Accreditation
SINTA 2Nationally Accredited Journal
Vol. 10 No. 7 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Articles
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Comparative Efficacy of Intra-articular Platelet-Rich Plasma Versus Dextrose Prolotherapy for Pain Reduction and Functional Recovery in Knee Osteoarthritis: A Meta-Analysis of Randomised Controlled Trials
Views: 138Downloads: 100Background: Knee osteoarthritis (OA) is a primary cause of chronic pain and disability. Intra-articular platelet-rich plasma (PRP) and hypertonic dextrose prolotherapy are emerging regenerative therapies, yet their comparative and long-term effectiveness remain incompletely characterized. This meta-analysis quantifies their pooled effect on pain and function, prioritizing the head-to-head comparison of PRP versus prolotherapy.
Methods: A systematic search of PubMed, Scopus, and Google Scholar (to July 2025) identified randomized and prospective comparative trials evaluating intra-articular PRP and/or prolotherapy in adults with Kellgren–Lawrence grade I–III knee OA. Pain and functional outcomes were extracted, and risk of bias was assessed using the Cochrane RoB 2 framework. Standardized mean differences (Hedges' g) were pooled using a restricted maximum likelihood random-effects model, alongside subgroup and small-study effect analyses.
Results: Ten studies (n=855) were included. The mixed-comparator pooled estimate significantly favored the active therapies (Hedges' g = −0.948, 95% CI −1.725 to −0.171; p=0.022; I²=94.9%). Subgroup analyses revealed an effect size of g = −1.302 for PRP versus prolotherapy, g = −1.049 for prolotherapy versus inactive comparators, and g = −0.412 for PRP versus saline placebo. Differences between subgroups were not statistically significant (p=0.627). Egger regression indicated small-study effects (p=0.016).
Conclusion: Both PRP and prolotherapy yield clinically meaningful improvements in knee OA pain and function. PRP demonstrates larger, more durable effects in direct comparisons, positioning it as the preferred regenerative option for sustained benefit beyond six months. Prolotherapy remains a practical alternative for shorter-term relief. However, substantial heterogeneity, small-study effects, and modest advantages over blinded saline necessitate cautious translational interpretation.
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Mycobacterium marinum Co-infection Masquerading as Treatment-Resistant Chromoblastomycosis: A Diagnostic and Therapeutic Challenge in Cutaneous Co-infection
Views: 139Downloads: 97Background: Co-infection of chromoblastomycosis and Mycobacterium marinum (fish tank granuloma) within a single cutaneous lesion is exceptionally rare and presents a formidable diagnostic challenge owing to overlapping clinical and histopathologic features. The chronic verrucous or nodular morphology, predilection for distal extremities, and aquatic exposure history common to both conditions can lead to misdiagnosis, prolonged ineffective therapy, and patient morbidity.
Case presentation: A 31-year-old Indonesian male with a fishkeeping hobby presented with a persistent erythematous plaque on the right middle finger, present since 2022, following a puncture injury sustained while collecting mosquito larvae and water fleas as fish food. He was initially diagnosed with chromoblastomycosis (Phialophora spp. on culture) in September 2023 and treated with itraconazole 200 mg daily and topical miconazole 2% for 48 weeks without resolution. Repeat biopsy in 2024 demonstrated negative periodic acid-Schiff and Ziehl-Neelsen stains but revealed non-caseating tuberculoid granulomas. Considering the patient's aquatic exposure, antifungal failure, and granulomatous histopathology, a diagnosis of fish tank granuloma due to M. marinum co-infection was established. Combination antimycobacterial therapy with rifampicin 600 mg and ethambutol 1500 mg daily produced clinical resolution at six-month follow-up.
Conclusion: This case underscores the necessity of considering M. marinum in patients with antifungal-refractory chronic skin lesions and aquatic exposure, and highlights the diagnostic value of repeat histopathology with directed staining when initial therapy fails.
