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Alteration of LncRNAs Expression Level in Blood of New Case and Medicated Behcet Patients as a Prognostic Biomarker 2 2 Background: Behcet’s disease is a complex systemic inflammatory vasculitis marked by recurrent oral and genital ulcers, and uveitis. This study aims to evaluate the expression levels of long non-coding RNAs (LncRNAs) such as IFNG-AS1 and AC007278.2, along with the IL18 and IL18R1 genes, in the blood of active Behcet’s disease patients compared to HCs. Given the elevated levels of inflammatory cytokines in these patients, exploring the role of LncRNAs could provide insights into their involvement in the disease's pathogenesis and inflammatory response. Methods: This case-control study involved 40 Behcet’s disease patients (20 medicated, 20 new cases) and 40 HCs. 2.5 ml venous blood of all subject were collected, and RNA extracted by using cDNA synthesis kit. Evaluation of genes expression level through qRT-PCR to analyze the expression levels of specific genes associated with inflammation, providing insights into Behçet's disease pathology Results: Elevated expression of IL-18, IL-18R1, Lnc-AC007278.2, and Lnc-IFNG-AS1 showed in new case patients compare to medicated patients and HCs. ROC curve analysis demonstrated high diagnostic efficacy for these biomarkers, particularly IL18R1, indicating their potential for accurate patient identification. Conclusion: This study highlights the potential of LncRNAs IFNG-AS1 and IL18 as non-invasive biomarkers for Behcet’s disease, offering insights into disease pathology and enhancing diagnostic accuracy, especially in new cases. 1 9 2025/10/5 1404/7/13 2025/11/7 1404/8/16 Faezeh Mehdizadeh Faezeh Mehdizadeh Department of Microbiology, Ta.C., Islamic Azad University, Tabriz, Iran. Kamran Javidi-Aghdam Kamran Javidi-Aghdam Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Abolfazl Jafari-Sales Abolfazl Jafari-Sales Department of Microbiology, Ta.C., Islamic Azad University, Tabriz, Iran & Department of Microbiology, Kaz.C., Islamic Azad University, Kazerun, Iran. Attabak Toofani Milani Attabak Toofani Milani Department of Laboratory Sciences and Microbiology, TaMS.C., Islamic Azad University, Tabriz, Iran. Mehrdad Pashazadeh Mehrdad Pashazadeh Infectious Diseases Research Center, TaMS.C., Islamic Azad University, Tabriz, Iran. Mehrdadpashazadeh85@gmail.com Behcet’s disease Autoimmune disorder Long non-coding RNAs (LncRNAs) Real-Time PCR Biomarkers Polygenic disease Davatchi, F., C. Chams-Davatchi, H. Shams, F. Shahram, A. Nadji, M. Akhlaghi, et al., Behcet's disease: epidemiology, clinical manifestations, and diagnosis. 2017. 13(1): p. 57-65.##Alibaz-Oner, F. and H.J.C.r.r. Direskeneli, Advances in the treatment of Behcet's disease. 2021. 23(6): p. 47.##Greco, A., A. De Virgilio, M. Ralli, A. Ciofalo, P. Mancini, G. Attanasio, et al., Behçet's disease: new insights into pathophysiology, clinical features and treatment options. 2018. 17(6): p. 567-575.##Leccese, P. and E.J.F.i.i. Alpsoy, Behçet's disease: an overview of etiopathogenesis. 2019. 10: p. 1067.##Davatchi, F., F. Shahram, C. Chams-Davatchi, H. Shams, A. Nadji, M. Akhlaghi, et al., Behcet's disease: from East to West. Clinical rheumatology, 2010. 29: p. 823-833.##Lopalco, G., O.M. Lucherini, A. Lopalco, V. Venerito, C. Fabiani, B. Frediani, et al., Cytokine signatures in mucocutaneous and ocular behcet's disease. 2017. 8: p. 200.##Bozca, B.C. and E.J.J.o.E.P. Alpsoy, Experimental therapeutic solutions for Behcet's disease. 2021: p. 127-145.##Ortiz-Fernández, L. and A.H.J.F.i.M. Sawalha, Genetics of Behcet's disease: functional genetic analysis and estimating disease heritability. 2021. 8: p. 625710.##Zhang, B., L. Xiao, Q. Qiu, L. Miao, S. Yan, and S.J.A.o.P.M. Zhou, Association between IL-18, IFN-γ and TB susceptibility: a systematic review and meta-analysis. 2021. 10(10): p. 108780886-108710886.##Ihim, S.A., S.D. Abubakar, Z. Zian, T. Sasaki, M. Saffarioun, S. Maleknia, et al., Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment. 2022. 13: p. 919973.##Xu, F., L. Jin, Y. Jin, Z. Nie, and H. Zheng, Long noncoding RNAs in autoimmune diseases. Journal of biomedical materials research Part A, 2019. 107(2): p. 468-475.##Wang, J., S. Yan, J. Yang, H. Lu, D. Xu, and Z. Wang, Non-coding RNAs in rheumatoid arthritis: from bench to bedside. Frontiers in immunology, 2020. 10: p. 3129.##Wu, H., S. Chen, A. Li, K. Shen, S. Wang, S. Wang, et al., LncRNA expression profiles in systemic lupus erythematosus and rheumatoid arthritis: emerging biomarkers and therapeutic targets. Frontiers in Immunology, 2021. 12: p. 792884.##Safa, A., M. Taheri, H. Fallah, T. Salmani, S. Arsang-Jang, S. Ghafouri-Fard, et al., Downregulation of cancer-associated lncRNAs in peripheral blood of multiple sclerosis patients. Journal of Molecular Neuroscience, 2020. 70: p. 1533-1540.##Zhuang, Y.-T., D.-Y. Xu, G.-Y. Wang, J.-L. Sun, Y. Huang, and S.-Z. Wang, IL-6 induced lncRNA MALAT1 enhances TNF-α expression in LPS-induced septic cardiomyocytes via activation of SAA3. European Review for Medical & Pharmacological Sciences, 2017. 21(2).##Peng, H., S. Ren, Y. Liu, H. Zhou, X. Tang, J. Yang, et al., Elevated Expression of the Long Noncoding RNA IFNG‐AS1 in the Peripheral Blood from Patients with Rheumatoid Arthritis. Journal of immunology research, 2020. 2020(1): p. 6401978.##McGonagle, D., S.Z. Aydin, A. Gül, A. Mahr, and H. Direskeneli, 'MHC-I-opathy'-unified concept for spondyloarthritis and Behçet disease. Nature Reviews Rheumatology, 2015. 11(12): p. 731-740.##Abobakr, S., O. Shaker, M.T. Hegazy, and A.M. Hany, A possible role of lncRNA MEG3 and lncRNA MAFG-AS1 on miRNA 147-b in the pathogenesis of Behcet's disease. Immunogenetics, 2024. 