Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis, but degenerative spinal changes and vascular calcifications can result in artefactual overestimation of bone mineral density (BMD) (3-5). Extreme elevations in T-scores in the absence of metabolic bone disease are exceptionally uncommon. We report a 95-year-old male with multiple chronic comorbidities who presented with poor oral intake and a urinary tract infection. DXA revealed a lumbar spine T-score of + 11.0. Laboratory and imaging evaluation showed no evidence of osteopetrosis, Paget's disease, secondary hyperparathyroidism, hematologic malignancy, or other metabolic bone disorders. Computed tomography demonstrated extensive abdominal aortic and iliac artery calcifications, vertebral deformities, endplate sclerosis, and severe degenerative changes. The extreme lumbar T-score was determined to be artefactual, caused by a combination of advanced vertebral degeneration and vascular calcification. This appears to be the first reported case of a lumbar spine T-score exceeding + 10 in a nonagenarian without metabolic bone disease. Clinicians should correlate DXA findings with clinical, laboratory, and imaging data to avoid misdiagnosis.

Saxagliptin mitigates doxorubicin-induced cardiotoxicity by modulating NLRP3/caspase-1/IL-1β and TLR-4/NF-κB pathways.

The microbiome in head and neck squamous cell carcinoma: Biological drivers, therapeutic interactions, and emerging clinical applications.

C-type lectin receptors (CLRs) present on myeloid cells provide crucial signals for the induction of innate and adaptive immune responses. Their broad ligand specificity places them in a perfect position to sense both microbial intruders and signs of tissue injury or cell death. In this article, we review the mechanisms that link CLR engagement to tailored cellular responses against those perceived threats. We discuss not only how molecular interplay between signaling by CLRs and by other pattern recognition receptors fine-tunes host-protective responses but also how these receptors can lead to pathological immune responses. An understanding of how these responses are regulated may offer strategies for treating not just infectious diseases but also autoimmune or malignant disorders.

Background Acute myeloid leukemia (AML) is a malignant disorder originating from myeloid hematopoietic stem and progenitor cells. Despite the availability of current treatment options, a significant number of patients fail to achieve complete remission after initial chemotherapy. CD33, a transmembrane protein highly expressed on AML cells, serves as a promising therapeutic target. This study aimed to develop and evaluate chimeric antigen receptor T cells (CAR-T) and antibody-drug conjugates (ADC) based on humanized antibodies, specifically targeting CD33, to assess their potential efficacy against AML. Methods Monoclonal antibodies specific to human CD33 were generated by immunizing mice and then humanized. These humanized antibodies were then used to construct CAR-T cells and ADCs, and their cytotoxic properties were evaluated both in vitro and in vivo . In the in vivo experiments, mice bearing Molm13-Luciferase tumor cells were assigned to different treatment groups and were administered with saline, Gemtuzumab-MMAE, or Clone3HM-MMAE. Results The in vitro experiments revealed that several antibody clones, including Clone2HM, Clone3HM, Clone5HM, Clone6HM, and Clone7HM, displayed strong cytotoxic effects against Molm13-Luciferase tumor cells when conjugated with MMAE, outperforming the positive control antibody Gemtuzumab-MMAE. In the in vivo studies, mice treated with Clone3HM-MMAE showed a significant reduction in tumor signals, which nearly disappeared in the latter stages of the experiment. This led to a substantially longer survival time compared to other groups. Additionally, the body weight of mice in all treatment groups remained stable throughout the treatment period, indicating a favorable safety profile. Conclusion The CAR-T cells and ADCs developed in this study, based on humanized antibodies, showed significant anti-tumor efficacy in the AML model. Clone3HM-MMAE, in particular, demonstrated excellent anti-tumor activity along with a strong safety profile. These results strongly support the further development of targeted therapeutic strategies for AML.