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Dose-Dependent Anti-Fibrotic Effect of Thymoquinone on Renal TGF-β1 Expression in Wistar Rats with Unilateral Ureteral Obstruction
Views: 118Downloads: 111Background: Renal fibrosis is the final common pathway of chronic kidney disease (CKD), regulated by the pro-fibrotic cytokine Transforming Growth Factor-β1 (TGF-β1). Thymoquinone, the principal bioactive constituent of Nigella sativa, has antioxidant, anti-inflammatory and anti-fibrotic activity in pre-clinical models, but its dose-response profile in obstructive nephropathy is incompletely characterised.
Methods: This in-vivo experimental study used a post-test-only with control-group design in 30 male Wistar rats (200–250 g) randomised into six groups (n=5): sham + olive-oil; UUO + olive-oil; UUO without olive-oil; and UUO with intra-peritoneal thymoquinone at 5, 10 or 20 mg/kg body-weight daily for 14 days. The primary outcome was renal cortical TGF-β1 mRNA expression by RT-PCR; secondary outcomes were IL-6 expression, serum urea and creatinine, Sirius-red percentage of positively-stained area (PSA) and a PAS-stained tubular injury score.
Results: UUO produced renal injury: urea rose from 41.3 ± 6.2 to 57.7 ± 7.6 mg/dL (p=0.003) and TGF-β1 expression rose from 473,500 ± 32,797 to 679,922 ± 27,998 densitometric units (p=0.001). Thymoquinone reduced TGF-β1 dose-dependently to 644,571 ± 25,457, 612,143 ± 23,822 and 581,571 ± 24,128 a.u. at 5, 10 and 20 mg/kg (ANOVA p=0.004); the 20 mg/kg dose was superior to lower doses (p<0.05). PSA and tubular injury improved in parallel and correlated strongly with TGF-β1 (r=0.85).
Conclusion: Thymoquinone exerts a dose-dependent anti-fibrotic effect via TGF-β1 down-regulation in obstructive nephropathy, supporting its evaluation as a complementary anti-fibrotic adjunct in CKD.
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Membranous β-Catenin Expression Inversely Correlates with WHO/ISUP Grading in Clear Cell Renal Cell Carcinoma: An Indonesian Cross-Sectional H-Score Study
Views: 90Downloads: 66Background: Clear cell renal cell carcinoma (ccRCC) is the most common adult renal malignancy and exhibits heterogeneous clinical behavior that is currently stratified by the WHO/ISUP nuclear grading system. β-catenin, the terminal effector of canonical Wnt signaling and an integral component of the cadherin–catenin adhesion complex, has been implicated in epithelial–mesenchymal transition (EMT) and tumor progression, but its quantitative relationship with WHO/ISUP grade in Indonesian ccRCC has not been reported.
Methods: This analytic observational cross-sectional study examined 73 archived formalin-fixed, paraffin-embedded ccRCC specimens collected at the Anatomical Pathology Installation of Dr. Saiful Anwar Regional General Hospital Malang between January 2019 and May 2025. Immunohistochemistry for β-catenin (Dako Clone 14, dilution 1:200) was scored independently and blindly by two anatomical pathologists using the H-score methodology across ten 400× high-power fields per case.
Results: The overall mean H-score was 236.4 ± 50.6 (range 20–295). Spearman rank correlation revealed a strong, statistically significant inverse association between membranous β-catenin H-score and WHO/ISUP grade (ρ = –0.664; 95% CI –0.778 to –0.503; p < 0.001). Mean H-scores declined monotonically from Grade 1 (285 ± 28) through Grade 2 (270 ± 32), Grade 3 (228 ± 30), to Grade 4 (175 ± 32), and Receiver Operating Characteristic analysis distinguished high-grade (G3–G4) from low-grade (G1–G2) tumors with an area under the curve of 0.84.
Conclusion: These findings support membranous β-catenin H-score as a biologically grounded, accessible immunohistochemical adjunct to WHO/ISUP grading and motivate further translational evaluation of the Wnt/β-catenin pathway as a stratification and therapeutic target in ccRCC.
