Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Elevated Fibroblast Growth Factor-23 as an Independent Predictor of All-Cause Mortality, Cardiovascular Events, and Progression to ESRD in Pre-Dialysis CKD: A Systematic Review and Meta-Analysis
Get PDFBackground: Fibroblast growth factor-23 (FGF23) is a central hormone in mineral metabolism, with levels rising early in chronic kidney disease (CKD). While its role in the pathophysiology of CKD–Mineral and Bone Disorder (CKD-MBD) is established, its independent prognostic value for adverse outcomes in the pre-dialysis population remains a subject of intense investigation. We aimed to systematically quantify the association between elevated FGF23 levels and the risks of all-cause mortality, cardiovascular (CV) events, and progression to End-Stage Renal Disease (ESRD) in patients with pre-dialysis CKD.
Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, EMBASE, and the Cochrane Library was performed for prospective cohort studies published between January 2014 and December 2024 that evaluated the prognostic value of FGF23 in adult, pre-dialysis CKD patients. The primary outcomes were all-cause mortality, a composite of major cardiovascular events, and progression to ESRD. Hazard Ratios (HRs) were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated with funnel plots and Egger's test.
Results: Seven prospective cohort studies involving 14,882 patients were included. The analysis revealed that elevated FGF23 was a significant independent predictor for all three outcomes. The pooled HR for all-cause mortality was 1.42 (95% CI: 1.28–1.58; I²=72%), for cardiovascular events was 1.39 (95% CI: 1.21–1.59; I²=78%), and for progression to ESRD was 1.55 (95% CI: 1.35–1.78; I²=65%). The associations remained significant after adjustment for traditional CKD-MBD markers and renal function in the primary studies. Sensitivity analyses confirmed the robustness of these findings.
Conclusion: This meta-analysis provides strong evidence that elevated FGF23 is a potent and independent predictor of all-cause mortality, cardiovascular events, and progression to ESRD in the pre-dialysis CKD population. These findings underscore the potential utility of FGF23 as a key biomarker for risk stratification and suggest it may be a critical therapeutic target to improve outcomes in this vulnerable population
Systemic Inflammatory Immune Index (SII) Predicts Disease Activity in Systemic Lupus Erythematosus (SLE) Patients: A Cross-Sectional Study
Get PDFBackground: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and diverse clinical manifestations. The systemic inflammatory immune index (SII), calculated as platelet count * neutrophil count/lymphocyte count, has emerged as a potential marker of systemic inflammation in various conditions. This study aimed to investigate the relationship between SII and disease activity in SLE patients.
Methods: We conducted a cross-sectional study involving 60 SLE patients diagnosed according to the 2019 EULAR/ACR classification criteria. Demographic and clinical data were collected, and disease activity was assessed using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Blood samples were analyzed to determine SII values. Statistical analysis included Spearman's correlation to assess the relationship between SII and MEX-SLEDAI scores.
Results: The study population predominantly consisted of women (98.3%), with a median age of 29 years. A strong positive correlation was observed between SII and MEX-SLEDAI scores (r = 0.931, p < 0.001). Patients with higher SII values exhibited significantly greater disease activity.
Conclusion: Our findings suggest that SII is a promising predictor of disease activity in SLE patients. This readily available index may aid clinicians in assessing disease severity and tailoring treatment strategies. Further research is warranted to validate these findings and explore the utility of SII in monitoring disease progression and treatment response
Pomegranate Extracts as a Natural Denture Cleanser: A Promising Alternative to Sodium Bicarbonate for Inhibiting Candida albicans
Get PDFBackground: Denture stomatitis, caused primarily by Candida albicans overgrowth, is a common oral health issue among denture wearers. Maintaining denture hygiene is crucial for prevention. This study investigated the efficacy of red pomegranate (Punica granatum L.) peel and fruit extracts as natural denture cleansers compared to sodium bicarbonate, a standard denture cleansing agent.
Methods: Heat-cured acrylic resin plates were fabricated and contaminated with C. albicans. Samples were divided into four groups and soaked for 8 hours in: 75% pomegranate peel extract, 75% pomegranate fruit extract, 5% sodium bicarbonate solution (positive control), and aquadest (negative control). C. albicans colony counts were performed using the spread plate technique and colony counter. Data were analyzed using Kruskal-Wallis and Mann-Whitney tests.
Results: Both pomegranate peel and fruit extracts significantly reduced C. albicans growth compared to the negative control (p<0.05). The peel extract showed comparable efficacy to sodium bicarbonate (p>0.05), while the fruit extract demonstrated slightly lower but still substantial antifungal activity.
