FDG PET biomarkers for prediction of survival in metastatic melanoma prior to anti-PD1 immunotherapy

AbstractOur aim was to analyse whether biomarkers extracted from baseline 18F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80–1), 56.1% (IC 95 37.1–85) and 19% (IC 95 0.06–60.2) and hazard ratios were respectively 0.11 (IC 95 0.025–0.46), P = 0.0028, 1.2 (IC 95 0.48–2.8), P = 0.74 and 5.9 (IC 95 2.5–14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials.

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Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide (EC or HEC) with cyclophosphamide, methotrexate, and fluorouracil (CMF) in 777 women with node-positive (N+) breast cancer (BC): 10-year follow-up results

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.568 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 568-568 ◽

Cited By ~ 2

Author(s):

E. Azambuja ◽

M. Paesmans ◽

C. Bernard-Marty ◽

M. Beauduin ◽

A. Vindevoghel ◽

...

Keyword(s):

Cox Regression ◽

Menopausal Status ◽

Survival Rates ◽

Dose Intensity ◽

Phase Iii ◽

Open Label ◽

Kaplan Meier ◽

Hazard Ratios ◽

Primary Hypothesis

568 Background: The purpose of this presentation is to provide an update, with longer follow up data, of the results of this Belgian multicentric trial, which had shown a dose response curve for epirubicin at a median follow up of 4 years (Piccart et al, J Clin Oncol 2001; 19:3103–3110) Methods: In this prospective, open label, randomized trial of the 1990’s, patients aged from 18 to 70 years were stratified by center, 1–3 vs 4 or more nodes, and menopausal status (pre- vs postmenopausal). The primary hypothesis was that HEC could be associated with an increase in event-free survival (EFS) compared with CMF. Patients received CMF (oral cyclophosphamide days 1–14) for six cycles, EC (epirubicin 60 mg/m2, cyclophosphamide 500 mg/m2 day 1 every 3 weeks) for eight cycles or HEC (epirubicin 100 mg/m2, cyclophosphamide 830 mg/m2 day 1 every 3 weeks) for eight cycles. Tamoxifen followed chemotherapy in postmenopausal women with positive or unknown hormone receptor (HR). Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Results: The trial results are now updated, with an actuarial median follow-up of 12.2 years. Using Kaplan-Meier estimation, the 10-year EFS is 55% for patients who received CMF, 48% for EC patients, and 58% for HEC patients. The hazard ratios obtained from Cox regression models (HR) are, for EC vs HEC, 1.30 (95% confidence interval [CI], 1.02 to 1.67, P = .03); for CMF vs HEC, 1.12 (95% CI, 0.87 to 1.44, P = .39); and for CMF vs EC, 1.17 (95% CI, 0.92 to 1.48, P = .21). Kaplan-Meier estimates of the 10-year overall survival rates are 65% for patients who received CMF, 65% for EC patients, and 70% for HEC patients, with no significant differences among the three arms. Conclusions: The short term results of this trial are nicely confirmed at 10 years: in patients unselected for HR or HER-2 status, the dose intensity of epirubicin matters. Analysis in subsets of patients is ongoing, but will be only hypothesis-generating. [Table: see text]

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High risk groups for severe COVID-19 in a whole of population cohort in Australia

BMC Infectious Diseases ◽

10.1186/s12879-021-06378-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bette Liu ◽

Paula Spokes ◽

Wenqiang He ◽

John Kaldor

Keyword(s):