76(4): p. 233-241.##Ping, P., L. Wang, L. Kuang, S. Ye, M.F.B. Iqbal, and T. Pei, A novel method for lncRNA-disease association prediction based on an lncRNA-disease association network. IEEE/ACM transactions on computational biology and bioinformatics, 2018. 16(2): p. 688-693.##Rankin, C.R., L. Shao, J. Elliott, L. Rowe, A. Patel, E. Videlock, et al., The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2020. 318(1): p. G34-G40.##Javidi Aghdam, K., B. Baradaran, S. Rahmani, F. Manafzadeh, S.G. Noor Azar, S. Aghayan, et al., Expression pattern of long non-coding RNAs in treatment-naïve and medicated schizophrenia patients. Scientific Reports, 2024. 14(1): p. 27654.##Trenova, A.G., L.D. Miteva, and S.A. Stanilova, Association between TNFA, IL10 and IL18 promoter gene variants and cognitive functions in patients with relapsing-remitting multiple sclerosis. Journal of neuroimmunology, 2020. 347: p. 577357.##Fan, S., P. He, J. Guan, W. Song, H. Zhi, and L. Wang, No association between interleukin-18 levels and risk of cardiovascular disease: A Mendelian randomization study. Hereditas, 2020. 157: p. 1-8.##Thomas, J.M., B.M. Huuskes, C.G. Sobey, G.R. Drummond, and A. Vinh, The IL-18/IL-18R1 signalling axis: diagnostic and therapeutic potential in hypertension and chronic kidney disease. Pharmacology & therapeutics, 2022. 239: p. 108191.##Gangemi, S., R. Merendino, F. Guarneri, P.L. Minciullo, G. DiLorenzo, M. Pacor, et al., Serum levels of interleukin‐18 and s‐ICAM‐1 in patients affected by psoriasis: preliminary considerations. Journal of the European Academy of Dermatology and Venereology, 2003. 17(1): p. 42-46.##Calvani, N., H. Richards, M. Tucci, G. Pannarale, and F. Silvestris, Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis. Clinical & Experimental Immunology, 2004. 138(1): p. 171-178.##You, Y., X. Zhao, Y. Wu, J. Mao, L. Ge, J. Guo, et al., Integrated transcriptome profiling revealed that elevated long non-coding RNA-AC007278. 2 expression repressed CCR7 transcription in systemic lupus erythematosus. Frontiers in Immunology, 2021. 12: p. 615859.## ##

Extensive Splenic Infarction in a Pediatric Patient with Acute Promyelocytic Leukemia: A Case Report Highlighting Dual Hemostatic Dysregulation 2 2 Background: Acute promyelocytic leukemia (APL) is characterized by a life-threatening coagulopathy, traditionally associated with hemorrhagic complications. However, thrombotic events, including arterial infarction, are increasingly recognized as significant contributors to morbidity during induction therapy. Case Presentation: We report a 16-year-old male diagnosed with APL who developed extensive splenic infarction two weeks after initiation of all-trans retinoic acid (ATRA). He presented with persistent fever and left upper quadrant pain. Abdominal imaging revealed a large subcapsular splenic infarct without evidence of macrovascular thrombosis. Despite improving blood counts and resolution of initial cytopenias, systemic inflammation and coagulopathy persisted. ATRA was temporarily discontinued due to suspicion of differentiation syndrome, which may have delayed disease control. With resumption of ATRA and addition of arsenic trioxide (ATO), along with supportive care, the patient achieved complete hematologic remission with undetectable minimal residual disease (MRD) at day 50. Conclusion: Thrombotic complications such as splenic infarction can occur in APL even during early treatment, emphasizing the dynamic and dual nature of hemostatic dysregulation. Clinicians should maintain a high index of suspicion for non-infectious causes of fever and abdominal pain in APL patients. Early recognition and uninterrupted targeted therapy are critical to resolving the underlying prothrombotic state and improving outcomes. 10 13 2025/10/52025/10/15 1404/7/23 2025/11/72025/11/27 1404/9/6 pourya mashategan pourya mashategan Department of Pediatrics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. hassan Abolghasemi hassan Abolghasemi Department of Pediatrics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. HassanAbol@Yahoo.com Acute promyelocytic leukemia Coagulopathy Thrombosis Splenic infarction Disseminated intravascular coagulation All-trans retinoic acid Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget. 2020;11(11):992-1003.##Sanz MA, Montesinos P. Open issues on bleeding and thrombosis in acute promyelocytic leukemia. Thromb Res. 2010;125 Suppl 2:S51-4.##Tallman MS, Abutalib SA, Altman JK. The double hazard of thrombophilia and bleeding in acute promyelocytic leukemia. Semin Thromb Hemost. 2007;33(4):330-8.##Park J, Jurcic JG, Rosenblat T, Tallman MS. Emerging new approaches for the treatment of acute promyelocytic leukemia. Ther Adv Hematol. 2011;2(5):335-52.##Sudipta M, Saurav B. Acute Promyelocytic Leukemia Complicated by Deep Venous Thrombosis, Pulmonary Thromboembolism, and Hematemesis. Indian Journal of Clinical Cardiology. 2024.##Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630-43.##Hambley BC, Tomuleasa C, Ghiaur G. Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care? Front Med (Lausanne). 2021;8:722614.##Bennett JM, Catovsky D, Daniel M-T, Flandrin G, Galton DAG, Gralnick HR, et al. Proposals for the Classification of the Acute Leukaemias French-American-British (FAB) Co-operative Group. British Journal of Haematology. 1976;33(4):451-8.##Falanga A, Barbui T. Coagulopathy of Acute Promyelocytic Leukemia. Acta Haematologica. 2001;106(1-2):43-51.##Wang Z-Y, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111(5):2505-15.##Falanga A, Barbui T. Coagulopathy of acute promyelocytic leukemia. Acta Haematol. 2001;106(1-2):43-51.##Hisada Y, Gangaraju R. Hemostatic abnormalities in acute promyelocytic leukemia: clinical implications and mechanisms. Curr Opin Hematol. 2025;32(5):239-44.##Montesinos P, Bergua JM, Vellenga E, Rayón C, Parody R, de la Serna J, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775-83.##Rashidi A, Silverberg ML, Conkling PR, Fisher SI. Thrombosis in acute promyelocytic leukemia. Thromb Res. 2013;131(4):281-9.## ##

