Vol. 10 No. 4 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Articles
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Levator Ani Avulsion as the Key Mediator Between Vaginal Delivery and Pelvic Organ Prolapse: A Systematic Review and Meta-Analysis of Imaging Studies
Views: 316Downloads: 476Background: Vaginal childbirth is universally recognized as the primary etiological factor for pelvic organ prolapse (POP), yet the precise biomechanical cascade remains a subject of intense investigation. While connective tissue attenuation contributes to support failure, recent advanced imaging evidence suggests that levator ani avulsion (LAA)—a macroscopic traumatic detachment of the puborectalis muscle from the pubic ramus—acts as the fundamental structural mediator. This study aimed to systematically review and meta-analyze imaging-based literature to quantify the mediating role of LAA in the pathogenesis of POP.
Methods: We conducted a systematic review and meta-analysis of observational studies utilizing magnetic resonance imaging (MRI) and 3D/4D Transperineal Ultrasound. The search strategy targeted longitudinal and cross-sectional studies comparing women with confirmed LAA to those with intact pelvic floors following vaginal delivery. Data were extracted regarding the prevalence of avulsion, pelvic organ prolapse quantification (POP-Q) stages, and levator hiatus dimensions. The primary outcome was the Odds Ratio (OR) of significant POP (Stage ³2). Secondary outcomes included quantitative analysis of hiatal ballooning. Data were synthesized using a random-effects model.
Results: The analysis included 3,218 women across 9 high-quality imaging studies. The pooled analysis revealed a profound and statistically significant association between LAA and POP, with a pooled Odds Ratio of 3.84 (95% CI: 2.65–5.56; p < 0.0001). Women with LAA demonstrated a significantly larger levator hiatal area on Valsalva compared to those with intact muscles (Mean Difference: +6.03 cm²), confirming that avulsion leads to intractable hiatal ballooning. Long-term follow-up data (up to 23 years) indicated that this muscular defect does not heal and is associated with a progressive deterioration in pelvic organ support over time.
Conclusion: Levator ani avulsion is the critical biomechanical mediator converting the event of vaginal delivery into the chronic pathology of prolapse. The injury compromises the dynamic closure of the levator hiatus, resulting in hiatal ballooning and subsequent apical and anterior compartment descent. These findings necessitate a paradigm shift in obstetric counseling and emphasize the need for preventative strategies to minimize traumatic muscle injury during the second stage of labor.
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The FAPI-FDG Mismatch: Unmasking an Occult Pancreatic Lesion via Fibroblast Activation Imaging Amidst Negative Glucose Metabolism and Morphological Findings
Views: 179Downloads: 213Background: Fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) has emerged as a promising modality for imaging the tumor microenvironment, specifically targeting cancer-associated fibroblasts (CAFs). While 18F-FDG targets glucose metabolism, 68Ga-FAPI targets stromal activation. Discrepancies between these modalities can offer unique insights into early pathogenesis. We report a rare case of incidental focal pancreatic uptake on 68Ga-FAPI PET/CT in a patient with prostate cancer, occurring in the absence of metabolic activity on 18F-FDG PET/CT or anatomical abnormalities on contrast-enhanced CT.
Case presentation: A 75-year-old male with a history of acinar adenocarcinoma of the prostate (Gleason 7, post-TURP) underwent multimodal staging to evaluate for metastasis. 68Ga-PSMA PET/CT showed intermediate uptake in the prostate but no distant metastasis. Subsequent 68Ga-FAPI-04 PET/CT revealed a striking, intense focal uptake in the pancreatic body. Conversely, follow-up 18F-FDG PET/CT demonstrated physiological background uptake in the pancreas, and abdominal CT showed no pancreatic mass. Laboratory results indicated a slightly elevated CA 19-9 (45.6 U/mL). The findings present a diagnostic dilemma between early stromal-rich malignancy and focal inflammatory processes.
Conclusion: This case highlights the FAPI-FDG Mismatch, suggesting that stromal remodeling may precede metabolic reprogramming and morphological changes in pancreatic lesions. 68Ga-FAPI PET/CT demonstrates superior sensitivity for detecting occult stromal activity, necessitating new diagnostic algorithms for incidentalomas in the era of stromal imaging.
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Circulating Syndecan-1 as a Biomarker of Endothelial Injury and Survival in Hemodialysis: A Systematic Review and Meta-Analysis of Hemodynamic and Prognostic Associations
Views: 209Downloads: 141Background: Cardiovascular disease remains the primary cause of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Conventional risk factors fail to fully explain the high prevalence of resistant hypertension and intradialytic hemodynamic instability in this population. Emerging evidence points to the degradation of the endothelial glycocalyx (eGC), a protective luminal layer regulating vascular tone and permeability. Syndecan-1 (SDC-1), a core component of the eGC, sheds into the circulation during vascular stress. This study aimed to synthesize evidence regarding the magnitude of dialysis-induced SDC-1 shedding and its validity as a prognostic biomarker for survival and vascular stiffness. M
ethods: We conducted a systematic review and associative meta-analysis of observational studies and clinical trials. We searched Scopus, PubMed, and Web of Science for studies quantifying serum SDC-1 in HD patients and relevant physiologic comparators. Data were stratified to analyze three domains: the second hit phenomenon (acute pre- vs. post-dialysis shedding), diagnostic correlations with pulse wave velocity (PWV) and fluid status, and prognostic hazard ratios (HR) for all-cause mortality. A random-effects model was employed to account for population heterogeneity, specifically stratifying hemodialysis cohorts from heart failure comparators.
Results: Ten pivotal studies involving over 1,500 patients were included. The analysis confirmed a substantial acute surge in serum SDC-1 post-hemodialysis (Standardized Mean Difference = 1.24, p < 0.001), indicating that the dialysis procedure actively injures the endothelium. Elevated baseline SDC-1 correlated significantly with arterial stiffness (PWV) and sodium overload, supporting a mechanism of salt-induced vascular stiffening. In prognostic analysis, high SDC-1 was a robust independent predictor of mortality (Pooled HR = 1.65, 95% CI: 1.12–2.43).
