Bioscientia Medicina : Journal of Biomedicine and Translational Research

Inadequate Preoperative Assessment and Its Clinicopathological Correlates in Patients Referred for Completion Thyroidectomy: A Tertiary Referral Center Analysis

Munawar — 2025-11-06

Background: 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 1^st, 2023, to June 30^th, 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.

Loss of E-cadherin Expression Stratifies Aggressive versus Non-Aggressive Papillary Thyroid Carcinoma

Dwi Yanti Fioni Putri — 2025-11-07

Background: Papillary thyroid carcinoma (PTC) is generally indolent, yet specific histological subtypes defined by the World Health Organization (WHO) are linked to aggressive behavior and poor prognosis. The loss of the cell-adhesion protein E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT), a process implicated in tumor aggression. However, its role in stratifying PTC subtypes versus its correlation with tumor stage remains a significant controversy in the literature. This study aimed to disentangle these two parameters by clarifying the relationship between E-cadherin expression and both histological phenotype and tumor stage.

Methods: This was an observational, cross-sectional pilot study on 40 randomly selected, formalin-fixed, paraffin-embedded (FFPE) PTC cases from a 2024 cohort (N=74) at a tertiary hospital in Indonesia. All cases were re-evaluated and classified according to the WHO 5th Edition (2022) criteria as non-aggressive (n=34) or aggressive (n=6). E-cadherin expression was assessed by immunohistochemistry (IHC) using a standardized semi-quantitative scoring system (product of intensity and proportion) adapted from previous studies, with inter-rater reliability assessed (Cohen’s Kappa = 0.88). Scores were dichotomized as 'High' (n=25) or 'Low' (n=15). The association between E-cadherin expression and both histological subtype and AJCC 8th Edition tumor stage (Early: I/II [n=32] vs. Advanced: III/IV [n=8]) was analyzed using Fisher's Exact Test, with Odds Ratios (OR) and 95% Confidence Intervals (CI) calculated.

Results: High E-cadherin expression was observed in 62.5% of cases. A statistically significant and strong association was found between E-cadherin expression and histological subtype (p=0.021; OR 12.0; 95% CI 1.2–118.9). Low E-cadherin expression was present in 83.3% (5 of 6) of aggressive-subtype tumors, versus only 29.4% (10 of 34) of non-aggressive subtypes. In contrast, no significant correlation was found between E-cadherin expression and advanced tumor stage (p=0.126; OR 3.67; 95% CI 0.7–18.6).

Conclusion: Loss of E-cadherin expression is a significant biomarker associated with high-risk, aggressive histological phenotypes in PTC. Its lack of correlation with tumor stage, confirmed by an uncertain OR, suggests E-cadherin's role is indicative of an inherent tumor biological phenotype (aggressiveness) rather than a linear marker of tumor progression (stage). This dichotomy, likely reflecting EMT/MET plasticity, positions E-cadherin IHC as a powerful ancillary tool for pathological risk stratification.

The Oral-Skin Axis in Autoinflammation: A Case Report of Severe Refractory Generalized Pustular Psoriasis (GPP) Resolved by Comprehensive Periodontal Intervention

Ni Putu Wina Widyastuti — 2025-11-14

Background: 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.

Angiofibroma Beyond the Nasopharynx: Diagnostic Challenges and Endoscopic Management of Two Atypical Cases Arising from the Ethmoid and Sphenoid Sinuses

Dolly Irfandy — 2025-11-18

Background: Angiofibroma is a histologically benign but locally aggressive vascular neoplasm almost exclusively associated with the nasopharynx of adolescent males (Juvenile Nasopharyngeal Angiofibroma, JNA). Extranasopharyngeal angiofibroma (ENA) is an exceptionally rare variant that originates outside the sphenopalatine foramen, posing significant diagnostic and management challenges due to its atypical locations, age of presentation, and clinical mimicry of other sinonasal pathologies.

Case presentation: We present two sophisticated cases of ENA managed at our tertiary center. Case 1: A 35-year-old male presented with unilateral nasal obstruction. Endoscopy and imaging revealed a hypervascular mass centered in the posterior ethmoid sinus, destroying the basal lamella and abutting the skull base. Histopathological analysis was initially confounded by features resembling a solitary fibrous tumor (SFT), requiring a comprehensive immunohistochemical panel (IHC) including STAT6 and nuclear beta-catenin to confirm the diagnosis of angiofibroma. Case 2: A 17-year-old male presented with symptoms and imaging (non-contrast CT) highly suggestive of a benign sphenochoanal polyp. An initial attempt at routine endoscopic removal was aborted due to unexpected, profuse hemorrhage. Subsequent advanced imaging (CTA/MRI) revealed a hypervascular sphenoid-based angiofibroma. Both patients underwent preoperative superselective embolization followed by successful, purely endoscopic tumor resection with no recurrence at 12 and 18-month follow-up, respectively.

