Bioscientia Medicina - Journal of Biomedicine and Translational Research
Not a member yet
1245 research outputs found
Sort by
The Molecular and Epidemiological Atlas of Primary Orbital Lymphoma: A Global Meta-Analysis of 3,832 Cases and Pathophysiological Correlates
Get PDFBackground: Primary orbital lymphoma is the most common orbital malignancy in adults, yet its global distribution and the prevalence of its histopathological subtypes remain poorly defined by large-scale evidence. This study provides a comprehensive quantitative synthesis of the global landscape of orbital lymphoma to inform diagnostic frameworks and guide future research.
Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of studies published between January 2015 and December 2023. We searched PubMed, Scopus, Web of Science, and Embase for observational studies reporting histopathological data on orbital lymphoma. Two independent reviewers performed study selection, data extraction, and quality appraisal using the Joanna Briggs Institute (JBI) checklist. Pooled prevalence for each lymphoma subtype was calculated using a random-effects model. Heterogeneity was explored via subgroup analyses and meta-regression, and the robustness of findings was confirmed with a sensitivity analysis.
Results: Fifteen studies comprising 3,832 patients met the inclusion criteria. Extranodal marginal zone lymphoma (EMZL) was the most prevalent subtype globally, with a pooled prevalence of 57.1% (95% CI: 51.5-62.7%). This was followed by diffuse large B-cell lymphoma (DLBCL) at 16.5% (95% CI: 13.1-20.0%), follicular lymphoma (FL) at 10.2% (95% CI: 8.0-12.4%), mantle cell lymphoma (MCL) at 5.1% (95% CI: 3.6-6.6%), and small lymphocytic lymphoma (SLL) at 3.4% (95% CI: 2.2-4.5%). Subgroup analysis revealed a significantly higher prevalence of EMZL in Asia (61.3%) compared to Europe (54.2%) and North America (55.8%) (p=0.04), while FL was more common in North American (14.1%) and European (12.8%) cohorts versus Asian cohorts (4.5%) (p<0.01). Sensitivity analysis confirmed the stability of these estimates.
Conclusion: This meta-analysis establishes EMZL as the predominant histopathological subtype of orbital lymphoma worldwide, while highlighting profound geographical disparities in the distribution of EMZL and FL. These findings provide a robust global benchmark critical for clinical practice and underscore the influence of distinct geographical, genetic, and microenvironmental factors in orbital lymphomagenesis
The Inflammatory Correlates of Hypothalamic-Pituitary-Gonadal Axis Dysfunction in Antiretroviral-Naïve Men with HIV: A Cross-Sectional Analysis of the TNF-α and Testosterone Relationship
Get PDFBackground: In men with untreated Human Immunodeficiency Virus (HIV), the mechanisms underlying testosterone deficiency remain incompletely defined. Chronic inflammation is hypothesized to be a key factor in disrupting the hypothalamic-pituitary-gonadal (HPG) axis. This study aimed to investigate the association between the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the HPG axis and to assess this relationship while accounting for nutritional status in ART-naïve men.
Methods: We conducted a cross-sectional study of 40 ART-naïve men with HIV in Palembang, Indonesia. We measured serum total testosterone, Luteinizing Hormone (LH), TNF-α, Interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). Hypogonadism was classified as primary (low testosterone, high LH) or secondary (low testosterone, low/normal LH). Spearman’s correlation was used to assess bivariate relationships. A multiple linear regression analysis was performed to determine the independent association of TNF-α and Body Mass Index (BMI) with testosterone levels.
Results: All 40 participants (100%) presented with secondary (hypogonadotropic) hypogonadism, characterized by a median total testosterone of 6.48 pg/mL and an inappropriately normal median LH of 3.86 mIU/mL. Serum TNF-α was significantly elevated (median: 10.32 pg/mL). A moderate negative correlation was found between TNF-α and total testosterone (ρ = -0.411, p = 0.008). In the multivariate regression model, both higher TNF-α levels (β = -0.38, p = 0.011) and lower BMI (β = 0.45, p = 0.003) were significant, independent predictors of lower total testosterone. The model explained 34.6% of the variance in testosterone levels (Adjusted R² = 0.346).