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Adjuvant Resveratrol Reduces Albuminuria and Serum Transforming Growth Factor-β Without Improving Glomerular Filtration Rate in Diabetic Kidney Disease: A 12-Week Randomized Controlled Trial
Views: 218Downloads: 186Background: Diabetic kidney disease (DKD) progresses through inflammation and fibrosis, with transforming growth factor-β (TGF-β) as the principal profibrotic mediator and albuminuria as a clinical surrogate of glomerular injury.
Methods: We conducted a 12-week, double-blind, placebo-controlled randomized trial at Dr. Mohammad Hoesin General Hospital, Palembang, between October 2025 and January 2026 to evaluate adjuvant resveratrol on serum TGF-β, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR).
Results: Of 61 randomized adults with DKD on standard care, 54 were analyzed (resveratrol n=27 received 25 mg twice daily, derived from Polygonum cuspidatum in 95% lecithin; placebo n=27). Within the resveratrol group, serum TGF-β fell from 123.7 to 77.1 pg/mL (p=0.008) and UACR from 94.1 to 89.8 mg/g (p=0.017); within placebo, UACR rose from 81.9 to 112 mg/g (p=0.029) while TGF-β change was non-significant (p=0.428). Between-group ΔUACR was significant (p<0.001), whereas ΔTGF-β (p=0.303) and ΔeGFR (p=0.567) were not. Multivariable linear regression identified resveratrol as an independent predictor of UACR reduction (B=−394.12 mg/g; 95% CI −659.53 to −128.71; p=0.004; adjusted R²=0.129). Baseline TGF-β was the dominant predictor of ΔTGF-β (B=−0.81; p<0.001; adjusted R²=0.701), and baseline LFG stage predicted ΔeGFR (B=−4.76; p=0.021). Mild bloating was reported in 14.8% of resveratrol versus 11.1% of placebo recipients; no serious adverse events occurred.
Conclusion: Adjuvant low-dose resveratrol reduces albuminuria and serum TGF-β over 12 weeks in DKD without short-term improvement in eGFR, supporting an antifibrotic biomarker signal that warrants longer trials.
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Topical Allium cepa Ethanol Extract Restores SOD and VEGF Without Increasing Hair Length in UV-B-Exposed Wistar Rats
Views: 135Downloads: 45Background: Ultraviolet B (UV-B) accelerates hair photoaging by depleting cutaneous superoxide dismutase (SOD) and dysregulating vascular endothelial growth factor (VEGF). Red onion (Allium cepa) is rich in flavonoids and organosulfur precursors of hydrogen sulphide that may enhance both antioxidant defenses and pro-angiogenic signaling. This study evaluated topical Allium cepa ethanol extract on cutaneous SOD, VEGF, and hair length in UV-B-exposed Wistar rats.
Methods: Twenty male Wistar rats (3–4 months, 180–200 g) were randomly allocated to five groups (n=4): normal control without UV-B (KN), placebo with UV-B and base preparation (K-), and three groups receiving topical Allium cepa ethanol extract at 1% (P1), 2% (P2), and 4% (P3). UV-B was administered at 65 mJ/cm² thrice weekly for 21 days. SOD and VEGF were measured by ELISA; hair length by digital calipers. Data were analyzed by one-way ANOVA with Tukey post-hoc tests.
Results: UV-B reduced SOD by 77.2% and VEGF by 61.7% versus normal. Topical Allium cepa restored both dose-dependently: SOD reached 13.85±0.27 U/mL and VEGF reached 43.00±1.13 ng/L at 4%, with 4% VEGF exceeding normal by 33% (p<0.001). The 2% concentration restored VEGF to physiological levels (p=0.493). Hair length did not differ across groups (p=0.394). The cross-group SOD–VEGF correlation was strongly positive (Pearson r=0.804).
Conclusion: Topical Allium cepa ethanol extract is a potent dose-dependent enhancer of cutaneous SOD and VEGF in UV-B-exposed rats. The dissociation between robust biochemical recovery and the unchanged hair-length endpoint supports Allium cepa as an antioxidant and pro-angiogenic adjunct for hair photoaging warranting extended-duration translational studies.
