Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Modulating Patellofemoral Joint Stress Through Targeted Neuromuscular Training in Runners: A Systematic Review and Meta-Analysis
Background: Patellofemoral pain syndrome remains a highly prevalent running-related injury, characterized by retropatellar pain exacerbated by knee flexion. While multifactorial, biomechanical imbalances and proximal neuromuscular deficits are primary contributors. This systematic review and meta-analysis evaluated the efficacy of targeted neuromuscular training and gait retraining on pain, functional capacity, and biomechanical parameters in runners with patellofemoral pain syndrome.
Methods: A systematic search and analysis were conducted, incorporating nine randomized controlled trials. Inclusion criteria focused on adult runners diagnosed with patellofemoral pain syndrome undergoing neuromuscular exercise or gait retraining compared to control or standard care. Primary outcomes included self-reported pain and functional status. Standardized Mean Differences with 95 percent confidence intervals were calculated using an inverse-variance random-effects model.
Results: Nine randomized controlled trials involving robust sample sizes were analyzed. The pooled meta-analysis for pain reduction demonstrated a statistically significant large effect size favoring targeted neuromuscular and gait retraining interventions (Standardized Mean Difference = -1.38, 95 percent confidence interval [-1.85, -0.91], p less than 0.001). Functional outcomes also showed significant improvement in the intervention groups (Standardized Mean Difference = 1.51, 95 percent confidence interval [1.02, 2.00], p less than 0.001). Biomechanical analyses indicated significant modulations in hip kinematics, notably reduced peak hip adduction.
Conclusion: Targeted neuromuscular training and gait retraining significantly reduced pain and improved lower extremity function in runners. These interventions successfully modulated patellofemoral joint stress through enhanced proximal control and altered strike mechanics
Outcomes of Surgical Resection versus Medical Management in Chronic Pulmonary Aspergillosis: A Systematic Review and Meta-Analysis of Comparative Cohorts
Background: Chronic pulmonary aspergillosis (CPA) is a progressive and debilitating fungal infection that complicates structural lung diseases, particularly in patients with a history of treated tuberculosis. The therapeutic strategy remains a subject of intense debate, polarized between surgical resection, which offers a potential definitive cure but carries significant operative risks, and long-term azole therapy, which is suppressive but prone to drug resistance and high relapse rates. This study aimed to systematically evaluate survival outcomes and recurrence risks between these two modalities, specifically addressing the clinical heterogeneity between simple aspergilloma (SA) and chronic cavitary pulmonary aspergillosis (CCPA).
Methods: We conducted a systematic review and meta-analysis of six pivotal retrospective cohort studies published between 2013 and 2022, representing the modern era of thoracic surgery. Databases including PubMed, Scopus, and Embase were searched for comparative studies reporting overall survival (OS) and recurrence rates. Data were pooled using a random-effects model to account for clinical heterogeneity. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), with specific adjustments for allocation bias and confounding factors.
Results: The meta-analysis integrated data from 268 patients. Surgical resection was associated with a significant reduction in all-cause mortality compared to medical therapy (Pooled Hazard Ratio [HR] 0.12; 95% CI 0.04–0.35). In stratified analysis, recurrence rates were 2.7% for simple aspergilloma versus 10.3% for CCPA in surgical arms, contrasting sharply with relapse rates of 36–50% in medical arms upon drug cessation. An analysis of adjuvant antifungal therapy in a subset of patients showed no statistical benefit in completely resected simple aspergilloma. Postoperative complications occurred in 24.5% of surgical cases, primarily consisting of prolonged air leaks.
Conclusion: Surgical resection offers superior recurrence-free survival in selected candidates with localized disease compared to medical therapy. While effectively curative for simple aspergilloma, surgery in CCPA acts as a cytoreductive measure with a persisting recurrence risk, necessitating a multimodal approach. Medical therapy remains the mainstay for patients with bilateral disease or poor pulmonary reserve, but requires indefinite duration to prevent relapse
Vitamin D Supplementation Efficacy in Severe Vitamin D-Deficient versus Insufficient COPD Patients: A Stratified Meta-Analysis of Exacerbation Risk
Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and recurrent exacerbations that accelerate disease progression. Vitamin D deficiency is highly prevalent in this population and correlates with impaired macrophage function. However, randomized controlled trials regarding supplementation have yielded conflicting results. We hypothesized that efficacy is limited by a ceiling effect, where benefits are strictly restricted to patients with profound baseline deficiency.
Methods: We conducted a systematic review and stratified meta-analysis of randomized controlled trials comparing Vitamin D supplementation to placebo in COPD. To ensure methodological homogeneity and avoid data duplication, we strictly included only primary RCTs and excluded aggregate IPD meta-analyses. Studies investigating acute treatment of active exacerbations were also excluded. Data were stratified by baseline serum 25-hydroxyvitamin D [25(OH)D] levels into Severe Deficiency (<10 ng/mL) versus Insufficiency/Sufficiency (≥10 ng/mL). The primary outcome was the risk of moderate-to-severe exacerbations, analyzed using pooled Odds Ratios (OR) with a random-effects model.