Conclusion: Hemodialysis acts as a vascular stressor, triggering acute shedding of the endothelial glycocalyx. This shedding is mechanistically linked to sodium dysregulation and vascular stiffness, independent of traditional uremic toxins. SDC-1 serves as a valuable prognostic marker for endothelial health and survival, suggesting a need for endothelium-protective dialysis strategies.
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Utility of Tc-99m DTPA Hybrid SPECT/CT Cisternography in the Detection of Occult Postoperative CSF Fistula in an Infant with Lipomeningomyelocele: A Diagnostic Challenge and Technical Considerations
Views: 215Downloads: 340Background: Lipomeningomyelocele represents a complex spectrum of closed spinal dysraphism where surgical repair is frequently complicated by cerebrospinal fluid leakage. While overt fistulas are clinically apparent, occult or intermittent leaks in the pediatric population pose a severe diagnostic challenge. Magnetic resonance imaging, despite being the anatomical gold standard, frequently fails to distinguish active extravasation from postoperative seroma or edema due to overlapping signal intensities. This study evaluates the diagnostic superiority of Tc-99m DTPA Hybrid SPECT/CT cisternography in resolving this dilemma.
Case presentation: A 5-month-old female underwent resection of a large lumbosacral lipomeningomyelocele. Postoperatively, she developed persistent, clear fluid discharge from the incision, suggestive of a fistula, yet initial surgical re-exploration was inconclusive. The patient underwent radionuclide cisternography using 37 MBq of intrathecal Tc-99m DTPA. Standard planar scintigraphy at 1 hour and 3 hours was equivocal due to background renal activity. However, Hybrid SPECT/CT performed at 3 hours precisely localized an abnormal radiotracer tract extending from the thecal sac at L5 into the right multifidus muscle, a finding invisible on conventional imaging.
Conclusion: The integration of physiological flow data from scintigraphy with the anatomical specificity of low-dose CT allows for the detection of slow-flow, occult leaks that evade MRI. In infants with distorted post-surgical anatomy, Hybrid SPECT/CT should be elevated from a problem-solving tool to a primary diagnostic modality when clinical suspicion persists. The technique facilitates targeted repair, minimizing morbidity in this vulnerable population.
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Metabolic Dysfunction Precedes Dopaminergic Loss in Early MSA-C: A Discordant 18F-FDG PET and 99mTc-TRODAT-1 Case Study
Views: 177Downloads: 199Background: Differentiating early-stage multiple system atrophy-cerebellar type (MSA-C) from other ataxia syndromes presents a significant diagnostic challenge. While striatal dopaminergic denervation is a hallmark of synucleinopathies, it may be absent in the early stages of the cerebellar subtype. This study investigates the temporal dissociation between metabolic and dopaminergic biomarkers.
Case Presentation: We report a 48-year-old male presenting with a 5-year history of progressive cerebellar ataxia and mild Parkinsonism, resistant to dopaminergic therapy. Written informed consent was obtained from the patient for the publication of this case details and images. To exclude mimics, a basic metabolic workup and High-resolution 3T MRI were performed. MRI revealed mild cerebellar atrophy but lacked the specific hot cross bun sign. Wilson’s disease screening was negative. Due to limited resources, advanced genetic panels for spinocerebellar ataxias were not performed. The patient underwent dual-modality molecular imaging. On Day 1, 18F-FDG PET/CT demonstrated profound hypometabolism in the cerebellum (Cerebellum/Whole-Brain SUVr: 0.68) and pons (SUVr: 0.72). Conversely, on Day 30, 99mTc-TRODAT-1 SPECT revealed robust, symmetrical striatal uptake with Specific Binding Ratios (SBR) of 1.15 (Right) and 1.12 (Left), indicating preserved presynaptic dopamine transporter density.
Conclusion: This case illustrates a critical temporal dissociation in MSA-C pathophysiology: widespread pontocerebellar metabolic failure occurs prior to structural nigrostriatal degeneration. Clinicians must recognize that a normal DAT scan does not exclude MSA-C. In limited-resource settings where genetic testing is unavailable, 18F-FDG PET offers superior sensitivity in the early diagnostic window to support the diagnosis.
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Therapeutic Outcomes of Secukinumab 300 mg in Severe Psoriasis Vulgaris with Metabolic Comorbidities: A Retrospective Cohort Study in Bali
Views: 224Downloads: 218Background: Psoriasis vulgaris is a systemic inflammatory disease increasingly prevalent in Southeast Asia, often complicated by metabolic syndrome. While Secukinumab, an IL-17A inhibitor, is established in Western cohorts, real-world data on its efficacy in Indonesian populations with high adiposity burdens are scarce. This study evaluates the therapeutic response and safety of Secukinumab 300 mg in a Balinese cohort characterized by severe disease and metabolic risk factors.
Methods: We conducted a retrospective cohort study at a tertiary referral center in Bali from January 2023 to December 2024. The study included 39 adult patients with moderate-to-severe psoriasis treated with Secukinumab 300 mg. The primary endpoint was the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) at Week 17. Fisher’s Exact Test was employed to analyze response differences between obese and non-obese subgroups.
Results: The cohort exhibited a high systemic burden: 44.2% were obese (Body Mass Index greater than or equal to 25 kg/m2), and 53.8% had concomitant psoriatic arthritis. Baseline disease severity was high with a median body surface area of 25.0%. At week 17, 32 patients (82.1%; 95% confidence interval: 67.3–91.0%) achieved PASI 75. Subgroup analysis revealed no statistically significant difference in response rates between obese and non-obese patients (p > 0.99), suggesting efficacy is maintained despite metabolic burden. No severe adverse events or discontinuations were documented in the medical records.
Conclusion: Secukinumab 300 mg demonstrates substantial efficacy in an Indonesian population with a severe phenotypic profile, maintaining therapeutic clearance in metabolically compromised patients. The safety profile appears favorable, though limited by retrospective data capture.
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The Cardiovascular Burden of Fine Particulate Matter in Asia: A Systematic Review and Meta-Analysis of Hypertension Risk
Views: 170Downloads: 151Background: The epidemiological transition in Asia has precipitated a double burden of disease, where rapid industrialization intersects with an aging demographic to drive a surge in cardiovascular mortality. Hypertension remains the predominant modifiable risk factor in this context. While the correlation between fine particulate matter (PM2.5) and elevated blood pressure is documented in Western literature, evidence regarding Asian populations remains fragmented. This region faces a unique toxicological phenotype characterized by extreme exposure concentrations, distinct particulate composition including biomass and dust, and specific genetic susceptibilities, necessitating a dedicated regional analysis.
