cancers, including non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (ICIs). However, the roles of other IL-6 signaling components, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130), in the plasma have not been elucidated. Methods: Blood was collected from 106 patients with NSCLC before initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Plasma levels of IL-6, sIL-6R, sgp130, and their complexes were assessed by Cox regression hazard model to evaluate their clinical significance. The clinical role of IL-6 or IL-6R genetic polymorphisms was also analyzed. Results: Cox regression analysis showed that higher plasma IL-6 levels significantly predicted unfavorable overall survival (OS; hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.05-1.68, p = 0.012) in NSCLC patients treated with ICIs. However, plasma sIL-6R and sgp130 levels showed no prognostic significance (p = 0.882 and p = 0.934, respectively). In addition, the estimated concentrations of binary IL-6:sIL-6R and ternary IL-6:sIL-6R:sgp130 complexes and their ratios (binary/ternary complex) were not significantly associated with OS (p = 0.647, p = 0.727, and p = 0.273, respectively). Furthermore, the genetic polymorphisms of IL-6 (-634G>C) and IL-6R (48892A>C) showed no clinical role by Kaplan-Meier survival analysis (p = 0.908 and p = 0.639, respectively). Discussion: These findings demonstrated the clinical significance of plasma levels of IL-6, but not of other IL-6 signaling components, sIL-6R and sgp130, suggesting that classical IL-6 signaling, but not trans-signaling, may be related to anti-tumor immune responses in cancer patients treated with ICIs.

Association between obesity and fracture risk in Chinese women above 50 years of age: a prospective cohort study.

Fractures present serious health challenges for older adults, including premature mortality and reduced quality of life. Obesity has become significantly prevalent in China. However, the association between obesity and fractures remains unclear. This study aimed to assess the association between obesity and fractures among Chinese women above 50years of age. A prospective cohort study was designed based on the China Health and Nutrition Survey, using data from 1997 to 2015. The average follow-up duration was seven years. Trained investigators measured body mass index (BMI) and waist circumference (WC) at baseline. Obesity was defined according to World Health Organization recommendations. Waist-to-height ratio (W-HtR) was calculated, with 0.5 as the cutoff value. Onset of fractures, self-reported by the participants during the follow-up period, was the primary outcome. Cox hazard regression models were used to assess the association between BMI, WC, W-HtR and subsequent risk of fracture. A sensitivity analysis was conducted by multiple imputation of missing data on the variables at baseline. A total of 2,641 women aged ≥ 50 years were involved in the study. In all the models, no significant association existed between BMI and fracture risk. However, women with WC ≥ 88cm had significantly higher risk of fracture than those with WC < 80cm according to both the unadjusted (HR = 1.744, 95% CI: 1.173-2.591) and adjusted models (HR = 1.796, 95% CI: 1.196-2.695). In addition, W-HtR and fracture risk were positively associated according to both the unadjusted (HR = 1.798, 95% CI: 1.230-2.627) and adjusted models (HR = 1.772, 95% CI: 1.209-2.599). Results of the sensitivity analysis were consistent with those of the above analyses. Abdominal obesity increased the risk of all-cause fractures in Chinese women ≥ 50years old. Intervention strategies and measures to prevent or address abdominal obesity would be helpful to decrease the fracture incidence.

The Baseline Pan-Immune‑Inflammation Value (PIV) and PILE in Predicting Clinical Outcomes and Therapeutic Response for Primary Central Nervous System Lymphoma.

To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL). A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan-Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined. Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778-8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175-7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075-4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2-3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0-1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05-0.46; p < 0.001). High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.

Prognostic Significance of the Lymph Node Ratio for Overall Survival after Curative Surgery for Rectal Cancer: A Retrospective Cohort Study

