The Province of Ontario (Canada) experienced a generational scale outbreak of measles in 2025. We applied wastewater surveillance concurrently with clinical-based surveillance to track measles incidence in southwestern Ontario adjacent to the United States. Measles virus (MeV) signal in wastewater was positively associated with clinical cases but did not provide early alert of changes in measles incidence when resolved by epidemiological week. Assessment of virus partitioning showed MeV RNA was broadly distributed in the liquid phase but is most concentrated in the solids. An assay was adapted for differentiation of vaccine and wildtype MeV and used to detect vaccine genotype measles following an inoculation campaign targeting underserved groups in the region. MeV shedding in wastewater was estimated through repeated sampling of sewer laterals serving a hospital treating confirmed measles infections. This measles outbreak serves as a case study highlighting the application of wastewater surveillance for measles while supporting method development in real-time. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by INSPIRE (Integrated Network for the Surveillance of Pathogens: Increasing REsilience and capacity in Canada's pandemic response), a program funded through the Canada Biomedical Research Fund Stage 2 (grant no. CBRF2-2023-00008), the Biosciences Research Infrastructure Fund Stage 2, and the Ontario Research Fund. Additional support was provided by the CIHR Applied Public Health Research Chair in Environment, Climate Change and One Health, awarded to Robert Delatolla. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research ethics approval was provided by the Windsor Regional Hospital Research Ethics Board (REB# 25-529) and the University of Windsor Research Ethics Board (REB# 25-127). The Windsor Regional Hospital Research Ethics Board issued a Category A approval-full approval of the research project (granted clearance for ethical acceptability). The University of Windsor Research Ethics Board (REB), which is organized and operates according to the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans and the University of Windsor Guidelines for Research Involving Human Participants, has granted clearance for the ethical acceptability of your research project. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.
B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody-drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways.
Purpose: Pembrolizumab combined with chemotherapy is the standard of care for early-stage triple-negative breast cancer (TNBC) following KEYNOTE-522. However, real-world data on immune-related adverse events (irAEs) remain limited. We evaluated the incidence, severity, and clinical consequences of irAEs in a real-world cohort and compared outcomes with KEYNOTE-522. Methods: We conducted a retrospective cohort study of patients with stage II–III TNBC treated according to the KEYNOTE-522 regimen at two Ontario cancer centres between June 2022 and May 2024. Data on irAEs, treatment discontinuation, and pathological complete response (pCR) were collected and contextualized against trial outcomes. Results: Among 79 patients, the pCR rate was higher than that reported in KEYNOTE-522 (77.2% vs. 64.8%). irAEs were documented in 51.9% of patients, compared with 33.5% in the trial. Permanent discontinuation due to irAEs occurred in 22.8% of patients, compared with 15.7% reported in KEYNOTE-522. Most discontinuations occurred during the neoadjuvant phase. Conclusions: Real-world patients experienced higher observed rates of low-grade irAEs and treatment discontinuation than reported in KEYNOTE-522; however, differences in study design limit direct comparison. These findings highlight the need for optimized toxicity management and further study of the impact of treatment duration on long-term outcomes.
Patient navigation is a promising intervention to address barriers and improve access to cancer clinical trials. Although navigation has been widely studied across the cancer continuum, its role in facilitating clinical trial participation has not been systematically evaluated. This scoping review aims to identify, characterize, and synthesize evidence on patient navigation interventions designed to increase access to cancer clinical trials. Nine databases were searched for English peer-reviewed articles from inception through 5 March 2025. Two independent researchers screened titles, abstracts, and full texts and extracted data using standardized forms. The results were interpreted using descriptive statistics and collated using predetermined conceptual frameworks. Of 10,238 citations identified, 23 studies met inclusion criteria. All were conducted in North America, and five (21.7%) were randomized controlled trials. Thirteen studies (56.5%) evaluated enrollment outcomes, with mixed results. One randomized trial and two observational studies found no significant effect, while three observational studies and seven single-arm reports suggested improved enrollment. Navigation interventions most commonly included education/information provision (100%), care coordination (60.9%), and empowerment (47.8%). Navigators were primarily lay navigators (73.9%), often selected for community or lived experience; training varied widely, and only two programs reported certification. Fifteen studies (65.2%) targeted equity-deserving groups, most frequently racial and ethnic minorities, with reports of increased representation in trial enrollment. Patient navigation shows promise in improving access to cancer clinical trials, particularly for equity-deserving populations, but current evidence is limited, heterogeneous, and largely observational. Standardized definitions, rigorous trial designs, and reporting of navigator training and outcomes are needed to clarify effectiveness.
Purpose of review: Cardiovascular disease (CVD) accounts for nearly half of deaths among people receiving maintenance hemodialysis. Observational and interventional data suggest that higher serum magnesium, achieved through higher dialysate magnesium concentrations or oral supplementation, may improve cardiovascular outcomes and survival. This review synthesizes current evidence and provides context for an ongoing cluster-randomized trial that is testing whether a center-wide dialysate magnesium concentration of 0.75 mmol/L, versus ≤0.50 mmol/L, delivered as a policy and sustained for up to four years, reduces the risk of major cardiovascular-related hospitalizations. Sources of information: Peer-reviewed articles. Methods: We searched MEDLINE and EMBASE for observational and interventional studies evaluating serum or dialysate magnesium concentrations and cardiovascular outcomes in patients with chronic kidney disease and/or kidney failure. We appraised the methodological quality of interventional trials. This review is divided into four sections: (1) epidemiological associations between serum magnesium concentrations and CVD outcomes, (2) the impact of a higher concentration of dialysate magnesium on CVD outcomes, (3) the impact of oral magnesium supplementation on CVD outcomes, and (4) ongoing trials. Key findings: Twenty studies, including 10 randomized controlled trials, were reviewed. Systematic reviews and meta-analyses show that hypomagnesemia is associated with higher risks of cardiovascular events and all-cause mortality in hemodialysis. Interventional studies indicate that higher dialysate magnesium concentrations or oral supplementation can improve surrogate markers of vascular health, including less vascular calcification and stiffness. Higher dialysate concentrations may also lower cardiovascular mortality. Given encouraging but predominantly surrogate-based evidence, adequately powered randomized trials are warranted. Limitations: Most trials were small, single-center, and of short duration. They relied on surrogate endpoints, and there was heterogeneity in interventions and outcome measures.