Methods: We conducted a systematic review and meta-analysis of observational studies published between 2017 and 2024, searching PubMed, Scopus, and Embase. We critically appraised exposure assessment methods, distinguishing between satellite-based estimates and ground monitoring, and performed a quality audit using the Newcastle-Ottawa Scale. To minimize temporal bias, we stratified analyses by study design into Incident Hypertension (Cohort studies) and Prevalent Hypertension (Cross-sectional studies).
Results: Nine pivotal studies encompassing over 600,000 participants from China, Taiwan, India, South Korea, and Thailand were synthesized. The random-effects meta-analysis revealed a significant pooled Hazard Ratio of 1.12 (95% CI 1.06 to 1.18) per 10 micrograms per cubic meter increase in long-term PM2.5. Heterogeneity was significant (I2 equals 90.2%), driven by regional variations. High-altitude cohorts in Tibet and high-exposure regions in India demonstrated synergistic risks with Odds Ratios exceeding 1.50 compared to moderate-exposure regions in Taiwan.
Conclusion: Long-term PM2.5 exposure is a potent, independent driver of hypertension in Asia. The data suggest a synergistic interaction between hypoxia and pollution, and a non-linear dose-response curve at high concentrations. Clinicians should consider residence in high-pollution zones a cardiovascular risk enhancer equivalent to traditional risk factors.
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Feasibility of Facial Nerve Preservation in Locally Advanced Parotid Squamous Cell Carcinoma Following Extended Neoadjuvant Chemotherapy: A Case Report
Views: 191Downloads: 177Background: Primary squamous cell carcinoma (SCC) of the parotid gland is a rare, aggressive malignancy often requiring radical parotidectomy with facial nerve sacrifice, particularly in T4b stage disease. The utility of neoadjuvant chemotherapy (NACT) in downstaging these tumors to facilitate functional nerve preservation remains controversial and under-reported in the literature.
Case presentation: A 58-year-old male presented with a fixed, rapidly enlarging left preauricular mass classified as cT4bN2M0 (Stage IVA). The tumor involved the sternocleidomastoid muscle and encased the external carotid artery. Following a multidisciplinary tumor board decision, the patient underwent an extended course of six cycles of Paclitaxel and Carboplatin. The tumor exhibited a partial clinical response and significant central necrosis on imaging. Subsequently, a total parotidectomy was performed. Despite intraoperative fragility and adherence to deep vascular structures, the main trunk and primary divisions of the facial nerve were anatomically and functionally preserved. Histopathology confirmed high-grade SCC with perineural invasion limited to the distal excised branches, achieving clear margins. The patient received 66 Gy of adjuvant radiotherapy. At the 18-month follow-up, the patient remains disease-free with House-Brackmann Grade I facial function.
Conclusion: Long-term facial nerve preservation is feasible in selected cases of locally advanced parotid SCC using a multimodal approach. Extended NACT may induce tumor necrosis and facilitate dissection along the neuro-vascular interface, provided that perineural invasion does not involve the main nerve trunk.
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Immediate Reconstruction of Massive Gluteal Defects Following Giant Malignant Peripheral Nerve Sheath Tumors Excision: Application of the Fasciocutaneous Rotational Flap in a Resource-Stratified Setting
Views: 188Downloads: 214Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas often requiring radical excision. In the gluteal region, achieving oncological clearance for giant tumors creates massive defects characterized by dead space and tension. This study evaluates the utility of the fasciocutaneous rotational flap for immediate closure when free tissue transfer is unavailable.
Case presentation: A 56-year-old female presented with a rapidly enlarging, Grade III MPNST on the right buttock measuring 18 cm in diameter. Wide local excision resulted in a defect measuring 18 cm by 16 cm by 10 cm, exposing the gluteus maximus. Due to resource limitations preventing intraoperative frozen section analysis, wide anatomical clearance was prioritized. Immediate reconstruction was performed using a random-pattern fasciocutaneous rotational flap based on inferior gluteal artery perforators. The flap arc length measured 52 cm with a 1:3.25 defect-to-arc ratio. Postoperative histopathology confirmed Grade III MPNST with positive deep margins (R1), necessitating adjuvant radiotherapy. The flap healed completely by day 14 without necrosis, and the patient was discharged on day 5. At the 3-month follow-up, the wound remained stable with no dehiscence during radiation.
Conclusion: The gluteal fasciocutaneous rotational flap is a robust technique for closing massive defects where primary closure is impossible. While it provides excellent durable coverage for adjuvant therapy, the inability to confirm negative margins intraoperatively poses significant oncological risks. Immediate flap coverage should be weighed carefully against staged reconstruction in resource-stratified settings.
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From Nasal Vestibulitis to Maxillofacial Abscess: Reconstruction of Extensive MRSA-Induced Defects in a Diabetic Patient
Views: 225Downloads: 377Background: Nasal vestibulitis is frequently regarded as a benign localized infection. However, in immunocompromised hosts, specifically those with uncontrolled diabetes mellitus, it can rapidly escalate into a life-threatening maxillofacial abscess involving the danger triangle of the face. The synergistic destructive potential of Methicillin-resistant Staphylococcus aureus (MRSA) and hyperglycemia poses a formidable challenge for reconstructive surgery due to extensive tissue necrosis and compromised microvasculature. This study evaluates the efficacy of a dual-flap approach—combining Rotation and V-Y Advancement flaps—for restoring extensive midfacial defects.
Case presentation: A 51-year-old male with uncontrolled Type 2 Diabetes presented with a massive, ruptured maxillofacial abscess originating from neglected nasal vestibulitis exacerbated by rhinotillexomania. The infection resulted in extensive necrosis spanning the nasal dorsum, infraorbital regions, and forehead. Microbiological analysis confirmed MRSA. Laboratory markers indicated severe sepsis with leukocytosis of 34,840 /mm³ and hyperglycemia of 328 mg/dL. Following acute stabilization and surgical debridement, the patient sustained a complex soft-tissue defect crossing multiple aesthetic subunits. A staged reconstruction was performed three weeks post-debridement. A V-Y advancement flap was utilized for the infraorbital and medial cheek defects to minimize ectropion risk, while a rotation flap was designed for the glabella and nasal dorsum to recruit forehead tissue.