Meis1 Negatively Regulates Epithelial-Mesenchymal Transition via Wnt/β-catenin Pathway in Oral Submucous Fibrosis

While oral submucous fibrosis (OSMF) in Asia associated to betel nut usage has been extensively characterized both clinically and histologically, the effects of snus (a traditional Scandinavian oral tobacco product) use in Europe are far less well understood. With the growing popularity of snus across Europe, its impact on oral mucosal pathology has become an issue of increasing clinical relevance. In this study, 50 patients were examined, presenting with clinically detectable oral mucosal alterations, associated with habitual snus use. Clinically, the lesions typically appeared as leukoplakic, firm mucosal changes with surface corrugation. In the most severe cases, biopsies were obtained and histopathologically and immunohistochemically analyzed. This evaluation revealed lymphocytic infiltration, epithelial hyperplasia with keratinization, and varying degree of submucosal fibrosis. These findings demonstrate that snus use can induce significant pathohistological manifestations in the oral mucosa, closely analogous to those of the established potentially malignant disorder OSMF. Additional periodontal and dental effects, including gingival recession, erosions, and tooth discoloration, were also recorded. This study provides novel insights into the potential link between snus use and OSMF-like pathology and underscores the importance of vigilant clinical monitoring of affected individuals.

Hematopoietic stem cells (HSCs) are critical for lifelong blood cell generation. After mutation accumulation and functional disruption, HSCs may transform into leukemic stem cells (LSCs), leading to malignant hematological disorders. However, both HSCs and LSCs are highly heterogeneous, which hinders our comprehensive understanding of their biological characteristics and clinical application. Here, we identified multimerin 1 (Mmrn1) as a reliable marker for the most primitive HSCs and LSCs. We found that Mmrn1 was abundantly present in human and mouse HSCs. Interestingly, HSCs with high levels of Mmrn1 displayed increased quiescence and regenerative capacity, accompanied by megakaryocytic lineage commitment. Importantly, Mmrn1 deficiency gradually impairs HSC self-renewal under stress of transplantation due to reduced quiescence. Additionally, we noticed that Mmrn1 was specifically upregulated in acute myeloid leukemia (AML) cells, and its overexpression predicted poor patient prognosis. Further investigation revealed that Mmrn1 marked a subset of quiescent LSCs responsible for AML initiation and development, and that deletion of Mmrn1 delays AML progression. Collectively, these data broaden our knowledge of stem cell heterogeneity in the context of normal and malignant hematopoiesis and advance the precision diagnosis and therapy of AML in the clinic.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that may affect any organ. Prostatic involvement is uncommon and under-recognised. The presentation often mimics benign prostatic hyperplasia or prostate carcinoma, causing diagnostic uncertainty. This systematic review synthesises evidence on IgG4-related prostatitis, focusing on clinical manifestations, diagnostic approaches, treatment, and outcomes. Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Ovid were searched from inception to 12 February 2025. Eligible studies included English-language case reports, case series, and observational studies describing prostatic involvement in IgG4-RD. Data on demographics, clinical and laboratory findings, management, and outcomes were extracted and analysed descriptively. Fifty studies reporting 66 cases were included. Median age was 64 years (range 20-82). Serum IgG4 concentrations were elevated in most (median 832 mg/dL, range 5-4,500), while prostate-specific antigen (PSA) levels varied widely (0.01-180 ng/mL). Multiorgan involvement occurred in 57.8%, isolated disease in 6.2%. Lower urinary tract symptoms were most frequent (39.6%). Glucocorticoids, mainly prednisone, were the main therapy (69.2%), followed by surgery, chiefly transurethral resection of the prostate. Complete and partial responses occurred in 50.9% and 43.4%. Treatment type correlated with outcome (χ²=49.70; p<0.001). Malignancy (18.5%) was associated with higher mortality (p=0.028). IgG4-related prostatitis is a rare and likely under-recognised manifestation of IgG4-RD. Its overlap with benign and malignant prostatic disorders delays diagnosis. Serum IgG4 and PSA are unreliable markers of disease and monitoring. Glucocorticoids remain first-line therapy, with surgery in obstructive cases. Multicentre studies are needed to define prevalence, natural history, and optimal management.

Oral lichen planus (OLP) is a relatively common chronic inflammatory condition of unknown origin and is classified among oral potentially malignant disorders (OPMDs). Emerging evidence suggests that oxidative stress (OS) and compromised antioxidant defense may play a role in its pathogenesis. OPMDs represent morphologically altered tissues with a risk of progression to oral cancer. Therefore, identifying high-risk lesions with a greater likelihood of malignant transformation is crucial. This study aimed to evaluate and compare OS levels by assessing the immunohistochemical (IHC) expression of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation (LPO), in OLP tissues versus normal oral mucosa. The study included 30 formalin-fixed, paraffin-embedded tissue samples from histopathologically confirmed cases of OLP and 10 normal oral mucosa samples serving as the control group. All tissue sections were subjected to immunohistochemical staining using the 4-HNE antibody and examined under a light microscope. Statistical analysis was performed using Fisher's exact test. A significantly elevated cytoplasmic expression of 4-HNE protein was observed in the epithelial cells of lichen planus (LP) tissues compared to normal oral mucosa (P < 0.001). Approximately 90% of the normal tissue samples showed no detectable 4-HNE immunoreactivity. These oxidative modifications suggest underlying pathophysiological changes primarily localized to the basal cell layer and the epithelial-connective tissue interface in LP tissues. Further research is needed to explore the role of OS across different clinical and histopathological variants of LP, to enhance early prediction of malignant transformation.