Conclusion: ENA is a critical, albeit rare, diagnostic consideration for any vascular sinonasal mass, regardless of patient age or tumor location. These cases underscore the unreliability of "classic" clinical and radiological signs, the diagnostic pitfalls of histopathological mimics like SFT and polyps, and the critical role of advanced IHC (nuclear beta-catenin) for definitive diagnosis. A modern, multidisciplinary approach combining preoperative embolization with endoscopic resection offers a safe and effective pathway to cure.

Divergent Inflammatory Trajectories: Independent Predictive Value of Admission Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratios for Acute Ischemic Stroke Severity in a Southeast Asian Cohort

Kadek Kristian Dwi Cahya — 2025-11-21

Background: Systemic sterile inflammation acts as a critical pathophysiological driver in the acute phase of ischemic stroke, mediating secondary brain injury through blood-brain barrier disruption and microvascular thrombosis. While the Neutrophil-to-Lymphocyte Ratio (NLR) and Lymphocyte-to-Monocyte Ratio (LMR) have emerged as potential biomarkers in Western populations, their independent prognostic utility and specific diagnostic thresholds within Southeast Asian populations remain under-explored. This region presents unique challenges due to potential variations in baseline hematological profiles driven by genetic polymorphisms and environmental factors. This study aims to elucidate the association between admission NLR and LMR levels and the severity of Acute Ischemic Stroke (AIS) and to determine optimal population-specific prognostic cut-offs.

Methods: We conducted a retrospective cross-sectional comparative study involving 128 patients with confirmed AIS admitted to Wangaya Regional General Hospital, Indonesia, between January 2025 and August 2025. Patients were stratified based on admission National Institutes of Health Stroke Scale (NIHSS) scores into a Mild Group (NIHSS ≤ 6, n=64) and a Moderate-Severe Group (NIHSS > 6, n=64). Infection was strictly excluded using clinical and radiological criteria independent of admission leukograms to prevent circular bias. Receiver Operating Characteristic (ROC) curve analysis was performed to determine diagnostic accuracy and identify optimal cut-offs. To address potential multicollinearity between NLR and LMR, two separate multivariate binary logistic regression models were constructed to determine independent predictors of severity.

Results: The study population had a mean age of 60.5 years. The Moderate-Severe Group exhibited significantly higher NLR (6.12 ± 3.41 vs. 2.85 ± 1.20; p < 0.001) and lower LMR (2.15 ± 0.92 vs. 4.22 ± 1.50; p < 0.001) compared to the Mild Group. ROC analysis identified optimal cut-offs of ≥ 4.82 for NLR (AUC: 0.782; Sensitivity: 76.6%) and ≤ 2.89 for LMR (AUC: 0.724; Sensitivity: 71.9%). In the multivariate analysis Model 1, NLR ≥ 4.82 remained an independent predictor of severity (Adjusted Odds Ratio [aOR]: 4.12; 95% CI: 1.78–9.54; p = 0.001). In the separate Model 2, LMR ≤ 2.89 was also confirmed as an independent predictor (aOR: 2.85; 95% CI: 1.24–6.55; p = 0.014).

Conclusion: Elevated NLR and reduced LMR at admission are robust, independent indicators of stroke severity in this Indonesian cohort. These accessible hematological biomarkers reflect the divergent trajectories of post-ischemic neuroinflammation—innate immune hyperactivity and adaptive immune exhaustion. They provide a cost-effective method for risk stratification in resource-limited settings, warranting their integration into routine initial assessment protocols.

Therapeutic Plasma Exchange as Adjuvant Rescue Therapy for Weil’s Disease-Associated Acute Liver Failure in a Hemodialysis-Dependent Patient: A Case Report

Ardana Tri Arianto — 2025-11-21

Background: 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

Ayu Aksara — 2025-11-24

Background: 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 8^th 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.

Achieving Resectability in Giant Primary Breast Leiomyosarcoma Via Transarterial Chemoembolization: A Novel Neoadjuvant Strategy

Alfred Hamonangan L Toruan — 2025-11-25

Background: Primary leiomyosarcoma (LMS) of the breast is an exceptionally rare and aggressive non-epithelial malignancy, constituting less than 0.1% of all breast neoplasms. Due to the scarcity of cases, no standardized consensus exists regarding neoadjuvant protocols. Large, locally advanced tumors often present with chest wall fixation, rendering upfront resection difficult or impossible without extensive morbidity. This study explores the novel application of Transarterial Chemoembolization (TACE)—traditionally reserved for hepatic malignancies—as a neoadjuvant strategy to downstage a giant breast LMS.

Case presentation: We present the case of a 40-year-old female presenting with a rapidly enlarging, painless, giant mass in the right breast measuring 19 x 18 x 15 cm. Clinical and radiological evaluation (CT Thorax) revealed a heterogeneous, hypervascular mass fixed to the pectoralis major muscle, classified as BIRADS 5. Core needle biopsy confirmed high-grade Leiomyosarcoma. Due to the tumor’s size and fixation to the chest wall, the patient underwent preoperative TACE using 35 mg Doxorubicin followed by embolization of the supplying branches of the right internal mammary and thoracoacromial arteries. Post-procedure, the tumor volume significantly decreased (downsized to approx. 15 cm), and critically, the mass detached from the chest wall, becoming mobile. The patient subsequently underwent a successful total mastectomy with clear margins (R0 resection).