Conclusion: The combination of V-Y advancement and rotation flaps provides a robust, anatomically adaptable, and aesthetically superior solution for complex midfacial defects where skin laxity is compromised. This approach allows for tension-free closure in the aesthetic subunits of the face, even in patients with compromised perfusion due to diabetes. Early recognition of MRSA in diabetic vestibulitis is critical to preventing catastrophic tissue loss.
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Modular Megaprosthesis as a Definitive Salvage Strategy for Recalcitrant Distal Femoral Non-Unions: A Biological and Mechanical Reset in the Hostile Environment
Views: 158Downloads: 168Background: The management of recalcitrant distal femoral non-unions characterized by massive bone loss and exhausted biological potential presents a formidable challenge in orthopedic surgery. This study evaluates the early functional outcomes and safety of modular knee megaprostheses as a radical salvage strategy, utilizing oncologic reconstructions as a benchmark for comparative analysis.
Methods: A descriptive case series of eight consecutive patients, including six oncologic and two non-oncologic cases, was conducted between December 2022 and March 2025. Non-oncologic cases involved elderly patients with a mean age of 48.5 years and multiple failed prior fixations. A standardized infection rule-out protocol was strictly applied, involving serological markers and joint aspiration. Functional outcomes were quantified using the Musculoskeletal Tumor Society (MSTS) score with a mean follow-up of 14.8 months.
Results: The mean MSTS score across the cohort was 20.2 out of 30. Non-oncologic patients demonstrated lower physical performance scores, averaging 18.5 compared to 20.8 in the oncologic group, primarily due to long-standing disuse atrophy and age-related confounders. However, these patients reported significantly higher emotional acceptance, averaging 4.5 out of 5, following the immediate restoration of limb stability. No acute periprosthetic infections or mechanical failures were observed within the short-term follow-up period.
Conclusion: Megaprosthesis serves as a viable biological and mechanical reset for complex non-unions, converting a failed biological healing process into a reliable mechanical solution. While the procedure requires rigorous infection screening and carries long-term risks, it offers immediate stability and transformative pain relief in elderly or multiply-operated patients.
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Axial Length as the Primary Determinant of Refractive Severity in High Myopia: A Swept-Source OCT Analysis
Views: 176Downloads: 131Background: The escalating prevalence of high myopia represents a critical global health crisis, particularly in Southeast Asia. This pathological refractive status is driven by complex structural changes, primarily axial elongation, which predisposes the eye to sight-threatening complications. While the dominance of axial length in myopia is established, the compensatory role of the anterior segment—specifically whether the cornea or anterior chamber undergoes adaptive morphological changes to counteract elongation—remains a subject of debate. This study utilized high-resolution Swept-Source Optical Coherence Tomography (SS-OCT) to precisely quantify the relationship between Spherical Equivalent (SE) and ocular biometric parameters, isolating the specific contributions of posterior segment elongation versus anterior segment adaptation.
Methods: This observational analytic study with a cross-sectional design was conducted at the Ophthalmology Clinic of Dr. M. Djamil General Hospital, Padang, Indonesia. The study recruited patients aged 18–40 years diagnosed with high myopia (SE defined as -6.00 Diopters or worse). Strict exclusion criteria were applied to eliminate confounding anterior segment pathologies. Ocular biometry was performed using the IOLMaster 700, which employs Swept-Source OCT technology for full-eye length tomography. We analyzed Axial Length (AL), Mean Keratometry (K), Central Corneal Thickness (CCT), and Anterior Chamber Depth (ACD). Statistical analysis utilized Pearson and Spearman correlation tests and linear regression modelling.
Results: A total of 32 eyes from 32 high myopia patients were analyzed. The mean SE was -8.14 plus or minus 2.09 D, and the mean AL was 26.93 plus or minus 1.92 mm. We found a robust, statistically significant negative correlation between SE and AL (r = -0.86; p less than 0.001), confirming AL as the primary determinant of refractive severity. Notably, a moderate negative correlation was observed between AL and K (r = -0.41; p = 0.02), indicating a paradoxical corneal flattening in longer eyes. No significant correlations were found between SE and CCT or ACD.
Conclusion: Axial elongation is the predominant structural mechanism driving high myopia in this cohort. The study identified a distinct compensatory response where the cornea flattens as the eye elongates; however, this emmetropization mechanism is insufficient to neutralize the profound refractive shift caused by posterior segment expansion. These findings suggest that high myopia is a disease of focal posterior scleral remodelling rather than global ocular expansion.
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Beyond Revascularization: Impact of Exercise-Based Cardiac Rehabilitation on Functional Capacity in ACS Complicated by Heart Failure – A Systematic Review and Meta-Analysis
Views: 213Downloads: 119Background: Acute coronary syndrome (ACS) complicated by heart failure (HF) represents a distinct, high-risk phenotype. Even after successful revascularization via percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), these patients remain vulnerable to maladaptive ventricular remodeling and functional decline. The role of exercise-based cardiac rehabilitation (CR) in this specific "double-hit" population remains underutilized and inconsistently applied. This study aimed to evaluate the effectiveness of exercise-based CR on functional capacity, left ventricular ejection fraction (LVEF), and major adverse cardiac and cerebrovascular events (MACCE) in patients with ACS complicated by HF following revascularization.
Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and high-quality cohort studies published between 2019 and 2025. Seven pivotal studies involving 23,663 participants were analyzed. The primary outcome was functional capacity, measured by the 6-Minute Walk Distance (6MWD) or peak oxygen consumption (VO2peak). Secondary outcomes included LVEF and MACCE. Data were pooled using random-effects models.
