Perioperative Geriatric Assessment as A Predictor of Long-Term Hepatectomy Outcomes in Elderly Patients with Hepatocellular Carcinoma

This retrospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for recurrence-free survival (RFS) and overall survival (OS) after hepatectomy in 100 consecutive patients aged ≥70 years with hepatocellular carcinoma. Patients had geriatric assessments of cognition, nutritional and functional statuses, and comorbidity burden, both preoperatively and at six months postoperatively. The rate of change in each score between preoperative and postoperative assessments was calculated by subtracting the preoperative score from the score at six months postoperatively, then dividing by the score at six months postoperatively. Patients with score change ≥0 comprised the maintenance group, while patients with score change <0 comprised the reduction group. The change in Geriatric 8 (G8) score at six months postoperatively was the most significant predictive factor for RFS and OS among the tested geriatric assessments. Five-year RFS rates were 43.4% vs. 6.7% (maintenance vs. reduction group; HR, 0.19; 95%CI, 0.11–0.31; p < 0.001). Five-year OS rates were 73.8% vs. 17.8% (HR, 0.12; 95%CI, 0.06–0.25; p < 0.001). Multivariate Cox proportional hazards analysis showed that perioperative maintenance of G8 score was an independent prognostic indicator for both RFS and OS. Perioperative changes in G8 scores can help forecast postoperative long-term outcomes in these patients.

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Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

10.21203/rs.3.rs-30583/v1 ◽

2020 ◽

Author(s):

Heng Zou ◽

Wenhao Chen ◽

Huan Wang ◽

Li Xiong ◽

Yu Wen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Grading System ◽

Term Survival ◽

Proportional Hazards Regression ◽

Disease Outcomes ◽

Single Tumor

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

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Prognostic value of the ALBI grade among patients with single hepatocellular carcinoma without macrovascular invasion

10.21203/rs.3.rs-30583/v2 ◽

2020 ◽

Author(s):

Wenhao Chen ◽

Zijian Zhang ◽

Huan Wang ◽

Li Xiong ◽

Yu Wen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Grading System ◽

Term Survival ◽

Proportional Hazards Regression ◽

Disease Outcomes ◽

Single Tumor

Abstract Background: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

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Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/03000605211016265 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110162

Author(s):

Yangming Hou ◽

Xin Wang ◽

Junwei Wang ◽

Xuemei Sun ◽

Xinbo Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Proportional Hazards ◽

Enrichment Analysis ◽

Gene Signature ◽

Cyclin B1 ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

Tumor Promoter ◽

Protein Protein Interaction

Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

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Reduction in Short- and Long-term Pneumonia Rate With Laryngoplasty for Unilateral Vocal Fold Paralysis

Otolaryngology ◽

10.1177/01945998211015174 ◽

2021 ◽

pp. 019459982110151

Author(s):

Cheng-Ming Hsu ◽

Yao-Te Tsai ◽

Geng-He Chang ◽

Yao-Hsu Yang ◽

Tuan-Jen Fang ◽

...

Keyword(s):

Lower Incidence ◽

Vocal Fold ◽

Proportional Hazards ◽

Vocal Fold Paralysis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Voice Therapy ◽

Unilateral Vocal Fold Paralysis ◽

Short And Long Term

Objective To examine the association of laryngoplasty, voice therapy, and pneumonia rate in patients with unilateral vocal fold paralysis (UVFP). Study Design Population-based retrospective cohort study. Setting Data were collected from the LHID2000 (Longitudinal Health Insurance Database 2000), containing the information of 1 million randomly selected patients in Taiwan. Methods In the LHID2000, we identified 439 patients having new diagnoses of UVFP from 1997 to 2013. We grouped the aforementioned patients according to UVFP treatment and probed the occurrence of pneumonia: 305 patients underwent laryngoplasty or voice therapy, and 134 patients did not undergo treatment. Follow-up procedures were executed for the enrollees until death or December 31, 2013, representing the end of the study period. We assessed the association of UVFP treatment and pneumonia by executing Cox proportional hazards regression. Results The pneumonia cumulative incidence was significantly higher among enrolled patients without treatment than in those receiving treatment ( P < .001). The pneumonia incidence was significantly lower in patients receiving UVFP treatment (hazard ratio, 0.49; 95% CI, 0.27-0.88; P = .018), as validated by the Cox proportional hazards model after adjustment. Patients undergoing laryngoplasty with or without voice therapy had a significantly lower incidence of pneumonia at 6 months and 1, 3, and 5 years, whereas those undergoing voice therapy alone did not. Conclusion Laryngoplasty was associated with a lower incidence of short- and long-term pneumonia in patients with UVFP. Physicians should encourage patients with UVFP at risk of aspiration to receive prompt evaluation as well as treatment.

