Publications by authors named "Branagan A"
Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing.
View Article and Find Full Text PDFElotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial.
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- - Neonatal encephalopathy (NE) leads to multiorgan injury in newborns, with therapeutic hypothermia being the common treatment; this study aims to identify effective scoring systems for assessing organ dysfunction in NE.
- - A systematic review of 628 articles was conducted, identifying 12 relevant studies, which showed a correlation between the severity of NE and multiorgan dysfunction, but highlighted significant differences across scoring systems used.
- - For a comprehensive scoring system, the study suggests including assessments of various organ systems (renal, hepatic, respiratory, neurological, hematological, and cardiovascular), while noting that further validation and standardization are necessary for effective use, especially considering the impact of therapeutic hypothermia.
Article Synopsis
- Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are effective in treating MYD88-mutated Waldenstrom's macroglobulinaemia by inhibiting key signaling pathways that promote tumor growth.* -
- BTK mutations can lead to treatment resistance by reactivating ERK1/2, which causes increased inflammatory cytokine production and helps BTK wild-type tumor cells survive.* -
- Pirtobrutinib, a non-covalent BTK-inhibitor, has been shown to successfully block damaging ERK1/2 activity and can overcome resistance in MYD88 lymphoma cells with mutated BTK.*
Neurologic depression in term/near-term neonates (neonatal encephalopathy, NE) is uncommon with modern obstetric care. Asphyxial birth, with or without co-factors, accounts for a minority of NE, while maldevelopment (congenital malformations, growth aberrations, genetic, metabolic and placental abnormalities) plays an enlarging role in identifying etiologic subgroups of NE. The terms NE and hypoxic-ischemic encephalopathy (HIE) have not been employed uniformly, hampering research and clinical care.
View Article and Find Full Text PDFAim: Systematically review the management of infants with severe bronchiolitis in a paediatric intensive care unit (PICU) setting with a focus on high-risk infants to identify gaps in evidence-based knowledge.
Methods: This systematic review utilised Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) to examine the literature on the PICU management of bronchiolitis in infants <24 months old. Three databases, Embase, PubMed and Medline, were searched and higher levels of evidence I, II and III were included.
Background: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families.
View Article and Find Full Text PDFOutcomes of interventions in neonatal sepsis: A systematic review of qualitative research.
Int J Gynaecol Obstet
November 2024
Article Synopsis
- This study looked at how different people, like parents and doctors, feel about the effects of treatments for neonatal sepsis, which is a serious infection in newborns.
- The researchers found 19 important outcomes that matter to these people, like how the treatment affects parents and their babies' organs.
- They concluded that it's important to include these personal views in future research to get a full picture of what's important in treating neonatal sepsis, since the views shared were different from what doctors usually report in clinical trials.
Aim: Retinopathy of prematurity is a significant global cause of childhood blindness. This study aims to identify serum biomarkers that are associated with the development of ROP.
Methods: A systematic review and meta-analysis was conducted using PRISMA guidelines.
Purpose: Gastric residual measurement is routinely performed in premature infants prior to feeding despite a lack of evidence of benefit. We aimed to evaluate if the exclusion of routine gastric residual measurement and evaluation has an impact on the time taken to achieve full enteral feeding in preterm neonates.
Methods: International multi-centre randomised controlled trial.
Purpose: Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary.
Materials And Methods: We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity.
Article Synopsis
- The study investigates the use of diuretics in treating bronchopulmonary dysplasia (BPD), a respiratory condition in premature infants, to evaluate their effectiveness.
- A systematic review was conducted, analyzing 13 studies from various databases, focusing on combinations of diuretics like spironolactone and furosemide and their impact on lung function.
- Results indicate that the effectiveness of diuretics for BPD is still unclear due to limited high-quality studies, suggesting a need for more rigorous randomized controlled trials to assess their safety and efficacy.
Article Synopsis
- Advances in perinatal and neonatal care have improved the survival rates of preterm infants, shifting the focus to enhancing long-term neurological outcomes.
- Current therapies like antenatal steroids show short-term benefits, but there's little evidence for long-term neurodevelopmental improvement, necessitating further research into effective neuroprotective strategies.
- Promising treatments under investigation include multipotential stem cells and anti-inflammatory therapies, while immediate care methods that nurture brain health in NICUs are crucial for fostering neuroplasticity.
Article Synopsis
- Neonatal sepsis is a serious illness in newborns, and different studies measure its effects in different ways, making it hard to compare results.
- Researchers want to create a Core Outcome Set (COS) to standardize what outcomes should be measured for treatments of neonatal sepsis, using input from parents, healthcare workers, and researchers.
- By getting everyone to agree on what to measure through online surveys and meetings, this project hopes to make research on neonatal sepsis clearer and more useful.
Article Synopsis
- A clinical trial was conducted to investigate the effects of combining two drugs, ibrutinib and venetoclax, for treating symptomatic, treatment-naïve patients with MYD88-mutated Waldenström macroglobulinemia (WM).
- Out of 45 patients enrolled, 42% achieved a very good partial response (VGPR), and the study noted significant adverse events, including a concerning rate of ventricular arrhythmia.
- After a median follow-up of 24.4 months, the study reported strong progression-free survival (76%) and overall survival (96%) rates, even though it was terminated early due to safety concerns.
Neonatal brain injury and associated inflammation is more common in males. There is a well-recognised difference in incidence and outcome of neonatal encephalopathy according to sex with a pronounced male disadvantage. Neurodevelopmental differences manifest from an early age in infancy with females having a lower incidence of developmental delay and learning difficulties in comparison with males and male sex has consistently been identified as a risk factor for cerebral palsy in epidemiological studies.
View Article and Find Full Text PDFIntroduction: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied.
Methods: Infants with NE and neonatal controls were prospectively recruited.
Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials.
View Article and Find Full Text PDFConsensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.
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- The Consensus Panel 1 (CP1) of IWWM-11 focused on updating guidelines for managing symptomatic, treatment-naïve Waldenstrom's Macroglobulinemia (WM) patients, asserting that watchful waiting is best for asymptomatic cases.
- Current first-line treatments include chemoimmunotherapy regimens like DRC and Benda-R, which are effective, usually well-tolerated, and cost-effective; covalent BTK inhibitors like zanubrutinib also provide a viable alternative, showing fewer side effects and better remissions compared to ibrutinib.
- The panel also noted the importance of testing for MYD88 and CXCR4 mutations prior to treatment, as these can influence the effectiveness of certain
Thresholds for surfactant use in preterm neonates: a network meta-analysis.
Arch Dis Child Fetal Neonatal Ed
July 2023
Objective: To perform a network meta-analysis of randomised controlled trials of different surfactant treatment strategies for respiratory distress syndrome (RDS) to assess if a certain fraction of inspired oxygen (FiO) is optimal for selective surfactant therapy.
Design: Systematic review and network meta-analysis using Bayesian analysis of randomised trials of prophylactic versus selective surfactant for RDS.
Setting: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Science Citation Index Expanded.