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Single-Stage Bilateral Sinusectomy with Methylene Blue Tract Delineation for Familial Classic Preauricular Sinus Following Right-Sided Abscess Control: A Case Report
Views: 99Downloads: 129Background. Preauricular sinus is a congenital anomaly arising from incomplete fusion of the auricular hillocks of the first and second branchial arches. The condition shows marked ethnic variation, with bilateral presentations strongly associated with hereditary transmission. Surgical excision remains the only definitive treatment for symptomatic or recurrently infected lesions, yet operative recurrence rates of up to 42% have been historically reported.
Case presentation. A 24-year-old Indonesian Minangkabau male presented with bilateral preauricular openings present since birth and a recent right preauricular abscess that had been treated with incision and drainage twenty days prior. His father had a unilateral left-sided preauricular pit, consistent with familial transmission. Examination confirmed bilateral classic-type preauricular fistulae anterior to the ascending helix without active discharge, and a quiescent right post-incision wound. Preoperative blood work, renal and hepatic profiles, and chest radiography were within normal limits. The patient underwent simultaneous bilateral preauricular sinusectomy under general anesthesia using methylene blue tract delineation, elliptical skin incision, complete tract dissection with adjacent granulation removal, and primary closure over a small-calibre drain. Postoperative recovery was uneventful; the drain was removed on day three, sutures were removed on day ten, and the surgical wound remained quiescent without recurrence or hypertrophic scarring at the 39-day follow-up.
Conclusion. Simultaneous single-stage bilateral sinusectomy combined with methylene blue tract delineation, prior infection control, and closed-system drainage produced excellent early outcomes in an adult with familial bilateral classic preauricular sinus.
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Determinants of In-hospital Mortality in Preterm Neonates Admitted to a Tertiary Indonesian NICU: A One-Year Retrospective Cohort of 209 Infants
Views: 88Downloads: 57Background. Preterm birth is the largest single contributor to global neonatal mortality, and Southeast Asia carries a disproportionate burden, yet contemporary multivariable data from Indonesian tertiary neonatal intensive care units (NICUs) remain limited. We aimed to identify maternal, perinatal and neonatal determinants of in-hospital mortality among preterm neonates at the NICU of Prof. I.G.N.G Ngoerah Hospital, Denpasar, Bali.
Methods. In a single-centre retrospective cohort, 209 preterm neonates (gestational age <37 weeks and birth weight <2500 g) admitted between September 2024 and September 2025 were enrolled by total sampling. Bivariate logistic regression with p<0.25 inclusion threshold was followed by multivariable binary logistic regression; intermediate-outcome variables (RDS and surfactant therapy) were excluded a priori to avoid over-adjustment bias.
Results. In-hospital mortality was 42.1% (88/209) and decreased monotonically across birth-weight strata, from 75.0% in infants <1000 g to 41.9% in 1000–1499 g and 22.9% in ≥1500 g (Cochran–Armitage trend p<0.001). Sepsis (56.8%) and respiratory distress syndrome (30.7%) accounted for 87.5% of deaths. In the multivariable model, birth weight 1000–1499 g (adjusted odds ratio [aOR] 0.36, 95% CI 0.15–0.90; p=0.029) and ≥1500 g (aOR 0.17, 95% CI 0.06–0.51; p=0.001) and each 1-point increment in 5-minute Apgar score (aOR 0.81, 95% CI 0.67–0.98; p=0.031) were independently associated with lower mortality. Maternal urinary tract infection trended toward higher mortality (aOR 2.85, 95% CI 0.97–8.35; p=0.057).
Conclusion. Birth weight and 5-minute Apgar score are independent, immediately measurable predictors of in-hospital preterm mortality in this Indonesian tertiary NICU. Combining bedside risk stratification with antenatal corticosteroid coverage audit and universal antenatal urine-culture screening offers a translational pathway to reduce neonatal mortality in resource-constrained Southeast Asian settings.
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Incidence of Intraocular Inflammation, Retinal Vasculitis, and Retinal Vascular Occlusion Following Intravitreal Brolucizumab in Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis
Views: 126Downloads: 123Background. Brolucizumab is a humanized single-chain anti-VEGF antibody fragment licensed for neovascular age-related macular degeneration (nAMD). Post-marketing surveillance identified intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RVO) as adverse events of special interest, sometimes causing irreversible visual loss. Published incidence estimates range from below 1% to above 10%. We aimed to estimate the pooled cumulative incidence of these events and characterize heterogeneity drivers.