Conclusion: Our findings demonstrate a universal prevalence of secondary hypogonadism in ART-naïve men with HIV. This HPG axis dysfunction is strongly and independently associated with both the magnitude of systemic inflammation, marked by TNF-α, and the severity of malnutrition. These results suggest a complex interplay where inflammation and poor nutritional status act as distinct, synergistic contributors to the profound endocrine disruption seen in untreated HIV infection
Erythema Nodosum Leprosum as a Harbinger of Relapse in Multibacillary Leprosy: A Clinico-Histopathological Case Study
Get PDFBackground: Leprosy, a chronic granulomatous disease caused by Mycobacterium leprae, presents formidable long-term management challenges. In the post-elimination era, differentiating a true bacteriological relapse from a late-onset Erythema Nodosum Leprosum (ENL) reaction in patients who have completed multidrug therapy (MDT) is a critical diagnostic dilemma. Misdiagnosis can lead to inappropriate treatment, risking disease progression and irreversible nerve damage.
Case presentation: A 30-year-old male presented with a severe, systemic inflammatory illness two years after completing MDT for lepromatous leprosy. His symptoms included crops of painful, erythematous nodules, fever, and arthralgia. While clinically suggestive of a severe ENL reaction, a slit-skin smear revealed a paradoxically high bacterial index (BI) of +5 with a morphological index (MI) of 0%. A skin biopsy was performed for definitive diagnosis. Histopathology revealed a dual pathology: a diffuse infiltrate of foamy macrophages typical of lepromatous leprosy, alongside a dense neutrophilic panniculitis characteristic of ENL. Crucially, Fite-Faraco staining demonstrated vast numbers of intact, solid-staining acid-fast bacilli, providing unequivocal evidence of active bacterial proliferation.
Conclusion: This case demonstrates that a diagnostic algorithm integrating a high index of clinical suspicion with comprehensive bacteriological and histopathological methods is essential for accurately identifying relapse masked by ENL. The presence of viable bacilli confirms that ENL can be a direct clinical harbinger of relapse, mandating a dual therapeutic strategy that combines aggressive anti-inflammatory treatment with the immediate re-initiation of MDT
Efficacy of the Full Mesenchymal Stromal Cell Secretome versus Purified Small Extracellular Vesicles in Preclinical Models of Erectile Dysfunction: A Systematic Review and Parallel Meta-Analysis
Get PDFBackground: Acellular therapies from Mesenchymal Stromal Cells (MSCs), including the full secretome (conditioned medium, CM) and purified small extracellular vesicles (sEVs), are promising restorative treatments for erectile dysfunction (ED). It remains unknown if the therapeutic benefit is driven by the complete secretome or if purified sEVs are the primary, sufficient component. This study aimed to systematically review and meta-analyze the preclinical evidence.
Methods: We conducted a systematic review and parallel meta-analysis adhering to PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from January 1st, 2014, to July 31st, 2025. Studies were eligible if they were preclinical ED models evaluating MSC-CM or purified sEVs against a control. Two parallel meta-analyses were performed using a random-effects model. Primary outcomes were erectile function (Intracavernous Pressure / Mean Arterial Pressure ratio; ICP/MAP) and histopathology (Smooth Muscle / Collagen ratio; SM/Col).
Results: Our search yielded 1,942 records, with 87 full-text articles assessed. After applying strict PICO criteria, 7 primary studies were eligible for the meta-analysis (3 secretome, 4 sEVs). The overall risk of bias was moderate to high (0% allocation concealment). No studies directly compared secretome versus sEVs. The first meta-analysis (Secretome vs. Control, 3 studies, 4 data points, n=70) demonstrated a large, significant improvement in ICP/MAP (Standardized Mean Difference [SMD]: 2.40; 95% CI [1.65, 3.15]; p-value < 0.001), with extreme heterogeneity (I-squared=85%). The second meta-analysis (sEVs vs. Control, 4 studies, n=68) also showed a large, significant improvement (SMD: 2.75; 95% CI [1.90, 3.60]; p-value < 0.001), also with extreme heterogeneity (I-squared=88%).
