Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Synergistic Attenuation of the TNF-α/NF-κB Inflammatory Axis in Colorectal Carcinogenesis: Lactococcus lactis D4 as a Mucosal-Protective Adjuvant to Capecitabine
Get PDFBackground: Capecitabine serves as a standard chemotherapeutic agent for colorectal cancer, but its clinical efficacy is frequently hindered by severe gastrointestinal toxicity and incomplete suppression of the inflammatory tumor microenvironment. We evaluated the synergistic potential of Lactococcus lactis D4, a probiotic strain isolated from traditional fermented buffalo milk, as an immunonutritional adjuvant to Capecitabine in a 1,2-dimethylhydrazine-induced colorectal cancer rat model.
Methods: Sprague-Dawley rats were maintained on a standardized AIN-93G diet and induced with 1,2-dimethylhydrazine. Animals were randomized into Negative Control, Cancer Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Treatments were administered for 14 days. We assessed cachexia, macroscopic microadenoma multiplicity, and TNF-α expression utilizing immunohistochemistry. Synergy was mathematically validated using the Coefficient of Drug Interaction.
Results: The Combination group significantly prevented chemotherapy-induced cachexia, demonstrating a 2.1% weight gain compared to a 4.5% weight loss in the Capecitabine monotherapy group (p < 0.05). Macroscopic microadenomas were rapidly reduced in the combination group. Furthermore, the combination therapy synergistically suppressed colonic TNF-α protein expression (Coefficient of Drug Interaction = 0.83). Additionally, L. lactis D4 entirely mitigated capecitabine-induced mucositis.
Conclusion: L. lactis D4 functions as a highly potent adjuvant to Capecitabine. It prevents cachexia, protects mucosal architecture, and exerts a mathematically proven synergistic suppression of the TNF-α inflammatory axis
Catastrophic Zone I Open Globe Injury: Pathophysiological Insights and Staged Surgical Triumphs in a Case of Corneal Rupture, Lens Extrusion, and "Blackball" Hyphema
Get PDFBackground: Complex open globe injuries (OGIs) involving the simultaneous destruction of multiple anterior segment structures represent a formidable challenge in ophthalmic traumatology. These injuries necessitate a staged surgical approach to restore ocular integrity and optimize the potential for visual rehabilitation.
Case presentation: A 44-year-old male presented with a severe Zone I OGI in the left eye from a high-velocity projectile stone. His initial best-corrected visual acuity was limited to light perception. Examination revealed an 8-mm corneal rupture with uveal prolapse, complete anterior extrusion of the crystalline lens, and a Grade IV "blackball" hyphema. The Ocular Trauma Score (OTS) was calculated as 1, predicting a very poor visual outcome. Immediate primary repair involved anterior vitrectomy, lensectomy, hyphema evacuation, and corneal suturing. After a six-month stabilization period, a secondary scleral-fixated intraocular lens (IOL) was implanted using a double-needle Yamane technique.
Conclusion: Despite the devastating nature of the initial injury and a grim prognosis as per the OTS, a principled, staged surgical strategy resulted in a final best-corrected visual acuity of 20/50. This case highlights that adherence to damage-control principles—prioritizing anatomical restoration in the primary surgery and deferring refractive correction—can lead to unexpectedly favorable functional outcomes in the most severe categories of ocular trauma
Ecthyma Contagiosum (Orf Virus) Masquerading as Subcorneal Pustular Dermatosis: A Diagnostic Pitfall in an Adolescent
Get PDFBackground: Ecthyma contagiosum (Orf) is a zoonotic viral infection caused by a Parapoxvirus, typically presenting as a self-limiting, solitary cutaneous lesion on the hands of occupationally exposed individuals. Atypical, multifocal, or pustular presentations can pose a significant diagnostic challenge, mimicking various inflammatory dermatoses.
Case presentation: We present the case of a 17-year-old female with no direct animal contact who developed a progressive, widespread, and painful pustular eruption on her extremities over three weeks. The clinical presentation was highly suggestive of Subcorneal Pustular Dermatosis (SPD), prompting treatment with systemic corticosteroids, which led to clinical worsening. A delayed epidemiological history revealed an environmental link to a nearby goat farm and a family cluster of similar, milder lesions. A diagnostic punch biopsy was pivotal, revealing viral cytopathic effects, including extensive ballooning degeneration and epidermal necrosis, inconsistent with SPD. Subsequent bacterial culture confirmed superinfection with Enterobacter cloacae ssp. cloacae. The diagnosis was established by the pathognomonic histopathological findings.