Background: Accurate rectal cancer N staging requires the histopathological evaluation of at least 12 lymph nodes. Retrieval of that count is not always possible. The purpose of the study is to evaluate the lymph node ratio (LNR) prognostic significance on overall survival. Methods: The current study is a retrospective cohort study of 229 patients who underwent curative surgery for resectable rectal cancer. Receiver Operating Characteristic (ROC) curve analysis was used to determine the optimal cut-off value for Lymph Node Count (LNC), Positive Lymph Nodes count (PLN), and LNR for overall survival (OS). The Kaplan-Meier product limit method was used for univariate analysis of factors affecting OS. Log Rank (Mantel-Cox) test was used to test significance. A Cox-Regression Hazard model was used to detect the most significant factor affecting OS. Results: ROC curve analysis of the PLNs revealed a poor prognostic value of the test, with a sensitivity of 51.9% at PLNs 4 cutoff value, with a shorter mean OS above it (21.71±11.597 vs. 31.20 ± 16.634 for ≥4 vs. &lt;4). ROC curve analysis of LNC revealed the poor value of the test, with a sensitivity of 56% at LNC 12 cutoff value, with longer mean Overall Survival (OS) above it (28.21±15.432 vs. 22.22±12.97 for LNC ≥12 vs. &lt;12). ROC curve analysis of the LNR revealed good value of the test for predicting survival, with a sensitivity of 95% at LNR 18.82% cutoff value, with longer mean OS above it (21.44±11.607 vs. 39.82±15.085 for LNR ≥18.8% vs. &lt;18.8%). According to our univariate analysis, the factors significantly affecting OS were histopathological examination (p =.000), Lympho-Vascular Invasion (LVI) (p =.014), and the LNC cutoff value (p=.002), the PLN cutoff value (p =.008), and the LNR cutoff value (p =.000. According to our multivariate analysis, the LNR cutoff value of 18.8% was the most significant factor affecting OS (p =.000). Conclusions: A high LNR with an 18.82% cutoff value is an independent adverse prognostic factor affecting OS after curative surgery for cancer rectum. The LNR could be considered a good alternative to the absolute number of PLNs, particularly in patients with a low LNC. A higher LNC ≥12 was associated with a longer OS; maximum possible lymphadenectomy should be performed for each patient.

Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis.

Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.

Association of Serum Potassium Variability With 60-day Mortality and Cardiovascular Events after COVID-19 Infection in Maintenance Hemodialysis Patients.

Objective: This study aimed to investigate the association between serum potassium variability and 60-day mortality and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients following the coronavirus disease 2019 (COVID-19) infection. Methods: We conducted a retrospective study on MHD patients treated at the affiliated hospital of Qingdao University hemodialysis center who were infected with the novel coronavirus between December 1, 2022, and January 31, 2023. Baseline characteristics of patients were collected from electronic medical records. Kaplan-Meier survival analysis was used to obtain patient survival probabilities, and multivariate Cox hazard regression models and binary Logistic regression models were used to obtain hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (95% CI) between exposure and outcomes. Results: A total of 296 patients were included in this study, with a mean age of 57.2±16.3 years, and 59.8% were male. The 60-day mortality rate was 10.8%, and the incidence of CVD was 32.8%. Kaplan-Meier curves showed that a higher potassium variability coefficient was associated with higher all-cause mortality (P = 0.024). After adjusting for potential confounders, multivariate Cox regression analysis showed that the HR for 60-day mortality in the Q4 group compared to the Q1 group was 2.06 (95% CI = 1.03-4.09, P = 0.040), and binary Logistic regression analysis showed that the OR for 60-day CVD in the Q4 group compared to the Q1 group was 4.09 (95% CI = 1.52-10.97, P = 0.005). Conclusion: Increased serum potassium variability in MHD patients after COVID-19 infection significantly increased the likelihood of 60-day mortality and CVD.

Long-term late effects in older gastric cancer survivors: Survival analysis using Cox hazard regression model by retrospective electronic health records

PurposeBecause the population of older gastric cancer survivors (GCSs) is growing, understanding the long-term late effects experienced by these GCSs and their impact on survival outcomes is crucial for optimizing survivorship care. This study aims to identify and characterize these effects and investigate their association with survival outcomes.MethodsA retrospective analysis of electronic health records was conducted on 9,539 GCSs diagnosed between 2011 and 2017. The GCSs were divided into two age groups (< 65 and ≥ 65 years) and the long-term late effects were categorized by age using Cox proportional hazard models. The impact of clinical factors and age-specific late effects on survival was evaluated in the older GCSs.ResultsAmong the total GCSs, 37.6% were over and 62.4% were under 65 years of age. Significant differences between the age groups were observed in the cumulative hazard ratios (HRs) for iron and vitamin B12 levels and prognostic nutritional index (PNI) scores. In older GCSs, abnormal iron levels (HR 1.98, 95% CI 1.16–3.41, p = .013) and poor PNI scores (HR 1.59, 95% CI 1.03–2.47, p = .038) were associated with poorer survival outcomes. Additionally, being female was identified as a risk factor for lower survival rates (if male, HR 0.42, 95% CI 0.18–0.98, p = .045).ConclusionThis study highlights the typical long-term late effects experienced by older GCSs. By tailoring survivorship care to address nutritional-, age-, and gender-related factors, the overall survival and quality of life of older GCSs can be improved.