Conclusion: Red pomegranate peel and fruit extracts hold promise as natural denture cleansers for inhibiting C. albicans and potentially preventing denture stomatitis. Further research is warranted to evaluate their long-term effects on denture materials and clinical efficacy
Giant Gastric GIST Manifesting as Profound Iron Deficiency Anemia: A Case Report of a Diagnostic Pitfall
Get PDFBackground: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, yet they remain rare, particularly in patients under 40. Their clinical presentation is highly variable, often posing a diagnostic challenge. Severe anemia as the initial manifestation is common, but diagnostic confusion with benign lesions on initial biopsy is a significant clinical pitfall.
Case presentation: A 39-year-old male presented with a three-month history of epigastric pain, early satiety, significant weight loss, and profound fatigue. His initial hemoglobin was a life-threatening 3.8 g/dL, consistent with profound iron deficiency anemia. Esophagogastroduodenoscopy (EGD) revealed a large, partially obstructing mass in the gastric corpus. However, initial endoscopic biopsies were paradoxically reported as a benign hyperplastic polyp. In contrast, contrast-enhanced computed tomography (CT) of the abdomen characterized a massive, 9.9 x 7.3 x 13.5 cm heterogeneously enhancing mass suggestive of malignancy. Given the stark discrepancy between imaging and histology, a decision was made for surgical intervention. The patient underwent a total gastrectomy. Final histopathological analysis of the resected specimen, supported by immunohistochemistry, confirmed a high-risk gastrointestinal stromal tumor with a high mitotic rate.
Conclusion: This case underscores the critical importance of maintaining a high index of suspicion for GIST in patients with unexplained iron deficiency anemia, even in younger age groups. It highlights the potential for sampling error with endoscopic biopsies of large submucosal tumors, which can lead to dangerously misleading diagnoses. Clinicians must integrate clinical, radiological, and endoscopic findings to guide management, especially when histopathological results are incongruent with the overall clinical picture
Harnessing Nature's Adjuvant: A Systematic Review and Meta Analysis of Phyllanthus niruri's Immunomodulatory and Chemosensitizing Mechanisms in Colorectal Cancer
Get PDFBackground: Colorectal cancer (CRC) poses a significant global health burden, and the limitations of conventional therapies necessitate the exploration of effective adjuvants. Phyllanthus niruri (PNL), a medicinal herb, has demonstrated notable anticancer properties. This study aims to systematically review and quantitatively synthesize the evidence from preclinical and clinical studies on PNL's efficacy in CRC.
Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for in vitro, in vivo, and clinical trials on PNL and CRC published up to December 2023. Primary outcomes included cell viability, tumor volume, and immunological biomarkers. Data were extracted for meta-analysis, calculating standardized mean differences (SMD) with 95% confidence intervals (CI) using a random-effects model to account for heterogeneity, which was assessed using the I² statistic.
Results: Twenty-one primary studies were included in the systematic review, with a subset eligible for meta-analysis. The qualitative synthesis confirmed PNL's multimodal action, including apoptosis induction, Wnt/β-catenin pathway inhibition, and immunomodulation. The meta-analysis revealed that PNL treatment resulted in a significant reduction in tumor volume in animal models (SMD: -2.54; 95% CI: -3.87 to -1.21; p < 0.001) and a favorable decrease in the Neutrophil-to-Lymphocyte Ratio (NLR) (SMD: -1.89; 95% CI: -2.78 to -1.01; p < 0.001). Significant heterogeneity was observed across studies.
Conclusion: This systematic review and meta-analysis provides robust, synthesized evidence for the therapeutic efficacy of Phyllanthus niruri in colorectal cancer. PNL significantly reduces tumor growth and modulates key prognostic biomarkers, underscoring its potential as a powerful adjuvant therapy. These findings strongly advocate for the initiation of large-scale, standardized clinical trials to translate this promising natural agent into clinical practice
The Temporal Windows of Glycemic Injury: Association of Early and Late First-Week Hyperglycemia with Retinopathy of Prematurity in Low-Birth-Weight Infants
Get PDFBackground: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, driven by aberrant retinal vascular development in preterm infants. While hyperglycemia is a recognized risk factor, its impact may vary depending on its timing relative to the biphasic pathogenesis of ROP. This study aimed to generate a hypothesis regarding the differential association of hyperglycemia on postnatal day 1 versus day 7 with the incidence of ROP in a high-risk neonatal population.
Methods: We conducted a retrospective, cross-sectional, hypothesis-generating study at Prof. Dr. I.G.N.G. Ngoerah General Hospital. Medical records of 68 preterm (<37 weeks gestation) and low-birth-weight (<2500 grams) infants who underwent ROP screening were reviewed. The exposures of interest were hyperglycemia (blood glucose >125 mg/dL) on postnatal day 1 (D1) and day 7 (D7). The primary outcome was the diagnosis of any stage of ROP. Statistical analysis involved Chi-square tests and exploratory multivariate logistic regression to adjust for select confounders.
