The Abstract includes the Background giving brief information about the reason to conduct the research; Methods that have described briefly about the how they assessed the process to select the patient and the study design and method being used in article; Results that have described whether the study has done has positive or negative results; Conclusion stating the research question and the result. Therefore, yes, the abstract has been written as per norms.
l About 20% of patient with classic Hodgkin’s Lymphoma is not cured by current therapies & other 20% are overtreated.
l It is still a challenge to identify the patients whose disease cannot be cured by standard therapies.
l Although 50% of patients those who are uncured by primary therapies have the disease eradicated by the use of autologous hematopoietic stem cell transplantation.
l Initial clinical decision and risk stratification- depends on clinical variable.
l The international prognostic score is the standard for risk stratification of advanced-stage Hodgkin’s lymphoma but does not apply to limited stages.
l Neither prognostic score nor individual clinical components can accurately predict the outcome of autologous stem-cell transplantation.
l Therefore, reliable Biomarkers can be a good source to predict long-term survival in classic Hodgkin’s Lymphoma.
STUDY DESIGN: Blinded Independent Central Review(BICR).
MATERIALS AND METHODS/DATA SOURCES
l Fresh-frozen lymph-node specimen was obtained from 133 patients with Hodgkin Lymphoma at the time of diagnosis for Gene-Expression Profiling.
l Samples were obtained from British Columbia Cancer Agency(BCCA) and Nebraska Medical Center.
l To confirm the outcome of gene-expression profiling, we performed immunohistochemical analysis on tissue microarray on 166 independent cases enriched for treatment failure.
l The gene-expression profiling study shows that matrix metallopeptidase(MMP11) was significantly over-expressed with the treatment failure cohort.
l The Immunohistochemical Microarray found that CD68+ shows significant correlation with shortened progression-free survival.
l The Secondary Treatment Failure rate was lower in the patient with score 1 of CD68+ marker compared to score 2 & 3.
l Analysis of limited-stage disease shows the long-term disease-specific survival rate was 100% with a score of 1 for a CD68+ marker.
l Decrease/absent CD68+ cells in classic Hodgkin’s Lymphoma shows 100% rate of long-term disease-specific survival with use of available treatments.
No, the keywords are not mentioned in the article but according to me the following could be the relevant keywords:
1. Classic Hodgkin’s Lymphoma.
2. Biomarkers in Hodgkin’s Lymphoma.
3. Tumor-Associated Macrophages.
The introduction describes reasons to conduct the research which are as follows:
ü Out of all the patients with Classic Hodgkin’s Lymphoma, about 20% are uncured and 20% are overtreated.
ü The patients who cannot be cured by standard therapies are not identified.
ü Only 50% patients are cured by Autologous Hematopoietic Stem Cell Transplantation when the primary therapy fails.
ü Neither prognostic score nor individual clinical components can accurately predict the outcome of the auto transplant.
Therefore, Reliable Biomarkers can be a good source to predict long-term survival at the time of diagnosis in a patient with Hodgkin Lymphoma.
Thus, yes, the introduction adequately sets the stage for the rest of the article and the information given is relevant.
RESEARCH QUESTION: Is there any association between classic Hodgkin’s Lymphoma treatment survival prediction and Tumor-Associated Macrophages?
HYPOTHESIS: Classic Hodgkin’s Lymphoma treatment survival prediction in association with tumor-associated macrophages.
NULL HYPOTHESIS: There is no significant association of Classic Hodgkin’s Lymphoma treatment survival prediction and Tumor-Associated Macrophages.
ALTERNATIVE HYPOTHESIS: There is a significant association of Classic Hodgkin’s Lymphoma treatment survival prediction and Tumor-Associated Macrophages.
Ø Yes, the hypothesis adequately addresses the research question.
Ø This research article rejects the null hypothesis.
The research methodology used in this article is CENTRAL REVIEW aka BLINDED INDEPENDENT CENTRAL REVIEW.
Ø The process by which radiographic exams and selected clinical data performed as part of a clinical trial protocol are submitted to a central location (In this article – institutional review boards at the University of British Columbia– BCCA and the University of Nebraska Medical Center) for blinded review by independent physicians not involved in the treatment of the patients.
GENE-EXPRESSION PROFILING – Tissue Samples were obtained from 130 patients at the time of diagnosis from tissue archives at the British Columbia Cancer Agency(BCCA) and University of Nebraska Medical Center.
ü Primary diagnosis of Classic Hodgkin’s Lymphoma after central review.