Methods. PubMed/MEDLINE, Cochrane CENTRAL, and Google Scholar were searched for phase 3 randomized controlled trials (RCTs), phase IIIb prospective studies, and retrospective/registry studies (≥30 eyes) reporting IOI, RV, or RVO incidence after intravitreal brolucizumab 6 mg in nAMD. A DerSimonian–Laird random-effects model with Freeman–Tukey arcsine transformation was applied; REML, Paule–Mandel, and GLMM (logit link) estimators were used in sensitivity analyses.
Results. Ten independent datasets (33,280 brolucizumab-treated eyes; 1,130 events) were included. Pooled cumulative incidence of any IOI/RV/RVO was 5.54% (95% CI 4.23–7.02%; I² = 94.0%; Q = 150.48). Prospective studies yielded higher pooled incidence (8.42%, 95% CI 4.12–14.04%) than retrospective/registry studies (4.35%, 95% CI 3.28–5.56%). Leave-one-out sensitivity ranged 4.98–6.19%. Funnel-plot asymmetry was detected (Egger t = 3.27; p = 0.011). More than 75% of events occurred within six months of the first injection.
Conclusion. Cumulative incidence of IOI/RV/RVO after brolucizumab 6 mg in nAMD approached 5.5%, with markedly higher rates under independent adjudication. These findings support careful patient selection, baseline screening for prior IOI history, and intensified monitoring after brolucizumab initiation.
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Occupational and Environmental Ultraviolet–Sunlight Exposure, Including Outdoor Agricultural Work, and the Risk of Cataract: A Systematic Review and Meta-Analysis of Observational Studies
Views: 110Downloads: 87Background.Cataract remains the leading cause of avoidable blindness worldwide, and occupational sunlight exposure is suspected as a modifiable risk factor among outdoor workers, including agricultural workers in tropical low- and middle-income countries (LMICs) such as Indonesia. Previous quantitative syntheses pooled mixed exposure-contrast metrics into a single estimate and obtained heterogeneity in excess of I2 = 95%, providing limited interpretable guidance for clinicians and policy makers.
Methods.A systematic search of PubMed/MEDLINE was conducted and supplemented by citation tracing and translated search strings for Scopus, Embase, Web of Science and Cochrane CENTRAL. Eligible studies were observational analyses of adults reporting an OR, HR or relative risk with a 95% CI for occupational or environmental UV-sunlight exposure and cataract. Risk of bias was assessed using the Newcastle-Ottawa Scale. Effect estimates were pooled using DerSimonian-Laird random-effects models with REML and Hartung-Knapp-Sidik-Jonkman sensitivity estimators.
Results.Seven observational studies (combined n approximately 60,000) met the inclusion criteria. Pooled OR from four extreme high-vs-low contrast studies: 6.52 (95% CI 4.12-10.33; I2 = 67%). Three modest per-unit/ever-vs-never studies pooled at OR/HR 1.09 (95% CI 1.04-1.14; I2 = 0%). The contrast-type moderator explained approximately 45% of between-study heterogeneity (p < 0.001).
Conclusion.Occupational and environmental UV-sunlight exposure is associated with a clinically significant increase in cataract risk. The magnitude depended on the exposure contrast. The findings support targeted ocular-protection programmes for outdoor agricultural workers in high-insolation LMICs such as Indonesia.
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Prophylactic Statin Therapy for the Prevention of Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies
Views: 79Downloads: 55Background. Anthracycline-based chemotherapy remains a cornerstone of curative-intent breast-cancer treatment but carries a dose-dependent risk of cancer therapy-related cardiac dysfunction (CTRCD). Statins exert pleiotropic anti-inflammatory, antioxidative, and endothelial-stabilizing effects that may attenuate myocardial injury; however, prior meta-analyses pooled breast-cancer and lymphoma populations, obscuring breast-cancer-specific signals.
