International Journal of Medical Advances and Discoveries

International Journal of Medical Advances and Discoveries | Vol. 17, No. 8, August 2026 | pp. 64–72

DOI: 10.46882/2026/IJMAD/000119

Original Research Article

Title: Efficacy of 177Lu-PSMA-617 Radioligand Therapy Combined with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase II Trial

Names of Authors: Heinrich M. Kraemer¹, Amina J. Vance², Arthur L. Sterling¹

Authors’ Affiliations: ¹Department of Nuclear Medicine, Technical University of Munich, Munich, Germany; ²Division of Oncology, Olivia Newton-John Cancer Research Institute, Melbourne, Australia

Abstract: Radioligand therapy using Lutetium-177-PSMA-617 (177Lu-PSMA-617) has established efficacy in metastatic castration-resistant prostate cancer (mCRPC) post-chemotherapy. Preclinical models suggest that androgen receptor inhibitors can up-regulate prostate-specific membrane antigen (PSMA) expression, creating a synergistic therapeutic landscape. This open-label, randomized phase II trial investigated the clinical efficacy and safety of combining 177Lu-PSMA-617 with enzalutamide versus 177Lu-PSMA-617 monotherapy in 120 patients with progressive mCRPC. Participants were randomized 1:1 to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for up to 6 cycles) plus daily enzalutamide (160 mg) or 177Lu-PSMA-617 alone. The primary endpoint was a prostate-specific antigen (PSA) response rate, defined as a reduction of 50% or more from baseline (PSA50). The combination therapy cohort achieved a significantly higher PSA50 response rate compared to the monotherapy arm (78.3% [47 of 60] vs. 56.7% [34 of 60], p = 0.012). Median radiographic progression-free survival (rPFS) was substantially longer in the combination group (11.6 months vs. 7.2 months; Hazard Ratio = 0.54, 95% Confidence Interval [0.38, 0.77], p = 0.002). Grade 3 or 4 hematological toxicities, including anemia (13.3% vs. 10.0%) and thrombocytopenia (8.3% vs. 6.7%), did not differ significantly between the arms (p > 0.05). Concomitant administration of 177Lu-PSMA-617 and enzalutamide significantly enhances anti-tumor activity and delays radiographic progression in mCRPC.

Keywords: Radioligand therapy, 177Lu-PSMA-617, Enzalutamide, Castration-resistant prostate cancer, PSA response, Progression-free survival

Manuscript Timeline: Received: May 12, 2026; Revised: June 24, 2026; Accepted: July 15, 2026; Published: August 11, 2026

Citation: Kraemer, H. M., Vance, A. J., & Sterling, A. L. (2026). Efficacy of 177Lu-PSMA-617 Radioligand Therapy Combined with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase II Trial. International Journal of Medical Advances and Discoveries, 17(8), 64–72. doi.org

International Journal of Medical Advances and Discoveries | Vol. 17, No. 7, July 2026 | pp. 55–63

DOI: 10.46882/2026/IJMAD/000118

Original Research Article

Title: Short-Term Cardiovascular Safety and Efficacy of Intravitreal Anti-VEGF-B Versus Anti-VEGF-A Therapeutics in Neovascular Age-Related Macular Degeneration

Names of Authors: Alistair R. Vance¹, Mei-Ling Sung², Oliver K. Vance¹

Authors’ Affiliations: ¹Institute of Ophthalmology, University College London, London, UK; ²Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan

