Association of pectoralis muscle area and survival outcomes after chemotherapy.

e24094 Background: Chemotherapy use may be associated with muscle wasting, a marker of frailty that can predispose individuals to poor outcomes. We assessed the association between pre-treatment pectoralis muscle area and overall mortality following chemotherapy. Methods: We identified individuals diagnosed with breast cancer (N=221), lymphoma (N=216), or sarcoma (N=115) who received chemotherapy at the University of Minnesota Masonic Cancer Clinic and had CT scans prior to chemotherapy 2009-2014. Using CoreSlicer, right pectoral muscle area was measured at baseline and indexed to body surface (right pectoralis muscle area [cm2] / body surface [m2]) and divided into quartiles. Restricting to individuals who started chemotherapy within 6 months after their CT, we used cox regression (adjusted for age, sex, cancer type, stage, ever-smoking, BMI, and chemotherapy type) to assess associations between baseline muscle area and overall survival, testing for nonlinear effects using cubic splines. Results: 536 individuals (66% female) were identified who were treated with anthracyclines based chemotherapy (N=408), Trastuzumab (N=64), or both (N=64). Mean baseline muscle area was 14.9 (4.6) cm2 in females and 26.3 (9.3) cm2 in males. Median follow-up was 4.6 years. Larger baseline pectoralis muscle area (per m2 body surface) was associated with improved survival (adjusted model, overall effect, P=0.01), with some nonlinear effects (P=0.05). With muscle area (per m2 body surface) categorized as quartiles, individuals in the 3rd and 4th quartiles were at lower risk of dying (compared with people in the 1st quartile, hazard ratios 0.59 and 0.55 respectively, 95% CI range 0.35-0.90, P=0.01). There were no differences comparing the 4th vs the 3rd quartile (P=0.79), or the 2nd vs the 1st quartile (P=0.5). Conclusions: We found a protective association between larger right pectoral muscle size (relative to body surface) and overall survival after chemotherapy. There may be ceiling and threshold effects given evidence for nonlinear effects, since neither the 2nd vs. 1st quartile, nor the 4th vs. 3rd quartile comparisons in the categorical model were significant. Hazard ratios and confidence intervals of overall mortality by pectoral muscle area at baseline indexed to body surface, N=536, 2009-14. [Table: see text]

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Pectoralis muscle wasting during chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e24069 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e24069-e24069

Author(s):

Jason Wiederin ◽

Christina Gu ◽

Patricia Jewett ◽

Anne Hudson Blaes

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Muscle Mass ◽

Body Surface ◽

Cox Regression ◽

Nonlinear Effects ◽

Pectoralis Muscle ◽

Muscle Loss ◽

Muscle Area

e24069 Background: Chemotherapy is often followed by muscle mass loss which has been associated with frailty. We explored factors associated with change in pectoralis muscle mass after chemotherapy. We hypothesized greater muscle loss with time would be associated with poorer overall survival. Methods: We identified individuals with breast cancer (N = 221), sarcoma (N = 115), and lymphoma (N = 216) who received chemotherapy at the University of Minnesota MHealth Fairview and had CT scans before and after chemotherapy. Right pectoralis muscle area was measured using CORESLICER and indexed to body surface (right pectoralis muscle area [cm2] / body surface [m2]). We calculated quartiles of the indexed pectoralis measure. We restricted our analyses to participants who received a follow-up CT within two years after starting chemotherapy. In a multivariate linear regression, we explored associations of sex, age, BMI, ever-smoking, time since start of chemotherapy, indexed baseline muscle area, stage, type of diagnosis, and cumulative anthracycline dose with relative (%) change in muscle area. In a Cox regression we tested the association of relative muscle change with overall mortality. We used cubic splines to test for nonlinear effects. Results: Of 477 participants (66% female; mean age 61.3 (10.1) years), 366 received anthracyclines, 61 Trastuzumab, and 60 both. The average loss in right pectoral muscle area was -10% for women and -12% for men. We detected nonlinear effects of indexed baseline muscle area, P = 0.03. In a model using quartiles of indexed baseline muscle area, significant predictors of muscle loss included sex (women vs. men, -9.0%, 95% confidence interval (CI) -14.2- -3.7%, P = 0.0008), larger indexed baseline muscle area (quartiles 2, 3, 4 compared with quartile 1, change range -7 - -24%, 95% CI range, -2 - -30%, P-range < 0.0001 – 0.006), smoking (ever vs. never, -4.1%, 95% CI -7.6 - -0.7%, P = 0.02), and diagnosis (sarcoma vs breast cancer, -5.7%, 95% CI -11.1 - -0.3%, P = 0.04). There was no significant association between muscle change and overall survival (median follow-up time 4.1). Conclusions: Being female, larger baseline muscle mass (per m2 body surface), ever-smoking, and a sarcoma diagnosis were associated with greater relative muscle loss after chemotherapy. More data is needed to understand the course of sarcopenia in terms of recovery and survivorship. [Table: see text]

