Benefit of Avasopasem Manganese on Severe Oral Mucositis in Head and Neck Cancer in the ROMAN Trial: Unplanned Secondary Analysis.

Purpose: Oral mucositis (OM) is a debilitating side effect of cisplatin and intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. The phase 3 ROMAN trial showed avasopasem manganese (AVA) significantly decreased individual endpoints of incidence and duration of severe oral mucositis (SOM, World Health Organization [WHO] grade 3-4), with nominal decrease in severity (WHO grade 4) and significant increase in the delay in onset of SOM. We sought to determine the Net Treatment Benefit (NTB) of AVA versus placebo (PBO) using the generalized pairwise comparisons (GPC) method.

Subclinical malaria among pregnant women living in refugee settlements in Northern Uganda.

Background: Malaria during pregnancy contributes to significant perinatal morbidity and mortality, accounting for almost 25% of global maternal mortality. However, the epidemiology and risk factors for subclinical malaria among pregnant women living in refugee settlements is poorly understood.

Objective: To determine the prevalence and predictors of subclinical malaria among pregnant women in refugee settlements in Northern Uganda.

Child feces disposal practices in humanitarian and non-humanitarian settings across 34 low- and middle-income countries.

Globally, safe sanitation has improved significantly in the last two decades, but unsafe child feces disposal remains a growing challenge in many regions, exposing household members and communities to infectious pathogens. The drivers associated with child feces disposal in several contexts including humanitarian settings are not well understood. This study investigated child feces disposal (CFD) practices and associated factors in low- and middle-income countries, including in humanitarian settings.

Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues.

Patient-centric Comparability Assessment of Biopharmaceuticals.

The comparability assessment of a biological product after implementing a manufacturing process change should involve a risk-based approach. Process changes may occur at any stage of the product lifecycle: early development, clinical manufacture for pivotal trials, or post-approval. The risk of the change to impact product quality varies.

The antioxidant and anti-inflammatory activities of avasopasem manganese in age-associated, cisplatin-induced renal injury.

Purpose: Cisplatin contributes to acute kidney injury (AKI) and chronic kidney disease (CKD) that occurs with greater frequency and severity in older patients. Age-associated cisplatin sensitivity in human fibroblasts involves increased mitochondrial superoxide produced by older donor cells.

Experimental Design: Young and old C57BL/6 J murine models of cisplatin-induced AKI and CKD were treated with the SOD mimetic avasopasem manganese to investigate the potential antioxidant and anti-inflammatory effects.

Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial.

Background: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma.

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Polatuzumab vedotin, marketed under the trade name POLIVY, is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in combination with rituximab and bendamustine was approved by the United States Food and Drug Administration for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least two prior therapies. Recent Health Authority guidance recommendations for submitting an Integrated Summary of Immunogenicity were followed including a comprehensive immunogenicity risk assessment, bioanalytical strategy, and immunogenicity data to support the registration of polatuzumab vedotin.

Mass spectrometry-based multi-attribute method in protein therapeutics product quality monitoring and quality control.

The multi-attribute method (MAM), a liquid chromatography-mass spectrometry (LC-MS)-based peptide mapping method, has gained increased interest and applications in the biopharmaceutical industry. MAM can, in one method, provide targeted quantitation of multiple site-specific product quality attributes, as well as new peak detection. In this review, we focus on the scientific and regulatory considerations of using MAM in product quality attribute monitoring and quality control (QC) of therapeutic proteins.

Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo.

Mitochondrial Superoxide Dismutase in Cisplatin-Induced Kidney Injury.

Cisplatin is a chemotherapy agent commonly used to treat a wide variety of cancers. Despite the potential for both severe acute and chronic side effects, it remains a preferred therapeutic option for many malignancies due to its potent anti-tumor activity. Common cisplatin-associated side-effects include acute kidney injury (AKI) and chronic kidney disease (CKD).

Factors associated with safe child feces disposal in Ethiopia, India, and Zambia.

Safe child feces disposal (CFD) is defined as a child or caregiver placing or rinsing child feces into an improved sanitation facility. In low- and middle-income countries (LMICs), 48% of households with children under five report that child feces were safely disposed. Despite its widespread prevalence and harmful health effects, little is known about the determinants of safe CFD.

Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide.

Avasopasem manganese (AVA or GC4419), a selective superoxide dismutase mimetic, is in a phase 3 clinical trial (NCT03689712) as a mitigator of radiation-induced mucositis in head and neck cancer based on its superoxide scavenging activity. We tested whether AVA synergized with radiation via the generation of hydrogen peroxide, the product of superoxide dismutation, to target tumor cells in preclinical xenograft models of non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, and pancreatic ductal adenocarcinoma. Treatment synergy with AVA and high dose per fraction radiation occurred when mice were given AVA once before tumor irradiation and further increased when AVA was given before and for 4 days after radiation, supporting a role for oxidative metabolism.

25 vs. 27-gauge micro-incision vitrectomy surgery for visually significant macular membranes and full-thickness macular holes: a retrospective study.

