scholarly journals Doppler Ultrasound in Prostate Cancer: It’s Utility for the Diagnosis of High-Grade Tumors

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Elisa Carvalho de Siqueira
Keyword(s):  
Prostate Cancer ◽  
Doppler Ultrasound ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Indirect Inference ◽  
Independent Variables ◽  
Ultrasound Findings ◽  
Aggressive Tumors ◽  
Worse Prognosis ◽  
Advanced Tumors

Purpose: The aim of the present study was to evaluate the association between prostate vascularization seen in Doppler ultrasound and histopathological grade (Gleason score) in patients with a diagnosis of prostate cancer. Methods: A Gleason score >7 was the dependent variable and Doppler ultrasound findings (vascular analysis, presence of nodule and prostate weight) were the independent variables. Univariate analysis was performed considering advanced tumors (Gleason >7) as the dependent variable and area of hypervascularization, age and PSA as the independent variables. Multivariate analysis was performed using a binary regression model with the occurrence of advanced tumors (Gleason >7) as the dependent variable. Results: In the univariate analysis, samples with Gleason ≤7 had a lower chance of being hypervascularized (OR: 0.44, 95% CI: 0.29-0.69), whereas those with Gleason scores >7 had a fourfold greater chance of being hypervascularized (OR: 4.136, 95% CI: 2.598-6.554, p<0.001). Moreover, hypervascularized tumors had a 7.4-fold greater chance of having a score >7. Conclusion: The present study reveals an association between tumor hypervascularization detected using Doppler ultrasound and higher Gleason scores (more aggressive tumors), enabling an indirect inference of a worse prognosis for hypervascularized prostatic tumors. These findings should be confirmed in longitudinal studies.

scholarly journals Essential Updates in Grading, Morphotyping, Reporting, and Staging of Prostate Carcinoma for General Surgical Pathologists

2019 ◽  
Vol 143 (5) ◽  
pp. 550-564 ◽  
Author(s):  
Gladell P. Paner ◽  
Jatin Gandhi ◽  
Bonnie Choy ◽  
Mahul B. Amin
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Prostate Carcinoma ◽  
Multidisciplinary Care ◽  
Tnm Staging ◽  
International Consensus ◽  
Gleason Pattern ◽  
Consensus Conferences ◽  
Worse Prognosis

Context.— Within this decade, several important updates in prostate cancer have been presented through expert international consensus conferences and influential publications of tumor classification and staging. Objective.— To present key updates in prostate carcinoma. Data Sources.— The study comprised a review of literature and our experience from routine and consultation practices. Conclusions.— Grade groups, a compression of the Gleason system into clinically meaningful groups relevant in this era of active surveillance and multidisciplinary care management for prostate cancer, have been introduced. Refinements in the Gleason patterns notably result in the contemporarily defined Gleason score 6 cancers having a virtually indolent behavior. Grading of tertiary and minor higher-grade patterns in radical prostatectomy has been clarified. A new classification for prostatic neuroendocrine tumors has been promulgated, and intraductal, microcystic, and pleomorphic giant cell carcinomas have been officially recognized. Reporting the percentage of Gleason pattern 4 in Gleason score 7 cancers has been recommended, and data on the enhanced risk for worse prognosis of cribriform pattern are emerging. In reporting biopsies for active surveillance criteria–based protocols, we outline approaches in special situations, including variances in sampling or submission. The 8th American Joint Commission on Cancer TNM staging for prostate cancer has eliminated pT2 subcategorization and stresses the importance of nonanatomic factors in stage groupings and outcome prediction. As the clinical and pathology practices for prostate cancer continue to evolve, it is of utmost importance that surgical pathologists become fully aware of the new changes and challenges that impact their evaluation of prostatic specimens.

Correlation of percent of core biopsies positive for prostate cancer and biochemical outcome following I-125 prostate brachytherapy or external beam radiation.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 40-40
Author(s):  
R. D. Tendulkar ◽  
K. L. Stephans ◽  
C. A. Reddy ◽  
K. Martires ◽  
A. R. Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Univariate Analysis ◽  
External Beam Radiation ◽  
Prostate Brachytherapy ◽  
Beam Radiation ◽  
T Stage ◽  
Psa Testing ◽  
Biopsy Gleason Score