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Discovery and Validation of Circulating EVL mRNA as a Prognostic Biomarker in Pancreatic Cancer

Journal of Oncology ◽

10.1155/2021/6656337 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yan Du ◽

Kai Yao ◽

Qingbo Feng ◽

Feiyu Mao ◽

Zechang Xin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Mrna Expression ◽

Cox Regression ◽

Expression Profiles ◽

Differentially Expressed ◽

Cancer Type ◽

Mrna Levels ◽

Plasma Samples ◽

Patient Prognosis

Background. Circulating plasma mRNAs can be analyzed to identify putative cancer biomarkers. This study was conducted in an effort to detect plasma mRNA biomarkers capable of predicting pancreatic cancer (PACA) patient prognosis. Material and Methods. First, prognostic mRNAs that were differentially expressed in PACA in The Cancer Genome Atlas (TCGA) were established, after which microarray expression profiles from PACA patient plasma samples were utilized to specifically identify potential prognostic plasma mRNA biomarkers associated with this cancer type. In total, plasma samples were then collected from 79 PACA patients and 19 healthy controls to confirm differential mRNA expression via qPCR, while Kaplan–Meier analyses were used to examine the link between mRNA expression and patient overall survival. Results. In total, three prognostic differentially expressed genes were identified in PACA patient plasma samples, including SMAP2, PTPN6, and EVL (Ena/VASP-like). Plasma EVL levels were confirmed via qPCR to be correlated with tumor pathology p < 0.01 , while the overall survival of patients with low plasma EVL levels was poor p < 0.01 . Multivariate Cox regression analyses further confirmed that plasma EVL levels were independent predictors of PACA patient prognosis. Conclusion. We found that PACA is associated with the downregulation of plasma EVL mRNA levels, indicating that this mRNA may be a viable biomarker associated with patient prognosis.

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The Prognosis Role of AST/ALT (De Ritis) Ratio in Patients with Adult Secondary Hemophagocytic Lymphohistiocytosis

Mediators of Inflammation ◽

10.1155/2020/5719751 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Guangli Yin ◽

Changfeng Man ◽

Shengen Liao ◽

Hongxia Qiu

Keyword(s):

Overall Survival ◽

Hemophagocytic Lymphohistiocytosis ◽

Cox Regression ◽

Treatment Strategies ◽

Entire Study ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Study Population ◽

Restricted Cubic Splines ◽

Secondary Hemophagocytic Lymphohistiocytosis

Purpose. Secondary hemophagocytic lymphohistiocytosis (sHLH) accompanied by liver involvement, characterized by hepatomegaly and increased liver enzymes, is usually associated with elevated mortality. However, the magnitude of these associations remains unknown. Our objective was to assess the associations of the aspartate transaminase/alanine transaminase (AST/ALT, De Ritis) ratio with overall survival among adult patients with sHLH. Methods. A retrospective analysis was performed on 289 patients aged 18–86 years with complete serum transaminase data at diagnosis of sHLH. Multivariate Cox regression analyses and restricted cubic splines were conducted to address the association between the De Ritis ratio and the risk of mortality. Results. The median De Ritis ratio for the entire study population was 1.34 (IQR: 0.84-2.29). After a median follow-up time of 60 (range 17-227.5) days, 205 deaths occurred. After fully adjusting for hepatomegaly, albumin, fibrinogen, EBV, ferritin, etiologies, and treatment strategies, the adjusted hazard ratios (HRs) with corresponding confidence intervals (CIs) of mortality for the 2 st tertile and 3 st tertile were 1.2 (0.8-1.7) and 1.6 (1.1-2.2), respectively ( P < 0.01 for trends). Restricted cubic spline confirmed a linear association between the log2-transformed De Ritis ratio and the risk of mortality. Moreover, this trend persisted in subgroups with MHLH, hyperferrinaemia, sCD 25 ≤ 20,000 ng / L , patients without EBV infection, and those received treatment. Conclusions. The De Ritis ratio is a strong and independent predictor for overall survival in patients with sHLH. As a readily available biomarker in routine clinical practice, it is used to identify patients with sHLH with inferior overall survival.