Background: To evaluate visual and safety outcomes for 25-gauge (25G) and 27-gauge (27G) micro-incision vitrectomy platforms (MIVS) for the treatment of epiretinal membrane and full-thickness macular holes.

Methods: Retrospective analysis of all patients who underwent internal limiting membrane (ILM) peel surgery from January 2017 through December 2018. 207 cases met the eligibility criteria for inclusion.

A view of physical mechanisms for transporting harmful algal blooms to Massachusetts Bay.

Physical dynamics of Harmful Algal Blooms in Massachusetts Bay in May 2005 and 2008 were examined by the simulated results. Reverse particle-tracking experiments suggest that the toxic phytoplankton mainly originated from the Bay of Fundy in 2005 and the western Maine coastal region and its local rivers in 2008. Mechanism studies suggest that the phytoplankton were advected by the Gulf of Maine Coastal Current (GMCC).

Multilevel information storage using magnetoelastic layer stacks.

The use of voltages to control magnetisation via the inverse magnetostriction effect in piezoelectric/ferromagnet heterostructures holds promise for ultra-low energy information storage technologies. Epitaxial galfenol, an alloy of iron and gallium, has been shown to be a highly suitable material for such devices because it possesses biaxial anisotropy and large magnetostriction. Here we experimentally investigate the properties of galfenol/spacer/galfenol structures in which the compositions of the galfenol layers are varied in order to produce different strengths of the magnetic anisotropy and magnetostriction constants.

Superoxide Dismutase Mimetic GC4419 Enhances the Oxidation of Pharmacological Ascorbate and Its Anticancer Effects in an H₂O₂-Dependent Manner.

Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂.

Comparison of Outcomes between Endoscopic and Transcleral Cyclophotocoagulation.

: Traditionally cyclophotocoagulation has been reserved as a treatment of last resort for eyes with advanced stage glaucoma, but increasingly it is offered to eyes with less severe disease. Endoscopic approaches in particular are utilized in increasing numbers of patients despite only a small number of publications on its results. : The purpose of this study was to compare the efficacy and safety of endoscopic and transcleral cyclophotocoagulation (ECP and TCP) procedures in eyes with refractory glaucomas.

Understanding systemic lupus erythematosus patients' desired outcomes and their perceptions of the risks and benefits of using corticosteroids.

Introduction The use of corticosteroids in systemic lupus erythematosus (SLE) patients requires difficult trade-offs between efficacy and risk of toxicity. This qualitative study examined SLE patients' most desired outcomes and their concerns with corticosteroid use in SLE treatment. Methods SLE patients with current/past experience with using corticosteroids were recruited from the clinics at the Johns Hopkins Lupus Center and the University of Maryland Medical Center.

Deterministic control of magnetic vortex wall chirality by electric field.

Concepts for information storage and logical processing based on magnetic domain walls have great potential for implementation in future information and communications technologies. To date, the need to apply power hungry magnetic fields or heat dissipating spin polarized currents to manipulate magnetic domain walls has limited the development of such technologies. The possibility of controlling magnetic domain walls using voltages offers an energy efficient route to overcome these limitations.

Imaging Current-Induced Switching of Antiferromagnetic Domains in CuMnAs.

The magnetic order in antiferromagnetic materials is hard to control with external magnetic fields. Using x-ray magnetic linear dichroism microscopy, we show that staggered effective fields generated by electrical current can induce modification of the antiferromagnetic domain structure in microdevices fabricated from a tetragonal CuMnAs thin film. A clear correlation between the average domain orientation and the anisotropy of the electrical resistance is demonstrated, with both showing reproducible switching in response to orthogonally applied current pulses.

Effect of lithographically-induced strain relaxation on the magnetic domain configuration in microfabricated epitaxially grown FeGa.

We investigate the role of lithographically-induced strain relaxation in a micron-scaled device fabricated from epitaxial thin films of the magnetostrictive alloy FeGa. The strain relaxation due to lithographic patterning induces a magnetic anisotropy that competes with the magnetocrystalline and shape induced anisotropies to play a crucial role in stabilising a flux-closing domain pattern. We use magnetic imaging, micromagnetic calculations and linear elastic modelling to investigate a region close to the edges of an etched structure.

Strategies for Improving Patient Comfort During Intravitreal Injections: Results from a Survey-Based Study.

Introduction: Many ocular diseases require intravitreal injections of pharmacological agents. Optimizing patients' experiences during injections is important to ensure compliance and maintenance of quality of life. The objective of this study was to identify strategies to help alleviate discomfort during intravitreal injections.

Heterodyne mixing of millimetre electromagnetic waves and sub-THz sound in a semiconductor device.

We demonstrate heterodyne mixing of a 94 GHz millimetre wave photonic signal, supplied by a Gunn diode oscillator, with coherent acoustic waves of frequency ~100 GHz, generated by pulsed laser excitation of a semiconductor surface. The mixing takes place in a millimetre wave Schottky diode, and the intermediate frequency electrical signal is in the 1-12 GHz range. The mixing process preserves all the spectral content in the acoustic signal that falls within the intermediate frequency bandwidth.