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All Journal Jurnal Kedokteran Diponegoro Jurnal Kedokteran IJEMS (Indonesian Journal of Environmental Management and Sustainability) Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research Indonesian Journal of Cancer
Yan Wisnu Prajoko
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Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Decision Sciences, Operations Research & Management Energy Environmental Science Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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Whey Protein as an Adjuvant Therapy for Wound Healing and Infection Control: A Systematic Review and Meta-Analysis of Clinical and Preclinical Evidence Aliva Nabila Farinisa; Niken Puruhita; Yan Wisnu Prajoko; Felix Setiawan
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1483

Abstract

Background: Impaired wound healing and subsequent infections represent a significant clinical and economic burden. Nutritional status, particularly high-quality protein provision, is a critical, modifiable determinant of healing outcomes. Whey protein (WP), a rich source of essential amino acids and unique bioactive components, has emerged as a promising adjuvant therapy. Methods: We conducted a systematic review and meta-analysis adhering to PRISMA guidelines. We searched PubMed, Scopus, and Web of Science from January 2015 to December 2024 for clinical randomized controlled trials (RCTs) and preclinical controlled studies evaluating WP supplementation on wound healing and infection. Rigorous inclusion criteria led to the selection of seven studies (four clinical RCTs, three preclinical) for quantitative synthesis. Data were pooled using a random-effects model to calculate Standardized Mean Differences (SMD) for continuous outcomes and Odds Ratios (OR) for dichotomous outcomes. Results: The meta-analysis of four clinical RCTs (n=340 patients) demonstrated that WP supplementation significantly accelerated wound healing (SMD = 0.78; 95% CI 0.45, 1.11; p < 0.0001) with moderate heterogeneity (I²=38%). Furthermore, WP significantly reduced the odds of wound infection by 48% (OR = 0.52; 95% CI 0.31, 0.87; p=0.01) with no heterogeneity (I²=0%). Preclinical synthesis (3 studies, n=62 animals) revealed a significant reduction in pro-inflammatory cytokines (TNF-α, IL-6) at the wound site (SMD = -1.15; 95% CI -1.67, -0.63; p < 0.0001). Conclusion: This meta-analysis provides robust quantitative evidence that whey protein functions as an effective adjuvant therapy, significantly enhancing wound repair and providing clinically relevant infection control. These benefits appear to be mediated by a dual mechanism: providing essential anabolic substrates for tissue repair and exerting potent immunomodulatory and antioxidant effects via bioactive components like lactoferrin and cysteine.
Vitamin D in the Breast Cancer Continuum: A Systematic Review and Meta-Analysis of Primary Prevention, Patient Prognosis, and Adjunctive Treatment Response Felix Setiawan; Yan Wisnu Prajoko; Niken Puruhita; Aliva Nabila Farinisa
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1486

Abstract

Background: The role of vitamin D across the breast cancer spectrum remains complex and contested. Compelling preclinical antineoplastic mechanisms contrast with inconsistent clinical findings. Large randomized controlled trials (RCTs) show null effects for primary prevention, while observational studies often link higher vitamin D status at diagnosis with better prognosis. Key conflicts include this prevention-prognosis disconnect, debates over linear versus J-shaped prognostic dose-responses, and a "receptor-status paradox" where estrogen receptor-positive (ER-positive) disease shows prognostic links, but hormone receptor-negative (HR-negative)/triple-negative (TNBC) subtypes derive greater benefit (improved pathological complete response, pCR) from vitamin D intervention during neoadjuvant chemotherapy (NACT). This study systematically synthesizes evidence across these distinct clinical contexts. Methods: Following PRISMA guidelines, we systematically reviewed PubMed, EMBASE, and CENTRAL (January 1st, 2014–September 2nd, 2025) for high-impact RCTs and large prospective cohort studies evaluating vitamin D supplementation or serum 25-hydroxyvitamin D (25(OH)D) levels regarding breast cancer incidence, prognosis (survival/recurrence), or pCR after NACT. Quality was assessed (Cochrane RoB 2; Newcastle-Ottawa Scale). Data were extracted dually. Findings were synthesized stratigraphically (prevention, prognosis, treatment). A random-effects meta-analysis pooled pCR data from NACT RCTs. Results: Six high-quality studies (3 RCTs, 3 cohorts; N=31,026) were included. (1) Prevention: The VITAL RCT (N=25,871; mean baseline 25(OH)D 30.8 ng/mL) found no reduction in incident invasive breast cancer with 2000 IU/day vitamin D3 (HR 1.02, 95% CI 0.79–1.31). (2) Prognosis: Cohort studies (N=4,835) showed higher 25(OH)D linked to better OS (Adj HR T3 vs T1: 0.72). Complexity emerged: one study linked benefit specifically to ER-positive recurrence (Adj HR 0.87), while another reported a J-shaped curve for EFS, with worse outcomes at both low (≤52 nmol/L; Adj HR 1.63) and high (≥99 nmol/L; Adj HR 1.37) levels versus intermediate. (3) Treatment: Meta-analysis of two NACT RCTs (N=310) showed vitamin D supplementation significantly increased pCR rates (38.1% vs 22.6%; Pooled RR 1.69, 95% CI 1.21–2.36; P=0.002; I²=0%). Subgroup data strongly suggested greater benefit in HR-negative/TNBC and baseline-deficient patients. Conclusion: Vitamin D supplementation appears ineffective for primary breast cancer prevention in replete populations. Its prognostic role is complex, suggesting an optimal 25(OH)D range (potentially ~30-40 ng/mL) and possible ER-specific hormonal modulation effects, though causality from observational data remains uncertain. Critically, vitamin D intervention during NACT significantly improves pCR, particularly in HR-negative/TNBC, likely via distinct chemosensitization/immunomodulatory mechanisms. This synthesis provides a framework for understanding these context-dependent roles, supporting vitamin D assessment and potentially adjunctive NACT supplementation, especially in deficient patients with aggressive subtypes, pending necessary validation in larger trials.
Adaptive Radiotherapy (ART) versus Non-Adaptive IMRT for Locoregionally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of Dosimetric Advantages, Clinical Outcomes, and Organ-at-Risk Sparing Gina Amalia; Yan Wisnu Prajoko; Niken Puruhita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1488