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Inter-pregnancy interval and later pediatric cardiovascular health of the offspring – a population-based cohort study

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420001130 ◽

2020 ◽

pp. 1-5

Author(s):

Majdi Imterat ◽

Tamar Wainstock ◽

Eyal Sheiner ◽

Gali Pariente

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cardiovascular Morbidity ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Kaplan Meier ◽

Inter Pregnancy Interval

Abstract Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

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Abstract 2791: Silent Brain Infarction Predicts Cardiovascular Events And Mortality In Long-term Hemodialysis Patients

Circulation ◽

10.1161/circ.116.suppl_16.ii_620 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Toru Aoyama ◽

Hideki Ishii ◽

Hiroshi Takahashi ◽

Takanobu Toriyama ◽

Toru Aoyama ◽

...

Keyword(s):

Proportional Hazards ◽

Brain Infarction ◽

Cox Proportional Hazards ◽

Powerful Predictor ◽

Cardiac Events ◽

Cox Proportional Hazards Models ◽

Silent Brain Infarction ◽

Cv Disease ◽

Overall Mortality

Background: The cardiovascular (CV) events and mortality are significantly higher in hemodialysis (HD) patents compared to the general population. Although it is of clinical concern to predict the occurrence of CV events in long-term HD patients, more powerful predictor has under exploration. We investigated as to whether silent brain infarction (SBI) would be a predictable factor for future CV events and mortality in a large cohort of patients with long-term HD patients. Methods: After cranial magnetic resonance imaging to detect SBI, 202 long-term HD patients (7.1 ± 5.9 years) without symptomatic stroke were prospectively followed up until the incident of CV events (stroke, cardiac events, and death). We analyzed the prognostic role of SBI in CV events with the Kaplan-Meier method and Cox proportional hazards analysis. Results: The prevalence of SBI was quite higher compared to the previous reports (71.8% in all the patients). In overall patients, 60 patients suffered from CV disease (31 for coronary artery disease, 7 for congestive heart failure, 14 for symptomatic stroke) and 29 patients died (16 for CV death) during a follow up period (mean= 23 ± 13 months). In subgroup analysis regarding the presence of SBI, CV event-free survival rate for 4 years was significantly lower in the patients with SBI compared to those without SBI (54.6% vs. 86.7%, p=0.0003). CV and overall mortality were also significantly higher in SBI patients compared with No-SBI patients (CV mortality; 20.5 % vs. 4.3 %, overall mortality; 29.0% vs. 9.1% p< 0.01, respectively). Cox proportional hazards models showed that the presence of SBI was a significant predictor of cerebrovascular and CV events and CV and overall mortality even after adjustment for other CV risk factors listed on the Table . Conclusion: SBI detected with MRI would be powerful predictor of CV events and mortality in long-term HD patients. Hazard ratio (HR) of SBI for future events and mortality

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Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry

Cancers ◽

10.3390/cancers13235996 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5996

Author(s):

Maximilian Merz ◽

Hartmut Goldschmidt ◽

Parameswaran Hari ◽

Mounzer Agha ◽

Joris Diels ◽

...

Keyword(s):

Multiple Myeloma ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Average Treatment Effect ◽

T Cell Therapy ◽

Intention To Treat ◽

Proportional Hazards Regression ◽

Overlap Population ◽

German Registry

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.

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Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.690151 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shenglan Huang ◽

Dan Li ◽

LingLing Zhuang ◽

Liying Sun ◽

Jianbing Wu

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Expression ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

Prognostic Biomarkers ◽

Migration And Invasion ◽

Regression Analyses ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

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Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety

Circulation Heart Failure ◽

10.1161/circheartfailure.120.007433 ◽

2021 ◽

Author(s):

David A. Baran ◽

Justin Lansinger ◽

Ashleigh Long ◽

John M. Herre ◽

Amin Yehya ◽

...

Keyword(s):

Drug Use ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Heart Transplants ◽

Term Survival ◽

Ischemic Time ◽

Cox Proportional Hazards Models ◽

Donor Shortage ◽

United Network

Background: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. Methods: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. Results: The number and percent of donors with drug use has significantly increased over the study period ( P <0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival ( P <0.0001). Conclusions: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

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