40 Background: The percentage of positive cores (PPC) on biopsy for prostate cancer has been identified as a predictor of outcome following definitive local treatment. We aim to identify whether this observation holds true for a modern cohort of patients (pts) treated at Cleveland Clinic with permanent prostate brachytherapy (PB) or external beam radiation therapy (EBRT). Methods: We retrospectively reviewed pathology reports of pts treated with either PB or EBRT from our IRB-approved prospective prostate cancer registry. No pts underwent both PB and EBRT. The number of biopsy cores sampled, number of cores positive for prostate cancer, and maximum length of any core positive for prostate cancer were collected. Cox proportional hazards regression was used to analyze biochemical relapse free survival (bRFS) using the nadir + 2 ng/ml definition. Results: We identified 1253 PB and 879 EBRT pts with complete pathology and clinical information. Among PB pts, 46% were low risk, 40% intermediate risk, and 14% high risk, while 78% had <50% PPC, and 22% had >=50% PPC. The 5-year bRFS for PB was 92.0% for <50% PPC, vs. 83.1% for >=50% PPC (HR 2.1, p=0.0005). For PB pts, significant predictors of bRFS on univariate analysis included: PPC, clinical T stage, PSA, biopsy Gleason score, androgen deprivation, and frequency of PSA testing. On multivariate analysis, only PPC, biopsy Gleason score, and PSA frequency remained significant predictors following PB. Among EBRT pts, 11% were low risk, 36% intermediate risk, and 53% high risk, while 55% had <50% PPC, and 45% had >=50% PPC. The 5-year bRFS for EBRT was 85.6% for <50% PPC, vs. 77.1% for >=50% PPC (HR 1.8, p<0.0001). For EBRT pts, significant predictors of bRFS on univariate analysis included: PPC, clinical T stage, PSA, biopsy Gleason score, androgen deprivation, EBRT dose, and frequency of PSA testing. On multivariate analysis, only PPC, biopsy Gleason score, and PSA frequency remained significant predictors following EBRT. Conclusions: Following PB or EBRT, the percent of positive cores for prostate cancer was a significant predictor of bRFS on multivariate analysis, more so than conventional predictors such as T stage and PSA. No significant financial relationships to disclose.

Clinical significance of plasma fibrinogen level in patients with prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16077-e16077
Author(s):  
Xiao-Kun Ma ◽  
Jing-Yun Wen ◽  
Zhan-Hong Chen ◽  
Qu Lin ◽  
Xing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Gleason Score ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Tnm Stage ◽  
Plasma Fibrinogen ◽  
T State ◽  
Coagulation Analyzer ◽  
Worse Prognosis

e16077 Background: Most of malignant tumor patients have hypercoagulable state with plasma fibrinogen (Fib) levels increased. In this study, we aimed to investigate correlation of plasma Fib with routine prognostic factors of prostate cancer patients, including Gleason score, prostate specific antigen (PSA), TNM 7th Stage. Methods: From January 2007 to December 2012, 107 patients with prostate cancer and 44 cases of benign prostatic hyperplasia (BPH) were included in our study. Automated coagulation analyzer was used to determine the plasma fibrinogen levels. Results: The patients presented a mean age of 70.6 years, a mean PSA level of 28.73 ng/ml, clinically localized prostate cancer in 47 cases, locally advanced condition in 27cases, and distant metastatic disease in 33 cases. The fibrinogen levels were increased in cancer patients compared to that in patients with BPH (P = 0.031). Higher fibrinogen levels related to metastasis, higher TNM stage and increased PSA (p = 0.000, 0.041 and 0.004 respectively). Fib levels were irrelevant to T state, N state, and Gleason score. Conclusions: Prostate cancer patients displayed increased Fib levels. Plasma Fib is significantly increased in patients with higher PSA level,worse TNM stage and distant metastasis. The patients with high Fib might presented relative worse prognosis and should be monitored closely. [Table: see text]

Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Independent Predictor ◽  
Performance Status ◽  
Univariate Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]

Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Genetic Constitution ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

scholarly journals Neuroendocrine Immunophenotype as Predictor of Clinical Recurrence in 110 Patients with Prostate Cancer

2007 ◽  
Vol 20 (4) ◽  
pp. 765-770 ◽  
Author(s):  
R. Autorino ◽  
M.G. Lamendola ◽  
G. De Luca ◽  
M. De Sio ◽  
F. Giugliano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Univariate Analysis ◽  
Localized Prostate Cancer ◽  
Clinical Recurrence ◽  
Psa Recurrence ◽  
Well Differentiated