Abstract

Background: Intensity-modulated radiotherapy (IMRT) is the cornerstone of treatment for nasopharyngeal carcinoma (NPC), offering high dose conformity. However, anatomical variations during the multi-week therapy course can compromise dosimetric accuracy. Adaptive radiotherapy (ART), which adjusts the treatment plan based on intra-treatment imaging, aims to mitigate these effects. This meta-analysis synthesized contemporary comparative evidence (2014–2025) on the efficacy and safety of ART versus non-adaptive IMRT in locoregionally advanced NPC. Methods: Following PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library were searched for studies comparing ART with non-adaptive IMRT (cohorts or hybrid/phantom plan comparisons) in locoregionally advanced NPC. Primary outcomes were locoregional recurrence-free survival (LRFS) and overall survival (OS); secondary outcomes included progression-free survival (PFS), distant metastasis-free survival (DMFS), and dosimetric metrics for targets (D98, Conformity Index [CI]) and organs-at-risk (OARs: parotid Dmean, spinal cord Dmax, brainstem Dmax). Hazard Ratios (HR) and Mean Differences (MD) were pooled using random-effects models. Data estimation methods (Tierney, Wan, Cochrane) were employed where necessary. Heterogeneity was assessed using I². Results: Nine studies (2 cohort, 7 dosimetric/anatomical) involving 362 patients (clinical) and 215 datasets (dosimetric) were included. ART significantly improved LRFS compared to non-adaptive IMRT (pooled HR = 0.53, 95% CI 0.32–0.88; I²=0%). No significant differences were found for OS (HR=0.98, 95% CI 0.64–1.50), PFS (HR=0.70, 95% CI 0.45–1.07), or DMFS (HR=0.88, 95% CI 0.48–1.62). Compared to hybrid/phantom plans, ART significantly enhanced target coverage (pooled PTV D98 MD = 2.15 Gy, 95% CI 1.10–3.20 Gy; I²=78%) and conformity (pooled CI MD = 0.05, 95% CI 0.02–0.08; I²=85%). ART significantly reduced OAR doses: parotid Dmean (pooled MD = -3.50 Gy, 95% CI -4.95 to -2.05 Gy; I²=90%), spinal cord Dmax (pooled MD = -3.95 Gy, 95% CI -5.80 to -2.10 Gy; I²=93%), and brainstem Dmax (pooled MD = -2.75 Gy, 95% CI -4.40 to -1.10 Gy; I²=91%). Dosimetric analyses exhibited high heterogeneity. Conclusion: ART significantly improves LRFS in locoregionally advanced NPC compared to non-adaptive IMRT. It provides substantial dosimetric advantages, enhancing target coverage and conformity while critically reducing doses to parotid glands, spinal cord, and brainstem. Despite high dosimetric heterogeneity and no demonstrated OS benefit, the improvements in LRFS and dose delivery support the thoughtful implementation of ART.
Co-Authors Albertus Ari Adrianto Aliva Nabila Farinisa Ani Margawati Emmanuel Joseph Bagus Hestu Pradipta Endang Mahati Firdaus Wahyudi Gina Amalia Ivandy Fam Niken Puruhita Olvaria Misfa Paramita Nindya Hapsari Ratna Widayati Renni Yuniarti Reyhan Zuhdi Gofita Widyawigata Selamat Budijitno Setiawan, Felix Udadi Sadhana