Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence.

Introduction: We have previously described preclinical literature which supports umbilical cord blood-derived cell (UCBC) therapy as an efficacious treatment for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient population and intervention characteristics.Objectives: To systematically review the effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand the contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage, and number of doses.Methods: A systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible.Results: Differential benefits of UCBCs were seen across a number of subgroup analyses including intraventricular hemorrhage (IVH) vs. hypoxia ischemia (HI) model (apoptosis white matter (WM): chi2 = 4.07; P = .04, neuroinflammation-TNF-α: chi2 = 5.99; P = .01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2 = 5.01; P = .03, neuroinflammation-TNF-α: chi2 = 3.93; P = .05, apoptosis grey matter (GM), astrogliosis WM), and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2 = 7.51; P = .02, astrogliosis WM: chi2 = 12.44; P = .002). We identified a serious risk of bias and overall low certainty of evidence.Conclusions: Preclinical evidence suggests UCBCs to show greater efficacy in the injury model of IVH compared to HI, the use of UCB-MSCs compared to UCB-MNCs and the use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence and address knowledge gaps.

Introduction: Lung injuries, such as bronchopulmonary dysplasia (BPD), remain a major complication of preterm birth, with limited therapeutic options. One potential emerging therapy is umbilical cord blood (UCB)-derived therapy. Objectives: To systematically assess the safety and efficacy of UCB-derived therapy for preterm lung injury in preclinical and clinical studies. Methods: A systematic search of MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO International Trials Registry Platform was performed. A meta-analysis was conducted with Review Manager (5.4.1) using a random effects model. Data was expressed as standardized mean difference (SMD) for preclinical data and pooled relative risk (RR) for clinical data, with 95% confidence intervals (CI). Potential effect modifiers were investigated via subgroup analysis. Certainty of evidence was assessed using the GRADE system. Results: Twenty-three preclinical studies and six clinical studies met eligibility criteria. Statistically significant improvements were seen across several preclinical outcomes, including alveolarization (SMD, 1.32, 95%CI [0.99, 1.65]), angiogenesis (SMD, 1.53, 95%CI [0.87, 2.18]), and anti-inflammatory cytokines (SMD, 1.68, 95%CI [1.03, 2.34]). In clinical studies, 103 preterm infants have received UCB-derived therapy for preterm lung injury and no significant difference was observed in the development of BPD (RR, 0.93, 95%CI [0.73, 1.18]). Across both preclinical and clinical studies, administration of UCB-derived therapy appeared safe. Certainty of evidence was assessed as “low.” Conclusions: Administration of UCB-derived therapy was associated with statistically significant improvements across several lung injury markers in preclinical studies. Early clinical studies demonstrated the administration of UCB-derived therapy as safe and feasible but lacked data regarding efficacy.

Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.

Background: The COVID‐19 pandemic has significantly disrupted global healthcare systems. Melanoma, a highly aggressive skin cancer whose prognosis is closely tied to early detection, has been particularly impacted. Lockdowns, changes to healthcare resource reallocation and patient hesitancy in seeking care have all contributed to delays in melanoma diagnoses and treatment modifications. Understanding the extent of this disruption is crucial to inform future healthcare planning during global crises. Objectives: To evaluate the impact of the COVID‐19 pandemic on melanoma incidence, diagnostic delays and disease severity by comparing findings from pre‐pandemic and pandemic periods through a systematic review of existing literature. Methods: A systematic search was conducted across PubMed, Scopus, Web of Science and Cochrane Library in September 2024, adhering to PRISMA guidelines. Eligible studies included clinical trials, observational studies, reviews and case series that reported melanoma incidence, diagnostic delays or changes in treatment between pre‐COVID‐19 (2015−2019) and COVID‐19/post‐COVID‐19 (2019−2024) periods. Data extraction focused on incidence rates, Breslow thickness, ulceration, treatment changes and patient outcomes. Study quality was assessed using the Newcastle−Ottawa Scale and Joanna Briggs Institute tools. Results: Out of 503 studies screened, 55 met the inclusion criteria. Most studies reported a decline in diagnosed melanoma cases during the pandemic, accompanied by an increase in Breslow thickness and ulceration rates, indicating delayed presentations and more advanced disease. Significant disruptions in treatment pathways, including reduced surgical excisions, were frequently noted. Conclusions: The COVID‐19 pandemic contributed to delayed melanoma diagnoses and a shift towards more advanced disease at presentation. These findings highlight the critical need for resilient cancer care systems to maintain timely diagnostic and treatment services during future public health emergencies.

The lethal triad of trauma (acidemia, coagulopathy, and hypothermia) is associated with substantial morbidity and mortality. Patients with severe burn injuries, defined as > 20 % total body surface area (TBSA), are one group of trauma patients at risk of developing this triad. However, there is currently limited evidence on how the lethal triad affects this cohort of patients. To describe the prevalence of the lethal triad in patients with severe burns on arrival to an adult burns service hospital. The secondary aim was to investigate potential factors associated with presence of the lethal triad. Adult patients (> 18 years of age) with severe burns (> 20 %TBSA) admitted to a Victorian Adult Burns Service (VABS) tertiary hospital between January 1, 2019 and 31 December, 2023, were included in the study. From 158 patients identified through the VABS registry, 142 patients met inclusion criteria. Among 106 patients with available data, the lethal triad was present on arrival to hospital in 6 patients (5.7 %; 95 %CI: 2.1-11.9 %). Acidemia was present in 58 of 116 (50.0 %; 95 %CI: 40.6-59.4), coagulopathy in 18 of 125 (14.4 %; 95 %CI: 8.8-21.8) and hypothermia in 53 of 140 (37.9 %; 95 %CI: 29.8-46.4). Among patients with the lethal triad, all 6 patients (100 %) died, compared to 27 patients (27.0 %) without the lethal triad (odds ratio 21.0; 95 %CI: 2.91->99.9). A small proportion of patients with severe burns presented to hospital with all three components of the lethal triad of trauma. Acidemia and hypothermia were more commonly observed when compared to coagulopathy. Recognition, prevention, and early management may result in improved outcomes.