Conclusion: Both the full MSC secretome and purified sEVs demonstrate large, significant therapeutic effects. However, this quantitative conclusion is severely limited by the exceptionally small number of studies and the profound biomolecular heterogeneity (in cell source and purification) that invalidates direct comparison. The primary finding remains the total lack of comparative data
Inadequate Preoperative Assessment and Its Clinicopathological Correlates in Patients Referred for Completion Thyroidectomy: A Tertiary Referral Center Analysis
Get PDFBackground: Completion thyroidectomy (CT) for differentiated thyroid carcinoma (DTC) is a high-risk procedure, frequently performed following an oncologically incomplete primary operation. This study characterizes the preoperative diagnostic assessment deficiencies in a cohort of DTC patients referred to a tertiary center for re-operation and identifies factors associated with residual disease.
Methods: We conducted a retrospective, single-center analysis of all patients who underwent CT for DTC at Hasan Sadikin General Hospital, Indonesia, over a 30-month period (January 1st, 2023, to June 30th, 2025). Data on preoperative assessments at the referring hospitals (ultrasonography (US) quality, fine-needle aspiration biopsy (FNAB), hormonal tests), primary surgical indications, and clinicopathological outcomes from both operations were extracted and analyzed using descriptive and bivariate statistics (Fisher's Exact Test).
Results: A total of 27 patients met the inclusion criteria. Analysis of their initial workup revealed significant omissions: 14/27 (51.9%) lacked FNAB, and 5/27 (18.5%) lacked hormonal testing. While 24/27 (88.9%) underwent a primary US, only 20.8% of these reports (5/24) were ATA-compliant staging examinations. Only 5/27 patients (18.5%) received a complete trimodal assessment. Upon re-operation, 10/27 (37.0%) had residual carcinoma. This finding was significantly associated with the omission of primary FNAB (57.1% vs. 15.4%, p = 0.027).
Conclusion: In this cohort of referred patients, incomplete preoperative assessment was nearly universal and strongly associated with adverse pathological findings. These data highlight the urgent need for standardized, evidence-based preoperative protocols and strengthened referral systems to ensure patients receive the correct primary operation
The Oral-Skin Axis in Autoinflammation: A Case Report of Severe Refractory Generalized Pustular Psoriasis (GPP) Resolved by Comprehensive Periodontal Intervention
Get PDFBackground: Generalized pustular psoriasis (GPP) is a severe, IL-36-driven autoinflammatory dermatosis, distinct from psoriasis vulgaris. Chronic periodontitis (CP) is a dysbiotic inflammatory disease sharing pathogenic pathways (IL-1, IL-17). An "oral-skin axis" has been hypothesized, but definitive clinical evidence of CP driving a GPP flare is scarce.
Case presentation: We present a 37-year-old male with a history of plaque psoriasis who developed a severe, refractory GPP flare (GPPASI 35.8) with high-grade fever (38.9°C), profound neutrophilic leukocytosis (22.5 x 10³/µL), and markedly elevated CRP (150 mg/L). The flare was resistant to maintenance methotrexate. Workup revealed severe CP with multiple periapical abscesses, culture from which grew Porphyromonas gingivalis and Fusobacterium nucleatum. The patient underwent a comprehensive dental intervention, including emergency extractions and full-mouth debridement, with concurrent peri-operative Amoxicillin-Clavulanate therapy. This combined intervention led to a rapid resolution of fever, neutrophilia, and cutaneous pustulation within 72 hours, without any escalation of systemic immunomodulators. He achieved complete remission (GPPASI 1.0) at 3-month follow-up.