Conclusion: TACE offers a promising, minimally invasive neoadjuvant alternative for hypervascular, giant breast sarcomas. By inducing tumor necrosis and reducing vascularity, TACE can facilitate resectability in initially fixed tumors, potentially converting inoperable cases into candidates for R0 resection while minimizing intraoperative blood loss.

The Sandwich Dual-Tissue Salvage: Synergistic Anteriorly-Based Tongue Flap and Autologous Dermofat Graft for Recalcitrant Pittsburgh Class V-VI Palatal Fistulas

Anak Agung Gde Rama Kaesara — 2025-11-27

Background: Recurrent palatal fistulas following cleft palate repair, particularly Pittsburgh Class V and VI defects, represent a distinct reconstructive challenge characterized by tissue ischemia, scarring, and volumetric deficiency. The "failure of failure" in these cases often precludes the use of local mucoperiosteal flaps due to the poor quality of the recipient bed. This study evaluates a standardized "dual-tissue" salvage protocol combining an anteriorly-based dorsal tongue flap with an autologous dermofat graft.

Case presentation: A 21-year-old female with a recurrent, symptomatic Pittsburgh Class V-VI fistula measuring 15 mm by 12 mm underwent a two-stage reconstruction. The surgical protocol involved three distinct layers: (1) nasal lining closure via turnover flaps; (2) interposition of an inguinal dermofat graft oriented with the fatty surface facing the nasal layer to obliterate dead space; and (3) oral coverage using an anteriorly-based tongue flap. Speech outcomes were quantified using the Pittsburgh Weighted Speech Scale (PWSS) by an independent, blinded Speech-Language Pathologist. The procedure successfully achieved complete closure with no evidence of necrosis, dehiscence, or donor site morbidity. The total operative time was 145 minutes. Quantitative assessment revealed a robust improvement in speech resonance; the PWSS score improved from a severe 18/30 pre-operatively to a clinically competent 4/30 at 6 months post-operatively. The dermofat graft maintained volumetric stability, preventing the concave collapse often observed in single-layer repairs.

Conclusion: The sandwich technique potentially reduces recurrence risk in high-grade fistulas by addressing the triad of failure: tension, ischemia, and dead space. The vascularized tongue flap protects the underlying graft, while the dermofat graft acts as a biological spacer and source of adipose-derived stem cells. This protocol offers a reproducible solution for complex craniofacial defects where local tissues are exhausted.

Masquerading as an Orbital Malignancy: A Rare Presentation of Pott’s Puffy Tumor with Intraorbital Extension in a Diabetic Adult

Suhery — 2025-11-28

Background: Pott’s puffy tumor (PPT) is a rare, life-threatening clinical entity characterized by frontal bone osteomyelitis and subperiosteal abscess, typically resulting from untreated frontal sinusitis. While predominantly a pediatric diagnosis, adult presentation is exceptionally rare and often associated with immunocompromised states. The clinical mimicry of PPT, particularly when presenting with bone destruction and orbital extension, frequently leads to misdiagnosis as a malignant neoplasm. This study aims to report a rare and instructive case of Pott’s puffy tumor in a 52-year-old diabetic female.

Case presentation: We report a case of a 52-year-old female with uncontrolled Type 2 Diabetes Mellitus presenting with progressive left ocular proptosis, globe displacement, and blurred vision persisting for two months. Imaging revealed a heterogeneous mass in the frontoethmoidal sinus with extensive osteolytic destruction of the orbital roof and frontal bone, initially raising strong suspicion of a sinonasal malignancy or metastasis. The patient underwent a bicoronal craniectomy and debridement. Intraoperative findings revealed a purulent subperiosteal collection and necrotic bone, confirming the diagnosis of PPT with intraorbital extension. The defect was repaired via craniofacial reconstruction using bone cement. Post-operative culture analysis confirmed a polymicrobial infection.

Conclusion: This case underscores the necessity of maintaining a high index of suspicion for PPT in diabetic adults presenting with proptosis and osteolytic radiographic findings. Although rare, PPT can masquerade as a malignancy. Early recognition and a multidisciplinary approach combining aggressive surgical debridement with targeted antibiotic therapy are imperative to prevent catastrophic intracranial and orbital complications.

Diagnostic Value of Platelet-to-Lymphocyte Ratio Versus Neutrophil-to-Lymphocyte Ratio in Early-Onset Neonatal Sepsis: A Retrospective Analysis in a Limited-Resource Setting

Delicia Rudy — 2025-12-01

Background: Early-onset neonatal sepsis remains a critical cause of mortality in developing nations. Blood culture, the gold standard, suffers from delay and low sensitivity. While hematologic indices such as neutrophil-to-lymphocyte ratio (NLR) are used in adults, their utility in the first 72 hours of life is confounded by physiological instability. This study evaluates the diagnostic accuracy of the platelet-to-lymphocyte ratio (PLR) compared to NLR, mean platelet volume (MPV), and red cell distribution width (RDW) in early-onset neonatal sepsis.