Results: Of the 68 infants included (mean gestational age 30.5 ± 2.2 weeks, mean birth weight 1447.5 ± 373.0 grams), 11 (16.2%) were diagnosed with ROP. Hyperglycemia was present in 29.4% of infants on D1 and 13.2% on D7. In logistic regression analysis, a strong statistical association was observed between hyperglycemia and ROP for both D1 (Adjusted Odds Ratio [AOR] = 55.7; 95% Confidence Interval [CI]: 5.1–611.0; p=0.001) and D7 (AOR = 74.5; 95% CI: 9.0–613.4; p<0.001). However, the profoundly wide confidence intervals indicate significant statistical instability and imprecision.
Conclusion: This study found a strong, albeit statistically imprecise, association between hyperglycemia on both the first and seventh day of life and the incidence of ROP. These findings support the hypothesis that the timing of glycemic dysregulation may be critical, potentially impacting different phases of ROP pathogenesis. The results, while preliminary, underscore the need for larger, prospective studies to confirm these associations and elucidate the role of glycemic control in ROP prevention
Laparoscopic Primary Crural Repair for Acute-on-Chronic Organoaxial Gastric Volvulus Secondary to a Type II Paraesophageal Hernia: A Case Report and Review of Surgical Strategy
Get PDFBackground: Gastric volvulus, an abnormal rotation of the stomach, is a rare surgical emergency that can lead to life-threatening gastric ischemia and perforation, particularly when associated with a large paraesophageal hernia (PEH). While paraesophageal hernias are the most common predisposing factor in adults, the optimal surgical management, especially regarding the use of fundoplication and gastropexy, remains a subject of debate.
Case presentation: We present the case of a 46-year-old male with a six-month history of intermittent epigastric pain and early satiety, who presented with a three-week history of acute-on-chronic gastric outlet obstruction. His symptoms included intractable postprandial vomiting. Laboratory findings were significant for hemoconcentration and a hypochloremic, hypokalemic metabolic state, indicative of severe dehydration. A contrast-enhanced computed tomography scan confirmed a Type II PEH with an organoaxial gastric volvulus, causing complete obstruction. Following aggressive resuscitation, the patient underwent successful laparoscopic surgery. The procedure involved reduction of the herniated and volvulized stomach, complete excision of the hernia sac, and a primary posterior crural repair with pledgeted, non-absorbable sutures. A fundoplication or gastropexy was not performed. Intraoperative endoscopy confirmed successful de-rotation, a patent pylorus, and viable gastric mucosa. The patient had an uneventful recovery and remained asymptomatic with no evidence of reflux at a six-month follow-up.
Conclusion: This case highlights the classic "acute-on-chronic" presentation of gastric volvulus secondary to a PEH. It underscores the efficacy and safety of a laparoscopic approach, which facilitates rapid recovery. Furthermore, it suggests that in carefully selected cases with a moderate-sized hiatal defect and preserved anatomy post-reduction, a meticulous primary crural repair without routine fundoplication or gastropexy can be a sufficient and durable treatment, avoiding the potential morbidity of these additional procedures
Corticosteroids, Azole Antifungals, and Biologic Agents for the Management of Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Network Meta-Analysis
Get PDFBackground: The management of allergic bronchopulmonary aspergillosis (ABPA) requires control of complex type 2 inflammation and reduction of fungal burden. The comparative efficacy of the primary therapeutic classes—corticosteroids, azole antifungals, and biologics—is not well established through direct evidence. This network meta-analysis was conducted to determine the optimal hierarchical treatment strategy for ABPA.
Methods: A systematic review of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was performed for randomized controlled trials (RCTs) published from January 2015 to July 2025. We included RCTs in patients with ABPA comparing oral corticosteroids (OCS) alone to OCS plus itraconazole or OCS plus a biologic agent (omalizumab, mepolizumab, benralizumab). The primary outcome was a composite therapeutic response (≥25% IgE reduction plus clinical stability). A Bayesian random-effects network meta-analysis was performed, with results presented as odds ratios (OR) and 95% credible intervals (CrI).
Results: Seven RCTs enrolling 988 patients were included, forming a star-shaped evidence network anchored by a common placebo comparator. All active add-on therapies were superior to OCS alone for the primary outcome. Based on probabilistic rankings (SUCRA), OCS plus mepolizumab was most likely to be the most effective treatment (OR vs. OCS alone: 5.12; 95% CrI, 2.89-9.15; SUCRA: 94.5%), followed by OCS plus benralizumab (OR: 4.65; 95% CrI, 2.15-8.98; SUCRA: 87.2%), OCS plus omalizumab (OR: 3.88; 95% CrI, 2.10-7.15; SUCRA: 75.1%), and OCS plus itraconazole (OR: 2.54; 95% CrI, 1.55-4.17; SUCRA: 43.2%). Biologic agents demonstrated the greatest reduction in exacerbation rates.