Methods. A systematic review and random-effects meta-analysis was conducted per PRISMA 2020. PubMed, Cochrane, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and propensity-matched cohort studies enrolling adult breast-cancer patients receiving anthracycline-based chemotherapy with or without trastuzumab. Co-primary outcomes were CTRCD incidence and standardized change in left-ventricular ejection fraction (LVEF, Hedges' g). Risk of bias was assessed using RoB 2.0 and ROBINS-I. Sensitivity analyses included leave-one-out exclusion and restriction to breast-cancer-only RCTs.
Results. Ten studies (1,239 patients; six RCTs, four cohort studies) were included. The pooled risk ratio for CTRCD was 0.49 (95% CI 0.28–0.85; p = 0.011; I² = 0%). The pooled standardized mean difference for LVEF change was 0.38 (95% CI −0.06 to 0.81; I² = 81%), corresponding to approximately +2.1 LVEF percentage points. Sensitivity analyses restricted to breast-cancer-only RCTs strengthened the CTRCD effect (RR 0.36, 95% CI 0.16–0.82). HER2-positive subgroup analyses yielded a pooled RR of 0.28 (95% CI 0.10–0.80).
Conclusion. Prophylactic statin therapy is associated with a clinically meaningful and statistically significant reduction in CTRCD in breast-cancer patients receiving anthracyclines. The protective effect is particularly pronounced in HER2-positive patients. A cautious, risk-stratified use of statins as a cardioprotective adjunct is supported pending adequately powered, breast-cancer-specific randomized trials.
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Repeated Optical Biometry Failure as an Underrecognized Marker of Late In-the-Bag Intraocular Lens Decentration in Axial Myopia: A Case Report
Views: 91Downloads: 59Background: Late in-the-bag intraocular lens (IOL) dislocation is a delayed complication of cataract surgery driven by progressive zonular weakness, with axial myopia recognized as an independent risk factor. Its role as a hidden cause of optical biometry failure, however, has received little emphasis in the literature.
Case presentation: A 58-year-old woman with longstanding axial myopia presented seven years after uneventful right-eye phacoemulsification with progressively blurred vision, monocular diplopia, and ghost images. Best-corrected visual acuity (BCVA) was 6/38 in the right eye improving to 6/15 with pinhole; refractometry revealed a new −4.00 D cylinder at axis 90° with persistent visual distortion consistent with irregular astigmatism. Slit-lamp examination showed inferior decentration of an in-the-bag posterior chamber IOL with a visible inferior haptic. Posterior segment evaluation through the displaced optic was hazy. Repeated optical biometry of the affected eye failed to acquire a valid axial-length signal across three sessions, whereas the fellow eye yielded reliable measurements. The patient was referred to a tertiary vitreoretinal center for IOL repositioning or exchange with possible pars plana vitrectomy and scleral fixation.
Conclusion: In a myopic pseudophakic eye presenting with new-onset monocular diplopia and an astigmatic shift, repeated failure of optical biometry should be recognized as a critical diagnostic clue to underlying IOL instability, prompting timely tertiary referral and individualized surgical planning.
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Efficacy and Safety of Travoprost Intraocular Implants in Open-Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis
Views: 115Downloads: 65Background: Open-angle glaucoma (OAG) and ocular hypertension (OHT) are leading causes of irreversible visual impairment and require lifelong reduction of intraocular pressure (IOP). Topical prostaglandin analogues are the standard first-line therapy, yet their effectiveness is constrained by poor adherence. The travoprost 75 µg intracameral implant has emerged as a sustained-release alternative designed to bypass these adherence barriers. The present systematic review and meta-analysis quantitatively synthesised the efficacy and safety of this device in adults with OAG or OHT.
Methods: PubMed was searched in accordance with the PRISMA 2020 statement. Original research articles evaluating the travoprost 75 µg intracameral implant in adults with OAG or OHT were eligible. Two reviewers screened, extracted data, and independently appraised risk of bias using Cochrane RoB 2.0 (RCTs) or the Newcastle–Ottawa Scale (non-randomised). Standardised mean changes in IOP were synthesised as Hedges' g under a DerSimonian–Laird random-effects model with Knapp–Hartung adjustment. Pre-specified sensitivity, leave-one-out, alternative-pool, and design sub-group analyses were performed. The funnel plot was inspected; Egger's test was deferred because k < 10.