Conclusion: The patient’s steroid therapy was immediately ceased, and targeted antibiotic therapy was initiated, leading to complete resolution. This case highlights the Orf virus as a critical clinical chameleon and a diagnostic pitfall for generalized pustular eruptions. It underscores the necessity of a high index of suspicion for zoonoses, even in non-occupational settings, and confirms the indispensable role of histopathology in differentiating viral cytopathy from sterile neutrophilic dermatoses to prevent iatrogenic harm from inappropriate immunosuppression
Therapeutic Plasma Exchange as Adjuvant Rescue Therapy for Weil’s Disease-Associated Acute Liver Failure in a Hemodialysis-Dependent Patient: A Case Report
Get PDFBackground: Weil’s disease, the severe form of leptospirosis, manifests as a triad of jaundice, renal failure, and hemorrhage. In patients with pre-existing end-stage renal disease (ESRD), the management of superimposed acute liver failure (ALF) is exceptionally challenging due to altered pharmacokinetics, fluid intolerance, and the inability of standard hemodialysis to clear protein-bound hepatic toxins.
Case presentation: We present a 32-year-old anuric male with ESRD on maintenance hemodialysis who presented with fever, jaundice, and altered mental status following floodwater exposure. He developed severe metabolic encephalopathy (GCS E2V2M4), profound coagulopathy (INR 6.04), and hyperbilirubinemia (Total Bilirubin 18.31 mg/dL). Following the failure of broad-spectrum antibiotics and sustained low-efficiency dialysis (SLED) to halt clinical deterioration, two sessions of therapeutic plasma exchange (TPE) were initiated as salvage therapy. The intervention utilized 100% fresh frozen plasma (FFP) replacement to address hemostatic failure. TPE resulted in rapid biochemical clearance and clinical stabilization. Post-intervention, the INR decreased from 6.04 to 1.57 (74% reduction), Total bilirubin declined from 18.31 to 5.57 mg/dL (69.5% reduction), and platelet counts recovered from 45,000 to 142,000/µL. Neurological status normalized (GCS 15) within 48 hours of the second session.
Conclusion: TPE served as an effective bridge to recovery by clearing albumin-bound toxins and restoring coagulation factors in a high-risk patient where standard renal replacement was insufficient
Nuclear β-Catenin Accumulation Correlates with Poor Survival in Undifferentiated Nasopharyngeal Carcinoma: A Retrospective Cohort Study in an Endemic Region
Get PDFBackground: Nasopharyngeal carcinoma (NPC) is highly endemic in Indonesia, characterized by a prevalence of undifferentiated subtypes and late-stage presentation. While the Epstein-Barr virus (EBV) is a primary driver, the limitations of TNM staging in predicting individual outcomes necessitate the identification of molecular biomarkers. This study investigates the prognostic utility of aberrant Wnt/β-catenin signaling, specifically nuclear accumulation, in predicting overall survival (OS).
Methods: A retrospective cohort study was conducted on 44 patients diagnosed with undifferentiated NPC at Dr. Kariadi General Hospital, Indonesia, between 2020 and 2024. Immunohistochemistry (IHC) for β-catenin was performed, with scoring specifically targeting nuclear and cytoplasmic reactivity (excluding physiological membranous staining) using the Allred system. Clinicopathological variables, including TNM staging (AJCC 8th edition), were analyzed. Survival analysis utilized Kaplan-Meier curves and multivariate Cox Proportional Hazards regression.
Results: The cohort exhibited advanced disease, with 81.8% of patients presenting at Stage III or IV. Nuclear β-catenin overexpression (moderate-to-strong) was observed in 97.7% of cases. Strong nuclear expression was significantly associated with advanced T-stage (p=0.032) and distant metastasis (p=0.045). Kaplan-Meier analysis revealed a significant reduction in 5-year overall survival for the strong expression group (0%) compared to the weak/moderate group (p < 0.001). In multivariate analysis adjusted for age and TNM stage, strong β-catenin expression remained a significant predictor of mortality (Hazard Ratio: 2.15; 95% CI: 1.05–4.42; p=0.036), alongside Stage IV disease.
Conclusion: Nuclear accumulation of β-catenin is a prevalent molecular event in Indonesian NPC and serves as a significant prognostic biomarker independent of tumor stage. These findings suggest potential utility for risk stratification and targeted Wnt-inhibitor therapies
The Uncoupling Phenomenon: Dissociation Between Albuminuria and Glomerular Filtration Rate in an Advanced Diabetic Kidney Disease Phenotype
Get PDFBackground: The classical paradigm of diabetic kidney disease (DKD) assumes a synchronous, linear trajectory where increasing albuminuria predicts the decline of glomerular filtration rate (GFR). However, emerging epidemiology suggests these markers may dissociate in advanced disease stages, particularly under modern renoprotective pharmacotherapy. We aimed to investigate this uncoupling phenomenon by evaluating the correlation between urine albumin creatinine ratio (UACR) and estimated GFR (eGFR) in a specific cohort of advanced DKD patients in Indonesia.
