Expression of tryptophan metabolizing enzymes (TMEs) and its transporter, LAT1, in metastatic melanoma (MM): Prognostic and therapeutic implications.

e21014 Background: The ECHO-301/KEYNOTE-252 trial failed to show clinical benefit of adding epacadostat to pembrolizumab in PD-1 inhibitor-naïve MM. We reasoned that the expression of other TMEs and/or LAT1 by melanoma cells plays a more important role. Methods: Melanoma tissues from stage III/IV pts were stained for the 4 TMEs (TPH1, TPH2, TDO2, IDO1) and LAT1 by single-color immunohistochemistry. Tissues were scored for the status of tumor-infiltrating lymphocytes (TILs) and the expression of 5 proteins separately in melanoma cells and TILs (if present). Association between protein expression, TIL status, and melanoma-specific overall survival was performed. Results: Tissues from 87 pts (stage IV, n = 25) were available. Expression of all 4 TMEs and LAT1 was significantly higher in melanoma cells compared to TILs ( p< 0.001); TPH1, TPH2, and TDO2 expression in melanoma cells was significantly higher than IDO1 (p < 0.001). Lower TPH1 expression in melanoma cells was associated with presence of TILs. Multivariate analysis using a Cox proportional hazards model that included expression of the 5 proteins in melanoma cells showed that high IDO1 was a favorable and high LAT1 expression was an adverse prognostic factor. Conclusions: Expression of TMEs and LAT1 by melanoma cells may have more important role in metastatic melanoma by depleting an essential amino acid from the tumor microenvironment. Pharmacologic targeting of TPH1/TPH2 (e.g. telotristat) may be more clinically relevant in MM as opposed to IDO1 inhibition.

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Evaluation of spatiotemporal heterogeneity of PDL1 expression in gastroesophageal adenocarcinoma (GEA) at baseline diagnosis and after chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4528 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4528-4528 ◽

Cited By ~ 1

Author(s):

Katherine I. Zhou ◽

Bryan Peterson ◽

Anthony Serritella ◽

Natalie Reizine ◽

Yan Wang ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Stage Iv ◽

Predictive Marker ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Molecular Heterogeneity ◽

Therapeutic Implications ◽

Hazards Model ◽

Before And After

4528 Background: PDL1 expression is a predictive marker for response to anti-PD1/PDL1 agents (IO) for GEA. As a prognostic biomarker, data are conflicting. Molecular heterogeneity of various biomarkers for GEA has been established. To characterize heterogeneity of PDL1 expression and its clinical relevance, we compared PDL1 expression in primary (10) and metastatic (met) tumors of newly diagnosed stage IV advanced GEA (aGEA), and before and after chemotherapy treatment (tx) for stage II–IV GEA. We assessed the prognostic relevance of PDL1 expression in aGEA. Methods: We retrospectively reviewed a cohort of 130 patients (pts) diagnosed with GEA in 2013–2019, with a total of 328 tumor samples with PDL1 expression data. PDL1 was defined as positive if combined positive score (CPS) was ≥1 using the 22C3 pharmDx assay. Analysis was performed by McNemar’s test for paired PDL1 and univariate Cox proportional-hazards model for overall survival (OS). Results: Of 328 tumors, 45% were PDL1+ and 55% PDL1-. CPS ranged 0–100 (median 1, IQR 0–5), and CPS was ≥10 for 19% of tumors. Concordance between PDL1 status of paired baseline 10 and baseline met tumors was 63% (32/51) (Table). Of 31 PDL1+ baseline 10 tumors, 52% (16/31) had PDL1- paired baseline met tumors, while of 20 PDL1- baseline 10 tumors, only 15% (3/20) had PDL1+ paired baseline met tumors. Only 35% (18/51) of met tumors were PDL1+, compared to 61% (31/51) PDL1+ 10 tumors ( p< 0.003). Post-tx tumors exhibited 62% (46/74) concordance of PDL1 status compared to pre-tx 10 tumors. Of 43 PDL1+ baseline tumors, 35% (15/43) were PDL1- post-tx; of 31 PDL1- baseline tumors, 42% (13/31) were PDL1+ post-tx ( p= 0.71). In pts with aGEA at diagnosis, OS did not significantly differ depending on baseline 10 tumor PDL1 status (median OS of 17.9 [95% CI 14.6–26.5] months for PDL1- and 16.7 [12.0–26.3] months for PDL1+; p= 0.6), nor depending on baseline met PDL1 status. Conclusions: PDL1 expression demonstrated notable baseline discordance between 10 and met tumors, particularly directional from PDL1+ 10 tumor to PDL1- met. Discordance before and after chemotherapy was also observed, but with similar proportions of PDL1+ pre-tx and post-tx tumors. These findings may have predictive IO therapeutic implications if confirmed in larger independent analyses. [Table: see text]