Results: Five pivotal prevention trials (Lehouck, PRECOVID, ViDA, Hornikx, and Rafiq Pilot) comprising approximately 1,212 participants were included in the quantitative synthesis. In the unstratified analysis, Vitamin D showed no significant benefit (OR 0.78; 95% CI 0.55–1.10). However, stratification revealed a distinct therapeutic window. Patients with severe deficiency (<10 ng/mL) experienced a statistically significant reduction in exacerbation risk (Pooled OR 0.51; 95% CI 0.32–0.87; p=0.012). This effect was driven primarily by trials utilizing high-dose bolus supplementation. Conversely, patients with baseline levels ≥10 ng/mL showed no benefit (OR 0.98; p=0.72), confirming the biological ceiling effect.
Conclusion: Vitamin D supplementation confers a significant protective benefit against COPD exacerbations exclusively in patients with severe baseline deficiency (<10 ng/mL). The results support a precision medicine approach—screen, stratify, and target—while cautioning that efficacy appears dependent on correcting profound deficiency, potentially utilizing high-dose intermittent regimens
Levator Ani Avulsion as the Key Mediator Between Vaginal Delivery and Pelvic Organ Prolapse: A Systematic Review and Meta-Analysis of Imaging Studies
Background: 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
The FAPI-FDG Mismatch: Unmasking an Occult Pancreatic Lesion via Fibroblast Activation Imaging Amidst Negative Glucose Metabolism and Morphological Findings
Background: 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
Admission Serum Procalcitonin Thresholds and the PELOD-2 Score: A Prospective Analytical Study for Identifying Risk Ratios of Severe Organ Dysfunction in Pediatric Critical Care
Background: Multiple organ dysfunction syndrome (MODS) remains a predominant cause of mortality in Pediatric Intensive Care Units (PICUs). While the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score is the established standard for assessing severity, it requires time-consuming serial calculations. There is an urgent need for a rapid, admission-based prognostic biomarker. This study evaluates the association between serum procalcitonin (PCT) and the severity of organ dysfunction in critically ill children.
Methods: A prospective cross-sectional study was conducted at Dr. Moewardi Regional General Hospital, Indonesia, involving 25 children aged 1 month to 18 years with suspected infection. Organ dysfunction was quantified using the PELOD-2 score, and serum PCT was measured via Enzyme-Linked Fluorescent Assay (ELFA) within 24 hours of admission. Statistical analysis utilized Spearman’s rank correlation, multivariate linear regression, and Receiver Operating Characteristic (ROC) curve analysis.
Results: The cohort had a median age of 12 months. The median PCT level was 0.88 ng/mL. A significant positive correlation was observed between serum PCT and PELOD-2 scores (r = 0.39, p = 0.051; multivariate beta = 0.42, p = 0.043). ROC analysis identified a PCT threshold of greater than 11 ng/mL as the optimal indicator for moderate-to-severe organ dysfunction (AUC 0.82). Patients exceeding this threshold had a significantly elevated risk (Risk Ratio = 2.20; 95 percent CI: 1.15–4.24; p = 0.035).
Conclusion: Early serum procalcitonin measurement serves as a powerful independent factor associated with organ dysfunction severity. A cutoff value of greater than 11 ng/mL significantly stratifies risk, allowing clinicians to anticipate the progression of organ failure
Intraoperative Vagal Excitation During Rigid Esophagoscopy for an Esophageal Earring in a 4-Month-Old Infant: A Case Report
Background: Esophageal foreign body ingestion is a prevalent otorhinolaryngologic emergency in the pediatric population but is epidemiologically rare in infants under six months of age. While rigid esophagoscopy remains the gold standard for extraction, it involves stimulating the highly innervated aerodigestive tract. This case highlights a life-threatening vagal reflex—an underreported complication in infants—during foreign body removal.
Case presentation: A 4-month-old female infant presented with a history of accidental earring ingestion three days prior, manifesting as hypersalivation and feeding refusal. Radiographic imaging confirmed a radiopaque foreign body at the T1 vertebral level or thoracic inlet. The patient underwent rigid esophagoscopy under general anesthesia. During the extraction phase, mechanical manipulation of the esophageal mucosa triggered profound vagal excitation, resulting in severe bradycardia and oxygen desaturation. The procedure was immediately paused, and the patient was successfully resuscitated using vagolytic agents and hyperoxygenation by the anesthesiology team. A second attempt was successful without recurrence of the reflex. Post-operative recovery was uneventful.
Conclusion: Foreign body ingestion in early infancy requires a high index of suspicion and meticulous perioperative planning. The manipulation of the esophageal inlet can trigger potent vagovagal reflexes, particularly in infants with high vagal tone. This case underscores the necessity of deep anesthetic planes, prophylactic vagolytic preparation, and seamless communication between the surgeon and anesthesiologist to manage hemodynamic instability
Therapeutic Outcomes of Secukinumab 300 mg in Severe Psoriasis Vulgaris with Metabolic Comorbidities: A Retrospective Cohort Study in Bali
Background: 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
Feasibility of Facial Nerve Preservation in Locally Advanced Parotid Squamous Cell Carcinoma Following Extended Neoadjuvant Chemotherapy: A Case Report
Background: 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
Comparative Long-Term Durability and Repeatability of Selective versus Argon Laser Trabeculoplasty in Open-Angle Glaucoma: A Systematic Review and Meta-Analysis
Background: 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