Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Lucknow
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On Aug 2018




Dr. Arundhathi. S
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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
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Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : March | Volume : 17 | Issue : 3 | Page : OC21 - OC24 Full Version

Inflammatory Markers in Lung Cancer- A Comparative Cross-sectional Study


Published: March 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/59920.17663
Manisha Jain, Mohammed Javed Qureshi, Narendra Khippal, Chand Bhandari, VM Jaanakhi, Karthika Prasad

1. Resident, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India. 2. Associate Professor, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India. 3. Senior Professor, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India. 4. Senior Professor, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India. 5. Resident, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India. 6. Resident, Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India.

Correspondence Address :
Manisha Jain,
E 182, Opposite Shiv Park, Ambabari, Jaipur, Rajasthan, India.
E-mail: manishajain34046@gmail.com

Abstract

Introduction: Lung cancer is the most common cause of cancer mortality worldwide, principally because of its late diagnosis. Chronic inflammation plays a significant role in tumour growth and progression via increasing the levels of inflammatory markers in blood. Inflammatory markers are expected to be valuable prognostic biomarkers in cancer. Markers like Absolute Neutrophil Count (ANC), Absolute Lymphocyte Count (ALC), platelet count, Neutrophil Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) may aid in assessing prognosis of lung cancer.

Aim: To study the inflammatory markers (ANC, ALC, Platelet count, NLR and PLR) in lung cancer and correlate these markers with cancer stage and histopathological type.

Materials and Methods: A hospital-based comparative cross-sectional study was conducted in lung cancer patients at Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India. Sixty patients with lung cancer and sixty controls were included. The clinical characteristics, ANC, ALC, platelet count, NLR and PLR of cases and controls were assessed and compared. Also, the comparison of these inflammatory markers with Tumour, Nodes and Metastases (TNM) staging and histopathological type of lung cancer were documented and results were interpreted. The data analysis was done with the use of Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, (Ver.) 26.

Results: Mean age (years) of the case and control groups was 60.17 and 61.03, respectively. Distribution of gender in cases and controls was comparable. The major histology of lung cancer was Non-Small Cell Lung Cancer (NSCLC, 81.66%) out of which squamous cell carcinoma constituted 55.00% and adenocarcinoma 21.67%, followed by small cell carcinoma at 18.33%. Overall, 46.67% of the patients belonged to TNM staging IVA followed by IIIB (25.00%). The levels of ANC, platelet count, NLR and PLR were significantly elevated and ALC was decreased in cases as compared to control. There was no statistically significant association between the inflammatory markers ANC, ALC, platelet counts, NLR and PLR with the histopathological type of lung cancer. Mean ANC, platelet count, NLR and PLR were found to be significantly elevated in late stages of lung cancer, whereas, ALC had no such association with the stages of lung cancer.

Conclusion: Inflammatory markers (ANC, platelet count, NLR, PLR, ALC) can serve as valuable prognostic biomarkers in lung cancer and can easily be used in resource-limited areas.

Keywords

Absolute neutrophil count, Lymphocyte count, Neutrophil lymphocyte ratio, Platelet lymphocyte ratio, Platelet count

Globally, lung cancer contributed to 2.21 million (11.4%) of all new cases diagnosed in 2020. Lung cancer is the most common cause of cancer mortality worldwide accounting to 1.80 million deaths (18%) in the year 2020 (1). Smoking is the major risk factor for lung cancer which leads to chronic inflammation. Inflammation itself is recognised both as a condition that leads to cancer development and also as a condition that arises due to oncogenic changes in cancer cells. Inflammation plays a critical role in the progression of many cancers, stimulating cancer cell-proliferation and angiogenesis. The ability of oncogenic cells to establish themselves in a niche and subsequently metastasise depends not only on their own intrinsic cellular signalling pathways but also on complex interaction with immune cells. Predominant cells involved in tumourigenesis are neutrophils, lymphocytes and platelets and these cells serve as inflammatory biomarkers in different cancers (2).

Neutrophils are the dominant leukocytes in the blood, and are the first line of defense against inflammation and infection (3). The evaluation of tumour associated neutrophils as prognosis index in many tumours has been clearly assessed high neutrophil number and/or elevated NLR do correlate a poor outcome of the patient (4). Lymphocytes are major cells involved in defense against tumour formation in the body. Decreasing levels of tumour-infiltrating lymphocytes are associated with a poor prognosis in lung cancer (5). A prognostic significance between platelet count and lung cancer has been identified. Elevated pretreatment platelet counts are related to poor Overall Survival (OS) and Disease-Free Survival (DFS)/Progression-Free Survival (PFS)/Time To Progression (TTP) in lung cancer patients and are an independent prognostic predictor of lung cancer patients (6). Other simple indices of measuring the levels of tissue inflammation are the NLR and PLR. In NSCLC, an elevated PLR is associated with poor OS and PFS (7). A meta-analysis demonstrated that high pretreatment NLR was closely related to poorer PFS and OS in patients with lung cancer (8).