Results: Of 30 PubMed records, 10 original research studies were eligible and 6 contributed to the primary quantitative synthesis (2,152 total enrolled participants; 1,525 implant-arm participants pooled in the within-group synthesis). The pooled within-group Hedges' g for IOP reduction was 4.35 (95% CI 3.14 to 5.56; p = 0.0002). Heterogeneity was very high (I² = 96.1%, τ² = 1.121, Q = 53.64, p < 0.0001). The 95% prediction interval, derived from the same model, spanned approximately 1.13 to 7.56. The randomised-controlled-trial-only pool (k = 4) yielded a more conservative pooled estimate of g = 3.76 (95% CI 2.94 to 4.58; I² = 88.6%). Leave-one-out analyses confirmed robustness (g range 3.98–4.56). Serious ocular adverse events were rare (one endophthalmitis in the slow-eluting arm of the GC-010 phase 3 trial, with no further cases in the remaining cohorts); transient ocular hyperemia, iritis, and elevated IOP were the most common, broadly consistent with the topical-travoprost class profile.
Conclusion: The travoprost 75 µg intracameral implant produced a large and consistent reduction in IOP across designs and follow-up windows, with a safety profile non-inferior to topical timolol 0.5%. The substantial heterogeneity, near-uniform sponsor footprint, and limited head-to-head comparisons against topical prostaglandin monotherapy temper the certainty of the evidence and warrant pragmatic, independent, multi-ethnic trials. Within these limits, the implant is a clinically meaningful addition to interventional glaucoma therapy, particularly for patients in whom topical adherence is the dominant driver of disease progression.
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Intraoperative Incisional Wound Irrigation with 0.05% Chlorhexidine versus 0.9% Saline to Prevent Surgical Site Infection after Laparotomy for Hollow-Viscus Perforation Peritonitis: A Double-Blind Randomized Controlled Trial
Views: 98Downloads: 74Background: Surgical site infection (SSI) is the most frequent complication of abdominal surgery and a major source of morbidity, prolonged hospitalization and cost, particularly in dirty (class IV) wounds created by gastrointestinal perforation; intraoperative incisional irrigation may lower wound bioburden, yet the optimal irrigant is undefined.
Methods: We conducted a double-blind randomized controlled trial at a tertiary referral center in Bandung, Indonesia (November 2019–August 2020) comparing incisional irrigation with 0.05% chlorhexidine versus 0.9% saline in adults undergoing emergency laparotomy for hollow-viscus perforation peritonitis. After fascial closure, incisions were irrigated by allocation and patients were followed for 30 days, with superficial SSI (ASEPSIS score) as the primary outcome.
Results: Of 141 patients screened, 96 were analyzed (49 chlorhexidine, 47 saline). Superficial SSI occurred in 5/49 (10.2%) chlorhexidine versus 14/47 (29.8%) saline patients (χ²=5.795, p=0.016; Fisher exact p=0.021; OR 0.268, 95% CI 0.088–0.818; relative risk 0.343; absolute risk reduction 19.6%; number-needed-to-treat 5.1). In multivariable logistic regression, chlorhexidine remained independently protective (adjusted OR 0.228, 95% CI 0.062–0.836, p=0.026), while intra-abdominal contamination (aOR 1.377 per 100 mL, p=0.008) and operative time (aOR 1.645 per 30 min, p=0.027) increased risk; the model discriminated well (AUC 0.835). No irrigation-related adverse events occurred.
Conclusion: Incisional irrigation with 0.05% chlorhexidine markedly reduced superficial SSI after laparotomy for perforation peritonitis and offers a low-cost strategy for dirty abdominal wounds.