Oral potentially malignant disorders (OPMDs) can lead to oral cancer, which is one of the most common cancers worldwide. Prevention is crucial in the avoidance of malignant transformations of OPMDs. Artificial intelligence (AI) provides a new and noninvasive tool for analyzing medical data, such as patient data, radiologic images, and clinical photographs. These AI-based tools can help in the decision-making process. However, histological examination is still the gold standard for diagnosing OPMDs. This systematic review and meta-analysis aimed to investigate the diagnostic accuracy of artificial intelligence on intraoral photographs of patients with OPMDs. A systematic search was conducted on 5 major databases (MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science) on November 10, 2023. Included studies compared AI methods to histology examination as the reference. A quantitative analysis was carried out to assess sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) calculated with 95% confidence intervals (CIs). Six eligible articles were included, with 898 images out of 4,046 tested using AI-based architectures. Five studies investigated at least 2 AI models. The overall sensitivity, specificity, DOR, LR+, and LR- were 0.94 (95% CI, 0.88 to 0.95), 0.95 (95% CI, 0.85 to 0.98), 212.39 (95% CI, 56.39 to 800.00), 16.89 (95% CI, 5.72 to 48.68), and 0.08 (95% CI, 0.05 to 0.13) for the best-performing AI-based architectures in terms of sensitivity, respectively. AI-based diagnostic tools have high negative predictive value that could help identify OPMD lesions using intraoral photographs.Knowledge Transfer Statement:This systematic review on AI-based methods to diagnose oral potentially malignant disorders showed that although their high negative predictive value could reduce unnecessary specialist consultations, clinical judgment remains paramount. Further prospective studies are needed to evaluate the integration of AI diagnostics into routine care and screening and policies to enhance efficiency and support early detection and prevention of oral cancer.

Background: Oral potentially malignant disorders (OPMDs) often exhibit heterogeneous clinical features, making the early detection of dysplasia very difficult. Several chemiluminescence-based devices, like ViziLite®, have been suggested as non-invasive adjuncts that can enhance the visualization of suspicious mucosal changes. However, their true diagnostic value remains unclear. Methods: A systematic review and meta-analysis were conducted in line with PRISMA 2020 guidelines. Thirteen clinical studies met the inclusion criteria, necessitating chemiluminescence as index test and histopathology as reference standard, with extractable 2 × 2 diagnostic data. For all OPMDs and leukoplakia-only subgroups, pooled sensitivity and specificity, DOR, SROC curves, and device-specific diagnostic accuracy were determined. Results: Of all the OPMDs, chemiluminescence demonstrated a high pooled sensitivity of 0.82 and a low specificity of 0.48 with considerable heterogeneity among studies. The results in the leukoplakia subgroup improved sensitivity of 0.87 and a specificity of 0.51 were recorded with a more concave SROC curve, which illustrated a better discriminative ability in keratinized lesions. Comparison of devices illustrates accuracy was best for ViziLite + Lugol iodine (~0.82) followed by standard ViziLite (~0.62) and ViziLite Plus (~0.53). Conclusions: Chemiluminescence, while it may demonstrate good sensitivity, has repeatedly shown to have limited specificity in a consistent manner, particularly in populations with mixed OPMD where inflammatory and benign lesions inflate the false-positive rates. Notably, diagnostic performance was higher in leukoplakia, suggesting that keratinized lesions benefit most from this adjunctive tool. Overall, chemiluminescence may facilitate lesion visualization and biopsy site selection but cannot supplant histopathological examination as a definitive diagnostic modality.