Socioeconomic Status ◽

New South ◽

Severe Disease ◽

Risk Groups ◽

Prevention Strategies ◽

Complete Case ◽

Relative Risks ◽

South Wales ◽

Hazard Ratios

Abstract Background Increasing age is the strongest known risk factor for severe COVID-19 disease but information on other factors is more limited. Methods All cases of COVID-19 diagnosed from January–October 2020 in New South Wales Australia were followed for COVID-19-related hospitalisations, intensive care unit (ICU) admissions and deaths through record linkage. Adjusted hazard ratios (aHR) for severe COVID-19 disease, measured by hospitalisation or death, or very severe COVID-19, measured by ICU admission or death according to age, sex, socioeconomic status and co-morbidities were estimated. Results Of 4054 confirmed cases, 468 (11.5%) were classified as having severe COVID-19 and 190 (4.7%) as having very severe disease. After adjusting for sex, socioeconomic status and comorbidities, increasing age led to the greatest risk of very severe disease. Compared to those 30–39 years, the aHR for ICU or death from COVID-19 was 4.45 in those 70–79 years; 8.43 in those 80–89 years; 16.19 in those 90+ years. After age, relative risks for very severe disease associated with other factors were more moderate: males vs females aHR 1.40 (95%CI 1.04–1.88); immunosuppressive conditions vs none aHR 2.20 (1.35–3.57); diabetes vs none aHR 1.88 (1.33–2.67); chronic lung disease vs none aHR 1.68 (1.18–2.38); obesity vs not obese aHR 1.52 (1.05–2.21). More comorbidities was associated with significantly greater risk; comparing those with 3+ comorbidities to those with none, aHR 5.34 (3.15–9.04). Conclusions In a setting with high COVID-19 case ascertainment and almost complete case follow-up, we found the risk of very severe disease varies by age, sex and presence of comorbidities. This variation should be considered in targeting prevention strategies.

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Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

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Survival Rate of 1008 Short Dental Implants with 21 Months of Average Follow-Up: A Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm9123943 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3943

Author(s):

João Caramês ◽

Ana Catarina Pinto ◽

Gonçalo Caramês ◽

Helena Francisco ◽

Joana Fialho ◽

...

Keyword(s):

Retrospective Study ◽

Survival Rate ◽

Dental Implants ◽

Cox Regression ◽

Survival Rates ◽

High Survival ◽

Implant Survival ◽

Posterior Maxilla ◽

Clinical Records

This retrospective study evaluated the survival rate of short, sandblasted acid-etched surfaced implants with 6 and 8 mm lengths with at least 120 days of follow-up. Data concerning patient, implant and surgery characteristics were retrieved from clinical records. Sandblasted and acid-etched (SLA)-surfaced tissue-level 6 mm (TL6) or 8 mm (TL8) implants or bone-level tapered 8 mm (BLT8) implants were used. Absolute and relative frequency distributions were calculated for qualitative variables and mean values and standard deviations for quantitative variables. A Cox regression model was performed to verify whether type, length and/or width influence the implant survival. The cumulative implant survival rate was assessed by time-to-event analyses (Kaplan–Meier estimator). In all, 513 patients with a mean age of 58.00 ± 12.44 years received 1008 dental implants with a mean follow-up of 21.57 ± 10.77 months. Most implants (78.17%) presented a 4.1 mm diameter, and the most frequent indication was a partially edentulous arch (44.15%). The most frequent locations were the posterior mandible (53.97%) and the posterior maxilla (31.55%). No significant differences were found in survival rates between groups of type, length and width of implant with the cumulative rate being 97.7% ± 0.5%. Within the limitations of this study, the evaluated short implants are a predictable option with high survival rates during the follow-up without statistical differences between the appraised types, lengths and widths.

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Association between selenium intake, diabetes, and mortality in adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2014

British Journal Of Nutrition ◽

10.1017/s000711452100177x ◽

2021 ◽

pp. 1-24

Author(s):

Bushra Hoque ◽

Zumin Shi

Keyword(s):

National Health ◽

Cox Regression ◽

Inverse Association ◽

Nutrition Examination Survey ◽

Health And Nutrition ◽

Hazard Ratios ◽

The Us ◽

All Cause Mortality ◽

Cvd Mortality

Abstract Selenium (Se) is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18,932 adults who attended the 2003-2014 National Health and Nutrition Examination Survey (NHANES) were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. Comparing extreme quartiles of Se intake, the odds ratio (OR) for diabetes was 1.44 (95% CI: 1.09–1.89). During a mean of 6.6 years follow-up, there were 1627 death (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios (HRs) for all-cause, CVD mortality, cancer mortality and other mortality were: 0.77 (95% CI 0.59-1.01), 0.62 (95% CI, 0.35-1.13), 1.42 (95% CI, 0.78-2.58) and 0.60 (95% CI,0.40-0.80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