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Survival by line of therapy of older patients with advanced biliary tract cancer (BTC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.497 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 497-497 ◽

Cited By ~ 1

Author(s):

Sarah Bobiak ◽

Mark D. Danese ◽

Deborah P. Lubeck ◽

Michelle L. Gleeson

Keyword(s):

Systemic Chemotherapy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Systemic Treatment ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Second Line ◽

Mobility Limitations ◽

Line Of Therapy

497 Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.

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Incidence and Predictors of Tuberculosis among Adult PLWHA at Public Health Facilities of Hawassa City

International Journal of Public Health Science (IJPHS) ◽

10.11591/ijphs.v6i3.9294 ◽

2017 ◽

Vol 6 (3) ◽

pp. 266

Author(s):

Henok Bekele ◽

Mesfin Kote ◽

Aman Yesuf ◽

Tadele Girum

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Clinical Stage ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Incidence Density ◽

People Living With Hiv ◽

Base Line

Tuberculosis (TB) is the most frequently diagnosed opportunistic infection (OI) and disease in people living with HIV/AIDS (PLWHA), world-wide. This study aimed at determining the incidence and predictors of tuberculosis among people living with HIV.A Six year retrospective follow up study was conducted among adult PLHIV. The Cox proportional hazards model was used to identify predictors.A total of 554 patients were followed and produced 1830.3 person year of observation. One hundred sixty one new TB cases occurred during the follow up period. The overall incidence density of TB was 8.79 per 100 person-year (PY). It was high (148.71/100 PY) in the first year of enrolment. The cumulative proportion of TB free survival was 79% and 67% at the end of first and sixth years, respectively. Not having formal education(AHR=2.68, 95%CI: 1.41, 5.11 ), base line WHO clinical stage IV (AHR = 3.22, 95% CI=1.91-5.41), CD4 count <50 cell/ul (AHR=2.41, 95%CI=1.31, 4.42), Being bed redden (AHR= 2.89, 95%CI=1.72, 3.78), past TB history (AHR=1.65, 95% CI = 1.06,2.39), substance use (AHR=1.46, 95% CI=1.03,2.06) and being on pre ART (AHR=1.62, 95%CI:1.03-2.54 ) were independently predicted tuberculosis occurrence. Advanced WHO clinical stage, limited functional status, past TB history, addiction and low CD4 (<50cell/ul) count at enrollment were found to be the independent predictor of tuberculosis occurrence. Therefore early initiation of treatment and intensive follow up is important.

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Expression of breast cancer resistance protein (BCRP) in esophageal cancers (EC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e13529 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e13529-e13529

Author(s):