Multiple myeloma is a malignant plasma cell disorder primarily involving the bone marrow and skeleton, leading to anemia, renal dysfunction, and lytic bone lesions. Extramedullary disease, seen in about 9% of cases, reflects aggressive disease biology with poor prognosis. Common sites include the pleura, liver, and gastrointestinal tract, while pericardial involvement is exceedingly rare and often detected postmortem. Fewer than 25 cases of pericardial effusion or cardiac tamponade due to multiple myeloma have been reported, usually in advanced disease. The mechanism likely involves hematogenous spread or direct extension from adjacent lesions, often associated with high-risk cytogenetic abnormalities. This case presents an unusual first manifestation of multiple myeloma as pericardial effusion with tamponade physiology, emphasizing the need to consider hematologic malignancy in unexplained pericardial effusion, especially in resource-limited settings. A 60-year-old Ethiopian man presented with a 6-month history of progressive dry cough, dull chest pain, and worsening shortness of breath. He had been repeatedly treated for pneumonia and pulmonary tuberculosis without improvement. Chest computed tomography revealed a large pericardial effusion with features of cardiac tamponade. Echocardiography confirmed pericardial fluid causing right atrial and ventricular collapse. Pericardiocentesis drained 800mL of hemorrhagic fluid, and cytology showed atypical plasma cells. Further evaluation, including serum protein electrophoresis and bone marrow biopsy, confirmed multiple myeloma. The patient was managed with Pericardiocentesis and systemic chemotherapy, showing clinical and radiologic improvement, highlighting the rarity of pericardial involvement as an initial presentation of multiple myeloma. Pericardial involvement in multiple myeloma is an extremely rare and serious manifestation, usually signifying advanced or aggressive disease. While malignant pericardial effusions are commonly due to solid tumors, multiple myeloma should also be considered when no other cause is identified. Early echocardiography-guided pericardiocentesis is lifesaving, and definitive procedures such as a pericardial window may prevent recurrence. This case highlights the importance of suspecting hematologic malignancy in patients with unexplained pericardial effusion or cardiac tamponade. Early recognition and prompt initiation of systemic therapy can improve survival, particularly in resource-limited settings where diagnostic challenges are common.

Background and objectiveChronic myelomonocytic leukemia (CMML) is a malignant clonal disorder characterized by both myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN) features. Due to its relatively low incidence, there remains a lack of consensus regarding diagnostic criteria and therapeutic strategies within the academic community, which poses significant challenges in clinical management. This study aims to investigate the clinical manifestations, diagnostic approaches, therapeutic interventions, and prognostic factors associated with CMML, with the goal of providing evidence-based insights for future basic research and clinical practice in the field of hematology.MethodsClinical data from 271 CMML patients treated at five tertiary hospitals between January 2015 and May 2025 were collected and analyzed. The clinical characteristics, treatment modalities, and outcomes were systematically reviewed. Comprehensive prognostic evaluation was conducted using the Kaplan–Meier method, Log-rank test, and Cox proportional hazards regression model.ResultsA total of 271 CMML patients were enrolled, including 178 males (65.68%) and 93 females (34.32%), with a median age at diagnosis of 66 years (range: 26–89). According to the FAB classification, 109 cases (40.22%) were classified as myelodysplastic-type CMML (MD-CMML), and 162 cases (59.78%) as myeloproliferative-type CMML (MP-CMML). Based on the WHO classification, the distribution was as follows: 59 cases (21.77%) of CMML-0, 66 cases (24.35%) of CMML-1, and 146 cases (53.87%) of CMML-2. First-line treatment primarily involved chemotherapy, while 107 patients received only supportive care. Treatment response was evaluable in 199 patients: 97 cases achieved complete remission (CR), 63 cases achieved partial remission (PR), 32 cases had stable disease (SD), and 7 cases experienced disease progression (PD). Follow-up was completed by June 30, 2025. Among the 271 patients, 159 cases (58.67%) were alive, 97 cases (35.79%) had died, and 15 cases (5.54%) were lost to follow-up. The median overall survival (OS) was 23.5 months (range: 0.5–109). Multivariate analysis identified that factors associated with poor OS included elevated neutrophil count, increased monocyte count, decreased hemoglobin (HB) levels, elevated lactate dehydrogenase (LDH), increased β2-microglobulin (β2-MG), and peripheral blood blast count ≥5% (p < 0.05), while the decreased HB and peripheral blood blast count ≥5% was independent adverse prognostic factors for OS.ConclusionCMML is a highly heterogeneous disease with generally unfavorable clinical outcomes. Although chemotherapy can induce remission in some cases, long-term survival remains limited. The enrollment in clinical trials should be encouraged to improve patient prognosis.