ü Representative lymph-node tissue at least 1cm2 in sections.
ü Negative for HIV Infection.
ü First-line Treatment with ABVD chemotherapy (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine) or an ABVD-like regimen
ü Radiation Therapy (including Widefield Radiation for patients with the limited-stage disease).
The Gene-Expression cohort was stratified on the basis of treatment outcome (Treatment success/Treatment Failure) to analyze the difference between both of them.
IMMUNOHISTOCHEMICAL TESTING – Tissue Samples were collected from 166 independent cases of Classic Hodgkin’s Lymphoma and all the available cases of treatment failure obtained from Center for Lymphoid Cancer Database at BCCA.
ü Formalin-fixed, Paraffin-embedded diagnostic lymph-node specimen.
This cohort was stratified into progression-free survival and disease-specific survival 61 patients were provided with secondary therapy with curative intent.
CHI-SQUARE TEST: This test is applied when there are two categorical variables from a single population. It is used to determine whether there is a significant association between the two variables.
STUDENT’S T-TEST: This technique is used for testing the hypothesis. Determines a probability that two populations are the same with respect to the variable tested.
SPARSE MULTINOMIAL LOGISTIC REGRESSION: This model is used to predict the probabilities of the different possible outcomes of the categorically distributed dependent variable, given a set of independent variables.
In this article, it is used to test the power of gene-expression profiles to predict the outcome.
COX PROPORTIONAL-HAZARDS MODELS: It is used in the analysis of survival data to explain the effect of explanatory variables on hazard rates.
KAPLAN–MEIER METHOD: To estimate the survival function from lifetime data.
The software used for statistical analysis was SPSS software, version 11.0.
Two-sided P values of less than 0.05 were considered to indicate statistical significance.
The Conclusion in the article states that absence of an increase in CD68+ cells in classic Hodgkin’s Lymphoma shows 100% rate of long-term disease-specific survival with use of available treatments.
Yes, the conclusion has been adequately addressed and it disapproves the Null Hypothesis.
Vancouver Referencing Style has been used in the Article.
Vancouver Style Referencing (Numeric) Format:
Ref # à Author(s) à Title of Article à Subtitle à Title of Journal à Year à Volume (Issue); Pages
Referencing Used in the Article: (For Example)
5. Swerdlow SH, Campo E, Harris NL, et al., eds. WHO classification of tumors of hematopoietic and lymphoid tissues. 4th ed. Lyon, France: International Agency for Research on Cancer, 2008.
1. Expression of BCL-2 in Classical Hodgkin’s Lymphoma: An Independent Predictor of Poor Outcome.
2. Tumor Microenvironment and Mitotic checkpoint are key factors in the outcome of Classic Hodgkin’s Lymphoma.
3. Gene Expression Profiling defines molecular subtypes of Classical Hodgkin’s Disease.
The research article has answered many concerns along with has confirmed many other previously conducted researches.
The following are some good points about this research article:
Ø As we know that international prognostic score does not apply to limited stages and cannot predict the risk stratification, whereas the research has found that CD68 cells show correlation with long-term disease-specific survival in limited stage disease.
Ø CD68+ shows the applicability to all the stages of Classic Hodgkin’s Lymphoma at all the time including at the time of diagnosis as well as at the time of relapse.
Ø The use of different statistical analysis like chi-square test to find the significant association between two variables, t-test to predict the hypothesis and so on.
Ø Also, in this study by use of gene-expression profiling, we found the MMP-11 and by immunohistochemical, we concluded the importance of CD68+ marker.
Ø The Area of Weakness can be resolved by conducting new research regarding it.
Ø Overall, according to my perspective, this article was good enough to cover all concerns.
AREA OF WEAKNESS:
² In this study, MMP11 stained many different cell types also the macrophages leading to difficulty in identifying the particular cell responsible for this protein production.
² The exact cause of increase or decrease in a number of CD68+ cells in different patients with different subtypes of the disease.
This research has validated and confirmed the correlation between MMP11 and progression-free survival in patients.
This study has also given the clinical importance of CD68, single marker to identify tumor-associated macrophages by immunohistochemical analysis, which can be used in routine diagnostic approach.
The combination uses of this marker and well-known risk factors related to Classic Hodgkin’s Lymphoma can improve the predictive value.
v Trigger gene/protein responsible for the production of CD68 cells in patients with Classic Hodgkin’s Lymphoma.
v The cells causing the increase production of MMP11 involved in apoptotic remodeling of lymphatic tissue.