Conclusion: This case provides a strong temporal association supporting the oral-skin axis, highlighting severe periodontitis as a potent trigger and amplifier for GPP. The rapid resolution following a combined surgical and antibiotic intervention suggests that targeting the oral inflammatory and microbial reservoir is a critical, actionable strategy. We strongly recommend consideration of a comprehensive dental/oral screening in patients with refractory GPP
Selective Suppression of Prevotella and Modulation of Oral Dysbiosis in Stunted Children: The Role of Systemic Zinc as a Biological Adjuvant to Mechanical Therapy
Get PDFBackground: Gingivitis in stunted children represents a unique pathological entity driven by a compromised mucosal barrier and systemic zinc deficiency. These children exhibit a phenotype of acquired immunodeficiency, where standard mechanical debridement often fails to resolve inflammation, leading to a phenomenon known as dysbiotic rebound. This study investigated the biomolecular efficacy of systemic Zinc supplementation combined with scaling and root planing (SRP) in modulating the oral microbiome of nutritionally vulnerable children.
Methods: A randomized, single-blind, pre-post test controlled clinical trial was conducted in Padang, Indonesia, involving 30 stunted children (Height-for-age Z-score < -2 SD) diagnosed with generalized gingivitis. Participants were randomized into a Control group (SRP + Placebo, n=15) and an Intervention group (SRP + 20mg Zinc Sulfate Monohydrate daily, n=15) for a duration of 14 days. Microbial profiling was performed on unstimulated saliva utilizing high-throughput 16S rRNA gene sequencing (V3–V4 region). Bioinformatics processing utilized the DADA2 pipeline to generate Amplicon Sequence Variants (ASVs).
Results: Results indicated that SRP alone resulted in a pathogenic recolonization dominated by Firmicutes (+49.6%). Conversely, Zinc supplementation induced a significant Gram-negative crash, reducing Proteobacteria by 50.6%. Most notably, the key periodontal pathogen Prevotella was suppressed to undetectable levels in the Zinc group (p<0.05).
Conclusion: Systemic zinc acts as a potent biological scaffold in the enterosalivary cycle, likely repairing the epithelial barrier and starving hemin-dependent pathogens. It is strongly recommended as a therapeutic adjuvant to prevent the ecological recurrence of gingivitis in nutritionally vulnerable pediatric populations
Metabolic and Inflammatory Signatures of Neurotrauma: Correlating Early Glycemic and Leukocytic Shifts with Glasgow Coma Scale Scores
Get PDFBackground: Traumatic brain injury (TBI) precipitates a profound systemic physiological stress response, often termed the sympathetic storm, characterized by neuroendocrine dysregulation and widespread inflammation. While admission biomarkers such as White Blood Cell (WBC) count and Blood Glucose levels are routinely measured, their comparative utility in stratifying injury severity—particularly in distinguishing between moderate and severe phenotypes—remains under-characterized. This study aimed to evaluate the discriminatory power of these markers, hypothesizing that metabolic and immune responses exhibit distinct saturation kinetics relative to the Glasgow Coma Scale (GCS).
Methods: We conducted a retrospective analytical observational study at Dr. Hasan Sadikin General Hospital (RSHS), a level I trauma center in Bandung, Indonesia. From an annual pool of admitted neurotrauma patients (January–December 2021), a stratified sample of 238 patients aged 18-60 years was analyzed. Strict exclusion criteria were applied to minimize confounders, including a history of metabolic disease and alcohol intoxication. TBI severity was stratified into mild (GCS 13-15), moderate (GCS 9-12), and severe (GCS 3-8). Statistical analysis utilized the Kruskal-Wallis and Mann-Whitney tests to assess non-parametric relationships.
Results: The cohort was predominantly male (82.8%) and young (18-40 years, 68.9%). Both biomarkers correlated with overall severity; however, their trajectories diverged significantly. WBC counts exhibited a threshold effect, rising significantly from Mild (17.50 ± 6.56 x10³/µL) to Moderate (18.81 ± 5.27 x10³/µL) severity, but plateauing between moderate and severe groups (p>0.05), suggesting a saturation of the demargination response. Conversely, blood glucose displayed a graded linear escalation: Mild (133.11 ± 34.53 mg/dL), moderate (158.35 ± 49.59 mg/dL), and severe (226.14 ± 105.61 mg/dL) (p<0.001), with significant discrimination across all severity pairings.