Background: Plasma cell disorders encompass a spectrum of diseases ranging from benign to malignant. Among malignant plasma cell disorders, multiple myeloma is the most common and well-recognized entity. Aim: To identify the pattern of immunoglobulin production in secretory myeloma in Basra and correlate findings with hematological and clinical data. Methods: A retrospective study of 143 patients with plasma cell disorders was conducted at the Department of Pathology, Basrah Oncology Center, Iraq. Clinical data, relevant laboratory parameters (erythrocyte sedimentation rate, renal function tests, and serum calcium), bone marrow examination findings, radiological findings of bony lesions, and results from serum/urine protein electrophoresis and immunofixation or flow cytometric immunophenotyping were analyzed in conjunction with medical records. Results: Abnormal urine protein electrophoresis was found in 93.4% of patients, with most M bands located in the gamma region. The most prevalent subtype was IgG kappa, accounting for 68% of cases. This was followed by IgG lambda (17%), IgM lambda (6.5%), IgM kappa (3.2%), IgA kappa (1.3%), and free light chains (1.3%). Laboratory parameters showed wide variability, with a median hemoglobin of 9.1 g/dL, serum calcium of 9.9 mg/dL, and erythrocyte sedimentation rate of 80 mm/hr. Significant associations were found between immunofixation electrophoresis subtypes and erythrocyte sedimentation rate, serum calcium, and urea. Notably, the IgA kappa group had higher serum calcium (mean 12.45 mg/dL, p = 0.020). Radiological findings revealed multiple bony lesions in the majority of patients. Conclusions: Serum protein electrophoresis is a useful initial screening tool for detecting paraproteinemia, but it lacks sensitivity for accurately characterizing monoclonal proteins. Immunofixation, by contrast, provides higher sensitivity and allows precise identification of monoclonal immunoglobulin subtypes. In our cohort, IgG kappa was the predominant subtype, aligning with global trends, whereas patients with the IgA isotype exhibited more severe laboratory abnormalities.

Advances in oncological and haematological treatments have markedly improved childhood survival, yet gonadotoxic therapies often compromise testicular function. Testicular tissue extraction (TTE) with cryopreservation is increasingly offered to prepubertal boys at high risk of infertility; however, data on long-term endocrine and fertility outcomes remain limited. This study evaluated the long-term endocrine and exocrine testicular function of males who underwent TTE prior to gonadotoxic therapy. This was a retrospective, observational, single-centre study including 50 males treated between 2009 and 2022 at Lille University Hospital (median age at TTE: 5.6 years; median age at last follow-up: 14.6 years). Underlying conditions comprised malignant haematological disorders (52%), non-malignant diseases (34%), and solid tumours (14%); 80% underwent allogeneic haematopoietic stem cell transplantation. Serial clinical assessments and biochemical markers of Leydig and Sertoli cell function (LH, FSH, testosterone, inhibin B, AMH) were recorded from puberty onset to young adulthood. Data were stratified by treatment intensity, pubertal timing, and disease type. Post-pubertal semen analysis was performed in consenting individuals. All participants experienced spontaneous pubertal onset. Sertoli cell dysfunction, evidenced by elevated FSH and persistently low inhibin B, was detectable early in puberty and persisted into adulthood. At Tanner stage 5, 18% had elevated LH, 75% elevated FSH, and 89% low inhibin B; comparable rates were observed in adulthood. Radiotherapy was associated with higher gonadotropin levels at equivalent chemotherapy doses, and Sertoli cell impairment was more pronounced in malignant disease and peri-pubertal treatment. Among 12 semen analyses, spermatozoa were detected in 42%, all in non-malignant cases without radiotherapy. Males undergoing TTE prior to gonadotoxic therapy frequently develop persistent Sertoli cell dysfunction, with limited fertility potential in many cases. These findings underscore the importance of systematic, long-term andrological surveillance and personalised fertility counselling in this high-risk population.