We evaluated the relationship between NE expression and well-known prognostic factors and assessed whether tumor relapse after radical surgery correlates with the extent of NE differentiation. Radical prostatectomy specimens from 110 patients with clinically localized prostate cancer were assessed. Patients were followed up every three months for the first two years after surgery and six monthly for 5 additional years until failure, or for a mean of 48 months from the time of surgery for those who did not experience failure. The percentage of cells showing CgA immunoreactivity was evaluated using a visual quantitative method. Tumor staining was categorized as positive if >10% and negative if <10% of tumor cells were stained, to ensure that only cases with significant positivity were included in the positive group. The median follow-up was 5.4 years (range 1.8 to 7.2). The median time to clinical recurrence was 7.5 years and the median time to biochemical recurrence was 2.8 years. Of 31 patients (28%) who experienced a PSA recurrence, 15 developed a clinical recurrence. The mean preoperative PSA level was 9 ng/ml (range 2.7 to 25). Most cases were well differentiated (Gleason score <7), intraprostatic (≤pT2) tumors. Immunoreactivity in ≥10% of the cells was seen in 17.2% (n=19) of the tumor specimens. The preoperative PSA level, Gleason score, use of neoadjuvant or adjuvant therapy, lymphnode positivity were not statistically associated with NE expression. Only the primary pathologic stage appeared to be associated with CgA staining in the primary tumor (p=0.001). On the univariate analysis NE expression did not predict biochemical recurrence free survival, whereas it was associated with clinical recurrence. NE differentiation in clinically localized prostate cancer can be associated with failure after definitive surgical treatment, even if no conclusions can be drawn regarding its value as an independent prognostic factor.

scholarly journals Predicting the Diagnosis of Prostate Cancer with a Scoring System Based on Novel Biomarkers

2021 ◽  
Author(s):  
Durvesh Lachman Jethwani ◽  
Lameena Lalitha Sivamoorthy ◽  
Charng Chee Toh ◽  
Rohan Malek
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Prostate Biopsy ◽  
Scoring System ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Independent Variables ◽  
Prostate Specific Antigen Density ◽  
Novel Biomarkers ◽  
Disease Specificity

Abstract Objective: To predict prostate cancer using novel biomarker ratios and create a predictive scoring system.Materials and Methods: Data of a total of 703 patients who consulted Urology Department of Selayang Hospital between January 2013 and December 2017 and underwent prostate biopsy were screened retrospectively. Prostate specific antigen (PSA) levels, prostate volumes (PV), neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Prostate specific antigen density (PSAD)and histopathology were evaluated. Results: Ages ranged from43-89 years, divided into 2 groups as per biopsy results; positive for prostate cancer (n=290, 41.3%) and negative for malignancy (n=413; 58.7%). Intergroup comparative evaluations were performed. Independent variables with p<0.001 in the univariate analysis were age, DRE, PV, NLR, PSAD.A scoring system was modelled using NLR <0.9, PSAD >0.4, Age >70 and DRE. A score of 2 or more predicted prostate cancer with a Sensitivity of 83.8% and Specificityof 86.4%Conclusions: NLR is shown to be good predictor for prostate cancer its usage in this scoring system affords more disease specificity as compared to PSA alone.

scholarly journals Large Scale Genomic Instability as an Additive Prognostic Marker in Early Prostate Cancer

2009 ◽  
Vol 31 (4) ◽  
pp. 251-259
Author(s):  
Maria E. Pretorius ◽  
Håkon Wæhre ◽  
Vera M. Abeler ◽  
Ben Davidson ◽  
Ljiljana Vlatkovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Gleason Score ◽  
Large Scale ◽  
Dna Ploidy ◽  
Univariate Analysis ◽  
Disease Recurrence ◽  
Observation Time ◽  
Surgical Margins

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy.Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score.Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence.Conclusion: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours.