Methods: A retrospective observational study was conducted on 55 neonates (25 septic, 30 symptomatic non-septic controls) at a tertiary center in Indonesia. Sepsis was defined by clinical criteria and C-reactive protein positivity, independent of complete blood count parameters, to avoid incorporation bias. Diagnostic performance was assessed using Mann-Whitney U tests, receiver operating characteristic curve analysis, and multivariable logistic regression to control for confounders, including asphyxia.

Results: The median PLR was significantly lower in the sepsis group compared to controls (32.6 [IQR 3.4–100.4] versus 71.1 [IQR 45.3–82.9]; p = 0.016). Conversely, NLR (p = 0.80), MPV (p = 0.163), and RDW (p = 0.422) showed no significant discrimination. PLR yielded an area under the curve of 0.724. At a cut-off of equal to or less than 40.5, determined by the Youden Index, PLR demonstrated a sensitivity of 68.0%, specificity of 73.3%, positive likelihood ratio of 2.55, and negative likelihood ratio of 0.44. Multivariable regression confirmed PLR as an independent predictor (Adjusted Odds Ratio 0.96; 95% CI 0.93–0.99; p = 0.038) after adjusting for birth asphyxia.

Conclusion: PLR demonstrates superior discriminative ability over NLR for early-onset sepsis in this cohort. The distinct inverse PLR phenomenon reflects sepsis-induced thrombocytopenia and bone marrow suppression. While not a standalone diagnostic tool, PLR serves as a valuable, zero-cost adjunctive marker for risk stratification in resource-limited settings.

Efficacy and Safety of Adjunctive Corticosteroids in Non-HIV Pneumocystis jirovecii Pneumonia with Respiratory Failure: A Systematic Review and Meta-Analysis of Randomized and Observational Studies

Reza Rahmadinata — 2025-12-02

Background: Pneumocystis jirovecii pneumonia in HIV-negative immunocompromised patients carries a mortality rate significantly higher than in the HIV-positive population. While adjunctive corticosteroids are the standard of care for HIV-associated pneumonia to prevent Immune Reconstitution Inflammatory Syndrome, their efficacy in non-HIV patients remains controversial due to differing immunopathogenesis. This study evaluated the efficacy and safety of adjunctive corticosteroids in non-HIV patients with respiratory failure, specifically addressing the discordance between historical observational data and recent randomized evidence.

Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching databases from January 2014 to July 2025. We included randomized controlled trials and observational studies of non-HIV adults with pneumonia receiving adjunctive corticosteroids. To address methodological heterogeneity, we performed stratified analyses separating randomized trial data from observational cohorts and conducted sensitivity analyses to account for outliers. Risk of bias was assessed using Cochrane RoB-2 and the Newcastle-Ottawa Scale.

Results: Ten studies comprising 2,900 patients were analyzed. The randomized trial demonstrated no statistically significant reduction in 28-day mortality with corticosteroids (21.5% vs 32.4%, p=0.069). In the observational arm, initial pooled analysis suggested benefit, but sensitivity analysis removing a large administrative database study shifted the result to null. Crucially, higher cumulative steroid doses were associated with increased 90-day mortality (Hazard Ratio 1.01 per 100mg equivalent; p<0.05) and a significantly increased risk of secondary infections and hyperglycemia. Subgroup analysis revealed no benefit for pulse-dose regimens over standard dosing.

Conclusion: Unlike in HIV, adjunctive corticosteroids do not confer a consistent survival benefit in non-HIV Pneumocystis pneumonia and are associated with dose-dependent toxicity. The routine use of corticosteroids should be abandoned in favor of a cautious approach restricted to severe, early hypoxemia using standard rather than pulse doses.

Impact of Co-existing Adenomyosis on Pain Recurrence Following Deep Endometriosis Excision: A Systematic Review and Meta-Analysis of Multivariate-Adjusted Observational Cohorts

Ninda Frymonalitza — 2025-12-03

Background: Deep endometriosis (DE) represents a severe phenotype characterized by subperitoneal infiltration >5mm. While complete surgical excision is the gold standard, postoperative recurrence of pain and lesions remains clinically significant. Growing evidence implicates co-existing adenomyosis as a prognostic factor, yet its independent impact on DE surgery outcomes is debated.

Methods: We conducted a systematic review and meta-analysis of observational studies published between 2014 and 2025. Data were synthesized from seven high-quality studies involving 2,056 participants, focusing on those utilizing multivariate regression or propensity score matching. The primary outcomes were recurrence of pain (dysmenorrhea, dyspareunia), anatomical lesion recurrence, and surgical complications. Secondary outcomes included fertility.

Results: The prevalence of adenomyosis in DE patients ranged from 35.6% to 49.05%. Patients with adenomyosis had significantly higher preoperative pain scores. Postoperatively, adenomyosis was an independent predictor of pain persistence and lesion recurrence. Extrinsic adenomyosis was associated with a 2.5-fold increased risk of early recurrence (OR 2.5; 95% CI 1.2–3.4). Survival analysis showed a 60% recurrence-free probability at 5 years for those with adenomyosis vs. 81% for those without. Surgical complications were significantly higher in the adenomyosis group (OR 4.56; 95% CI 1.90–11.30).