Results: Implementation of CR was associated with a statistically significant improvement in functional capacity (Standardized Mean Difference [SMD] 1.66; 95% Confidence Interval [CI] 0.11–3.22; p=0.04). Cardiac function analysis revealed a clinically meaningful increase in LVEF (Mean Difference +2.58%; 95% CI -0.29 to 5.46; p=0.08) in the CR group. Furthermore, participation in CR was associated with a reduction in the risk of MACCE (Hazard Ratio [HR] 0.80; 95% CI 0.62–1.03; p=0.09), with long-term survival benefits observed in large cohort subsets.
Conclusion: Exercise-based CR provides critical physiological benefits beyond those achieved by revascularization alone. The significant restoration of functional capacity and favorable effects on cardiac remodeling underscore CR as an essential, non-negotiable pillar of care for patients with ACS complicated by heart failure.
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Eosinophilic Pustular Folliculitis Mimicking Varicella: A Diagnostic Challenge in an Adolescent Patient
Views: 217Downloads: 202Background: Eosinophilic pustular folliculitis (EPF), or Ofuji disease, is a rare non-infectious inflammatory dermatosis typically affecting middle-aged adults. Its clinical resemblance to infectious exanthems often leads to significant diagnostic delays, particularly in atypical age groups.
Case presentation: A 15-year-old male presented with a one-month history of progressive erythematous papules, pustules, and crusted erosions distributed across the face, trunk, and extremities. The patient was initially misdiagnosed with varicella and treated with acyclovir without clinical response. Physical examination and Gram staining ruled out primary bacterial infections. Laboratory investigations revealed significant peripheral eosinophilia (12.3%). A 5-mm punch biopsy confirmed the diagnosis, showing dense eosinophilic and neutrophilic infiltration of the hair follicles and peri-adnexal structures. Management with systemic and topical corticosteroids led to rapid resolution of lesions and normalization of eosinophil levels.
Conclusion: This case underscores the necessity of considering EPF in the differential diagnosis of persistent papulopustular eruptions in adolescents. Early histopathological intervention is critical to prevent unnecessary antimicrobial therapy and ensure targeted anti-inflammatory treatment.
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Comparative Long-Term Durability and Repeatability of Selective versus Argon Laser Trabeculoplasty in Open-Angle Glaucoma: A Systematic Review and Meta-Analysis
Views: 185Downloads: 125Background: Primary open-angle glaucoma (POAG) represents a chronic, progressive optic neuropathy necessitating sustained intraocular pressure (IOP) reduction to prevent irreversible visual field loss. For decades, argon laser trabeculoplasty (ALT) served as the standard laser intervention, yet its utility was circumscribed by thermal coagulative damage to the trabecular meshwork, rendering repeat treatments ineffective. Selective laser trabeculoplasty (SLT), utilizing selective photothermolysis, offers a theoretical advantage in tissue preservation. This study performed a systematic review and meta-analysis to evaluate the comparative long-term durability and repeatability of SLT versus ALT to determine the superior modality for chronic glaucoma management.
Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines using data from nine essential manuscripts encompassing randomized controlled trials and comparative cohort studies published between 1999 and 2025. The primary outcome was the standardized mean difference (SMD) in IOP reduction at 12 months and beyond. Secondary outcomes included medication burden reduction and success rates of repeat treatments. Statistical analysis utilized a random-effects model to calculate pooled SMD and 95% confidence intervals (CI).
Results: The analysis comprised data from over 800 eyes across diverse demographic cohorts. In the direct comparison of long-term efficacy, SLT demonstrated a non-inferior IOP reduction profile compared to ALT (Pooled SMD: -0.12; 95% CI: -0.28 to 0.05). However, SLT demonstrated statistically superior outcomes in medication reduction, with patients requiring significantly fewer adjuvant hypotensive drops post-laser (SMD: -0.45; 95% CI: -0.68 to -0.22). Repeatability analysis indicated that repeat SLT achieved a 67% success rate in maintaining drop-free status for 18 months, whereas repeat ALT efficacy was negligible due to trabecular scarring.
Conclusion: While both modalities effectively lowered IOP initially, SLT demonstrated superior long-term utility driven by significant medication reduction and a favorable safety profile for repeatability. The absence of coagulative damage in SLT supports its positioning as the primary laser intervention, offering a sustainable paradigm that ALT cannot match.
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Laparoscopic Versus Open Resection Following Stent-Bridge to Surgery for Obstructive Colorectal Cancer: A Systematic Review and Meta-Analysis of Perioperative Outcomes
Views: 161Downloads: 120Background: Obstructive colorectal cancer (OCRC) constitutes a surgical emergency historically managed by immediate open resection, a procedure fraught with elevated morbidity and mortality rates due to the physiological derangement of the patient. The paradigm of bridge to surgery (BTS) utilizing self-expanding metal Stents (SEMS) successfully transformed this emergency clinical scenario into an elective one, allowing for physiological optimization. However, the subsequent surgical approach—Laparoscopic (LAP) versus Open (OPEN) resection—remains a subject of intense debate. While laparoscopy offers minimally invasive benefits, concerns persist regarding technical difficulty due to stent-induced inflammation and potential oncologic compromise.
Methods: A systematic review and meta-analysis were conducted utilizing ten pivotal cohort studies derived from high-impact surgical databases. The study population consisted of patients with malignant large bowel obstruction who underwent successful SEMS decompression followed by curative resection. The intervention group comprised patients undergoing laparoscopic resection, while the control group underwent open resection. Primary endpoints included operative time, intraoperative blood loss, and length of hospital stay. Secondary endpoints encompassed oncologic lymph node harvest and postoperative complications including surgical site infection (SSI), anastomotic leakage, and postoperative ileus. Data were analyzed using a random-effects model to calculate Mean Differences (MD) and Risk Ratios (RR).
Results: The analysis synthesized data from 1,023 patients across ten studies. The laparoscopic approach resulted in a statistically significant reduction in intraoperative blood loss (Standardized Mean Difference -0.84; p < 0.001) and a shorter length of hospital stay (Mean Difference -3.12 days; p < 0.001). Conversely, the operative duration was significantly prolonged in the laparoscopic group (Mean Difference +24.50 minutes; p = 0.002). In terms of morbidity, laparoscopy demonstrated a protective effect, significantly reducing the risk of surgical site infection (Risk Ratio 0.42; p = 0.003) and postoperative ileus (Risk Ratio 0.58; p = 0.04). Oncologic safety, measured by lymph node yield, showed no significant disparity between the two approaches (p = 0.76).