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The impact of routine ESAS use on overall survival: Results of a population-based retrospective matched cohort analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6509 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6509-6509 ◽

Cited By ~ 6

Author(s):

Lisa Catherine Barbera ◽

Rinku Sutradhar ◽

Craig Earle ◽

Nicole Mittmann ◽

Hsien Seow ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Cohort Analysis ◽

Symptom Assessment ◽

Assessment System ◽

Cancer Type ◽

Matched Cohort ◽

Study Objective ◽

The Impact

6509 Background: The study objective was to examine the impact of routine Edmonton Symptom Assessment System (ESAS) use on overall survival among adult cancer patients. We hypothesized that patients exposed to ESAS would have better overall survival rates than those who didn’t have ESAS. Methods: The effect of ESAS screening on survival was evaluated in a retrospective matched cohort study. The cohort included all Ontario patients aged 18 or older who were diagnosed with cancer between 2007 and 2015. Patients completing at least one ESAS assessment during the study were considered exposed. The index date was the day of their first ESAS assessment. Follow up time for each patient was segmented into one of three phases: initial, continuing, or palliative care. Exposed and unexposed patients were matched 1:1 using hard (birth year ± 2 years, cancer diagnosis date ± 1 year, cancer type and sex) and propensity-score matching (14 measures including cancer stage, treatments received, and comorbidity). Matched patients were followed until death or the end of study at Dec 31, 2015. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the impact of ESAS on survival. Results: There were 128,893 pairs well matched on all baseline characteristics (standardized difference < 0.1). The probability of survival within the first 5 years was higher among those exposed to ESAS compared to those who were not (73.8% vs. 72.0%, P-value < 0.0001). In the multivariable Cox regression model, ESAS assessment was significantly associated with a decreased mortality risk (HR: 0.49, 95% CI: 0.48-0.49) and this protective effect was seen across all phases. Conclusions: ESAS exposure is associated with improved survival in cancer patients, in all phases of care. To the extent possible, extensive matching methods have mitigated biases inherent to observational data. This provides real world evidence of the impact of routine symptom assessment in cancer care.

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Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non–Small Cell Lung Cancer

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-15-1067 ◽

2016 ◽

Vol 26 (1) ◽

pp. 38-43 ◽

Cited By ~ 25

Author(s):

C. Matthew Kinsey ◽

Raul San José Estépar ◽

Jos van der Velden ◽

Bernard F. Cole ◽

David C. Christiani ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Pectoralis Muscle ◽

Small Cell Lung ◽

Muscle Area

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Irradiation of the Subventricular Zone and Subgranular Zone in High- and Low-Grade Glioma Patients: an Atlas-based Analysis on Overall Survival

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab193 ◽

2022 ◽

Author(s):

Danique E Bruil ◽

Szabolcs David ◽

Steven H J Nagtegaal ◽

Sophia F A M de Sonnaville ◽

Joost J C Verhoeff

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Low Grade ◽

Subgranular Zone ◽

Mr Images ◽

Repair Capacity ◽

Kaplan Meier ◽

Hazard Ratios ◽

Reduce Tumor Growth ◽

The Impact

Abstract Background Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p<0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p<0.001; multivariate: 1.055/Gy, p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, p<0.001). No correlations between dose and OS were found for LGG patients. Conclusion Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

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Irradiation of the Subventricular Zone and Subgranular Zone: an Atlas-based analysis on Overall Survival in High- and Low-grade Glioma Patients

10.1101/2021.08.17.21262102 ◽

2021 ◽

Author(s):