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Efficacy and Safety of Adding Antiangiogenic Therapy to EGFR-Tyrosine Kinase Inhibitors versus EGFR-Tyrosine Kinase Inhibitor Monotherapy in EGFR-Mutant Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
Views: 76Downloads: 81Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) limits the durability of targeted therapy in EGFR-mutant non-small cell lung cancer (NSCLC). Inhibiting the vascular endothelial growth factor (VEGF) axis has been proposed to delay this resistance, but individual trials diverge and the antiangiogenic class has not been synthesised together across treatment settings. This study quantified the effect of adding antiangiogenic therapy to an EGFR-TKI on progression-free survival (PFS) and toxicity.
Methods. Four databases were searched for randomised controlled trials (RCTs) comparing an EGFR-TKI plus an antiangiogenic agent (bevacizumab or ramucirumab) with the same EGFR-TKI alone in EGFR-mutant NSCLC. The pre-specified primary analysis was PFS in the first-line setting, expressed as the hazard ratio (HR) and pooled with an inverse-variance random-effects (DerSimonian-Laird) model; a restricted maximum-likelihood model confirmed it. Heterogeneity used I², τ² and a 95% prediction interval; risk of bias used Cochrane RoB 2.0.
Results. Seven RCTs (eight reports; 1,512 patients; six first-line, one second-line) were included. In the six first-line trials the combination prolonged PFS (pooled HR 0.61, 95% CI 0.53-0.70; p<0.0001) with no heterogeneity (I²=0%; prediction interval 0.50-0.74); the restricted maximum-likelihood estimate was identical. The benefit was consistent for bevacizumab (HR 0.62, 0.52-0.73) and ramucirumab (HR 0.59, 0.46-0.76), a mean prolongation of median PFS of about 5.5 months. Adding the second-line osimertinib/T790M trial attenuated the effect (HR 0.66, 0.56-0.77; I²=32%), driven by absence of benefit in that setting (HR 0.96). Leave-one-out estimates were stable (0.59-0.63); the Egger test was non-significant. Grade ≥3 adverse events were increased (risk ratio 1.95, 1.47-2.57; absolute increase about 29 percentage points; number needed to harm about 4).
Conclusion. Adding antiangiogenic therapy to a first-line EGFR-TKI consistently prolongs PFS in EGFR-mutant NSCLC as a VEGF-pathway class effect, at the cost of roughly doubled severe toxicity and without a demonstrated overall-survival gain. The benefit was not evident in the second-line osimertinib/T790M setting, suggesting the strategy delays rather than overcomes resistance.
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Retinal Neural Layer Thickness and Contrast Sensitivity in Type 2 Diabetes Without Clinical Retinopathy: A Cross-Sectional Study
Views: 34Downloads: 19Background: Retinal neural dysfunction may occur in type 2 diabetes mellitus (T2DM) before clinically visible diabetic retinopathy.
Objective: We evaluated whether retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCL-IPL) thickness were associated with contrast sensitivity in adults with T2DM without clinical retinopathy.
Methods: This cross-sectional study included 30 eyes from 16 participants examined from September 2024 to June 2025. Swept-source optical coherence tomography measured average and quadrant RNFL thickness and macular GCL-IPL thickness. Monocular contrast sensitivity was assessed with the Pelli-Robson chart. Source-reported analyses included exploratory Spearman correlations, generalized estimating equations (GEE) for inter-eye clustering, and exploratory receiver operating characteristic (ROC) analysis.
Results: Mean RNFL thickness was 101.3 ± 12.55 µm, GCL-IPL thickness was 81.53 ± 7.34 µm, and contrast sensitivity was 1.773 ± 0.227 logCS. Eye-level correlations with contrast sensitivity were ρ=0.758 for GCL-IPL and ρ=0.640 for average RNFL (both source-reported p<0.001). In the exploratory GEE model, coefficients were 0.0104 logCS per µm for GCL-IPL (95% CI 0.001-0.019) and 0.0062 for RNFL (95% CI 0.001-0.011). Exploratory AUCs were 0.872 and 0.804, respectively.
Conclusion: Thicker GCL-IPL and RNFL measurements were associated with better contrast sensitivity in this small cohort. The estimates are hypothesis-generating and require confirmation with participant-level data, larger samples, and external validation before clinical use.
