Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Garcinia mangostana L. Nanoextract Improves Early Inflammatory Phase Bone Fracture Healing in Diabetes Mellitus by Targeting IL-1β and TNF-α: A Comprehensive Meta-Analysis
Get PDFBackground: Diabetic fracture healing is often impaired due to prolonged and exaggerated inflammation, characterized by elevated levels of pro-inflammatory cytokines like IL-1β and TNF-α. Garcinia mangostana L. (mangosteen) has demonstrated anti-inflammatory properties, and nanoformulations may enhance its bioavailability and efficacy. This meta-analysis aimed to evaluate the effect of Garcinia mangostana L. nanoextract on IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models.
Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library databases for studies published between 2013 and 2024. Studies investigating the effects of Garcinia mangostana L. nanoextracts on IL-1β and TNF-α levels in in vivo or in vitro models of diabetic fracture healing were included. Data on cytokine levels, fracture healing parameters (where available), and study characteristics were extracted. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic.
Results: Nine studies met the inclusion criteria. Meta-analysis revealed that Garcinia mangostana L. nanoextract significantly reduced IL-1β levels (SMD = -2.85, 95% CI: -3.97 to -1.73, p < 0.00001; I² = 88%) and TNF-α levels (SMD = -2.14, 95% CI: -3.08 to -1.20, p < 0.00001; I² = 82%) compared to control groups in diabetic fracture healing models. Subgroup analyses indicated significant reductions in both in vivo and in vitro studies.
Conclusion: This meta-analysis provides evidence that Garcinia mangostana L. nanoextract significantly reduces IL-1β and TNF-α levels during the early inflammatory phase of fracture healing in diabetic models. These findings suggest that Garcinia mangostana L. nanoextract holds therapeutic potential for improving fracture healing outcomes in individuals with diabetes mellitus
A Hierarchy of Harm: A Meta-analysis of Infection, Thrombosis, and Mortality Risks Across Central Catheters, Arteriovenous Grafts, and Fistulas
Get PDFBackground: Vascular access is a critical lifeline for patients with end-stage kidney disease requiring hemodialysis. The optimal choice among central venous catheters (CVCs), arteriovenous grafts (AVGs), and arteriovenous fistulas (AVFs) is a subject of intense debate, as each modality carries a distinct profile of risks. This meta-analysis was performed to establish a definitive, quantitative hierarchy of these risks to better inform clinical and policy decisions.
Methods: A systematic search of PubMed, Scopus, and the Cochrane Library was conducted for studies published between January 2015 and September 2025 that compared complication rates among CVCs, AVGs, and AVFs in adult hemodialysis patients. Seven high-quality cohort studies met the inclusion criteria, encompassing 18,542 patients. Data on access-related bloodstream infections (ARBSI), access circuit thrombosis/dysfunction, and all-cause mortality were extracted. Pairwise meta-analyses using a random-effects model calculated pooled risk ratios (RR) and 95% confidence intervals (CI).
Results: Central venous catheters were associated with a profoundly higher risk of ARBSI compared to both AVFs (RR 8.12, 95% CI 6.98–9.45, p < 0.001) and AVGs (RR 4.55, 95% CI 3.89–5.33, p < 0.001). Arteriovenous grafts demonstrated a markedly higher risk of access circuit thrombosis compared to AVFs (RR 2.78, 95% CI 2.41–3.21, p < 0.001). All-cause mortality was highest in patients with CVCs, showing a significantly increased risk compared to AVF users (RR 1.92, 95% CI 1.68–2.19, p < 0.001).
Conclusion: This meta-analysis provides robust, contemporary quantitative evidence for a clear hierarchy of harm in hemodialysis access. CVCs pose the greatest risk for infection and mortality, AVGs present the highest risk for thrombosis, and AVFs represent the safest option. These data provide a powerful rationale for reinforcing systemic healthcare initiatives aimed at minimizing CVC exposure and promoting timely AVF placement
The Diagnostic Accuracy of IgG Avidity Testing for Differentiating Acute from Chronic Toxoplasmosis in Pregnant Women: A Meta-Analysis
Get PDFBackground: Differentiating acute from chronic Toxoplasma gondii infection during pregnancy is a critical diagnostic challenge. Persistent Immunoglobulin M (IgM) antibodies create ambiguity, complicating clinical management. The IgG avidity test serves as a key tool to estimate infection timing. This meta-analysis aimed to systematically evaluate and quantify the diagnostic accuracy of the IgG avidity test for identifying acute toxoplasmosis in pregnant women.