Conclusion: Co-existing adenomyosis is a robust independent risk factor for failure of DE surgery, leading to persistent pain, lesion recurrence, and increased surgical morbidity. This supports the outside-in theory of pathogenesis. Preoperative screening for adenomyosis via TVS/MRI is mandatory for accurate counseling and surgical planning.

Fatal Disseminated Tuberculosis in Vaccinated Children with Failed BCG Scar Formation: A Clinical-Pathological Correlation and Immunological Review

Delicia Rudy — 2025-12-04

Background: The Bacillus Calmette-Guérin (BCG) vaccine remains the cornerstone of preventative strategies against severe pediatric tuberculosis (TB), specifically disseminated forms such as miliary TB and tuberculous meningitis (TBM). While the formation of a cutaneous scar is historically viewed as a surrogate marker for successful vaccine uptake and delayed-type hypersensitivity (DTH), its absence is often clinically overlooked. This study investigates the correlation between the lack of BCG scarring, immunological anergy, and fatal disseminated disease outcomes.

Case presentation: We report a clinical-pathological analysis of two pediatric patients admitted to a tertiary care center in Indonesia. Case 1, an 11-month-old male vaccinated at birth, presented with status epilepticus and was diagnosed with Probable TBM Stage III. Despite vaccination, he lacked a BCG scar and exhibited Tuberculin Skin Test (TST) anergy (0 mm). Case 2, a 2-year-8-month-old female vaccinated at birth, presented with Type 1 respiratory failure due to severe miliary TB. She demonstrated profound wasting and TST anergy (0 mm). Both patients succumbed to the disease (Day 9 and Day 14, respectively) despite aggressive management.

Conclusion: The absence of a BCG scar in vaccinated children serves as a critical clinical indicator of "immunological silence." It correlates with a failure to mount the Th1-mediated granulomatous response necessary for containing lymphohematogenous spread. We recommend that scar failure be treated as a risk factor requiring enhanced surveillance and a lower threshold for preventative therapy.

Precipitation of Occult Lymphomatous Hemorrhage by Early Initiation of Factor Xa Inhibitors: A Pharmacovigilance Case Study and Critical Reappraisal of DOAC Safety

Kadek Cahya Adwitya — 2025-12-05

Background: The concurrent management of cancer-associated thrombosis (CAT) and active malignancy represents a precarious clinical equilibrium, particularly when the neoplasm involves occult extranodal gastrointestinal (GI) sites. While direct oral anticoagulants (DOACs) have largely supplanted low-molecular-weight heparin (LMWH) as the standard of care for CAT, emerging pharmacovigilance data suggest a specific vulnerability in patients with luminal GI malignancies.

Case presentation: We report the case of a 76-year-old frail female presenting with extensive left iliofemoral deep vein thrombosis (DVT). Diagnostic evaluation identified a perfect storm of pathology: Stage IV diffuse large B-cell lymphoma (DLBCL) with bulky retroperitoneal lymphadenopathy encasing the inferior vena cava (IVC) and a suspicious infiltrative mass in the proximal jejunum. Following standard guidelines, the patient was initiated on rivaroxaban. However, this intervention precipitated a catastrophic upper GI hemorrhage (hemoglobin drop to 6.5 g/dL) within 96 hours. A retrospective pharmacokinetic audit revealed critical predisposing factors: severe hypoalbuminemia (1.6 g/dL) increasing the free drug fraction, and an estimated glomerular filtration rate (eGFR) <30 mL/min, suggesting the patient was effectively overdosed relative to her physiological clearance.

Conclusion: The empiric use of rivaroxaban in elderly patients with uncharacterized abdominal masses, renal impairment, and cachexia carries unacceptable hemorrhagic risks. We advocate for a systematic bleed-risk stratification protocol, prioritizing LMWH or Apixaban, and the judicious use of IVC filters as bridging therapies in high-risk phenotypes.

Tear Reservoir Thickness and Vector-Resolved Refractive Outcomes in Indonesian Corneal Ectasia: A Scleral Lens Pilot Study

Anak Agung Ayu Putri Prematura Sri Anasary — 2025-12-05

Background: Corneal ectasia is characterized by high-order aberrations and irregular astigmatism, presenting significant optical challenges. Scleral lenses neutralize these irregularities via a post-lens tear reservoir. However, the precise optical contribution of the tear reservoir thickness itself to residual refractive error remains under-characterized, particularly in Southeast Asian populations where aggressive ectasia phenotypes are common. This study aimed to determine if tear reservoir thickness correlates with residual refractive error using vector analysis.

Methods: This retrospective pilot study analyzed 12 eyes of 8 patients with severe corneal ectasia fitted with scleral lenses in Indonesia. Refractive outcomes were converted to Thibos power vectors (M, J0, J45). To account for bilateral eye correlations, linear mixed models (LMM) were employed with Patient ID as a random effect. A theoretical thick-lens model compared predicted versus observed over-refraction.