Abstract B079: Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment in Arizona

Abstract Background: Hispanics and American Indians (AI) have a higher kidney cancer incidence and mortality in Arizona. This study assessed 1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability, measured using the social vulnerability Index (SVI), experience a longer time (in days) to surgical treatment for kidney cancer after clinical diagnosis, and 2) whether time to surgery, race and ethnicity, and neighborhood social vulnerability are associated with adverse pathology (upstaging to pT3), progression free survival (PFS), and overall survival (OS) in Arizona. Methods: Arizona Cancer Registry (2009-2018) data for kidney and renal pelvis cases were obtained. Logistic regression models were used to assess if SVI (&amp;lt;25, 25-49, 50-74, and ≥75 percentile) and race and ethnicity were associated with a longer time to surgical (&amp;gt;median time to surgery) and upstaging. Cox-regression hazard models were used to assess if time to surgery and SVI were associated with PFS and OS. Separate analyses were performed for each clinical stage (cT1a, cT1b, cT2, and cT3). Results: A total of 4,592 kidney and renal pelvis cases (16.6% Hispanics and 4.8% AI) were included. Hispanic and AI patients with T1 tumors had a longer time to surgery than NHW patients (median time of 56, 55, and 45 days respectively). In unadjusted models, Hispanic ethnicity was associated with a longer time to surgery for cT1a (OR 1.48, 95% CI:1.05-2.08) and cT1b (OR 1.87, 95% CI:1.14-3.07). Hispanic and AI patients were also more likely to live in neighborhoods with high SVI than NHW patients. Living in neighborhoods with high (≥75) versus low (&amp;lt;25) overall SVI increased odds of a longer time to surgical for cT1a (OR 1.54, 95% CI:1.02-2.31) and cT2 (OR 2.32, 95% CI:1.13-4.73) in adjusted models. In these adjusted models, Hispanic ethnicity was no longer significantly associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3 (OR 1.95, 95% CI: 0.99-3.84) and risk of mortality. A longer time to surgery was associated with PFS with HR 1.52 (95% CI: 1.17- 1.99) and OS with HR 1.63 (95% CI:1.26-2.11) even after adjusting for SVI. Living in neighborhoods with high concentrations of racial and ethnic minorities increased odds of upstaging (OR 2.88, 95% CI: 0.99-8.37) in cT1a and was associated with PFS in cT3 (HR 2.45, 95% CI: 1.01-4.77). Compared to patients living in neighborhoods with SVI&amp;lt;25, patients with cT1a and cT2 tumor living in neighborhoods with SVI≥75 had about a 60% increased risk of mortality (OS HR 1.57, 95% CI: 1.01-2.45 for cT1b and HR 1.66, 95%CI:1.07-2.57 for cT2). Conclusion: These findings demonstrate that high neighborhood social vulnerability is associated with increased time to surgery and risk of progression and mortality. Impact: Neighborhood-level social vulnerability partly accounts for kidney cancer disparities in Arizona. Interventions need to focus on neighborhoods with high social vulnerability to improve care coordination for kidney cancer. Citation Format: Celina I. Valencia, Patrick Wightman, Kristin Morrill, Chiu-Hsieh Hsu, Hina Arif-Tiwari, Eric Kauffman, Francine C. Gachupin, Juan Chipollini, Benjamin R. Lee, Ken Batai. Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment in Arizona [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B079.