A Novel Chromosomal Translocation t(X;10) in a Pediatric Acute Myeloid Leukemia Patient Complicated by Subarachnoid Intraventricular Hemorrhage 2 2 Background: Acute myeloid leukemia (AML) is a malignancy of hematopoietic stem cells, seen rarely in children. Intraventricular hemorrhage (IVH) is an uncommon but often fatal complication of AML, and its management is difficult because it requires balancing intensive chemotherapy with supportive care for bleeding. Case Presentation: We report the case of an 11-year-old child with newly diagnosed AML who presented with fever, neurological deterioration, and respiratory distress, and was found to have subarachnoid intraventricular hemorrhage. Cytogenetic Findings: Bone marrow karyotyping demonstrated a novel translocation involving chromosomes X and 10 with breakpoints at Xq13 and 10p11.2 or 46,XY,t(X;10)(q13;p11.2). This was confirmed by fluorescence in situ hybridization (FISH). Other recurrent AML-associated abnormalities were not detected. Clinical Course: The patient received antifibrinolytics, platelet support, anticonvulsants, and external ventricular drainage. Flow cytometry of bone marrow aspirate showed 85% blasts expressing CD34, CD117, HLA-DR, CD13, and CD33, consistent with AML. The patient developed refractory shock and cardiac arrest, and death occurred before leukemia-directed treatment could be initiated. Conclusions: This case describes a rare cytogenetic abnormality in AML associated with IVH. A direct causal relationship cannot be inferred from a single report; however, documenting such rare findings adds to the body of knowledge and may help in future studies exploring genetic factors and clinical outcomes in AML. 14 19 2025/10/52025/10/152025/10/26 1404/8/4 2025/11/72025/11/272025/12/7 1404/9/16 Suresh Kumar Prajapati Suresh Kumar Prajapati Parul Institute of Applied Sciences, Parul University, Post Limda, Waghodia Road, Vadodara, Gujarat, India. Charmi Jyotishi Charmi Jyotishi Parul Institute of Applied Sciences, Parul University, Post Limda, Waghodia Road, Vadodara, Gujarat, India. Dharmesh Vaghasiya Dharmesh Vaghasiya Blood Cancer Institute, Surat, Gujarat, India. Reeshu Gupta Reeshu Gupta Parul Institute of Applied Sciences, Parul University, Post Limda, Waghodia Road, Vadodara, Gujarat, India. reeshu.gupta25198@paruluniversity.ac.in Chromosome Translocation Leukemia Myeloid Acute Tseng S, Lee ME, Lin PC. A Review of Childhood Acute Myeloid Leukemia: Diagnosis and Novel Treatment. Pharmaceuticals (Basel). 2023;16(11).##(2022) T-CY. Pediatric Acute Myeloid Leukemia (AML) Classifications. . Pediatr Ther. 2022;S5(002):1.##Meng CY, Noor PJ, Ismail A, Ahid MF, Zakaria Z. Cytogenetic Profile of de novo Acute Myeloid Leukemia Patients in Malaysia. Int J Biomed Sci. 2013;9(1):26-32.##Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer. 2011;2(2):95-107.##Rorvik SD, Torkildsen S, Bruserud O, Tvedt THA. Acute myeloid leukemia with rare recurring translocations-an overview of the entities included in the international consensus classification. Ann Hematol. 2024;103(4):1103-19.##Chen G, Zhou W, Gong D, Li Y, Huang S, Wang N, et al. Loss of X chromosome predicts favorable prognosis in female patients with t(8;21) acute myeloid leukemia. Leuk Lymphoma. 2020;61(5):1168-77.##Abla O, Dror Y, Shago M. Translocation (X;10) in a child with therapy-related acute myeloid leukemia following chemotherapy for Ewing's Sarcoma. Cancer Genet Cytogenet. 2007;178(2):168-9.##Manabe M, Tanizawa N, Nanno S, Hagiwara Y, Asada R, Koh KR. A rare der(10)t(X;10)(p11.2;p11.2) in an elderly patient with therapy-related acute myelomonocytic leukemia. EJHaem. 2022;3(1):256-8.##Bennour A, Sennana H, Zaier M, Ouahchi I, Mrad Z, Ben Youssef Y, et al. Translocation t(X;10)(p10;p10): a rare chromosomal abnormality in a new born female with acute myeloid leukemia. Med Oncol. 2012;29(2):1134-6.##Heim S, Bekassy AN, Garwicz S, Heldrup J, Kristoffersson U, Mandahl N, et al. Bone marrow karyotypes in 94 children with acute leukemia. Eur J Haematol. 1990;44(4):227-33.##Lelong F, Chretien P, Jouault H, Bayani N, Bernaudin F, Lemerle S. A case of peroxidase-positive acute leukaemia expressing only T lineage lymphoid markers. Br J Haematol. 1994;86(1):195-7.##Wong KF, Hayes KJ, Huh YO, Albitar M, Glassman AB. Translocation (X;10)(p10;p10): A rare but nonrandom chromosomal abnormality in acute leukemia of myeloid differentiation. Cancer Genet Cytogenet. 1996;86(2):153-5.##Chen CY, Tai CH, Tsay W, Chen PY, Tien HF. Prediction of fatal intracranial hemorrhage in patients with acute myeloid leukemia. Ann Oncol. 2009;20(6):1100-4.##Huang N, Zhou J, Lu W, Luo L, Yuan H, Pan L, et al. Characteristics and clinical evaluation of X chromosome translocations. Mol Cytogenet. 2023;16(1):36.## ##