Inflammatory markers are expected to be valuable prognostic biomarkers in cancer. A limited number of studies are available, correlating the degree of systemic inflammatory marker levels at the time of diagnosis in patients with lung cancer. Thus, in the present study various blood inflammatory markers (platelet count, ANC, ALC, NLR, PLR levels) have been evaluated in patients with lung malignancy at the time of diagnosis and their relationships are assessed with cancer stage and cell type.

Material and Methods

This was a hospital-based comparative cross-sectional study carried out in the Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India. Approval was taken from Research Review Board (RRB) and Institutional Ethics Committee of the institute (Letter no.140/MC/EC/2020). The study was done from January 2020 to December 2021.

Sample size calculation: Sample size was calculated at 80% study power and alpha error of 0.05% assuming severity of NLR being 86% for detection of lung cancer. The required sample size for this study was 45. This was rounded off to 60 patients in both groups, expecting 20% attrition.

Inclusion and Exclusion criteria: Sixty patients of biopsy-proven lung cancer were recruited after excluding those having active infection, haematological disease, autoimmune disorders, history of thromboembolic disease, those who have already received chemotherapy or radiotherapy or having any other type of cancer. Also, sixty age and gender matched healthy controls (attendants of patients) were enrolled.

After recruitment, the patients and controls underwent blood investigations like complete blood count using Automated Elite 580 Haematology Analyser. The results of ANC, ALC, platelet count, NLR and PLR from lung cancer patients and healthy controls were compared. Also, intragroup comparison of the blood values of inflammatory markers of cases was done with staging and histopathological types.

Statistical Analysis

Collected data were entered in Microsoft excel data sheet which was tabulated for data interpretation. This was then subjected to statistical analysis using appropriate statistical tests and results were interpreted. The presentation of the categorical variables was done in the form of number and percentage (%) and the quantitative data were presented as the means±SD. The data normality was checked by using Kolmogorov-Smirnov test. For statistical significance, p-value of less than 0.05 was considered statistically significant. The statistical tests applied for the results were Mann-Whitney Test (for two groups) used for calculation of smoking status, ALC and NLR in cases and controls, Kruskal Wallis test (for more than two groups) for association of histology and staging of lung cancer with ALC and NLR, independent t-test (for two groups) for calculation of age, ANC, platelet count and PLR in cases and controls, ANOVA test (for more than two groups) for association of histology and staging with ANC, platelet count and PLR, Chi-square test for pack years and gender distribution in cases and controls and Fisher’s-exact test for distribution of BMI in cases and controls. The data analysis was done with the use of SPSS software, IBM manufacturer, Chicago, USA, (Ver.) 26.

Results

The distribution of age and gender of cases and controls was comparable. Proportion of smokers was significantly higher in cases as compared to controls. BMI in cases was significantly lower as compared to controls (Table/Fig 1).

The major histology of lung cancer was NSCLC (81.66%), followed by small cell carcinoma (18.33%); 46.67% of patients belonged to TNM staging IVA followed by IIIB (25.00%), IIIA (20.00%), IVB (5.00%) and IIIC (3.33%) (Table/Fig 2). Mean ANC (cells/μL), platelet count (105×cells/μL), NLR and PLR in cases was significantly higher as compared to controls, whereas that of ALC (cells/μL) was significantly lower as compared to controls (Table/Fig 3). There was no statistically significant association found between the levels of inflammatory markers ANC, ALC, platelet counts, NLR and PLR with the histopathological type of lung cancer (Table/Fig 4). Mean ANC, platelet count, NLR and PLR were found to be elevated in late stages of lung cancer as compared to early stages showing statistically significant association; whereas ALC had no such association with the stages of lung cancer (Table/Fig 5).

Discussion

Inflammation is the hallmark of any neoplastic process going on in the body. The body tries its best to check oncogenesis through its immune system. The immune system of the lung is represented by cells and cytokines, which have different functions under physiological conditions (9). Smoking is the most important modifiable risk factor of lung cancer. This study also showed a greater proportion of smokers in the lung cancer group as compared to the control group and the number of pack years was also significantly higher in the lung cancer group. This is due to the fact that smoking leads to chronic inflammation, which in turn, triggers the process of oncogenesis and that the risk for lung cancer increases with the duration of smoking and the number of cigarettes smoked per day. An average smoker has an approximately 10-fold risk for lung cancer, whereas heavy smokers had atleast a 20-fold risk (10).