A. Bharthuar ◽

T. Khoury ◽

K. N. Haas ◽

T. Mashtare ◽

J. Black ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Esophageal Mucosa ◽

Cancer Resistance ◽

Exact Test ◽

Hazards Model ◽

Stage 1

e13529 Background: EC patients face a dismal outcome despite tri-modality management strategy. Median survival remains 15–18 months despite platinum, fluropyrimidine & irinotecan based therapy. BCRP is an ATP-dependent efflux protein associated with chemotherapy (CT) (e.g. irinotecan) resistance. Role of BCRP expression in EC and normal esophageal cells is not known. We examined the expression of this protein and correlate it with survival (OS) in patients receiving irinotecan-based CT. Methods: With IRB approval, 40 cases of EC diagnosed between 2004 and 2008 were stained for BCRP expression by IHC & scored by the pathologist blinded to clinical data. Baseline demographics, therapy given & OS data were collected and correlated with BCRP expression. BCRP score (membrane or cytoplasm) >/= 30 was considered positive (calculated by multiplying BCRP intensity and % staining). Fisher's exact test used to determine association between BCRP expression & demographics. Cox proportional hazards model used for association of BCRP & OS. Results: Baseline patient and tumor characteristics: Gender: M 35, F 5; Histology: 37 Adenoca & 3 SCC; Stage 1-III 27, Stage IV 10, unknown 3; CT: cisplatin+irinotecan (n=16), oxaliplatin+fluoropyrimidine (n=8), other (n=16); IHC: 30 of 40 cancers (75%) expressed BCRP [strong (n=28) & intermediate (n=3); membranous (n=17), cytoplasmic (n=27) & both (n=14)]. Down-regulation of BCRP expression in tumor compared to normal cells seen in 40% of patients. Median OS was 19 months with no difference in OS between BCRP positive and negative patients (p=0.13). Estimated hazard ratio (HR) of death for BCRP positive patients was 2.29 (95% CI 0.79 - 6.64).There was no association between BCRP expression and stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line CT there was no difference in OS (p=0.39) of BCRP negative versus positive patients. Conclusions: BCRP expression is seen in a majority of EC & normal esophageal mucosa. Response rates to irinotecan based therapies are seen in 30–40 % of EC, whether the 40% with low tumor BCRP constitute a majority of the responders needs to be prospectively validated in a larger dataset & should include markers that predict response to 5-FU & platinum based CT to allow individualizing therapy for this cancer. No significant financial relationships to disclose.

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Evaluation of spatiotemporal heterogeneity of tumor mutational burden (TMB) in gastroesophageal adenocarcinoma (GEA) at baseline diagnosis and after chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4546 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4546-4546 ◽

Cited By ~ 1

Author(s):

Katherine I. Zhou ◽

Bryan Peterson ◽

Anthony Serritella ◽

Natalie Reizine ◽

Yan Wang ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Stage Iv ◽

Predictive Marker ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Molecular Heterogeneity ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Spatiotemporal Heterogeneity

4546 Background: Tumor mutational burden (TMB) may be a predictive marker for response to anti-PD1/PDL1 agents (IO). Molecular heterogeneity of various biomarkers for GEA has been established. To characterize heterogeneity of TMB and its clinical relevance, we compared TMB in primary (10) & metastatic (met) tumors at baseline newly diagnosed stage IV advanced GEA (aGEA), and before & after chemotherapy treatment (tx) for stage II–IV GEA. We assessed the prognostic relevance of TMB in aGEA. Methods: We retrospectively reviewed a cohort of 127 patients (pts) diagnosed with GEA in 2012–2019, for a total of 280 tumor samples with TMB data. TMB level was defined as low (≤5/Mb), intermediate (int) ( > 5/Mb, ≤15/Mb), or high (hi) (≥15/Mb), determined by Foundation One. Analysis was performed by Fisher’s exact test for PDL1/TMB, McNemar’s test for paired TMB, and univariate Cox proportional-hazards model for overall survival (OS). Results: Of 280 tumors, 50% (140/280) had low TMB, 45% (125/280) int TMB, & 5% (15/280) hi TMB. TMB ranged 0–58.6/Mb (median 5.3/Mb). Of tumors with hi TMB, 53% (8/15) were MSI-Hi, while of MSI-Hi tumors, 100% (8/8) were TMB hi. TMB level did not correlate with PDL1 status ( p= 0.83). Concordance between TMB levels of paired baseline 10 and baseline met tumors was 66% (29/44) (Table). TMB level was lower in the met than in the 10 in 23% (10/44) of cases, and higher in the met in 11% (5/44). Of 4 TMB hi baseline 10 tumors, 2 were not TMB hi in the met; of 40 TMB low/int baseline 10 tumors, 0 were TMB hi in the met ( p= 0.16). Post-tx tumors exhibited 71% (42/59) concordance of TMB levels compared to pre-tx 10 tumors. Of 2 TMB hi baseline tumors, 1 was not TMB hi in the post-tx tumor; of 57 TMB low/int baseline tumors, 0 were TMB hi in the post-tx tumor ( p= 0.32). In pts with aGEA at diagnosis, OS did not significantly differ depending on baseline 10 tumor TMB level (median OS of 21.4 [95% CI 15.4–27.9] months for TMB low, 14.6 [10.9–23.5] months for TMB int, and 9.6 [3.9–NA] for TMB hi; p= 0.3), nor depending on baseline met TMB level. Conclusions: Notable baseline spatial discordance of TMB was observed, particularly TMB hi 10 to low/int met. Discordance was also observed before & after tx, without significant increase towards TMB hi temporally. Spatiotemporal heterogeneity may impact the role of TMB as a predictive biomarker & warrants further study. [Table: see text]