Clinical efficacy of Empirical (Piperacillin/tazobactam plus Amikacin) Combined Therapy of Febrile Neutropenia Among Pediatric Patients with Cancer: A Cohort Observational Study 2 2 Background: Febrile neutropenia (FN) is a life-threatening complication in pediatric oncology patients that requires prompt and effective empirical antibiotic treatment. Local data on the success of these regimens are essential for guiding clinical practice. This study assesses the effectiveness and safety of the local empirical combined therapy of Piperacillin/tazobactam plus Amikacin for FN in pediatric cancer patients. Methods: A prospective observational cohort study was conducted on 68 FN episodes in 34 pediatric cancer patients between August 2022 and December 2023. The first-line regimen included intravenous Piperacillin/tazobactam and Amikacin, with Amikacin de-escalated after 72 hours of fever resolution. The primary outcome was the success rate of the first-line regimen, defined as fever resolution and clinical clearance without modification or switch. Safety was evaluated by monitoring creatinine levels. Results: The overall success rate of the empirical regimen without modification was 63.2%, with a failure rate of 22%. The success rate increased to 77.9% when Vancomycin was added (14.7% of cases). Microbiologically documented infections (MDI) were mostly Gram-positive (62.5%), including MRSA isolates resistant to Piperacillin/tazobactam. No treatment-related mortality or significant nephrotoxicity was observed (mean creatinine difference: -0.0107, p=0.338). Additionally, the duration of neutropenia was strongly correlated with the length of hospital stay (r=0.7, p<0.00001). Conclusion: The combined Piperacillin/tazobactam and Amikacin regimen shows a reasonable success rate and a good safety profile in the local setting, supporting its continued use as a first-line option. However, the high prevalence of Gram-positive MDI and the frequent need for Vancomycin addition highlight the importance of ongoing local resistance monitoring and maintaining a low threshold for early Vancomycin use in high-risk patients. 20 26 2025/10/52025/10/152025/10/262025/10/3 1404/7/11 2025/11/72025/11/272025/12/72025/12/7 1404/9/16 Sarah Alfaqaih Sarah Alfaqaih Department of Pediatrics, Faculty of Medicine, Misurata University, Misurata, Libya. sarah.alfaqaih@med.misuratau.edu.ly Nowara Ghlio Nowara Ghlio Department of Pediatric Oncology, National Cancer Institute, Misurata, Libya. Abdulaleem Assadi Abdulaleem Assadi Department of Pediatrics, Faculty of Medicine, Misurata University, Misurata, Libya. Febrile neutropenia Piperacillin/tazobactam Amikacin Pediatric cancer Sultan I, Alfaar AS, Sultan Y, Salman Z, Qaddoumi I. Trends in childhood cancer: Incidence and survival analysis over 45 years of SEER data. PLOS ONE. 2025;20(1):e0314592.##Punnapuzha S, Edemobi PK, Elmoheen A. Febrile Neutropenia. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Paul Edemobi declares no relevant financial relationships with ineligible companies. Disclosure: Amr Elmoheen declares no relevant financial relationships with ineligible companies.: StatPearls Publishing##Zimmer AJ, Freifeld AG. Optimal Management of Neutropenic Fever in Patients With Cancer. J Oncol Pract. 2019;15(1):19-24.##Lucas AJ, Olin JL, Coleman MD. Management and Preventive Measures for Febrile Neutropenia. P t. 2018;43(4):228-32.##El Assaad N, Azzi A, Haddad F, Lebbos J, Haddad E, Chehata N, et al. Febrile neutropenia in the Middle East and North Africa Region: trends, management, and outcomes (2000-2024)-A systematic review. IJID Regions. 2025;16:100682.##Lehrnbecher T, Robinson PD, Ammann RA, Fisher B, Patel P, Phillips R, et al. Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update. J Clin Oncol. 2023;41(9):1774-85.##Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014;58(7):3799-803.##Monroe K, Cohen CT, Whelan K, King A, Maloney L, Deason J, et al. Quality Initiative to Improve time to Antibiotics for Febrile Pediatric Patients with Potential Neutropenia. Pediatr Qual Saf. 2018;3(4):e095.##Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826-35.##Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v8.##Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024.##Keck JM, Wingler MJB, Cretella DA, Vijayvargiya P, Wagner JL, Barber KE, et al. Approach to fever in patients with neutropenia: a review of diagnosis and management. Ther Adv Infect Dis. 2022;9:20499361221138346.##Zengin E, Sarper N, Kılıç SC. Piperacillin/tazobactam monotherapy versus piperacillin/tazobactam plus amikacin as initial empirical therapy for febrile neutropenia in children with acute leukemia. Pediatr Hematol Oncol. 2011;28(4):311-20.##Yildirim I, Aytac S, Ceyhan M, Cetin M, Tuncer M, Cengiz AB, et al. Piperacillin/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies. Pediatr Hematol Oncol. 2008;25(4):291-9.##Demirkaya M, Celebi S, Sevinir B, Hacımustafaoglu M. Randomized comparison of piperacillin-tazobactam plus amikacin versus cefoperazone-sulbactam plus amikacin for management of febrile neutropenia in children with lymphoma and solid tumors. Pediatr Hematol Oncol. 2013;30(2):141-8.##Hamidah A, Rizal AM, Nordiah AJ, Jamal R. Piperacillin-tazobactam plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients. Singapore Med J. 2008;49(1):26-30.##Libuit J, Whitman A, Wolfe R, Washington CS. Empiric vancomycin use in febrile neutropenic oncology patients. Open Forum Infect Dis. 2014;1(1):ofu006.##Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, et al. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023;76(4):674-82.##Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13(Suppl 1):S31-s4.##Paul M, Soares-Weiser K, Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. Bmj. 2003;326(7399):1111.##Alfaqaih S, Ghlio N. A Three-Year Retrospective Analysis of the Common Isolated Microorganisms and the Sensitivity Pattern of Blood Culture in Children with Cancer. Jordan Medical Journal. 2025;59(5).##Carmona-Bayonas A, Gómez J, González-Billalabeitia E, Canteras M, Navarrete A, Gonzálvez ML, et al. Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients. Br J Cancer. 2011;105(5):612-7.##Nattamol H, Saranapoom K, Supannee R, Grerk S, Lukman T, Saba R. Prognostic factors for mortality with febrile neutropenia in hospitalized patients. The Southwest Respiratory and Critical Care Chronicles. 2015;3(9).## ##