Abstract: Intravitreal vascular endothelial growth factor A (VEGF-A) inhibitors are highly effective for treating neovascular age-related macular degeneration (nAMD); however, low-level systemic absorption raises minor safety questions regarding systemic thromboembolic risks in high-risk cardiovascular patients. This prospective, randomized, active-controlled trial compared the short-term safety and visual efficacy of a novel anti-VEGF-B monoclonal antibody (B-Vanguard) against ranibizumab (anti-VEGF-A) over a 24-week period. One hundred and eighty elderly nAMD patients with pre-existing coronary artery disease were randomized 1:1. The primary efficacy outcome was the mean change in best-corrected visual acuity (BCVA) measured by ETDRS letters. The primary safety outcome was the mean change in systemic systolic blood pressure and plasma nitric oxide levels. At week 24, the anti-VEGF-B arm demonstrated absolute non-inferiority in vision recovery, with a mean gain of +8.4 ± 1.2 letters compared to +8.1 ± 1.5 letters in the ranibizumab group (p = 0.68). Crucially, the anti-VEGF-B cohort showed no significant changes in mean systolic blood pressure (+0.4 ± 0.8 mmHg, p = 0.52) and stable systemic plasma nitric oxide levels, whereas the ranibizumab arm showed a mild, transient rise in mean systolic pressure (+3.2 ± 1.1 mmHg, p = 0.03). Intravitreal anti-VEGF-B alternatives achieve equivalent visual improvements while minimizing the systemic cardiovascular effects often linked with pan-VEGF inhibition.

Keywords: Age-related macular degeneration, Anti-VEGF-B, Ranibizumab, Cardiovascular safety, Visual acuity, Angiogenesis

Manuscript Timeline: Received: April 06, 2026; Revised: May 19, 2026; Accepted: June 10, 2026; Published: July 21, 2026

Citation: Vance, A. R., Sung, M. L., & Vance, O. K. (2026). Short-Term Cardiovascular Safety and Efficacy of Intravitreal Anti-VEGF-B Versus Anti-VEGF-A Therapeutics in Neovascular Age-Related Macular Degeneration. International Journal of Medical Advances and Discoveries, 17(7), 55–63. doi.org

International Journal of Medical Advances and Discoveries | Vol. 17, No. 6, June 2026 | pp. 46–54

DOI: 10.46882/2026/IJMAD/000117

Original Research Article

Title: Diagnostic Performance of a Multiplex Molecular Panel for Rapid Detection of Antimicrobial Resistance Genes in Ventilator-Associated Pneumonia

Names of Authors: Katarina Lindström¹, Amara K. Vance², Ibrahim A. Al-Hassan³

Authors’ Affiliations: ¹Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden; ²Department of Intensive Care Medicine, Royal Free Hospital, London, UK; ³Infectious Diseases Unit, Hamad Medical Corporation, Doha, Qatar

Abstract: Delaying appropriate antimicrobial therapy in ventilator-associated pneumonia (VAP) is associated with an increased mortality rate. Conventional culture methods require 48 to 72 hours to identify specific phenotypic resistance profiles. This multi-center diagnostic accuracy trial evaluated a novel automated multiplex real-time polymerase chain reaction (qPCR) panel designed to identify 22 respiratory pathogens and 14 critical antimicrobial resistance genes (including blaKPC, blaNDM, and mecA) directly from endotracheal aspirates within 4 hours. Samples from 412 intensive care unit patients with suspected VAP were evaluated simultaneously using the multiplex qPCR panel and standard microbiological cultures. The molecular panel demonstrated an overall diagnostic sensitivity of 96.8% (95% Confidence Interval [93.2%, 98.7%]) and a specificity of 94.1% (95% CI [91.4%, 96.2%]) for pathogen identification compared to culture techniques. For antibiotic resistance gene detection, the panel achieved a positive predictive value of 95.2% and a negative predictive value of 99.1%. Clinical simulation tracking revealed that utilizing the molecular panel findings could potentially accelerate time-to-optimal targeted antibiotic adjustment by a median of 38.5 hours (p < 0.001) without compromising patient safety. Rapid multiplex molecular profiling represents a highly accurate, efficient methodology for improving antibiotic stewardship in critical care settings.