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Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽

10.1027/0227-5910/a000468 ◽

2018 ◽

Vol 39 (1) ◽

pp. 27-36 ◽

Cited By ~ 5

Author(s):

Kuan-Ying Lee ◽

Chung-Yi Li ◽

Kun-Chia Chang ◽

Tsung-Hsueh Lu ◽

Ying-Yeh Chen

Keyword(s):

Young People ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Birth Registry ◽

Data Set ◽

Parental Suicide ◽

The Impact ◽

Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

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Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

Journal of Neurosurgery ◽

10.3171/2018.12.jns182775 ◽

2020 ◽

Vol 132 (4) ◽

pp. 998-1005 ◽

Cited By ~ 4

Author(s):

Haihui Jiang ◽

Yong Cui ◽

Xiang Liu ◽

Xiaohui Ren ◽

Mingxiao Li ◽

...

Keyword(s):

Survival Benefit ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Characteristic Curve ◽

Extent Of Resection ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

High Grade ◽

Extensive Resection ◽

High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

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Adapting the Default Weighted Survival Analysis Modelling Approach to Model IFRS 9 LGD

Risks ◽

10.3390/risks9060103 ◽

2021 ◽

Vol 9 (6) ◽

pp. 103

Author(s):

Morne Joubert ◽

Tanja Verster ◽

Helgard Raubenheimer ◽

Willem D. Schutte

Keyword(s):

Survival Analysis ◽

Financial Reporting ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Survival Curve ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Reporting Standard ◽

International Financial Reporting Standard ◽

Ifrs 9

Survival analysis is one of the techniques that could be used to predict loss given default (LGD) for regulatory capital (Basel) purposes. When using survival analysis to model LGD, a proposed methodology is the default weighted survival analysis (DWSA) method. This paper is aimed at adapting the DWSA method (used to model Basel LGD) to estimate the LGD for International Financial Reporting Standard (IFRS) 9 impairment requirements. The DWSA methodology allows for over recoveries, default weighting and negative cashflows. For IFRS 9, this methodology should be adapted, as the estimated LGD is a function of in the expected credit losses (ECL). Our proposed IFRS 9 LGD methodology makes use of survival analysis to estimate the LGD. The Cox proportional hazards model allows for a baseline survival curve to be adjusted to produce survival curves for different segments of the portfolio. The forward-looking LGD values are adjusted for different macro-economic scenarios and the ECL is calculated for each scenario. These ECL values are probability weighted to produce a final ECL estimate. We illustrate our proposed IFRS 9 LGD methodology and ECL estimation on a dataset from a retail portfolio of a South African bank.

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Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01834-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Farhadian ◽

Sahar Dehdar Karsidani ◽

Azadeh Mozayanimonfared ◽

Hossein Mahjub

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Cerebrovascular Events ◽

Long Term Follow Up ◽

Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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