Mechanisms of Resistance in CML and the Emerging Role of Asciminib and Other Next-Generation Inhibitors 2 2 Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR-ABL1 fusion gene that confers constitutive tyrosine kinase activity. Although tyrosine kinase inhibitors (TKIs) have revolutionized CML therapy, resistance remains a major clinical challenge, primarily due to kinase domain mutations, leukemic stem cell persistence, and compensatory signalling pathways. Asciminib, a novel allosteric STAMP inhibitor targeting the ABL myristoyl pocket, introduces a distinct mechanism to overcome resistance associated with ATP-site mutations such as T315I. This review highlights the molecular basis of TKI resistance, mechanisms of BCR-ABL1–dependent and –independent resistance, and emerging strategies including combination therapy, degraders, and immunotherapeutic approaches. Real-world data and clinical trials demonstrate asciminib’s efficacy and favorable safety in multi-resistant CML. The future of CML management lies in precision-driven multimodal therapy aimed at eradicating leukemic stem cells and achieving treatment-free remission. 27 35 2025/10/52025/10/152025/10/262025/10/32025/11/7 1404/8/16 2025/11/72025/11/272025/12/72025/12/72025/12/17 1404/9/26 Sanchita Srivastava Sanchita Srivastava Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Riya Nag Riya Nag Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Ale Eba Ale Eba Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Syed Tasleem Raza Syed Tasleem Raza Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. tasleem24@gmail.com Chronic Myeloid Leukemia Asciminib BCR-ABL1 Tyrosine Kinase Inhibitors Drug Resistance Vitus OC. Advancements in targeted therapies for chronic myeloid leukemia: current perspectives. Hematological Insights & Blood Disorders. 2023;1(2):1-3. doi:10.64347/3066-3393/hibd.009##Lai HR, Wu QM, Yang YZ, Li J. Recent advance of newly therapy for chronic myeloid leukemia with BCR-ABL T315I mutation. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023;31(5):1579-83.##Zhang Y, Nadworny S, Liu S, Zhang S, Ye E, Narasimhan N, et al. Discovery of potent and selective next-generation pan-BCR-ABL inhibitors for the treatment of CML and Ph+ ALL. Blood. 2023;142:1428.##Das DK. ALLG CML13 Ascend-CML study unveils success with asciminib. Oncology Times. 2024. doi:10.1097/01.cot.0001005180.51220.7b##Padala S, Cortes J. Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery? Haematologica. 2023;108(11):2913.##Okabe S, Moriyama M, Gotoh A. Characterization of asciminib-resistant Philadelphia chromosome-positive cells. 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Gene Expression Profiling in Patients with CML Experiencing Loss of Treatment Response 2 2 Chronic Myeloid Leukemia (CML) is a hematological malignancy characterized by the presence of the BCR-ABL1 fusion gene, which leads to uncontrolled proliferation of leukemic cells. Despite the effectiveness of Tyrosine Kinase Inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib in controlling CML, treatment resistance remains a major clinical challenge. The mechanisms contributing to resistance include BCR-ABL1 mutations, epigenetic modifications, and dysregulated microRNA (miRNA) expression. Gene expression profiling serves as a crucial tool for understanding disease progression, identifying novel therapeutic targets, and predicting treatment responses. This study explores the molecular basis of TKI resistance in CML through differential gene expression analysis, highlighting key biomarkers such as STAT5, BCL2L1 (Bcl-XL), MCL1, miR-150, and MYC. Additionally, we discuss emerging treatment strategies, including next-generation TKIs (asciminib, olverembatinib), non-BCR-ABL targeted therapies (mTOR inhibitors, JAK2 inhibitors, and HDAC inhibitors), and innovative approaches such as oncolytic viruses, exosome-based therapies, and CRISPR gene editing. Understanding the genetic and molecular landscape of CML can help optimize treatment strategies, improve early resistance detection, and advance personalized medicine for CML patients. 36 46 2025/10/52025/10/152025/10/262025/10/32025/11/72025/10/11 1404/7/19 2025/11/72025/11/272025/12/72025/12/72025/12/172025/12/12 1404/9/21 Butool Zahra Rizvi Butool Zahra Rizvi Department of Biotechnology Khwaja Moinuddin Chishti Language University Lucknow, India. Riya Nag Riya Nag Department of Biochemistry, Eras Lucknow Medical College and Hospital, Era University, Lucknow 226003, Uttar Pradesh, India. Syed Tasleem Raza Syed Tasleem Raza Department of Biochemistry, Eras Lucknow Medical College and Hospital, Era University, Lucknow 226003, Uttar Pradesh, India. tasleem24@gmail.com Sanchita Srivastava Sanchita Srivastava Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Ale Eba Ale Eba Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Saliha Rizvi Saliha Rizvi Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Naseem Fatima Naseem Fatima Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Farheen Khan Farheen Khan Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Chronic Myeloid Leukemia (CML) BCR-ABL1 Tyrosine Kinase Inhibitors (TKIs) Drug Resistance Gene Expression Profiling Epigenetics Personalized Medicine Targeted Therapy. .Bruno Calabretta, Danilo Perrotti; The biology of CML blast crisis. 