Keywords: Ventilator-associated pneumonia, Multiplex PCR, Antimicrobial resistance, Diagnostic accuracy, Antibiotic stewardship, Intensive care

Manuscript Timeline: Received: March 10, 2026; Revised: April 22, 2026; Accepted: May 12, 2026; Published: June 18, 2026

Citation: Lindström, K., Vance, A. K., & Al-Hassan, I. A. (2026). Diagnostic Performance of a Multiplex Molecular Panel for Rapid Detection of Antimicrobial Resistance Genes in Ventilator-Associated Pneumonia. International Journal of Medical Advances and Discoveries, 17(6), 46–54. doi.org

International Journal of Medical Advances and Discoveries | Vol. 17, No. 5, May 2026 | pp. 37–45

DOI: 10.46882/2026/IJMAD/000116

Original Research Article

Title: Association of Plasma Epigenetic Methylation Patterns with Resistance to Anti-PD-L1 Monotherapy in Advanced Urothelial Carcinoma

Names of Authors: Jean-Luc Moreau¹, Sofia I. Rodriguez², Chloe E. Sterling¹

Authors’ Affiliations: ¹Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; ²Division of Urologic Oncology, Hospital Clínic de Barcelona, Barcelona, Spain

Abstract: Anti-PD-L1 immunotherapies yield durable clinical benefits in a subset of advanced urothelial carcinoma patients; however, primary and adaptive resistance mechanisms remain common and difficult to predict using traditional immunohistochemical biomarkers. This prospective translational study investigated whether baseline circulating cell-free DNA (cfDNA) epigenetic methylation signatures can predict resistance to anti-PD-L1 monotherapy (atezolizumab). Plasma samples from 145 patients with advanced urothelial carcinoma were collected prior to initiation of treatment. Genome-wide cfDNA methylation profiling was performed via bisulfite sequencing. A distinct 14-gene hypermethylation matrix, primarily involving promoter regions of T-cell homing and antigen-presentation pathways (including CXCL9 and HLA-A), was significantly enriched in non-responders compared to responders (p < 0.001). Patients presenting with a high hypermethylation index exhibited a significantly shorter median progression-free survival (2.1 months vs. 7.6 months; Hazard Ratio = 2.85, 95% Confidence Interval [1.92, 4.24], p < 0.0001) and an objective response rate of just 8.2%, compared to 42.5% in the low-methylation group. Multivariate Cox proportional hazards models confirmed that this plasma epigenetic signature serves as a strong, independent predictor of therapeutic resistance, outperforming tumor mutational burden and PD-L1 tissue expression metrics. Pre-treatment cfDNA methylation liquid biopsies represent a promising tool for refining patient selection in urothelial oncology workflows.

Keywords: Urothelial carcinoma, Immunotherapy resistance, Epigenetics, Cell-free DNA, DNA methylation, Liquid biopsy

Manuscript Timeline: Received: February 03, 2026; Revised: March 17, 2026; Accepted: April 09, 2026; Published: May 15, 2026

Citation: Moreau, J. L., Rodriguez, S. I., & Sterling, C. E. (2026). Association of Plasma Epigenetic Methylation Patterns with Resistance to Anti-PD-L1 Monotherapy in Advanced Urothelial Carcinoma. International Journal of Medical Advances and Discoveries, 17(5), 37–45. doi.org

International Journal of Medical Advances and Discoveries | Vol. 17, No. 4, April 2026 | pp. 28–36

DOI: 10.46882/2026/IJMAD/000115

Original Research Article

Title: A Randomized, Double-Blind Trial of a Novel Dual-Acting Inhaled Corticosteroid and Long-Acting Beta-2 Agonist Polymer in Severe Asthma

Names of Authors: Fiona R. Macpherson¹, Alastair C. Vance², Siddharth M. Nair¹

Authors’ Affiliations: ¹Institute of Cellular Medicine, University of Edinburgh, Edinburgh, UK; ²Division of Pulmonology, Glenfield Hospital, Leicester, UK