Conclusion: Laparoscopic resection following stent placement served as a superior surgical strategy compared to open resection in the elective setting for obstructive colorectal cancer. It provided enhanced short-term recovery and reduced complication rates without compromising oncological radicality. The observed increase in operative time reflected the technical complexity of the post-stent anatomy but did not negate the perioperative benefits.
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Vascular Architecture Alterations Independent of Lipid Profiles: The Paradoxical Dissociation between Dyslipidemia and Carotid Intima-Media Thickness in Obese Adolescents
Views: 137Downloads: 151Background: Adolescent obesity is a global epidemic that initiates subclinical atherosclerosis. While lipid profiles are traditional markers, their correlation with structural vascular changes in the pediatric population remains a subject of intense academic debate. This study evaluates the relationship between traditional lipid parameters and carotid intima-media thickness (CIMT) in obese high school students.
Methods: An observational cross-sectional study was conducted between January 2025 and January 2026 involving 45 obese adolescents aged 15 to 18 years in Padang, Indonesia. Nutritional status was determined using the CDC 2000 growth charts, specifically targeting those with a body mass index at or above the 95th percentile. CIMT was measured via high-resolution B-mode ultrasonography. Lipid profiles, including total cholesterol, triglycerides, HDL, and LDL, were analyzed through laboratory testing. Statistical analysis utilized Fisher’s exact test through SPSS version 22.
Results: The subjects, of whom 68.9 percent were female, had a median BMI of 29.34 ± 2.03 kg/m². Remarkably, 68.9 percent exhibited CIMT thickening above the 75th percentile. Bivariate analysis revealed no significant association between CIMT and total cholesterol (p=0.402), triglycerides (p=0.696), HDL (p=0.563), or LDL (p=1.000).
Conclusion: Vascular remodeling in obese adolescents occurs independently of circulating lipid levels, suggesting that chronic inflammation may drive early atherosclerosis before clinical dislipidemia manifests.
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The Large-Mass Phenotype of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Clinicopathological Analysis of 37 Cases in Indonesia Using WHO 2021 and Modified Stanford Criteria
Views: 192Downloads: 160Background: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) presents a diagnostic dilemma, especially in Southeast Asian populations, where delayed presentation often leads to advanced tumor burden. This study aimed to characterize the clinicopathological profile of STUMP in Indonesia using the 2021 WHO Classification and modified Stanford parameters.
Methods: A descriptive study analyzed 37 STUMP cases diagnosed between 2023 and 2025 at a tertiary referral center in West Sumatra. A panel of pathologists re-evaluated archival slides for atypia, mitotic activity, necrosis, and growth patterns, establishing inter-observer reliability. Fisher’s Exact Test was employed to correlate tumor size with morphological markers of aggression.
Results: The cohort demonstrated a distinct large-mass phenotype, with 54.1% of tumors exceeding 10 cm and a median diameter of 14.5 cm. Pathological review classified 56.8% of cases into WHO Group 4 (atypia with ambiguous mitosis). A statistically significant correlation was identified between tumor size >10 cm and the presence of infiltrative growth margins (81.1%; p=0.034).
Conclusion: Indonesian STUMP cases are distinctively characterized by massive size and high rates of infiltrative growth, likely driven by prolonged natural history. The prevalence of ambiguous mitotic figures underscores the utility of the WHO Group 4 category in resource-limited settings. These findings advocate for aggressive surgical management and wider resection margins in large-mass variants to mitigate local recurrence risk.
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Beyond Serum Creatinine: Urinary KIM-1 as a Predictive Biomarker for Subclinical Acute Kidney Injury and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis
Views: 179Downloads: 153Background: The global burden of chronic kidney disease (CKD) is escalating, requiring earlier and more precise diagnostic modalities. Traditional reliance on serum creatinine and glomerular filtration rate (GFR) creates a significant blind spot regarding structural tubular integrity. A dangerous diagnostic window known as subclinical acute kidney injury (AKI) exists when tubular damage progresses despite preserved filtration function. This study aims to systematically analyze the diagnostic accuracy of urinary kidney injury molecule-1 (uKIM-1) in detecting subclinical injury and quantify its predictive value for CKD progression in populations where serum creatinine fails to provide an early warning.
Methods: A systematic review and meta-analysis of five pivotal studies were conducted, encompassing experimental models of ischemia-reperfusion and human cohorts involving Autosomal Dominant Polycystic Kidney Disease (ADPKD), Diabetic Nephropathy, and Contrast-Induced AKI. Data were synthesized using random-effects models to calculate Standardized Mean Differences (SMD) and pooled Hazard Ratios (HR) to assess the prognostic value of uKIM-1 for long-term renal decline.
Results: The analysis demonstrated that uKIM-1 levels remained significantly elevated during apparent functional recovery where serum creatinine had returned to baseline. In experimental models, persistent uKIM-1 elevation correlated strongly with histological evidence of interstitial fibrosis (r > 0.70). Clinical cohorts revealed that elevated KIM-1 is a robust independent predictor of progression to ESRD, with hazard ratios ranging from 1.34 to 3.30. Pooled analysis showed a Risk Ratio of 2.45 (95% CI: 1.55 – 3.88; p < 0.0001).
Conclusion: Urinary KIM-1 serves as a sensitive and specific biomarker for subclinical tubular injury, identifying the at-risk"phenotype missed by creatinine. Its persistent elevation signifies maladaptive repair and predicts the transition from AKI to CKD, supporting its clinical integration for early risk stratification.
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Precision Recovery in Interventional Pulmonology: A Randomized Controlled Trial Comparing Propofol Target-Controlled Infusion versus Sevoflurane Inhalation on Emergence Kinetics and Hemodynamic Stability
Views: 158Downloads: 244Background: Achieving a rapid and high-quality recovery is a cornerstone of modern procedural sedation, particularly in high-turnover ambulatory bronchoscopy suites. Patients presenting for bronchoscopy often exhibit significant pulmonary pathology, including ventilation-perfusion mismatch, which may theoretically impede the alveolar washout of volatile anesthetics. This study aimed to compare the recovery kinetics, hemodynamic stability, and adverse event profiles of Propofol Target-Controlled Infusion (TCI) utilizing the Schnider model versus standard Sevoflurane inhalational anesthesia.