Long-term outcomes of periprocedural coronary dissection and perforation for patients undergoing percutaneous coronary intervention in a Japanese multicenter registry

Long-term outcomes of iatrogenic coronary dissection and perforation in patients undergoing percutaneous coronary intervention (PCI) remains under-investigated. We analyzed 8,721 consecutive patients discharged after PCI between 2008 and 2019 from Keio Cardiovascular (KiCS) PCI multicenter prospective registry in the Tokyo metropolitan area. Significant coronary dissection was defined as persistent contrast medium extravasation or spiral or persistent filling defects with complete distal and impaired flow. The primary outcome was a composite of all-cause death, acute coronary syndrome, heart failure, bleeding, stroke requiring admission, and coronary artery bypass grafting two years after discharge. We used a multivariable Cox hazard regression model to assess the effects of these complications. Among the patients, 68 (0.78%) had significant coronary dissections, and 61 (0.70%) had coronary perforations at the index PCI. Patients with significant coronary dissection had higher rates of the primary endpoint and heart failure than those without (25.0% versus 14.3%, P = 0.02; 10.3% versus 4.2%, P = 0.03); there were no significant differences in the primary outcomes between the patients with and without coronary perforation (i.e., primary outcome: 8.2% versus 14.5%, P = 0.23) at the two-year follow-up. After adjustments, patients with coronary dissection had a significantly higher rate of the primary endpoint than those without (HR 1.70, 95% CI 1.02–2.84; P = 0.04), but there was no significant difference in the primary endpoint between the patients with and without coronary perforation (HR 0.51, 95% CI 0.21–1.23; P = 0.13). For patients undergoing PCI, significant coronary dissection was associated with poor long-term outcomes, including heart failure readmission.

Association of glycemic variability with death and severe consciousness disturbance among critically ill patients with cerebrovascular disease: analysis of the MIMIC-IV database

BackgroundThe association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death.MethodWe extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves.ResultsThe present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality.ConclusionHigh glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.

Association of life's essential 8 and risk of fragility fractures: A large cohort study.

Cardiovascular health (CVH) score is not only associated with cardiovascular diseases, but also some disorders in other systems. This study aims to investigate the association between CVH score and the risk of fragility fractures. The analysis enrolled 89,464 participants at baseline in Kailuan study initiated in 2006-2007. All participants were then followed up every 2 years and the incidence of fragility fractures was recorded annually. A total CVH score was classified as low (0-49 points), moderate (50-79 points), and ideal (80-100 points). The primary outcome was incident fragility fractures before December 31, 2021. Kaplan-Meier was used to estimate cumulative incidence. Multivariable adjusted Cox proportional hazards regression models and time-dependent Cox hazards regression models were used to estimate fragility fracture hazard ratios (aHR) and 95% confidence intervals (95%CI). After 13.98 ± 2.84 years of follow-up, a total of 1534 cases of fragility fractures were identified, with an incidence density of 1.23 per 1000 person-years. Compared with the low CVH group, the risk of fragility fractures was significantly lower in moderate (aHR = 0.78, 95%CI: 0.66-0.92) and ideal CVH groups (aHR = 0.65, 95%CI: 0.51-0.83), particularly in the age <60 group (aHR = 0.72, 95%CI: 0.59-0.88; aHR= 0.55, 95%CI: 0.41-0.73, respectively). Time-dependent Cox hazards regression models, sensitivity analysis, and death competition model confirmed the reliability of these findings. The ideal CVH score is associated with a decreased risk of fragility fractures. With the increase of CVH score, the risk of fragility fracture decreases.

Increased risk of myocardial infarction in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea

BackgroundThe risk of myocardial infarction (MI), the major form of CVD, in amyotrophic lateral sclerosis (ALS) is currently unknown. We investigated the risk of MI in ALS and analyzed the effect of ALS-related physical disability on the risk of MI using the Korean National Health Insurance Service database. MethodsA total of 659 ALS patients and 10,927 non-ALS participants were finally selected between January 1, 2011, and December 31, 2015. A Cox hazard regression model was used to examine the hazard ratios (HRs) for MI in ALS after adjustment for potential confounders. ResultsThe incidence rate of MI was 26.2 per 1000 person-years, and the adjusted HR (aHR) for MI in ALS patients was 10.6 (95% confidence interval [CI] 7.2–15.4) compared with the controls. ALS patients who developed physical disability had an even higher risk of MI (aHR 18.6, 95% CI 11.5–30.0) compared with those who did not develop disability (aHR 7.4, 95% CI 4.6–11.9). The increased risk of MI was more prominent in female subjects than in male subjects (aHR 17.8, 95% CI 10.8–29.4 vs. aHR 6.9, 95% CI 4.1–11.6, P for interaction 0.006) and in obese subjects than in non-obese subjects (aHR 17.8, 95% CI 10.5–30.1 vs. aHR 7.9, 95% CI 4.9–12.8, P for interaction 0.018). ConclusionsOur findings suggest that the risk of MI is high in ALS patients compared with a control population, and the risk is more prominent in those who develop physical disability, or who are female or obese.