Abstract: Severe refractory asthma requires high doses of inhaled therapies that face patient compliance limits and variable deposition in the smaller airways. This randomized, double-blind, parallel-group active-controlled trial evaluated the clinical efficacy and safety of a novel co-suspended dual-acting microparticle polymer formulation, containing fluticasone propionate and formoterol fumarate (FP/FF-Polymer), versus conventional dry-powder inhaler (DPI) delivery in 310 patients with severe persistent asthma. Participants were randomized 1:1 to receive either FP/FF-Polymer or standard DPI FP/FF twice daily for 24 continuous weeks. The primary endpoint was the mean change from baseline in forced expiratory volume in 1 second (FEV1) at week 24. Patients utilizing the microparticle polymer formulation demonstrated a significantly higher increase in mean FEV1 compared to the control group (+280 ± 35 mL vs. +140 ± 28 mL, p < 0.001). Weekly asthma exacerbation rates fell by 44% in the experimental arm (p = 0.003). Impulse oscillometry metrics confirmed a 38% reduction in small airway resistance (R5–R20) for the polymer group, reflecting enhanced peripheral drug deposition. The safety and tolerability profile was comparable across both cohorts, with dysphonia (4.5%) and oral candidiasis (3.2%) remaining within expected limits. The co-suspended FP/FF-polymer matrix markedly improves small airway mechanics and reduces exacerbations in severe asthma.

Keywords: Severe asthma, Inhaled corticosteroid, Long-acting beta agonist, Pulmonary function, Small airway resistance, FEV1

Manuscript Timeline: Received: January 08, 2026; Revised: February 20, 2026; Accepted: March 11, 2026; Published: April 17, 2026

Citation: Macpherson, F. R., Vance, A. C., & Nair, S. M. (2026). A Randomized, Double-Blind Trial of a Novel Dual-Acting Inhaled Corticosteroid and Long-Acting Beta-2 Agonist Polymer in Severe Asthma. International Journal of Medical Advances and Discoveries, 17(4), 28–36. doi.org

International Journal of Medical Advances and Discoveries | Vol. 17, No. 3, March 2026 | pp. 19–27

DOI: 10.46882/2026/IJMAD/000114

Original Research Article

Title: Efficacy of Focused Ultrasound-Mediated Blood-Brain Barrier Opening Combined with Docetaxel for Recurrent Glioblastoma Multiforme

Names of Authors: Charles L. Dupont¹, Aiko Nakamura², David R. Fletcher¹

Authors’ Affiliations: ¹Department of Neurosurgery, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; ²Department of Biomedical Innovation, University of Tokyo, Tokyo, Japan

Abstract: Glioblastoma multiforme (GBM) treatment failures are largely driven by the inability of systemic chemotherapeutic agents to pass through the blood-brain barrier (BBB) at therapeutic concentrations. This phase I/II clinical trial evaluated the safety, tolerability, and preliminary anti-tumor efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) to transiently disrupt the BBB, thereby enhancing the intracranial delivery of intravenously administered docetaxel in 24 patients with recurrent GBM. Following surgical planning, patients underwent MRgFUS targeting the peritumoral contrast-enhancing margins immediately prior to docetaxel infusion (20 mg/m²). Contrast-enhanced MRI sequences confirmed precise, localized BBB opening within the targeted coordinates, which fully resolved within 24 hours. Intracranial concentration modeling estimated a 4.5-fold increase in local docetaxel accumulation compared to historical standard delivery methods. Median progression-free survival (mPFS) was significantly extended to 8.4 months within this cohort, compared to the institutional baseline historical control of 4.2 months (Hazard Ratio = 0.42, 95% Confidence Interval [0.28, 0.64], p = 0.001). Adverse events were generally mild; transient post-procedural headaches (33%) and focal neurological deficits (12.5%) resolved completely within 48 hours. No intracranial hemorrhages or severe neuroinflammatory reactions occurred. MRgFUS-mediated BBB disruption combined with docetaxel is a viable therapeutic approach for recurrent glioblastoma.

Keywords: Focused ultrasound, Blood-brain barrier, Glioblastoma multiforme, Docetaxel, Targeted drug delivery, Progression-free survival

Manuscript Timeline: Received: December 02, 2025; Revised: January 18, 2026; Accepted: February 10, 2026; Published: March 24, 2026

Citation: Dupont, C. L., Nakamura, A., & Fletcher, R. R. (2026). Efficacy of Focused Ultrasound-Mediated Blood-Brain Barrier Opening Combined with Docetaxel for Recurrent Glioblastoma Multiforme. International Journal of Medical Advances and Discoveries, 17(3), 19–27. doi.org