Methods: In this single-blind, prospective, randomized controlled trial, 36 adult patients (ASA I–III) undergoing elective flexible bronchoscopy were recruited. Participants were randomly allocated to receive either Propofol TCI (Group P; Schnider model, target effect-site concentration 4–6 micrograms/mL) or Sevoflurane (Group S; 2 volume percent). The depth of anesthesia was strictly titrated using Bispectral Index (BIS) monitoring to maintain a range between 40 and 60. The primary outcome was recovery time, defined as the duration from anesthetic discontinuation to eye-opening upon verbal command. Secondary outcomes included intraoperative hemodynamic stability (Mean Arterial Pressure and Heart Rate), BIS values at the moment of emergence, and the incidence of postoperative nausea and vomiting (PONV).
Results: The Propofol TCI group demonstrated a statistically significant reduction in recovery time (9.72 ± 1.52 minutes) compared to the Sevoflurane group (12.11 ± 1.49 minutes; p < 0.001). Procedural duration was comparable between groups (p = 0.412), eliminating surgical time as a confounding variable. Group P exhibited superior hemodynamic stability, with significantly less deviation from baseline Mean Arterial Pressure at 10 and 15 minutes into the procedure (p < 0.05). Furthermore, BIS values at the moment of eye-opening were significantly higher in Group P (88.4 ± 4.2) compared to Group S (82.1 ± 5.1; p = 0.021), suggesting a distinct emergence neurophysiology. The incidence of PONV was notably lower in the Propofol group (5.5 percent) compared to the Sevoflurane group (22.2 percent).
Conclusion: Propofol target-controlled infusion facilitates significantly faster emergence and greater hemodynamic stability than Sevoflurane in patients undergoing flexible bronchoscopy. The pharmacokinetic independence of Propofol from pulmonary gas exchange offers a distinct physiological advantage in this specific patient population. These findings support the adoption of TIVA-TCI as the standard of care for optimizing throughput in interventional pulmonology.
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Periosteal Stripping Induces Comparable Early Callus Formation but Late-Phase Regression: A Histomorphometric and Machine-Learning Analysis in a Rat Femoral Fracture Model
Views: 198Downloads: 158Background: The periosteum is critical for fracture healing, serving as a reservoir for osteoprogenitor cells and vascular supply. A clinical paradox exists where periosteal stripping is considered detrimental yet is historically associated with hypertrophic overgrowth. This study investigates the temporal paradox of periosteal stripping, testing the hypothesis that it induces a biphasic response characterized by early inflammatory compensation followed by late-phase regenerative failure.
Methods: Twenty-four male Sprague-Dawley rats were randomized into four groups (n=6/group): Intact Periosteum (PI) and Periosteal Stripping (PS), evaluated at 14 and 28 days post-fracture. Mid-diaphyseal femoral fractures were stabilized with 1.0 mm K-wires. Healing was quantified using a validated Modified Allen-Huo Histological Score (0-10) and Trainable Weka Segmentation (TWS) for tissue classification. Osteoclast activity was assessed via Tartrate-Resistant Acid Phosphatase (TRAP) staining.
Results: At Day 14, the PS group exhibited healing comparable to the PI group (Median Score: 8.0 [IQR 8.0–9.0] vs. 8.0 [IQR 7.0–8.0]; p = 0.176), driven by hypertrophic soft callus formation rather than true osteogenesis. However, by Day 28, the PS group demonstrated significant regression (Median Score: 3.5 [IQR 3.0–4.8]) compared to the PI group (Median Score: 8.0 [IQR 8.0–8.0]; p = 0.006). Quantitative histomorphometry revealed significantly higher osteoclast density in the PS-28 group (TRAP+ cells: 18.5 ± 2.1/field) compared to PI-28 (4.2 ± 1.1/field; p < 0.001), indicating active resorption of the unstable callus.
Conclusion: Periosteal stripping does not accelerate early healing but induces a volume-matched inflammatory callus that fails to consolidate. The significant late-phase regression underscores the vital role of the cambium layer in definitive remodeling. Surgical preservation of the periosteum is mandated to prevent atrophic non-union.
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Dual-Modality Salvage of Recurrent Pacemaker Extrusion in Severe Malnutrition: A Technique Using PTFE Mesh Encapsulation and Fasciocutaneous Flap Coverage
Views: 153Downloads: 140Background: Permanent pacemaker implantation in pediatric patients with severe malnutrition presents a unique surgical challenge due to the absence of a viable subcutaneous protective envelope. In this population, standard device fixation frequently results in recurrent wound dehiscence and device extrusion, often necessitating lead abandonment or epicardial placement. This study evaluates the efficacy of a dual-modality salvage technique integrating a Polytetrafluoroethylene (PTFE) mesh barrier with vascularized fasciocutaneous tissue coverage.
Case presentation: We present the case of a 3-year-old male with congenital complete atrioventricular block and severe acute malnutrition, defined by a Weight-for-Height Z-score of less than -3 SD. The clinical course was complicated by three consecutive implant failures over an 8-month period, including two thoracic and one abdominal extrusion, characterized by aseptic pressure necrosis. To salvage the cardiac hardware, a novel sealed-device technique was employed. The pulse generator was encapsulated in a non-absorbable PTFE mesh to minimize the coefficient of friction and placed in a sub-fascial plane. Simultaneously, a random-pattern fasciocutaneous rotation flap was harvested to provide robust, vascularized coverage. Biochemical analysis revealed severe hypoalbuminemia (2.1 g/dL) and anemia pre-operatively.
Conclusion: At the 12-month follow-up, the surgical site demonstrated complete physiological integrity with no recurrence of erosion, seroma, or infection. The combination of PTFE encapsulation to mitigate mechanical shearing forces and a fasciocutaneous flap to restore perfusion offers a durable salvage strategy for refractory device extrusion in cachectic pediatric patients.