Results: The cohort (mean age 28 ± 10.2 years) achieved significant visual improvement (LogMAR 0.35 to 0.17; p = 0.005). The mean tear reservoir thickness was 263.33 ± 80.92 μm. LMM analysis revealed no statistically significant correlation between fluid thickness and Spherical Equivalent (M) (beta = -0.001, p = 0.72) or Blur Strength (p = 0.68). The theoretical model indicated that residual error was driven by uncorrected posterior corneal astigmatism rather than fluid depth.

Conclusion: In this Indonesian cohort, optical efficacy was driven by refractive index matching at the corneal interface, not reservoir thickness. Clinical fitting should prioritize physiological clearance over refractive manipulation.

Psoriasiform Digital Bowen’s Disease: A Diagnostic Challenge and Short-Term Response to Liquid Nitrogen Cryotherapy

Putu Resika Melarosa — 2025-12-12

Background: Bowen’s disease (BD), or squamous cell carcinoma in situ, classically presents as a slowly enlarging erythematous plaque on sun-exposed skin. However, digital Bowen’s disease represents a distinct and rare clinical subset that frequently poses a significant diagnostic dilemma. Due to its unique anatomical location and morphological variability, digital BD often masquerades as benign inflammatory dermatoses, particularly psoriasis or chronic eczema, leading to dangerous therapeutic delays.

Case presentation: We report the case of a 46-year-old male presenting with a solitary, rough, erythematous plaque on the dorsal aspect of the left index finger that had persisted for one year. The lesion was initially misdiagnosed and treated as an inflammatory condition without success. Detailed dermoscopic evaluation revealed a specific "psoriasiform" vascular pattern characterized by clustered glomerular vessels and surface scaling, raising suspicion for malignancy. Histopathological analysis confirmed the diagnosis of Bowen’s disease, demonstrating full-thickness epidermal atypia with psoriasiform hyperplasia. Notably, the presence of histological koilocytic atypia suggested a potential synergistic etiology involving Human Papillomavirus (HPV) infection alongside chronic ultraviolet exposure. The patient was treated with a tissue-sparing protocol of liquid nitrogen cryotherapy to preserve digital function.

Conclusion: Complete clinical resolution of the lesion was observed at the three-week follow-up interval, resulting in a hypopigmented macule with full preservation of joint mobility. This case highlights the critical necessity of distinguishing "psoriasiform" malignancies from true inflammatory diseases through the recognition of specific vascular arrangements in dermoscopy. Furthermore, it suggests that cryotherapy is a pragmatic, function-sparing alternative to surgical excision for digital malignancies, provided that rigorous long-term surveillance is maintained to monitor for recurrence.

Selective Suppression of Prevotella and Modulation of Oral Dysbiosis in Stunted Children: The Role of Systemic Zinc as a Biological Adjuvant to Mechanical Therapy

Nila Kasuma — 2025-12-13

Background: 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.

Combinatorial Efficacy of Human Mesenchymal Stem Cell Secretome and Ursodeoxycholic Acid in Ameliorating Renal Dysfunction: A Synergistic Approach in a Rat Model of Cholestatic Injury

Mariani Devi — 2025-12-16

Background: Cholestatic nephropathy, historically termed cholemic nephropathy, represents a critical intersection of hepatic and renal pathology where the systemic retention of nephrotoxic cholephiles induces severe acute kidney injury. The pathophysiological cascade involves direct tubular epithelial toxicity, mitochondrial oxidative stress, and intraluminal cast formation driven by hydrophobic bile acids and bilirubin. While ursodeoxycholic acid (UDCA) serves as the standard pharmacological intervention to displace toxic bile salts, its efficacy in reversing established secondary renal injury is limited. The secretome of human mesenchymal stem cells (Hu-MSC-S) has emerged as a potent regenerative agent, rich in trophic factors capable of mitigating inflammation and promoting tissue repair. This study investigates the synergistic potential of combining standard UDCA therapy with Hu-MSC-S to preserve renal excretory function in a surgically induced model of extrahepatic cholestasis.

Methods: A randomized experimental study was conducted using 24 male Wistar rats. Extrahepatic cholestasis was induced via common bile duct ligation (CBDL). Following a 2-week induction period to establish significant hepatic and secondary renal injury, rats were randomized into four groups (n=6): Control (untreated cholestasis), UDCA Monotherapy (4.5 mg/200g body weight orally), Hu-MSC-S Monotherapy (0.2 ml/kg intraperitoneally), and combination therapy (UDCA + Hu-MSC-S). Treatments were administered weekly for four weeks. Renal function was rigorously assessed through serum Urea (Urease-GLDH method) and Creatinine (Kinetic Jaffe method) levels.