Conclusion: Admission hyperglycemia serves as a superior, graded biomarker for stratifying TBI severity compared to leukocytosis, which functions primarily as a binary threshold marker. The observed immune plateau contrasts with the linear metabolic scaling, highlighting stress-induced hyperglycemia as a critical indicator of severe neuro-metabolic derangement
Argon Plasma Coagulation in Bronchoscopy: A Safe and Effective Treatment for Airway Obstruction
Get PDFBackground: Airway obstruction can significantly impair a patient's quality of life and even become life-threatening. Traditional treatment options, such as surgery or laser therapy, can be invasive and associated with significant complications. Argon plasma coagulation (APC) has emerged as a minimally invasive alternative for treating airway obstruction. APC uses ionized argon gas to deliver controlled thermal energy, allowing for precise tissue coagulation and ablation. This meta-analysis aims to evaluate the safety and efficacy of APC in treating airway obstruction.
Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases. Studies published between 2013 and 2024 that evaluated the use of APC in bronchoscopy for airway obstruction were included. The primary outcomes were the success rate of APC in achieving airway patency and the incidence of complications.
Results: Seven studies (n=342 patients) met the inclusion criteria. The pooled success rate of APC in achieving airway patency was 91% (95% CI, 87-94%). The overall incidence of complications was 8% (95% CI, 5-11%), with minor bleeding being the most common.
Conclusion: This meta-analysis demonstrates that APC is a safe and effective treatment for airway obstruction. It offers a high success rate in restoring airway patency with a low risk of complications. APC is a valuable tool for pulmonologists in managing patients with airway obstruction
Neuroinflammation and Sleep Dysfunction in Epilepsy: The Role of High Sensitivity C-Reactive Protein
Get PDFBackground: Emerging evidence suggests a bidirectional relationship between systemic inflammation and both epilepsy and sleep dysfunction. High-sensitivity C-reactive protein (Hs-CRP), a sensitive marker of low-grade systemic inflammation, is elevated in response to pro-inflammatory cytokines. However, the specific link between Hs-CRP levels and subjective sleep quality within the epilepsy population required further investigation. This study aimed to investigate the relationship between serum Hs-CRP levels and sleep quality in patients diagnosed with epilepsy.
Methods: A cross-sectional study was conducted involving 40 patients diagnosed with epilepsy attending the neurology clinic at Dr. M. Djamil General Hospital, Padang, Indonesia, between January and February 2025. Patients aged over 17 years diagnosed by a neurologist were included. Serum Hs-CRP levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Sleep quality over the preceding month was assessed using the validated Indonesian version of the Pittsburgh Sleep Quality Index (PSQI). Mann-Whitney U test was employed to analyze the difference in median Hs-CRP levels between patients with good and poor sleep quality. Relationships between baseline characteristics and sleep quality were assessed using Chi-square/Fisher's exact tests for categorical variables and the Mann-Whitney U test for continuous variables.
Results: Forty epilepsy patients (median age 25.5 years, range 17-50; 52.5% female) were enrolled. The median duration of epilepsy was 10 years (range 1-35). A majority of patients exhibited uncontrolled seizures (75%) and were receiving AED polytherapy (60%). Based on PSQI scores, 24 patients (60%) were classified as poor sleepers, while 16 (40%) were good sleepers. A significant difference was observed in median serum Hs-CRP levels between the two groups: patients with good sleep quality had significantly lower median Hs-CRP levels compared to those with poor sleep quality (1,271.50 ng/ml [range 58–5,837] vs. 2,771.50 ng/ml [range 509–27,187], p=0.027). Poor sleep quality was significantly associated with younger age (median 23 vs. 36 years, p=0.039) and AED polytherapy (75% vs. 25%, p=0.018).
Conclusion: This study demonstrated a significant association between elevated serum Hs-CRP levels and poor subjective sleep quality in patients with epilepsy. Epilepsy patients experiencing poor sleep exhibited significantly higher levels of this inflammatory biomarker. These findings underscore the potential role of systemic inflammation in the complex interplay between epilepsy and sleep disturbances, suggesting Hs-CRP could serve as a potential biomarker linking these conditions