The index study concluded that the levels of ANC were significantly elevated in patients with lung cancer as compared to controls, which is similar to a study done by S¸ ahin F and Aslan AF (11). Neutrophils are important cells for oncogenesis. They drive angiogenesis in malignancy by providing a significant source of MMP-9 which acts to release VEGF from the Extracellular Matrix (ECM) (12). In addition to roles in angiogenesis, MMP-9 is also postulated to aid the direct invasion of tumour cells via degradation of ECM/basement membrane, thus helping in metastasis.

The present study also observed that the levels of lymphocytes were significantly lower in the lung cancer patients as compared to the control group, similar to a study by Suzuki R et al., (13). This indicates that low level of ALC is associated with poor prognosis in lung cancer patients. Pretreatment elevated platelet counts in lung cancer patients have been observed in various studies. The present study also supports this observation where the levels of platelet count in lung cancer patients were significantly higher than control group as reported in a systematic review and meta-analysis (6). Thrombocytes increase as a reactive response to cancer in the body due to release of factors like Platelet-derived Growth Factor (PDGF), thrombopoietin etc., and they also play a significant role in the growth, progression and tumour spread, as shown by the association of the prevalence of elevated platelet counts with advancing disease stage reflecting the actual tumour load (14). It was also seen that the NLR and PLR levels were significantly raised in lung cancer group than in the control group which is similar to a study done by Zhu X et al., (15).

In this study, no statistically significant association was found between the inflammatory markers ANC, ALC, platelet counts, NLR and PLR with the histopathological type of lung cancer. This may be due to the fact that all histopathological subtypes of lung cancer exert more or less similar inflammatory response in the body.

In the present study, mean ANC, platelet count, NLR and PLR were found to be elevated in late stages of lung cancer. Whereas, ALC had no such association with the stages of lung cancer. With increasing stages of lung cancer, the degree of systemic inflammation increases which recruit more and more inflammatory cells like neutrophils and platelets with compensatory decrease in lymphocytes. These cells, through various mechanisms are responsible for angiogenesis and metastatic invasion so the levels of these blood inflammatory markers also increase proportionally.

Limitation(s)

This being a single-centred study is an important limitation. Majority of the cases belonged to late stage disease.

Conclusion

This study sheds light on the importance of assessing systemic inflammation in lung cancer patients. As inflammation increases with increasing stages of cancer so the inflammatory markers like ANC, ALC, platelet count, NLR and PLR can be used as prognostic indicators of lung cancer. These are simple and affordable tests which can be applied even in remote health facilities. By correlating the clinical history and physical examination with these inflammatory markers, physicians may get a clue to prognosticate lung cancer patients and hence it can aid in treatment planning and outcome.

References

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Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020. (https://gco.iarc.fr/today, accessed February 2021).
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Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med. 2019;18(3):121-26. Doi: 10.4103/aam.aam_56_18. PMID: 31417011; PMCID: PMC6704802. [crossref] [PubMed]
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Rosales C. Neutrophil: A cell with many roles in inflammation or several cell types? Front Physiol. 2018;9:113. Doi: 10.3389/fphys.2018.00113. PMID: 29515456; PMCID: PMC5826082. [crossref] [PubMed]
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Masucci MT, Minopoli M, Carriero MV. Tumour associated neutrophils. Their role in tumourigenesis, metastasis, prognosis and therapy. Front Oncol. 2019;9:1146. Doi: 10.3389/fonc.2019.01146. PMID: 31799175; PMCID: PMC6874146. [crossref] [PubMed]
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Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, et al. Assessing tumour-infiltrating lymphocytes in solid tumours: A practical review for pathologists and proposal for a standardized method from the International immuno-oncology biomarkers working group: Part 2: Tils in melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and mesothelioma, endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumours. Adv Anat Pathol. 2017;24(6):311-35. Doi: 10.1097/PAP.0000000000000161. PMID: 28777143; PMCID: PMC5638696. [crossref] [PubMed]
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Yuan Y, Zhong H, Ye L, Li Q, Fang S, Gu W, et al. Prognostic value of pretreatment platelet counts in lung cancer: A systematic review and meta-analysis. BMC Pulm Med. 2020;20(1):96. [crossref] [PubMed]
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Wang H, Li C, Yang R, Jin J, Liu D, Li W. Prognostic value of the platelet-to-lymphocyte ratio in lung cancer patients receiving immunotherapy: A systematic review and meta-analysis. PLoS ONE. 2022;17(5):e0268288. https://doi.org/10.1371/journal.pone.0268288. [crossref] [PubMed]
8.
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DOI and Others

DOI: 10.7860/JCDR/2023/59920.17663

Date of Submission: Sep 12, 2022
Date of Peer Review: Nov 04, 2022
Date of Acceptance: Dec 06, 2022
Date of Publishing: Mar 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Sep 24, 2022
• Manual Googling: Nov 03, 2022
• iThenticate Software: Nov 24, 2022 (24%)

ETYMOLOGY: Author Origin

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