Danique Bruil ◽

Szabolcs David ◽

Steven Nagtegaal ◽

Sophia de Sonnaville ◽

Joost Verhoeff

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Low Grade ◽

Subgranular Zone ◽

Mr Images ◽

Repair Capacity ◽

Kaplan Meier ◽

Hazard Ratios ◽

Reduce Tumor Growth ◽

The Impact

Background: Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods: We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results: Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p<0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p<0.001; multivariate: 1.055/Gy, p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, p<0.001). No correlations between dose and OS were not found for LGG patients. Conclusion: Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

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Variation in TRMT11 gene as a prognostic marker in advanced-stage castrate-resistant prostate cancer (CRPC) patients.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.255 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 255-255

Author(s):

Ben Yiming Zhang ◽

Shaun M. Riska ◽

Douglas W. Mahoney ◽

Ricardo Jorge Teixeira Ribeiro ◽

Rui Medeiros ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Statistical Significance ◽

Candidate Snps ◽

Nucleotide Polymorphisms ◽

Castration Resistance ◽

Single Nucleotide ◽

Hazard Ratios ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

255 Background: In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 candidate hormone-related genes (JAK2, TRMT11, NKX3-1 and HSD17B12) were associated with overall survival (OS) in CRPC stage in a North American cohort of 519 subjects. We attempt to replicate these findings in an independent cohort of Portuguese patients. Methods: A hundred and forty CRPC stage patients in the new cohort were genotyped fort he candidate SNPs. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. For SNP level results we estimated hazard ratios (HR) and 95% confidence intervals (CI) under the dominant allele model using Cox regression and adjusted for age and Gleason score (GS). Results: The median age of the Portuguese cohort was 69 years (range 53-84). The GS distribution was 48% subjects with GS≥8; 35% with GS=7 and 17% with GS<7. Median time from castration resistance to death for the cohort was 2.2 years (IQ range: 0.8-3.4, 93 deaths). One of the 3 SNPs (rs2295005; C>G; MAF = 0.16) in the TRMT11gene was associated with OS after adjustment for age and GS: (dominant model p=0.05, HR=0.56; 95 CI=0.31-1.00). No other SNP was observed to have statistical significance with OS (Table 1). Conclusions: Variation in the TRMT11 gene is significantly associated with overall survival in patients with CRPC and warrants further validation as a potential prognostic biomarker. [Table: see text]

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Immune Cell Infiltrate and Prognosis in Gastric Cancer

Cancers ◽

10.3390/cancers12123604 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3604

Author(s):

Niko Kemi ◽

Niko Hiltunen ◽

Juha P. Väyrynen ◽

Vesa-Matti Pohjanen ◽

Olli Helminen ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Gastric Adenocarcinoma ◽

Prognostic Value ◽

Immune Cell ◽

Cox Regression ◽

Diffuse Type ◽

Hazard Ratios ◽

The Difference ◽

Immune Cell Score

Purpose: To examine and compare the prognostic value of immune cell score (ICS) and Klintrup–Mäkinen (KM) grade in gastric cancer. Methods: Gastric adenocarcinoma tissues from samples of 741 patients surgically treated in two hospitals in Finland were assessed for ICS and KM grade. Cox regression with adjustment for confounders provided hazard ratios (HRs) and 95% CIs. Subgroup analyses were performed in intestinal and diffuse type subgroups. The primary outcome was 5-year overall survival. Results: High ICS was associated to longer 5-year survival (adjusted HR 0.70, 95% CI 0.52–0.94), compared to low ICS. The difference was significant in intestinal type subgroup (adjusted HR 0.54, 95% CI 0.36–0.81) but not in diffuse type subgroup (adjusted HR 0.92, 95% CI 0.58–1.46). High KM grade was an independent prognostic factor for longer 5-year overall survival (adjusted HR 0.59, 95% CI 0.45–0.77) in both intestinal (adjusted HR 0.61, 95% CI 0.44–0.85) and diffuse subgroups (adjusted HR 0.52, 95% CI 0.31–0.86). ICS and KM grade were moderately correlated (ρ = 0.425). When both immune cell score and KM grade were included in the regression analysis, only KM grade remained prognostic. Conclusions: Both ICS and KM grade are prognostic factors in gastric adenocarcinoma, but immunohistochemistry-based ICS might not have additional prognostic value over hematoxylin–eosin-based KM grade.