Oral cancer is a significant global health concern, particularly in countries like India, where tobacco and betel nut use are prevalent. Despite advances in therapy, the prognosis remains poor, largely due to late-stage diagnosis. Early detection is key to improving survival rates and reducing the burden of treatment. In recent years, Artificial Intelligence (AI) has emerged as a revolutionary tool in medical diagnostics, with promising applications in oral oncology. This article aims to explore the role of AI in the early detection of oral cancer, its current applications, diagnostic accuracy, limitations, and the future direction of its integration into routine oral healthcare. An extensive review of the current literature was conducted, focusing on AI techniques such as machine learning (ML), deep learning (DL), and convolutional neural networks (CNNs), as well as their applications in analyzing intraoral images, radiographs, histopathology slides, and salivary biomarkers. Clinical trials, pilot studies, and technological assessments were reviewed to evaluate the performance of AI in detecting oral potentially malignant disorders (PMDs) and early-stage squamous cell carcinoma. AI-based tools have shown considerable promise in the accurate and non-invasive diagnosis of oral lesions. These systems offer enhanced sensitivity and specificity, reduce human error, and provide objective assessments, even in low-resource or remote settings. DL algorithms, particularly CNNs, have demonstrated excellent performance in image recognition tasks relevant to oral pathology. However, challenges such as data standardization, algorithmic bias, lack of clinical validation, and ethical concerns still hinder widespread adoption. AI has the potential to transform early detection strategies for oral cancer by supporting clinicians in making faster and more accurate diagnoses. With proper validation, integration into clinical workflows, and adherence to ethical guidelines, AI can serve as an invaluable adjunct in oral medicine, especially for mass screening and personalized diagnostics. Continued research, investment in digital infrastructure, and training of dental professionals are essential for realizing its full potential in the future of oral healthcare.

The dynamic interplay between reactive free radicals (FR) and antioxidants (AO) can lead to either redox homeostasis or oxidative stress. Disruption of redox balance contributes to oxidative stress, a key factor in the pathogenesis of various conditions, notably oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). At low to moderate levels, FRs trigger adaptive mutations that initiate carcinogenesis and support neoplastic cell survival. In contrast, high concentrations of FRs exert cytotoxic effects, a mechanism exploited in radiotherapy and chemotherapy. Antioxidants counteract FRs, mitigating cellular damage-a benefit demonstrated in several clinical trials involving OPMDs. However, their efficacy in OSCC remains contentious. This review explores the multifaceted roles of FRs and AOs in OPMD and OSCC, with emphasis on their contributions to carcinogenesis and therapeutic strategies. Tracking the FR-AO ratio during treatment may offer predictive insights into malignant transformation and facilitate early OSCC detection.

Chylothorax is an uncommon cause of pleural effusion, most frequently associated with thoracic trauma, malignancy, or congenital lymphatic disorders. Development of chylothorax following abdominal surgery without direct thoracic intervention is rare. We report a 77-year-old female who developed delayed bilateral pleural effusions after cholecystectomy and was subsequently diagnosed with chylothorax. The clinical course was notable for an intervening enterocutaneous fistula. Diagnosis was confirmed by pleural fluid analysis demonstrating markedly elevated triglyceride levels. The patient was successfully managed with conservative treatment, including pleural drainage and total parenteral nutrition, without the need for surgical intervention. This case highlights a rare delayed presentation of chylothorax following abdominal surgery and underscores the importance of considering lymphatic complications in complex postoperative courses.

Oral submucous fibrosis is a potentially malignant disorder with a high malignant transformation rate. Areca nut, being the chief etiologic factor, when chewed, is known to be swallowed and absorbed into circulation resulting in several systemic effects. This is the first kind of report presenting serum organ-specific fibrosis biomarkers suggestive of functional and fibrotic changes in the visceral organs. Various fibrotic biomarkers such as kidney injury molecule-1 (KIM-1), alanine aminotransferace (ALT), aspartate aminotransferase (AST), and its ratio to platelet index (APRI), suppression of tumorigenicity-2 (ST2), Krebs von den Lungen-6 (KL-6) and von Willebrand factor (vWF) were analyzed. The present study evaluated potential systemic fibrotic involvement, modest elevations in ST2 and KL-6 levels in advanced OSF compared to early cases; however, all values remained within normal physiological limits. No significant differences were found between the OSF and healthy groups across all biomarkers. There was no renal involvement, no significant association between liver fibrosis and its systemic biomarkers, and there was minimal vascular involvement. Collectively, these findings support the hypothesis that OSF may be a localized fibrotic disorder with no detectable systemic biomarker alterations in its early to moderate stages. This study provides an important step in bridging localized oral pathology and systemic disease monitoring. No significant systemic fibrosis was observed but methodology, findings, and recommendations offer a strong basis for future research. Despite the presence of evidence that favors a localized disease model for OSF in its early and advanced stages, systemic monitoring in future clinical paradigms is acknowledged.