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Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-201096 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1601-1612

Author(s):

Johan Frederik Håkonsen Arendt ◽

Erzsébet Horváth-Puhó ◽

Henrik Toft Sørensen ◽

Ebba Nexø ◽

Lars Pedersen ◽

...

Keyword(s):

Vitamin B12 ◽

Vascular Dementia ◽

Cox Regression ◽

Population Based ◽

High Dose ◽

Plasma Vitamin ◽

Hazard Ratios ◽

B12 Deficiency ◽

First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

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NISAR-F SCORE: a simple risk stratification tool for patients implanted with cardiac resynchronization therapy

EP Europace ◽

10.1093/europace/euab116.457 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

J Correia ◽

L Goncalves ◽

I Pires ◽

J Santos ◽

V Neto ◽

...

Keyword(s):

Ejection Fraction ◽

Cardiac Resynchronization Therapy ◽

Cox Regression ◽

Nyha Class ◽

Prognostic Score ◽

Roc Curves ◽

Cardiac Resynchronization ◽

Class Iii ◽

Resynchronization Therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Outcomes in this group of patients are influenced by multiple factors and a comprehensive and customized approach to estimate prognosis after CRT is lacking Aims To develop and validate a simple prognostic score for patients implanted with CRT (NISAR-F score), based on readily available clinical and echocardiographic variables to predict the combined endpoints of death or hospitalization in 24 months. Methods A single-centre retrospective study was conducted with inclusion of all consecutive patients who underwent CRT implantation between 2012 and 2019. Follow-up started after CRT implantation and ended upon death, hospitalization or 24 months after study entry. Survival analysis was performed using a multivariate Cox regression model, in order to analyze the effect on survival /hospitalization in 24 months of the following factors: age, gender, NYHA Class III-IV, ischemic heart failure, type 2 diabetes, arterial hypertension, dyslipidemia and ejection fraction < 21%. According to the analysis, points were attributed to each factor. Afterwards, the NISAR-F score was calculated for each patient, summing the points of each variable. The authors finally created ROC curves for the NISAR-F score to predict the occurrence of the combined endpoint in 2 groups of patients: CRT responders (ejection fraction increase of at least 10% after CRT implantation) and CRT non-responders. The statistical analysis was performed in SPSS. Results 102 patients were included in the study (75.4% male, mean age 68 ± 10.46 years). 10(9.8%) of the patients were re-hospitalized and 8 (7.8%) died during the 24-month follow-up. After calculating NISAR-F score for each patient, area under ROC curves were obtained. The analysis of the ROC curves allows us to confirm the good performance of the score created [responders group (AUC 0.812) vs non-responders (AUC 0.721)]. Conclusion The NISAR-F score is a useful tool to predict the combined endpoint (mortality and hospitalization in 24 months) after CRT implantation, in both responders and non-responders, revealing good performance of this new and simple score based only on clinical and echocardiographic variables.

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A population-wide analysis of the familial risk of suicide in Utah, USA

Psychological Medicine ◽

10.1017/s0033291721003020 ◽

2021 ◽

pp. 1-10

Author(s):

Amanda V. Bakian ◽

Danli Chen ◽

Chong Zhang ◽

Heidi A. Hanson ◽

Anna R. Docherty ◽

...

Keyword(s):

Suicide Risk ◽

Cox Regression ◽

Familial Risk ◽

Risk Groups ◽

Population Based ◽

Unified Framework ◽

Population Database ◽

First Degree Relatives ◽

Hazard Ratios ◽

History Of

Abstract Background The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. Methods A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. Results Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26). Conclusions Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.