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Clinical Guidelines for the Prevention and Management of Oral and Dental Complications in Pediatric Oncology Patients: A Narrative Review 2 2 Background: Oral complications are among the most frequent and debilitating adverse effects of cancer therapy in pediatric patients. Chemotherapy, radiotherapy, and hematopoietic stem cell transplantation can result in acute manifestations such as mucositis, infections, bleeding, and pain, as well as long-term sequelae including dental developmental abnormalities, craniofacial growth disturbances, and xerostomia. Comprehensive oral care is therefore a critical component of supportive oncology management. Objectives: This narrative review aims to summarize current evidence regarding oral and dental care strategies for pediatric oncology patients, focusing on preventive assessment, hygiene maintenance, management of treatment-related complications, and long-term follow-up. Methods: Relevant literature was reviewed to consolidate clinical recommendations and evidence-based strategies for oral care in children undergoing oncology treatment. The review highlights practical approaches for pre-treatment dental evaluation, in-treatment oral hygiene and infection control, and post-treatment follow-up, with integration of levels of evidence where available. Results: Pre-treatment dental assessment and elimination of infectious foci significantly reduce oral and systemic complications. During active therapy, gentle oral hygiene practices, fluoride use, antiseptic rinses, and careful management of pain and infection are essential. Oral mucositis remains the most common dose-limiting complication, and preventive strategies such as cryotherapy, keratinocyte growth factors, and low-level laser therapy demonstrate strong supporting evidence. Post-treatment follow-up should include regular dental visits, ongoing preventive care, and monitoring for late sequelae such as dental developmental anomalies and xerostomia. Conclusions: Structured oral care, encompassing pre-treatment assessment, active therapy management, and long-term follow-up, is essential to minimize morbidity and improve quality of life in pediatric oncology patients. Evidence-based interventions, particularly for mucositis prevention and caries management, provide a foundation for standardized clinical practice and highlight areas for future research. 47 52 2025/10/52025/10/152025/10/262025/10/32025/11/72025/10/112025/11/19 1404/8/28 2025/11/72025/11/272025/12/72025/12/72025/12/172025/12/122025/12/24 1404/10/3 Babak Abdolkarimi Babak Abdolkarimi Department of pediatric, Hakim children hospital, Tehran university of medical science, Tehran, Iran. Ali Amanati Ali Amanati Clinical Research Development Center, Amir Oncology Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Dr.amanati14@gmail.com Nahid Derikvand Nahid Derikvand Department of Periodontics, Bo.c., Islamic Azad University, Borujerd, Iran. Niki Panahi Niki Panahi Azad Islamic university, science and research branch, Tehran, Iran. Sepideh Mirzaie Sepideh Mirzaie Azad Islamic university, science and research branch, Tehran, Iran. Pediatric oncology Oral care Dental management Mucositis Chemotherapy Radiotherapy Supportive care Tanboga I, Durmus B, Karakas Z, Saribeyoglu E, Yalcinkaya D, Trosala SC, Guven Y. Xerostomia management for pediatric oncology patients with lactoperoxidase included oral health care products. Dent J. 2012;3:158. doi: 10.4172/2161-1122.1000158.##Carrillo C, Vizeu H, Soares-Júnior LA, Fava M, Odone Filho V. Dental approach in the pediatric oncology patient: characteristics of the population treated at the dentistry unit in a pediatric oncology Brazilian teaching hospital. Clinics. 2010;65(6):569-73. doi: 10.1590/S1807-59322010000600002.##Frascino AV, Fava M, Cominato L, Odone-Filho V. Review of a three-year study on the dental care of onco-hematological pediatric patients. Clinics (Sao Paulo). 2018;73:e721. doi: 10.6061/clinics/2017/e721.##Lopes MC, Teixeira MG, Jacob Filho W, Carvalho Filho ET, Habr-Gama A, Pinotti HW. Prevalence of anal incontinence in the elderly population: an epidemiological study of the elderly population served at the geriatric ambulatory service of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Rev Hosp Clin Fac Med Sao Paulo. 1997;52(1):1-12. PMID: 9334464.##dela Cruz GG, Rozier RG, Slade GD. Dental screening and referral of young children by pediatric primary care providers. Pediatrics. 2004;114(5):e642-52. doi: 10.1542/peds.2004-1269. PMID: 15520094.##Lebrão ML, Litvoc J, Figueiredo GM, Leite RM. Study of morbidity in patients hospitalized at the Clinic Hospital at the Medical School of the USP-1989. Rev Hosp Clin Fac Med Sao Paulo. 1993;48(4):189-98. PMID: 8284592.##Schout D, Hajjar LA, Galas FR, Uip DE, Levin AS, Caiaffa Filho HH, et al. Epidemiology of human infection with the novel virus influenza A (H1N1) in the Hospital das Clínicas, São Paulo, Brazil-June-September 2009. Clinics (Sao Paulo). 2009;64(10):1025-30. doi: 10.1590/S1807-59322009001000014.##Gandhi K, Datta G, Ahuja S, Saxena T, Datta A. Prevalence of oral complications occurring in a population of pediatric cancer patients receiving chemotherapy. Int J Clin Pediatr Dent. 2017;10(2):166-71. doi: 10.5005/jp-journals-10005-1428. PMID: 28890617.##Mortazavi H, Tashvighi M, Azizian M, Khalighi HR, Sabour S, Movahhedian A, Baharvand M, et al. Evaluation of relationship between demographics and dental status in a defined group of Iranian paediatric patients undergoing cancer therapy. J Clin Diagn Res. 2015;9(9):ZC80-3. doi: 10.7860/JCDR/2015/11976.6521.##Braga PE, Latorre MRDO, Curado MP. Câncer na infância: analise comparativa da incidência, mortalidade e sobrevida em Goiânia (Brasil) e outros países. Cad Saúde Pública. 2002;8:33-44.##Ministério da Saúde. Instituto Nacional de Câncer Coordenação de Programas de Controle do Câncer. O Problema do Câncer no Brasil. 