Results: The study demonstrated a marked renoprotective gradient across the treatment groups. The untreated Control group exhibited severe renal dysfunction with a mean Urea of 42.60 mg/dL and Creatinine of 3.18 mg/dL. Both monotherapies significantly attenuated these markers compared to controls. However, the Combination group achieved superior efficacy, restoring renal parameters to near-physiological levels (Urea: 13.08 mg/dL; Creatinine: 1.32 mg/dL). Delta analysis confirmed that the combination therapy yielded the highest magnitude of recovery for both markers.

Conclusion: The concurrent administration of Hu-MSC-S and UDCA exerts a potent synergistic effect, significantly ameliorating renal dysfunction in cholestatic rats. The findings suggest that Hu-MSC-S acts as a crucial adjuvant, repairing tubular injury via paracrine mechanisms while UDCA mitigates the primary cholestatic insult, offering a novel multi-target therapeutic strategy for cholemic nephropathy.

Therapeutic Potential of Curcumin in Modulating the HMGB1/TLR4/NF-κB Axis in Polymicrobial Peritonitis: A Systematic Review and Dose-Response Meta-Analysis

Leonardo Aaron Hartanto — 2025-12-18

Background: Polymicrobial peritonitis and its systemic sequela, sepsis, represent a catastrophic dysregulation of the host immune response to infection, leading to multiple organ dysfunction syndrome and high mortality rates. The pathophysiology is driven by a hyperinflammatory cytokine storm followed by immunoparalysis, governed centrally by the high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling axis. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated potent immunomodulatory properties. However, its specific regulatory effects on this molecular axis, particularly regarding dose-dependency and novel cell death pathways like ferroptosis and lactylation, require systematic synthesis.

Methods: A systematic review and meta-analysis were conducted on preclinical and clinical studies published between 2014 and 2025. Ten pivotal manuscripts meeting strict inclusion criteria were analyzed, comprising rodent models of sepsis (Cecal Ligation and Puncture, Zymosan, Lipopolysaccharide) and human clinical trials. Primary outcomes included quantitative expression levels of HMGB1, TLR4, and NF-κB, alongside organ injury scores and survival rates. Secondary outcomes analyzed downstream cytokines (TNF-α, IL-6, IL-1β) and oxidative stress markers. Data were stratified by dosage to evaluate dose-response relationships.

Results: The analysis included data from 218 subjects. curcumin administration significantly attenuated the activation of the HMGB1/TLR4/NF-κB axis across all models. Quantitative analysis revealed a dose-dependent reduction in serum HMGB1 levels and a significant inhibition of NF-κB p65 nuclear translocation (p < 0.001). High-dose curcumin (100–200 mg/kg) exhibited superior efficacy in mitigating multi-organ injury compared to low-dose regimens. Novel mechanisms identified included the suppression of ferroptosis via the upregulation of the ACSL4/GPX4 axis and the inhibition of protein lactylation through p300 downregulation. Clinical data demonstrated that nano-curcumin formulations significantly reduced SOFA scores and inflammatory markers in septic patients, confirming enhanced bioavailability.

Conclusion: Curcumin functions as a robust, pleiotropic inhibitor of the HMGB1/TLR4/NF-κB axis in polymicrobial peritonitis. Its therapeutic efficacy is dose-dependent and involves the regulation of emerging epigenetic and cell death pathways. These findings support the clinical integration of nano-curcumin as an adjuvant therapy for surgical sepsis.

Longitudinal Observational Analysis of Traumatic Brain Injury Epidemiology and Pre-Hospital Intervals During the COVID-19 Pandemic in a West Java Tertiary Center

Ni Wayan Lisa Suasti — 2025-12-18

Background: The COVID-19 pandemic necessitated large-scale social restrictions (PSBB) in Indonesia, drastically altering population mobility and, consequently, the landscape of neurotrauma. While the reduction in road traffic Incidents (RTIs) during lockdowns is well-documented, the collateral impact on the golden hour—the critical pre-hospital interval for traumatic brain injury (TBI) resuscitation—remains under-researched in lower-middle income countries (LMICs). This study analyzes the longitudinal shifts in TBI epidemiology, injury mechanisms, and hospital admission intervals across pre-pandemic, pandemic, and relaxation phases.

Methods: This retrospective observational study analyzed 1,519 TBI patients admitted to the Emergency Department of Dr. Hasan Sadikin General Hospital (RSHS), a tertiary referral center in West Java, from January 2019 to December 2021. The cohort was stratified into three phases: Pre-Pandemic (2019), Pandemic/PSBB (2020), and Relaxation (2021). Variables included demographics, injury mechanisms, Glasgow Coma Scale (GCS), loss of consciousness (LOC), and Hospital Admission Interval (MRS).

Results: Total TBI admissions exhibited a sharp V-shaped trend, decreasing by 75% in 2020 compared to 2019, driven by a collapse in RTI volume (490 to 107 cases). Admissions rebounded in 2021 (n=705). Males (78.4%) and young adults (15-24 years) constituted the majority, with RTI accounting for 74.78% of all mechanisms. While pediatric (0-4 years) and geriatric (≥65 years) groups were prone to falls, the most critical finding concerned pre-hospital delays. Despite reduced traffic density, only 3.23% of patients arrived within the golden hour (<1 hour). The majority (40.42%) arrived between 5-12 hours, and a significant cohort (17.44%) experienced delays exceeding 12 hours, indicating persistent systemic barriers to rapid care regardless of road conditions.