Conclusion: In patients with ABPA, combination therapy is superior to OCS monotherapy. This analysis provides compelling indirect evidence that biologic agents, particularly IL-5 inhibitors, represent the most effective therapeutic class for achieving disease control. These findings provide a strong evidence base to guide a hierarchical treatment approach and support the early integration of targeted therapies into the ABPA management algorithm
Laser Therapy for Genitourinary Syndrome of Menopause (GSM): A Stratified Meta-Analysis of Histological, Clinical, and Safety Outcomes
Get PDFBackground: Genitourinary syndrome of menopause (GSM) is a prevalent and chronic condition that diminishes quality of life. Vaginal laser therapy is a non-hormonal treatment, but its efficacy and safety require rigorous synthesis. This study was conducted to systematically evaluate the efficacy of laser therapy for GSM by prioritizing high-quality evidence and separately analyzing findings from different study designs, while also providing the first meta-analytic overview of safety.
Methods: A systematic search of PubMed, Scopus, Embase, and the Cochrane Library was performed for studies published between January 2015 and December 2024. The primary analysis of efficacy was restricted to randomized controlled trials (RCTs). A separate, secondary analysis was performed on prospective cohort studies. Primary outcomes were changes in vaginal epithelial thickness and the Visual Analog Scale (VAS) for dryness. Secondary outcomes included VAS for dyspareunia, vaginal health index (VHI), female sexual function index (FSFI), and systematically extracted adverse events. Data were pooled using a random-effects model.
Results: Seven studies (2 RCTs, 5 cohort studies) involving 595 patients were included. In the primary analysis of RCTs, laser therapy resulted in a significant increase in epithelial thickness (Mean Difference [MD] 50.15 µm) and a significant reduction in VAS for dryness (MD -4.54) with low-to-moderate heterogeneity. The secondary analysis of cohort studies also showed significant improvements, but with extremely high and significant heterogeneity (I² > 80%). Across all studies, reported adverse events were consistently mild and transient, including temporary erythema, edema, and minor discharge. No serious adverse events were reported.
Conclusion: Based on high-quality evidence from RCTs, vaginal laser therapy produces statistically significant improvements in the histological and clinical parameters of GSM. Evidence from cohort studies supports this finding but demonstrates considerable variability in real-world settings. While short-term safety appears favorable, the inconsistent treatment effect and lack of long-term data necessitate a cautious approach to patient selection and counseling
Optic Neuritis After Viral Vector versus mRNA COVID-19 Vaccines: A Systematic Review and Comparative Meta-Analysis
Get PDFBackground: The global deployment of COVID-19 vaccines, utilizing distinct viral vector and mRNA technologies, has been followed by reports of rare neuro-ophthalmic adverse events, including optic neuritis (ON). This study aimed to systematically compare the clinical phenotypes, autoimmune serological profiles, and visual outcomes of ON cases with onset in temporal association with viral vector versus mRNA COVID-19 vaccination.
Methods: A systematic review was conducted across PubMed, Scopus, and EMBASE databases for case reports and case series published up to August 2025 detailing ON after COVID-19 vaccination. Data were extracted on clinical presentation, MRI findings, serostatus for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies, treatments, and visual outcomes. Separate meta-analyses of proportions and comparative odds ratios (OR) were calculated for key outcomes, including distinct analyses for NMOSD and MOGAD.
Results: Our analysis of published reports included 20 studies, comprising 90 patients (40 viral vector, 50 mRNA). Cases associated with viral vector vaccines had significantly higher odds of presenting with bilateral disease (OR 4.31, 95% CI [1.67, 11.11]). This platform was also associated with markedly increased odds of AQP4-IgG positivity (NMOSD) (OR 5.15, 95% CI [1.35, 19.61]) and MOG-IgG positivity (MOGAD) (OR 4.58, 95% CI [1.09, 19.21]). Consequently, these patients had higher odds of requiring aggressive immunotherapy and of suffering incomplete visual recovery (OR 3.41, 95% CI [1.14, 10.21]).
Conclusion: Our analysis of published case reports suggests that while ON following COVID-19 vaccination is a very rare event, its clinical phenotype may differ based on the vaccine platform. Cases associated with viral vector vaccines appear more likely to manifest as a severe, bilateral, antibody-mediated condition characteristic of NMOSD or MOGAD. These findings, which do not establish causality, underscore the critical importance of prompt autoantibody testing to guide appropriate management. The established benefits of vaccination continue to overwhelmingly outweigh the exceptionally low absolute risk of such adverse events