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Numbers of Lymphoma Associated Macrophages (LAMS) and Regulatory T-Cells (Tregs) in Follicular Lymphoma (FL) Patients (pts) Treated with and without Monoclonal Antibody (MoAb)-Containing Therapy Do Not Correlate with Overall Survival (OS): A Study from the Southwest Oncology Group (SWOG).

Blood ◽

10.1182/blood.v110.11.2602.2602 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2602-2602

Author(s):

John William Sweetenham ◽

Eric Hsi ◽

Bryan Goldman ◽

Michael LeBlanc ◽

Raymond R. Tubbs ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Prognostic Value ◽

Cox Regression ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

Continuous Variables ◽

Hazard Ratios ◽

Anti Cd20

Abstract Introduction: Conflicting results have been reported for the prognostic value of LAMs and Tregs in FL. A recent study from the SWOG suggested that survival for pts with FL has improved in the last 30 years, possibly due to the introduction of MoAb-based therapy. We examined the prognostic significance of LAMs and FOX-P3-positive Tregs using tissue microarrays (TMAs) from pts entered onto SWOG studies 8809 (no MoAb) and 9911chemotherapy followed by (including 131I-tositumomab). Pts & methods: Adequate tissue samples were identified from 87 pts on SWOG 8809 and 47 on 9911. Pt characteristics were as follows: 8809: median age - 47.4 yrs (26.1 – 69.4), male 53%, Follicular Lymphoma International Prognostic Index (FLIPI) score: 1–36%, 2–39%, 3–21%. 9911: median age - 49.9 (22.9 – 66.8), male-60%, FLIPI score: 1–36%, 2–45%, 9–19%. The pts with available tissue were comparable with those who did not have available tissue for clinical prognostic factors. Archival blocks were reviewed to confirm FL and to assess for preparation of TMAs containing two 1mm diameter cores per case. Automated immunostaining for CD68 (PGM1) and FOXP3 (236A/E7) was performed. Intrafollicular (IF) and extra follicular (EF) LAMs were quantitated by manual count (5 1000x high power fields [hpf]). FOXP3 was scored for pattern (follicular/perfollicular vs. other) and number/5 hpf .LAM and Treg numbers/patterns were correlated with OS Marker levels were categorized by medians, 3rd quartiles and as continuous variables. Survival differences by marker level/pattern were assessed within each study population by Cox regression. Results: Pt characteristics did not differ by SWOG study. Hazard ratios with 95% confidence intervals for OS according to FOX-P3 and CD68 staining are shown in table 1. LAMS were not associated with OS, except for IF LAMS in S9911. Levels or pattern of FOX-P3 staining were not associated with OS. Conclusion: Levels of LAMs and Tregs were not predictive of overall survival in FL pts on SWOG trials before and after the introduction of anti-CD20 radio-immunotherapy (RIT). While IF LAMs in pts receiving RIT may be associated with shorter OS, the number of cases/events is too small for firm conclusions. Further studies are required to determine the prognostic value of these biomarkers in FL patients receiving anti-CD20 MoAb-containing therapies. Hazard ratios (95% CI) for OS for biomarker levels S8809 S9911 Overall * p<0.05 FOX-P3 (follicular vs other) 0.66 (0.29, 1.46) 0.95 (0.11, 8.10) 0.69 (0.33, 1.46) FOX-P3 (above median vs below) 1.30 (0.66, 2.58) 0.60 (0.11, 3.26) 1.16 (0.62, 2.17) EF LAM (above median vs below) 1.24 (0.59, 2.61) 0.70 (0.16, 3.11) 1.11 (0.56, 2.18) EF LAM (above 3rd quartile vs below) 1.12 (0.42, 2.94) 0.64 (0.13, 3.32) 0.96 (0.41, 2.23) IF LAM (above median vs below) 0.79 (0.35, 1.76) 5.33 (1.03, 27.51)* 1.22 (0.58, 2.57) IF LAM (above 3rd quartile vs below) 1.38 (0.62, 3.06) 2.24 (0.43, 11.56) 1.50 (0.72, 3.11)

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