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Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as a risk factor for mortality in peruvian adults with chronic kidney disease.

10.22541/au.161224727.78237032/v1 ◽

2021 ◽

Author(s):

Gianfranco Umeres-Francia1 ◽

María Rojas-Fernández ◽

Percy Herrera Añazco ◽

Vicente Benites-Zapata

Keyword(s):

Risk Factor ◽

Cox Regression ◽

Outcome Variable ◽

Lymphocyte Ratio ◽

Hazard Ratios ◽

Ckd Stage ◽

All Cause Mortality ◽

The Relationship ◽

Crude Analysis

Objective: To assess the association between NLR and PLR with all-cause mortality in Peruvian patients with CKD Methods: We conducted a retrospective cohort study in adults with CKD in stages 1 to 5. The outcome variable was mortality and as variables of exposure to NLR and PLR. Both ratios were categorized as high with a cut-off point of 3.5 and 232.5; respectively. We carried out a Cox regression model and calculated crude and adjusted hazard ratios (HR) with their 95% confidence interval (95%CI). Results: We analyzed 343 participants with a median follow-up time of 2.45 years (2.08-3.08). The frequency of deaths was 17.5% (n=60). In the crude analysis, the high NLR and PLR were significantly associated with all-cause mortality (HR=2.01; 95% CI:1.11-3.66) and (HR=2.58; 95% CI:1.31-5.20). In the multivariate model, after adjusting for age, sex, serum creatinine, CKD stage, albumin and hemoglobin, the high NLR and PLR remained as an independent risk factor for all-cause mortality, (HR=2.10; 95% CI:1.11-3.95) and (HR=2.71; 95% CI:1.28-5.72). Conclusion: Our study suggests the relationship between high NLR and PLR with all-cause mortality in patients with CKD.

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Reported fried food consumption and the incidence of hypertension in a Mediterranean cohort: the SUN (Seguimiento Universidad de Navarra) project

British Journal Of Nutrition ◽

10.1017/s0007114514001755 ◽

2014 ◽

Vol 112 (6) ◽

pp. 984-991 ◽

Cited By ~ 10

Author(s):

Carmen Sayon-Orea ◽

Maira Bes-Rastrollo ◽

Alfredo Gea ◽

Itziar Zazpe ◽

Francisco J. Basterra-Gortari ◽

...

Keyword(s):

Food Consumption ◽

Cox Regression ◽

University Graduates ◽

The Sun ◽

Fried Food ◽

Hazard Ratios ◽

Fried Foods ◽

Frequent Consumption ◽

Incident Cases

Reported associations between the consumption of fried foods and the incidence of obesity or weight gain make it likely that fried food consumption might also be associated with the development of hypertension. However, evidence from long-term prospective studies is scarce. Therefore, the aim of the present study was to longitudinally evaluate this association in a prospective cohort. The SUN (Seguimiento Universidad de Navarra) project is a Mediterranean cohort study of university graduates conducted in Spain, which started in December 1999 and is still ongoing. In the present study, we included 13 679 participants (5059 men and 8620 women), free of hypertension at baseline with a mean age of 36·5 (sd 10·8) years. Total fried food consumption was estimated at baseline. The outcome was the incidence of a medical diagnosis of self-reported hypertension during the follow-up period. To assess the association between the consumption of fried foods and the subsequent risk of developing incident hypertension during the follow-up period, Cox regression models were used. During a median follow-up period of 6·3 years, 1232 incident cases of hypertension were identified. After adjusting for potential confounders, the adjusted hazard ratios for developing hypertension were 1·18 (95 % CI 1·03, 1·36) and 1·21 (95 % CI 1·04, 1·41) for those consuming fried foods 2–4 and >4 times/week, respectively, compared with those consuming fried foods < 2 times/week (P for trend = 0·009). In conclusion, frequent consumption of fried foods at baseline was found to be associated with a higher risk of hypertension during the follow-up period in a Mediterranean cohort of university graduates.

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