Methods: A systematic literature search was conducted across PubMed, Scopus, Web of Science, EMBASE, and LILACS for studies published between January 2015 and December 2025 evaluating the IgG avidity test's diagnostic accuracy in pregnant women. Included studies required data for a 2x2 contingency table. The QUADAS-2 tool was used for bias assessment. A bivariate random-effects model was used to pool sensitivity, specificity, likelihood ratios (PLR, NLR), and the diagnostic odds ratio (DOR).
Results: Seven studies, comprising 1,250 pregnant women, were included. The pooled sensitivity was 0.96 (95% Confidence Interval [CI]: 0.92–0.98), and the pooled specificity was 0.97 (95% CI: 0.94–0.99). The pooled PLR was 32.5 (95% CI: 15.1–69.8), the NLR was 0.04 (95% CI: 0.02–0.08), and the DOR was 785 (95% CI: 289–2134). The area under the SROC curve was 0.99 (95% CI: 0.97–1.00). Substantial heterogeneity was observed across studies. A sensitivity analysis excluding one study with a high risk of bias did not significantly alter the results, and Deeks' test showed no evidence of publication bias (p=0.21).
Conclusion: The IgG avidity test demonstrated excellent pooled diagnostic accuracy for differentiating acute from chronic toxoplasmosis in pregnancy. However, significant heterogeneity across studies underscores that a single performance estimate is not universally applicable. The test is a powerful tool for resolving diagnostic uncertainty, but results must be interpreted based on assay-specific performance and in the context of the complete clinical picture
Efficacy, Safety, and Metabolic Effects of Low-Molecular-Weight Heparin versus Unfractionated Heparin in Chronic Hemodialysis: A Systematic Review and Meta-Analysis of Clinical Studies
Get PDFBackground: The optimal anticoagulation for chronic hemodialysis (HD) remains debated. Unfractionated heparin (UFH) is the historical standard but carries risks of metabolic complications and requires intensive monitoring. Low-Molecular-Weight Heparin (LMWH) offers pharmacological advantages, but concerns over bleeding risk in end-stage renal disease (ESRD) have limited its use. This study aimed to provide a holistic comparison by synthesizing recent evidence on the efficacy, safety, and, uniquely, the key metabolic consequences of LMWH versus UFH.
Methods: This systematic review followed PRISMA 2020 guidelines. We searched PubMed, EMBASE, and CENTRAL from January 2014 to March 2025 for clinical studies comparing LMWH and UFH in chronic HD patients. We included 6 studies (3 prospective trials, 3 retrospective cohorts) totaling 7,890 patients. The primary efficacy outcome was circuit thrombosis; the primary safety outcome was major bleeding. Secondary outcomes focused on key metabolic markers (pre-dialysis potassium, lipid profile). Data from prospective trials and observational studies were analyzed separately using subgroup analysis and tested for interaction. Metabolic data were pooled using a random-effects model.
Results: The analysis of key metabolic outcomes, derived from homogenous prospective trials (I2=0%), was the most robust finding. LMWH use was associated with a clinically significant reduction in pre-dialysis serum potassium (Mean Difference [MD]: -0.30 mEq/L; 95% CI: -0.50 to -0.10) and a superior atherogenic profile, including lower triglycerides (MD: -20.10 mg/dL) and higher HDL (MD: +4.50 mg/dL). For safety, no difference in major bleeding was found, a finding that was consistent across prospective trials (OR: 0.78; 95% CI: 0.33-1.85) and large retrospective cohorts (OR: 0.87; 95% CI: 0.69-1.09), with no subgroup interaction (p=0.75). Efficacy for preventing circuit thrombosis was also similar.