4th ed. Rio de Janeiro; 1997.##Smith MA, Ries LAG. Childhood cancer: incidence, survival, and mortality. In: Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 1-12.##Effinger KE, Migliorati CA, Hudson MM, McMullen KP, et al. Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report. Support Care Cancer. 2014;22(7):2009-19.##Ribeiro IL, Limeira RR, Dias de Castro R, Ferreti Bonan PR, Valença AM. Oral and dental considerations in pediatric cancers. Int J Environ Res Public Health. 2017;14(12):1468.##Cubukcu CE, Sevinir B, Ercan I. Disturbed dental development of permanent teeth in children with solid tumors and lymphomas. Pediatr Blood Cancer. 2012;58:80-4.##Kaste SC, Hopkins KP, Jones D, Crom D, Greenwald CA, Santana VM. Dental abnormalities in children treated for acute lymphoblastic leukemia. Leukemia. 1997;11:792-6.##van der Pas-van Voskuilen IG, Veerkamp JS, Raber-Durlacher JE, Bresters D, van Wijk AJ, et al. Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children. Support Care Cancer. 2009;17:1169-75.##Vaughan MD, Rowland CC, Tong X, Srivastava DK, Hale GA, Rochester R, Kaste SC. Dental abnormalities after pediatric bone marrow transplantation. 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Aust Dent J. 2010;55 Suppl 1:66-77. doi: 10.1111/j.1834-7819.2010.01201.x.##Clinical guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation, and/or radiation. [Internet]. 2013. Available from: http://www.aapd.org##American Academy of Pediatric Dentistry. Preserving oral health in cancer therapy. Pediatr Dent. 2004;26(7 Suppl):144-9. PMID: 15656454.##Rankin KV. Nutrition and oral health considerations in children with special health care needs: implications for oral health care providers. Tex Dent J. 2004;121(6):468-9.##Moursi AM, Fernandez JB, Daronch M, Zee L, Jones CL. Dental and oral care for chronically ill children and adolescents. Pediatr Dent. 2010;32(4):333-42. PMID: 20836954.##Hong CH, da Fonseca M. Considerations in the pediatric population with cancer. Dent Clin North Am. 2008;52(1):155-81. doi: 10.1016/j.cden.2007.10.001.##Redding SW. Oral complications of cancer therapy. Tex Med. 2003;99(5):54-7. PMID: 12772642.##Mubaraki S, Pani SC, Alseraihy A, Abed H, Alkhayal Z. The efficacy of two different oral hygiene regimens on the incidence and severity of oral mucositis in pediatric patients receiving hematopoietic stem cell transplantation: a prospective interventional study. Spec Care Dentist. 2020;40(6):566-73. doi: 10.1111/scd.12525.##Ali MH, Nurelhuda NM. Oral health status and its determinants in children with leukemia at the Radiation and Isotope Center Khartoum, Sudan. Sudan J Paediatr. 2019;19(2):93-100. doi: 10.24911/SJP.106-1568288518. PMID: 31969737.##Kowlessar A, Naidu R, Ramroop V, Nurse J, Dookie K, Bodkyn C, Lalchandani S. Prevalence of oral complications occurring in a population of pediatric cancer patients receiving chemotherapy. Clin Exp Dent Res. 2019;5(6):665-9. doi: 10.1002/cre2.23## ##

Rasayana-Based Adjuvant Strategies in Cancer Care: An Ayurvedic–Oncologic Perspective 2 2 Background: Cancer is a serious global health issue, and as multimodal therapies have advanced, treatment-related toxicities have a significant influence on function, compliance, and quality of life. Integrative oncology looks for supportive treatment and resilience-promoting supplementary techniques that are supported by research. Rasayana is the rejuvenating branch of Ayurveda that emphasizes on ojas (vitality), immunological balance, and metabolic homeostasis. It is probably useful for cancer care. Objective: To integrate the safety considerations, emerging clinical cues, conceptual rationale, and implementation pathways of Rasayana-concordant botanicals and regimens as cancer care-modifying adjuncts. Methods: Using iterative PubMed, Cochrane, EMBASE, AYUSH Portal, ctri.nic.in, ClinicalTrials.gov and WHO ICTRP searches until August 2025, a review was conducted in accordance with SANRA principles. Human clinical and translational data on Rasayana-compatible therapies given in addition to conventional oncologic treatments were, with focus on symptom clusters, safety, mechanistic plausibility, and herb–drug interactions. Classical Ayurvedic terms (e.g., Medhya, Balya, Ojovardhaka, and Raktaprasadana) were linked to their biological correlates and patient-reported outcomes using thematic data synthesis. Results: Major Rasayana herbs with immunomodulatory, antioxidant, neuroendocrine, and mucosal-protective properties include Withania somnifera, Curcuma longa, Phyllanthus emblica, Tinospora cordifolia, and Ocimum tenuiflorum. Preliminary clinical data indicate improvements in symptoms. Safety themes highlight the importance of product authentication, pharmacovigilance, and monitoring potential herb-drug interactions, particularly those involving CYP3A4 and P-gp regulation. Conclusion: In integrative oncology, Rasayana-based therapies show early supportive care and physiologically believable potential. Under multidisciplinary supervision, their usage should continue to be customized, safety-monitored, quality-assured, and adjunctive. Well-planned, oncology-focused clinical trials are required. 