Conclusion: The pandemic successfully suppressed TBI volume through mobility restrictions but failed to improve pre-hospital admission times. The persistence of significant delays (>5 hours) for the vast majority of patients highlights that the barriers to the golden hour in Indonesia are structural rather than traffic-dependent. Future trauma systems must address these pre-hospital inefficiencies to improve outcomes.

The Anicteric Giant: A Rare Case of Giant Choledocholithiasis and Multiple Cholelithiasis Presenting with Paradoxically Normal Bilirubin Profiles

Sujek Miko Eka Putra — 2025-12-18

Background: Giant choledocholithiasis, defined as common bile duct (CBD) calculi exceeding 15 mm, typically presents with Charcot’s triad or marked biochemical cholestasis. The phenomenon of silent or anicteric giant stones remains a dangerous diagnostic blind spot. We present a rare case of a massive biliary stone burden presenting with paradoxically normal bilirubin and liver enzyme profiles, challenging standard screening algorithms.

Case presentation: A 61-year-old female presented with a 12-month history of intermittent epigastric pain and nausea, initially misdiagnosed as gastritis. Despite the chronicity, she denied jaundice or fever. Biochemical analysis revealed a Total Bilirubin of 0.39 mg/dL (Reference: 0.1–1.2 mg/dL) and normal gamma-glutamyl transferase (GGT) levels, indicating an absence of biochemical obstruction. Magnetic resonance cholangiopancreatography (MRCP) identified multiple cholelithiasis and a solitary giant CBD stone. Intraoperative exploration confirmed a CBD dilated to 22 mm containing a calculus measuring 28 mm × 22 mm. Due to the massive ductal dilation and risk of recurrent stasis, the patient underwent a retrograde cholecystectomy followed by biliary reconstruction via Roux-en-Y choledochojejunostomy.

Conclusion: Giant choledocholithiasis can exist in a silent phase due to ductal compliance and the ball-valve mechanism, rendering bilirubin an unreliable screening tool. This case underscores the necessity of cross-sectional imaging in chronic abdominal pain, even when biochemical markers are normal. Roux-en-Y reconstruction remains the definitive management for giant stones in significantly dilated ducts to prevent recurrence and sump syndrome.

Metabolic and Inflammatory Signatures of Neurotrauma: Correlating Early Glycemic and Leukocytic Shifts with Glasgow Coma Scale Scores

Ni Wayan Lisa Suasti — 2025-12-19

Background: 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.

The Hepatotoxicity and Adherence Advantage of Short-Course Rifapentine/Isoniazid (3HP) over Stratified Isoniazid Monotherapy (6H/9H): A Systematic Review and Meta-Analysis

Agus Subhan — 2025-12-19

Background: The global strategy to eliminate tuberculosis hinges critically on neutralizing the latent reservoir. For decades, the standard of care has been daily Isoniazid monotherapy for 6 or 9 months. However, the effectiveness of this regimen is historically compromised by poor adherence due to its duration and significant rates of hepatotoxicity, particularly in older adults. The 3-month once-weekly regimen of Rifapentine plus Isoniazid offers a promising alternative, yet a consolidated high-level analysis comparing it specifically against stratified Isoniazid monotherapy across diverse high-risk groups was necessary to justify global policy shifts.

Methods: We conducted a systematic review and meta-analysis of eight pivotal studies, including large-scale randomized controlled trials and programmatic surveillance studies. Outcomes included prevention of active tuberculosis, Grade 3/4 hepatotoxicity, and treatment completion. Data were pooled using a random effects model to account for clinical heterogeneity. Subgroup analyses stratified comparators by duration and administration method.

Results: The analysis of over 10,000 participants revealed that the short-course regimen was non-inferior to isoniazid monotherapy for tuberculosis prevention (Pooled Risk Ratio 0.54; 95% CI 0.30–0.97). Crucially, the Rifapentine-based regimen demonstrated a profound reduction in grade 3/4 hepatotoxicity compared to Isoniazid monotherapy (Pooled Risk Ratio 0.16; 95% CI 0.08–0.32), with the benefit most pronounced in elderly populations. Treatment completion was significantly higher in the short-course group (Pooled Risk Ratio 1.25; 95% CI 1.15–1.36), with programmatic data confirming adherence exceeding 85% even under self-administration.

Conclusion: The 3-month Rifapentine/Isoniazid regimen offers a superior safety profile and significantly higher treatment completion rates compared to Isoniazid monotherapy while maintaining equivalent efficacy. The regimen’s ability to minimize liver injury while maximizing adherence supports its adoption as a preferred standard of care, particularly for older adults.

The Uncoupling Phenomenon: Dissociation Between Albuminuria and Glomerular Filtration Rate in an Advanced Diabetic Kidney Disease Phenotype

Naufal Fathi Ashari — 2025-12-22

Background: 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.