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Structural Restoration of the Empty Nose: A Quantitative Case Report on Post-Infectious Saddle Nose Deformity Using Autologous Sixth Costal Cartilage
Views: 147Downloads: 200Background: Septal abscess represents a catastrophic failure of the nasal structural framework, often resulting in rapid ischemic necrosis of the quadrangular cartilage and a severe saddle nose deformity. This empty nose phenomenon poses unique reconstructive challenges due to the total loss of the L-strut and compromised mucosal envelope.
Case presentation: We report the case of a 34-year-old female presenting with a Type IV saddle nose deformity and bilateral nasal valve collapse following a septal abscess. Preoperative assessment demonstrated a severe Nasal Obstruction Symptom Evaluation (NOSE) score of 85 out of 100 and compromised Minimum Cross-Sectional Area (MCA) on acoustic rhinometry (mean 0.365 cm2). The patient underwent open septorhinoplasty utilizing autologous sixth costal cartilage. The graft was fabricated using the concentric carving principle to create extended spreader grafts and a columellar strut, re-establishing the dorsal and caudal support.
Conclusion: At the 6-month postoperative follow-up, the NOSE score improved by 82.3% (score 15 out of 100), and objective acoustic rhinometry confirmed a 54% expansion in mean MCA. Physical examination revealed a stable dorsal profile with no early evidence of graft warping or resorption. Autologous sixth costal cartilage provides the necessary biomechanical bulk and structural rigidity for restoring the post-infectious nasal skeleton, though long-term monitoring for cartilage memory remains essential.
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In Vitro Dissolution Profiling and Release Kinetics of Abelmoschus manihot L. Ethanolic Extract Mucoadhesive Granules: A Higuchi Diffusion Model Analysis
Views: 174Downloads: 128Background: Peptic ulcer disease presents a persistent clinical challenge characterized by a critical imbalance between mucosal defensive mechanisms and aggressive luminal factors, including Helicobacter pylori infection and non-steroidal anti-inflammatory drug administration. The ethanolic extract of Abelmoschus manihot L. possesses potent antioxidant flavonoids, specifically quercetin, which exhibit significant gastroprotective potential. However, the therapeutic efficacy of conventional herbal extracts is often compromised by rapid physiological gastric emptying. The aim of this study was to formulate gastroretentive mucoadhesive granules containing the ethanolic extract of A. manihot using Hydroxypropyl Methylcellulose (HPMC) as a matrix polymer and to elucidate the drug release mechanism through advanced mathematical kinetic modeling.
Methods: The extract was standardized for total flavonoid content and antioxidant activity using the DPPH assay. Mucoadhesive granules were engineered via wet granulation with varying concentrations of HPMC (F1: 15%, F2: 20%, F3: 25%) and a constant 15% Carbopol. The formulations underwent rigorous physicochemical characterization, ex vivo wash-off mucoadhesion testing on porcine tissue, and in vitro dissolution profiling in artificial pH 1.2, 6.8, and 7.4 media. Release data were evaluated using Zero-order, First-order, and Higuchi kinetic models, validated via the Akaike Information Criterion (AIC).
Results: The standardized extract demonstrated potent antioxidant activity with an IC50 of 27.14 +/- 1.05 mcg/mL and a high total flavonoid content of 162.8 mg QE/g. All granule formulations exhibited excellent flowability. Formula F3 (25% HPMC) displayed superior swelling capacity (15.2-fold expansion) and mucoadhesion (30.0% retention at 60 minutes). Dissolution testing revealed F3 retarded drug release significantly compared to F1, releasing only 41.92% in pH 1.2 over 6 hours. Kinetic analysis confirmed that F3 strictly followed the Higuchi diffusion model, indicating release governed by diffusion through the swollen polymer matrix.
Conclusion: The HPMC-Carbopol mucoadhesive granules of A. manihot successfully achieved sustained release and enhanced structural mucoadhesion. Formula F3 represents a mechanistically sound gastroretentive delivery system, driven by complex polymer hydration dynamics, for the localized management of peptic ulcers.
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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
Views: 167Downloads: 152Background: 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.
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Diagnostic Accuracy and Optimal CD4 Threshold for Detecting Cytomegalovirus Retinitis in Advanced HIV Disease: A Prospective Indonesian Study
Views: 7Downloads: 3Background: Cytomegalovirus retinitis (CMVR) is a leading preventable cause of AIDS-related blindness where systematic screening is absent, and World Health Organization guidance triggers ophthalmic assessment below a CD4 count of 50–100 cells/µL, a range not previously calibrated in an Indonesian population.
Objective: To determine the diagnostic accuracy of the CD4 count against adjudicated cytomegalovirus retinitis, and to derive an optimal CD4 threshold for triggering ophthalmic screening, in Indonesian adults with advanced HIV disease.
Methods: This prospective single-gate diagnostic accuracy study, reported to STARD 2015, enrolled 51 consecutive adults with HIV-1 infection and a CD4 count below 100 cells/µL at Dr. Mohammad Hoesin Central General Hospital, Palembang, from January 2024 to January 2025. The index test was the CD4 count by flow cytometry; the reference standard was masked adjudication by two retina specialists using dilated ophthalmoscopy, fundus photography and optical coherence tomography (Cohen's κ = 0.91). Because only aggregated summaries were released, estimands the data do not identify are reported as sharp bounds.
Results: CMVR was present in 17 of 51 participants (33.3%, 95% CI 22.0–47.0); the median CD4 count was 17.0 cells/µL (IQR 11.0–27.0) versus 48.0 (30.0–72.0). The area under the ROC curve was 0.863 (95% CI 0.741–0.985). At the Youden-derived threshold of 32.5 cells/µL apparent sensitivity was 88.2% (95% CI 65.7–96.7) and specificity 91.2% (77.0–97.0); after correction for in-sample threshold selection these became 80.5% and 93.8%, and across two admissible reconstructions sensitivity ranged from 76.5% to 88.2%. CD4 rose monotonically across fulminant, indolent and frosted-branch phenotypes (bounded Kruskal–Wallis p = 0.001–0.013).
Conclusion: A CD4 count of approximately 30–35 cells/µL, with an unconditional visual-symptom over-ride, prioritises dilated retinal examination within the World Health Organization stratum in Indonesian HIV services.