Methods: We conducted a cross-sectional analytic study from January to November 2025 at Dr. M. Djamil General Hospital Padang, a tertiary referral center. The study population comprised 30 patients with established DKD, predominantly in CKD Stages 3b and 4. The primary outcome was the Spearman rank correlation (r) between UACR and eGFR, reported with 95% Confidence Intervals (CI). An exploratory sub-analysis compared trends in patients receiving SGLT2 inhibitors (n=12) versus standard care (n=18).
Results: The cohort was elderly (mean age 61.93 years) with critical renal reserve depletion (median eGFR 32.50 mL/min/1.73 m²). Median UACR was 403.90 mg/g, yet exhibited massive heterogeneity (IQR: 170.82–1779.27). Spearman analysis revealed a complete lack of linear correlation between albuminuria and filtration function (r = 0.041; 95% CI: -0.322 to 0.395; p = 0.830). While SGLT2 inhibitor users (n=12) demonstrated numerically lower median UACR than non-users (n=18), the dissociation from eGFR persisted in both subgroups.
Conclusion: We demonstrate a distinct dissociation between albuminuria severity and filtration function in advanced DKD. This uncoupling suggests that in late-stage nephropathy, structural glomerulosclerosis and tubulointerstitial fibrosis progress independently of permeability changes. Consequently, albuminuria cannot serve as a sole surrogate for disease progression in this phenotype, supporting a dual-biomarker strategy where UACR and eGFR are monitored as independent risk factors
The Silent Saboteur: Chronic Refractory Erythema Nodosum Leprosum Perpetuated by Neglected Odontogenic Foci in a Post-RFT Borderline Lepromatous Patient
Get PDFBackground: Erythema nodosum leprosum (ENL) is a severe, immune-complex mediated complication of lepromatous leprosy that can manifest before, during, or after multidrug therapy (MDT). While the primary etiology involves the release of Mycobacterium leprae antigens, the chronicity of ENL is frequently driven by secondary, often occult, triggers. Focal infections, particularly of odontogenic origin, are frequently overlooked in standard dermatological assessments, leading to refractory clinical courses.
Case presentation: We report the case of a 32-year-old male with a history of borderline lepromatous (BL) leprosy who had achieved release from treatment (RFT). The patient presented with severe, chronic, and recurrent ENL characterized by painful erythematous nodules, high-grade fever, and acute neuritis, occurring more than one year post-RFT. Laboratory evaluation revealed significant inflammatory markers, including a C-Reactive Protein level of 172.7 mg/L and leukocytosis. Crucially, intraoral examination identified neglected chronic dental caries (gangrene radix) and generalized periodontal inflammation. Despite medical advice, the patient refused dental intervention. The reactional state was managed with a combination of intravenous methylprednisolone and high-dose oral clofazimine. While cutaneous symptoms improved, the persistence of the focal infection poses a substantial risk for further recurrence.
Conclusion: This case highlights the critical and often underestimated role of odontogenic focal infections as perpetuating factors in chronic ENL. It underscores the necessity for a multidisciplinary approach integrating dentistry and dermatology. We propose that recalcitrant ENL in post-RFT patients should trigger mandatory screening for occult dental infections to disrupt the cycle of systemic inflammation.
 
Intratympanic Corticosteroid Salvage for Pediatric Bilateral Sudden Sensorineural Hearing Loss Complicated by Methylprednisolone-Induced Hypertensive Urgency in an Obese Adolescent
Get PDFBackground: Bilateral sudden sensorineural hearing loss (SSNHL) is a rare otologic emergency, accounting for less than 5% of sudden deafness cases and occurring even less frequently in pediatric populations. Unlike unilateral cases, bilateral involvement strongly implicates systemic etiologies such as autoimmune inner ear disease (AIED). Systemic high-dose corticosteroids are the standard first-line therapy but pose significant risks of toxicity, including hypertensive crisis, particularly in adolescents with metabolic risk factors.
Case presentation: We report the case of a 17-year-old male (BMI 29.0 kg/m²) presenting with acute, simultaneous bilateral hearing loss (Pure Tone Average [PTA]: Right 82.5 dB, Left 81.25 dB) and severe tinnitus (Tinnitus Handicap Index [THI]: 78). Initial management with high-dose intravenous methylprednisolone (500 mg/day) was complicated on Day 7 by hypertensive urgency (Blood Pressure 150/95 mmHg) and neurological symptoms, necessitating immediate cessation of systemic therapy. Diagnostic investigation was limited by resource availability; however, elevated inflammatory markers supported a presumptive immune-mediated etiology. A salvage protocol was initiated using four weekly cycles of intratympanic Triamcinolone Acetonide. Following therapy, the patient demonstrated slight audiological recovery (PTA stabilized at 65 dB bilaterally) but achieved complete resolution of tinnitus (THI: 0).