Conclusion: This meta-analysis provides strong, high-quality evidence that LMWH confers significant and clinically relevant metabolic advantages over UFH, particularly in mitigating hyperkalemia and atherogenic dyslipidemia. Furthermore, our stratified analysis provides high confidence from real-world data that LMWH, when dosed appropriately, is as safe and effective as UFH
Loss of E-cadherin Expression Stratifies Aggressive versus Non-Aggressive Papillary Thyroid Carcinoma
Get PDFBackground: 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 Sandwich Dual-Tissue Salvage: Synergistic Anteriorly-Based Tongue Flap and Autologous Dermofat Graft for Recalcitrant Pittsburgh Class V-VI Palatal Fistulas
Get PDFBackground: 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
Impact of Co-existing Adenomyosis on Pain Recurrence Following Deep Endometriosis Excision: A Systematic Review and Meta-Analysis of Multivariate-Adjusted Observational Cohorts
Get PDFBackground: 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
Therapeutic Potential of Curcumin in Modulating the HMGB1/TLR4/NF-κB Axis in Polymicrobial Peritonitis: A Systematic Review and Dose-Response Meta-Analysis
Get PDFBackground: 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
Modulation of Inflammatory and Regenerative Pathways by Channa striata Extract in End-to-End Anastomotic Wound Repair: A Systematic Review
Get PDFBackground: Intestinal anastomotic healing is a complex process, often complicated by inflammation and impaired regeneration, leading to leakage and stricture. Channa striata (snakehead fish) extract, traditionally used for wound healing, possesses bioactive compounds with potential anti-inflammatory and regenerative properties. This systematic review aimed to critically appraise the in vivo evidence for the effects of Channa striata extract on inflammatory and regenerative pathways in end-to-end anastomotic wound repair.
Methods: A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library databases was conducted for studies published between 2013 and 2024. Inclusion criteria comprised in vivo studies using animal models with end-to-end intestinal anastomosis, evaluating Channa striata extract versus a control, and reporting on relevant inflammatory and regenerative markers. Data extraction and risk of bias assessment (using SYRCLE's tool) were performed.
Results: Seven studies met the inclusion criteria. These studies, primarily using rat models, demonstrated that Channa striata extract significantly modulated key inflammatory and regenerative pathways. Specifically, the extract reduced pro-inflammatory cytokines, increased anti-inflammatory cytokines, enhanced growth factor expression, and promoted collagen deposition at the anastomotic site. These effects were associated with improved anastomotic bursting pressure and reduced leakage rates. Risk of bias varied across studies, with some limitations in blinding and allocation concealment.
Conclusion: Channa striata extract shows promise as a therapeutic agent for promoting anastomotic healing by modulating key inflammatory and regenerative pathways. However, further high-quality, standardized studies are needed to confirm these findings, elucidate precise mechanisms, and optimize extract formulation and dosage before clinical translation
Pre- and Perioperative Optimization of a Geriatric Patient on Antithrombotic Therapy Undergoing Dermatologic Electrosurgery: A Case Report
Get PDFBackground: Electrosurgery is a common and effective technique for removing skin lesions and achieving hemostasis in dermatologic surgery. However, managing patients on antithrombotic therapy, especially geriatric patients with comorbidities, presents a significant challenge. This case report highlights the importance of meticulous pre- and perioperative optimization in such patients to ensure safe and successful outcomes.
Case presentation: A 69-year-old male patient with a history of congestive heart failure (CHF), Non-ST elevation myocardial infarction (NSTEMI), type 2 diabetes mellitus, and hypertension presented with a nevus exhibiting cornu cutaneous. The patient had been on long-term aspirin therapy. The case discusses the complexities involved in deciding whether to discontinue aspirin, weighing the risks of bleeding against the potential for thrombotic events. After a three-week delay and consultation with an internist to address elevated coagulation parameters, the electrocauterization excision was performed successfully.
Conclusion: This case underscores the critical role of multidisciplinary collaboration and evidence-based decision-making in the perioperative management of geriatric patients on antithrombotic therapy undergoing dermatologic procedures. It emphasizes the need for individualized risk assessment and optimization strategies to balance the competing risks of bleeding and thrombosis