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation

ObjectiveUncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival...

PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. Methods: We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent 68Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3). Patients were categorized as PSMA responders (PSMA-Rs) or PSMA nonresponders (PSMA-NRs) on the basis of both European Association of Urology/European Association of Nuclear Medicine (EAU/EANM) criteria and Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0. PSMA-R included patients with a complete response, a partial response, or stable disease, and PSMA-NR included those with progressive disease. On the basis of prostate-specific antigen (PSA), patients were classified as biochemical responders if PSA decreased by at least 50% and as nonresponders if it did not. The Φ-coefficient was used to evaluate the correlation of PSMA- and PSA-based responses. Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. Predictive accuracy was tested for both response criteria. Results: On the basis of PSMA PET/CT, 13 (43%) patients were PSMA-NR according to the EAU/EANM criteria and 11 (37%) patients were PSMA-NR according to RECIP 1.0. Significant correlations were observed between PSMA- and PSA-based responses for both criteria (Φ = 0.79 and 0.66, respectively). After a median follow-up of 25 mo (interquartile range, 21-43 mo), the median overall survival was significantly longer for PSMA-R than PSMA-NR (54 vs. 22 mo) for both the EAU/EANM criteria and RECIP 1.0, with hazard ratios of 6.9 (95% CI, 1.9-26; P = 0.004) and 5.6 (95% CI, 1.69-18.26, P = 0.005), respectively. No significant difference in predictive accuracy was found between the 2 criteria (C-index, 0.79 vs. 0.76, respectively, P = 0.54). Flare phenomena at the second PSMA PET study were not observed in our cohort. Conclusion: Our results demonstrate that PSMA PET/CT is a valuable imaging biomarker for response assessment and overall survival prediction when performed at 3 mo after ARPI treatment initiation in mCRPC patients. Both proposed PSMA response criteria (EAU/EANM and RECIP 1.0) seem to perform equally well. No PSMA flare was observed. Prospective validation of these findings is strongly needed.

Effects of concurrent TP53 mutations on the efficacy and prognosis of targeted therapy for advanced EGFR mutant lung adenocarcinoma

BackgroundHow concurrent TP53 mutations affect targeted therapy of advanced Epidermal Growth Factor Receptor (EGFR) mutant lung adenocarcinoma remains controversial, particularly the deep classification of TP53 mutations. MethodsThis study retrospectively analyzed the clinical data of advanced EGFR mutant lung adenocarcinoma patients treated with EGFR-tyrosine kinase inhibitors (TKIs) in the First Affiliated Hospital of Soochow University. The survival rates were compared using Log-rank tests. Potential prognostic factors were identified using multivariate Cox hazard regression models. ResultsTotal 156 advanced lung adenocarcinoma patients treated with EGFR-TKIs were included in this study. Multivariate analysis showed that male [hazard rate (HR): 1.537, 95% confidence interval (CI): 1.055–2.240, P = 0.025], brain metastasis (HR: 1.707, 95%CI: 1.086–2.682, P = 0.020) and concurrent TP53 mutations (HR: 1.569, 95%CI: 1.051–2.341, P = 0.028) were independent negative predictors of progression-free survival (PFS). EGFR L858R mutations (HR: 2.475, 95%CI: 1.443–4.248, p = 0.001), smoking history (HR: 2.530, 95%CI: 1.352–4.733, P = 0.004) and concurrent TP53 mutations (HR: 2.326, 95%CI: 1.283–4.218, P = 0.005) were associated with worse survival. Further analysis revealed that mutations in TP53 exons 4, 5 and 8 (P<0.05), missense mutations (P = 0.006) and nondisruptive mutations (P<0.001) were associated with shorter PFS, whereas mutations in TP53 exons 5 and 7 (P<0.05), missense mutations and non-missense mutations (P = 0.006; P = 0.007), disruptive mutations and nondisruptive mutations (P = 0.013; P = 0.013) were all associated with poorer survival times. In addition, the PFS and overall survival (OS) of nondisruptive mutations in exon 7 were worse than those in other exons (P = 0.041; P<0.001). ConclusionsConcurrent TP53 mutations conferred worse EGFR-TKIs efficacy and prognosis in advanced EGFR mutant lung adenocarcinoma and the effects of different TP53 mutation types were heterogeneous.