Prediction of survival by immunohistochemical stains (IHC) in stage D2 prostate cancer patients (pts): The importance of pTEN overexpression

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16019-e16019
Author(s):  
B. Kasimis ◽  
V. Chang ◽  
S. Gounder ◽  
M. Gonzalez ◽  
C. Finch-Cruz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Strong Predictor ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Small Sample ◽  
Pdgfr Beta ◽  
Pdgfr Alpha

e16019 Background: Several signal transduction pathways,important for apoptosis and angiogenesis were idendified and their expression and correlation with survival was studied by IHC in archival prostate cancer biopsies. All pts has androgen deprivation for stage D2 disease and were followed at 3 month intervals. Methods: In an IRB approved study,42 pts had adequate tissue preserved between 1992 and 2006 and their charts were reviewed retrospectively.IHC stains to detect tumor expression of S6(ribosomal),p70s6,pTEN,AKT-1,BCL-1(Cyclin D1),VEGF,c-KIT,PDGFR-alpha and PDGFR-beta were performed by US Labs(Irvine,CA).All results were independently evaluated by two pathologists.Immunoreactivity was scored using a semiquantitative system combining intensity of staining(0–3+) and percentage of cells staining positive(0–3+).The total score was obtained by adding the scores for indensity and the percentage of positive cells,then averaging the resuts obtained by each reader.For the purpose of this study, stain intensity of 0–1+ was considered negative and the intensity of 2–3+ was considered positive.A Cox regression survival model for each stain was developed with variables known to predict survival :Gleason score,Hemoglobin(Hgb),Alkaline Phosphatase(Alk Phos),Prostate Specific Antigen(PSA),Lactate Dehydrogenase(LDH) levels. Results: The median values were: age 70yrs(56–92),Gleason score 8(6–10), LDH 171 IU/L(97–350),Hgb 12.9gm/dl (6.8–16.3), PSA 188ng/ml(2–5677),Alk Phos 139U/L(60–1756),survival 851 days(163- 6102).In univariate analysis,VEGF staining was predictive of survival (p<0.037) but not in multivariate analysis.The pTEN staining correlated with survival (p<0.0367) and a hazard ratio of 0.040 in multivariate analysis. Conclusions: In this small sample of pts, overexpression of S6,p70s6,AKT-1,BCL-1,VEGF,c-KIT,PDGFR-alpha and PDGFR-beta by IHC staining did not predict survival independently.The pTEN staining,however was strong predictor of survival in the multivariate analysis. No significant financial relationships to disclose.

Outcomes of men who underwent treatment for prostate cancer from a prospective follow up of a racially diverse, multi-institutional active surveillance cohort.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e536-e536
Author(s):  
Nora M. Haney ◽  
Allison H. Feibus ◽  
James Liu ◽  
Gabriel Leinwand ◽  
Elisa M. Ledet ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Group ◽  
Active Surveillance ◽  
Gleason Score ◽  
Smoking Status ◽  
Univariate Analysis ◽  
Clinical Staging ◽  
Low Grade ◽  
Racially Diverse ◽  
Entire Cohort

e536 Background: Active surveillance (AS) is an increasingly accepted alternative to treatment for low-grade prostate cancer (PCa). However, it remains unclear what factors may predict which patients will upgrade to a higher grade cancer. We sought to analyze the characteristics at time of diagnosis and outcomes of those men in our racially diverse AS cohort who underwent treatment for PCa. Methods: Men from our AS database were analyzed. Inclusion criteria was PSA < 20 ng/mL, Gleason Score ≤ 7, and clinical stage ≤ T2a. Men who elected active treatment for their PCa at diagnosis or refused subsequent imaging and biopsy were excluded from this cohort. Univariate analysis was done to compare the clinical variables of the treatment group with the entire cohort. Results: We identified 56 men who were treated for PCa from the 308 men currently enrolled in our AS cohort. All 56 men in the treatment group had low risk PCa at diagnosis and initiation of AS. At diagnosis, the treatment group was not significantly different in comparison with our entire cohort with respect to age, BMI, family history of PCa, PSA at diagnosis, prior negative biopsy, TRUS volume, PSAD, smoking status and clinical staging. However the eventual treatment group did differ at diagnosis with respect to greater linear length of cancer per core (p < 0.01), greater % involvement of disease (p = 0.03), and greater number of total cores at time of diagnosis (p = 0.04). The men in this group underwent treatment for PCa for the following reasons: 36 for Gleason Score upgrading, 5 due to increased volume of disease, 6 due to rising PSA, 1 due to MRI findings, 1 due to rising PSA on Avodart and 7 elected treatment despite no significant changes in disease. 31 of the men had RARPs, 17 XRT, 4 had XRT + ADT, 3 had Brachytherapy, and 1 with XRT + salvage RP. Conclusions: Within our prospectively enrolled racially diverse AS cohort, the patients who underwent treatment for PCa had clinical factors that differed in comparison to the whole cohort. Further prospective study is needed to determine how these factors may ultimately impact long term outcomes.

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