Conclusion: This case highlights the critical role of intratympanic corticosteroids as a safe salvage modality when systemic therapy is contraindicated due to toxicity. The dissociation between modest audiometric gain and complete tinnitus resolution suggests successful mitigation of cochlear synaptopathy. The case underscores the necessity of cardiovascular monitoring and BMI-adjusted risk stratification in adolescents receiving high-dose steroids
The Complex Interplay of Prematurity, Respiratory Distress Syndrome, and Necrotizing Enterocolitis: Insights from a Case Study
Get PDFBackground: Necrotizing enterocolitis (NEC) remains a devastating inflammatory bowel disease predominantly affecting premature infants, carrying significant morbidity and mortality risks. Respiratory distress syndrome (RDS), common in this population, is increasingly recognized not just as a comorbidity but as a potential contributor to NEC pathogenesis, possibly through mechanisms involving gut hypoperfusion. Understanding the clinical progression and management challenges when these conditions coexist is crucial.
Case presentation: We present the case of a female infant born prematurely at 33-34 weeks gestation with a birth weight of 2280g. The infant developed early RDS, requiring Continuous Positive Airway Pressure (CPAP) support shortly after birth. On the second day of life, while RDS symptoms were improving, the infant developed signs suggestive of NEC, including abdominal distension, bilious gastric residuals, and subsequent irritability and feeding intolerance. The diagnosis of NEC (suspected Bell's stage II) was supported by clinical findings and radiological evidence of bowel wall thickening. Blood cultures identified Klebsiella pneumoniae. Initial antibiotic therapy proved insufficient, necessitating a change to meropenem and amikacin based on sensitivity testing. The infant was managed conservatively with bowel rest, parenteral nutrition, and targeted antibiotics, showing gradual clinical improvement. Enteral feeding with breast milk was successfully reintroduced, and the infant was discharged in good condition after 15 days of NICU care.
Conclusion: This case highlights the challenging clinical scenario where early-onset RDS in a premature, low-birth-weight infant precedes the development of NEC. It underscores the importance of high clinical suspicion for NEC even as respiratory status improves, the utility of microbial surveillance and sensitivity testing in guiding antibiotic therapy, and the potential for successful conservative management in NEC Bell's stage II. The interplay between RDS-induced physiological stress and intestinal vulnerability likely contributed to NEC development in this patient
Beyond Tumor Grade: Investigating the Heterogeneity of PD-L1 Expression in Soft Tissue Sarcomas and the Need for Subtype-Specific Analysis
Get PDFBackground: Soft tissue sarcomas (STS) represent a diverse group of malignant mesenchymal neoplasms with considerable histological variety and differing degrees of malignancy. Programmed Death-Ligand 1 (PD-L1) expression is a crucial immunotherapy target in various cancers, but its role and expression patterns in STS, particularly within the Indonesian population, remain inadequately defined. This study aimed to investigate the differences in PD-L1 expression between low-grade and high-grade STS and to determine the correlation between PD-L1 expression and histological grading in an Indonesian cohort.
Methods: This analytical observational study utilized a cross-sectional design, incorporating 29 archival paraffin-embedded tissue blocks from STS patients diagnosed at Dr. Saiful Anwar Regional General Hospital, Malang, Indonesia. PD-L1 expression was assessed immunohistochemically using the monoclonal antibody clone 22c3, and scoring was performed using the Combined Positive Score (CPS). Statistical analyses, including the Mann-Whitney U test and Spearman correlation, were employed to evaluate differences and correlations.
Results: The majority of STS cases (89.7%) exhibited negative PD-L1 expression. The mean PD-L1 CPS was 0.1429 in low-grade STS and 0.233 in high-grade STS. No statistically significant difference in PD-L1 expression was observed between the low-grade and high-grade groups (p=0.620). Furthermore, Spearman correlation analysis revealed no significant association between PD-L1 expression (numeric CPS and categorical positivity) and histological grade (r=0.094, p=0.629 for CPS; r=0.102, p=0.600 for interpretation).
Conclusion: This study found no significant difference in PD-L1 expression between low-grade and high-grade soft tissue sarcomas, nor a significant correlation with histological grade in the investigated Indonesian patient cohort. These findings suggest that PD-L1 expression, when assessed independently, may not be a reliable prognostic biomarker based solely on tumor grading in STS. Further research with larger sample sizes, encompassing diverse histological subtypes and incorporating additional immune biomarkers, is warranted