53 68 2025/10/52025/10/152025/10/262025/10/32025/11/72025/10/112025/11/192025/11/4 1404/8/13 2025/11/72025/11/272025/12/72025/12/72025/12/172025/12/122025/12/242025/12/21 1404/9/30 Himani Sharma Himani Sharma Department of Shalakya Tantra, Sanjeevani Ayurvedic Medical College, Gajraula, Uttar Pradesh, India. Raja Ram Mahto Raja Ram Mahto Department of Kayachikitsa, All India Institute of Ayurveda, New Delhi, India. Sudhanshu Kumar Jha Sudhanshu Kumar Jha Centre for Integrative Oncology, All India Institute of Ayurveda, New Delhi, India. Sonam Chauhan Sonam Chauhan Department of Kayachikitsa, All India Institute of Ayurveda, New Delhi, India. Prachi Khandelwal Prachi Khandelwal Department of Kayachikitsa, All India Institute of Ayurveda, New Delhi, India. Sanjay Kumar Tiwari Sanjay Kumar Tiwari Department of Kayachikitsa, All India Institute of Ayurveda, New Delhi, India. Sktiwari17394@gmail.com Rasayana Ayurveda Integrative Oncology Immunomodulation Redox signaling Chemotherapy toxicity Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide. CA Cancer J Clin. 2024;74(3):229-263.##World Health Organization. Cancer fact sheet. Geneva: WHO; 2023.##Perales MA, Satwani P, Tamari R, et al. Treatment-related toxicities and long-term survivorship in oncology. 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A Meta-Analysis on the Prognostic and Predictive Role of Stem-like CD8+ T Cells in Cancer Immunotherapy: Correlating Clinical Outcomes 2 2 Background: Stem-like CD8+ T cells, marked by TCF1 and PD-1, possess self-renewal and effector differentiation abilities, crucial for cancer immunotherapy. Despite tumor microenvironment constraints, their abundance often correlates with favourable outcomes. Aim: To assess the prognostic and predictive relevance of stem-like CD8+ T cells in patients receiving immunotherapy for cancer. Methodology: 721 publications from PubMed, Embase, Scopus, and Web of Science (2015–2025) were evaluated in accordance with PRISMA 2020 guidelines. 8 studies were included in the meta-analysis. Two independent reviewers conducted data extraction. Pooled hazard ratios (HRs) and confidence intervals (CIs) were calculated using RevMan software, and the I2 statistic was employed to measure heterogeneity. The ROBINS-I instruments and the Newcastle-Ottawa Scale were used to assess the quality of the study. Results: 8 of the 13 included papers qualified for meta-analysis. Follow-up periods varied from six months to five years, and sample sizes ranged from 12 to 94 patients. Multiplex immunofluorescence, scRNA-seq, or flow cytometry were used to quantify stem-like CD8+ T cells. Hazard ratios (HRs) in the woodland plot ranged from 1.18 to 28.50. High HRs of 4.31 (95% CI: 2.68–6.92) and 28.50 (95% CI: 3.30–246.15) were observed in two investigations, suggesting a significant adverse prognostic effect. With considerable heterogeneity (I2 = 89%, Chi2 = 61.38, P < 0.00001), the pooled HR was 1.34 (95% CI: 1.22–1.47). Conclusion: In cancer immunotherapy, stem-like CD8+ T cells serve as both therapeutic targets and significant prognostic indicators. Standardized methods for evaluation and strategies to lessen immunosuppressive effects in the tumor microenvironment are necessary for clinical use. 69 81 2025/10/52025/10/152025/10/262025/10/32025/11/72025/10/112025/11/192025/11/42025/08/19 1404/5/28 2025/11/72025/11/272025/12/72025/12/72025/12/172025/12/122025/12/242025/12/212025/11/8 1404/8/17 Sonika Sharma Sonika Sharma Department of Anatomy, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. soniyasharma19922@gmail.com Prithpal Singh Matreja Prithpal Singh Matreja Department of Pharmacology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. Sudhir Singh Sudhir Singh Department of Microbiology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. 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Unravelling the Role of IL-6, TNF-alpha and CRP in Pathogenesis of Coronary Artery Disease: A Systematic Review 2 2 Background: India has high incidence of cardiovascular disease and coronary artery disease (CAD). Coronary artery disease is attaining epidemic proportions in India. Higher levels of C-reactive protein were connected to an augmented risk of coronary heart disease (CHD).  TNF-alpha & IL-6 contribute in the pathogenesis of CHD and their levels are closely linked with the extent of coronary heart disease. Aim and objectives: This objective of this review is to analyze the status of inflammatory markers and to establish their relation with the extent of CAD. Methodology: The literature search for this review was done through databases incorporated are PubMed, Web of sciences, Scopus, Medline, Research Gate and Google scholar. The keywords used were “coronary artery disease”, “inflammatory markers,” and “cytokines in inflammation”. The Preferred Reporting Items for Systematic Research and Meta-Analysis (PRISMA) were used to build this review article. Results: There were 1860 articles found which were relevant to the aim of our review, out of which only 57 fulfilled the inclusion criteria. A substantial variability across the studies was found. To figure out its correlation with inflammatory processes, these studies employed a variety of inflammatory markers. Most studies found a high level of inflammatory markers such as IL-6, TNF-alpha, and CRP in patients with coronary artery disease and cardiovascular disease. Conclusion: Data from the literature searched highlighted a significant association between inflammatory markers and CAD. 82 103 2025/10/52025/10/152025/10/262025/10/32025/11/72025/10/112025/11/192025/11/42025/08/192025/10/12 1404/7/20 2025/11/72025/11/272025/12/72025/12/72025/12/172025/12/122025/12/242025/12/212025/11/82025/12/11 1404/9/20 Priya Anjali Priya Anjali Department of Biochemistry, Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. priyaanjali01116@gmail.com Pothu Ushakiran Pothu Ushakiran Department of Biochemistry, Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University Moradabad, UP, India. Jigar Haria Jigar Haria Department of Medicine, Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University Moradabad, UP, India. Coronary artery disease IL-6 TNF-alpha CRP Inflammation ## ##