Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study.

BACKGROUND: In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab emtansine (T-DM1) and manageable safety in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer. Here, patient-reported outcomes (PROs) are reported along with hospitalization data. PATIENTS AND METHODS: Patients in DESTINY-Breast03 were assessed for prespecified PRO measures, including European Organization for Research and Treatment of Cancer quality of life (EORTC-QoL) questionnaires [the oncology-specific EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and breast cancer-specific EORTC QLQ-BR45] and the generic EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) visual analogue scale. Analyses included change from baseline, time to definitive deterioration (TDD), and hospitalization-related endpoints. RESULTS: EORTC QLQ-C30 baseline global health status (GHS) scores for T-DXd (n = 253) and T-DM1 (n = 260) were similar, with no clinically meaningful change (<10-point change from baseline) while on either treatment (median treatment duration: T-DXd, 14.3 months; T-DM1, 6.9 months). TDD analyses of QLQ-C30 GHS (primary PRO variable) and all other prespecified PROs (QLQ-C30 subscales, the QLQ-BR45 arm symptoms scale, and the EQ-5D-5L visual analogue scale) suggested T-DXd was numerically favored over T-DM1 based on TDD hazard ratios. Of all randomized patients, 18 (6.9%) receiving T-DXd versus 19 (7.2%) receiving T-DM1 were hospitalized, and the median time to first hospitalization was 219.5 versus 60.0 days, respectively. CONCLUSIONS: In DESTINY-Breast03, EORTC GHS/QoL was maintained on both therapies throughout treatment, indicating that despite the longer treatment duration with T-DXd versus T-DM1, health-related QoL did not worsen on T-DXd. Furthermore, TDD hazard ratios numerically favored T-DXd over T-DM1 in all prespecified variables of interest including pain, suggesting T-DXd may delay time until health-related QoL deterioration compared with T-DM1. Median time to first hospitalization was three times longer with T-DXd versus T-DM1. Together with reported improved efficacy and manageable toxicity, these results support the overall benefit of T-DXd for patients with HER2+ metastatic breast cancer.

Learning to look from different perspectives - what can dental undergraduates learn from an arts and humanities-based teaching approach?

By its nature, clinical teaching involves supporting small groups of dental students at the chairside as they treat their own patients. Scaffolding their learning in this way enables observation at close quarters of the various stages of development from early novice, just commencing clinical treatment of patients, to those approaching qualification. The students' main concerns throughout are not primarily with the technical skills required, which they have already been taught in the clinical skills laboratories, but dealing with the complex realities and ambiguities of clinical practice; the 'hidden curriculum' of decision making, judgement calls, issues of communication and what it actually means to be professional. Yet, in an already packed curriculum little time is spent helping the students develop these higher order skills. In an effort to improve clinical reasoning and interpretative skills, many medical schools in the US and a number of leading medical schools here in the UK now incorporate arts and humanities-based initiatives into their curricula. This allows for a greater balance between the objectivity of evidence-based medicine and the pluralism and subjectivity of the arts and humanities, providing a more holistic, patient-centred education that promotes a tolerance of ambiguity. In this paper, we describe a pilot programme which sought to explore the value of this approach in the context of dental education, and share early indicators that balancing interventions of this type with clinical sciences can enhance dental students' capabilities in their professional and personal development. We conclude that in today's complex world we must educate not just for competence, but for capability and that the interdisciplinarity afforded by the 'clinical humanities' is both a promising area for further educational research and potentially a valuable addition to the curriculum.

Biotic and abiotic controls on co-occurring nitrogen cycling processes in shallow Arctic shelf sediments.

The processes that convert bioavailable inorganic nitrogen to inert nitrogen gas are prominent in continental shelf sediments and represent a critical global sink, yet little is known of these pathways in the Arctic where 18% of the world's continental shelves are located. Moreover, few data from the Arctic exist that separate loss processes like denitrification and anaerobic ammonium oxidation (anammox) from recycling pathways like dissimilatory nitrate reduction to ammonium (DNRA) or source pathways like nitrogen fixation. Here we present measurements of these co-occurring processes using 15N tracers. Denitrification was heterogeneous among stations and an order of magnitude greater than anammox and DNRA, while nitrogen fixation was undetectable. No abiotic factors correlated with interstation variability in biogeochemical rates; however, bioturbation potential explained most of the variation. Fauna-enhanced denitrification is a potentially important but overlooked process on Arctic shelves and highlights the role of the Arctic as a significant global nitrogen sink.

Immunophysiology of Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill), and the relationship to parasitic copepod, Dichelesthium oblongum (Abilgaard) infection.

The copepod parasite, Dichelesthium oblongum, is known to infect the Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus, within the area near New York city, USA, known as the NY Bight. The gross pathology associated with the juvenile and adult copepod stages along with the parasite's link in causing changes in sturgeon osmoregulatory capabilities has led us to investigate the host immunophysiology in relation to this host-parasite system. All the host variables, which included gill Na(+) -K(+) -ATPase activity, serum alkaline phosphatase (AP) and white blood cell differential counts, were affected in a non-linear manner by the copepod parasite. The parasites increased the host gill Na(+) -K(+) -ATPase activity and serum AP along with the percentage granulocytes while decreasing the percentage lymphocytes. A new method, developed to sample and preserve white blood cells in the field for future flow cytometry analysis, proved adequate. The effects of fish size, location and time of sampling were accounted for by the use of generalized linear models, and their effects on the host variables are discussed.

Genetic mixed-stock analysis of Atlantic sturgeon Acipenser oxyrinchus oxyrinchus in a heavily exploited marine habitat indicates the need for routine genetic monitoring.

Although a previous genetic mixed-stock analysis (gMSA) conducted in the early 1990s showed that marine-captured New York Bight Atlantic sturgeon Acipenser oxyrinchus oxyrinchus almost exclusively originated from the Hudson River, fish from southern U.S. rivers were well represented within this contemporary sample (n = 364 fish), at least during the autumn. Widely distributed spawning stocks are therefore exposed to heavy fishing activity and habitat degradation in this relatively small area, illustrating the need for spatial management across multiple management jurisdictions and routine gMSA to account for temporal change.

Arctic biogeography: The paradox of the marine benthic fauna and flora.

The marine benthic fauna and flora that inhabit the shallow arctic sublittoral zone comprise a relatively young marine assemblage characterized by species of either Pacific or Atlantic affinity and notably few endemics. The young character of nearshore arctic communities, as well as their biogeographical composition, is largely a product of the Pleistocene glaciation. However, analysis of more recent collections and comparison between the origins of the benthic fauna and flora present some interesting paradoxes to biogeographers. One enigma is the low frequency of algal species with Pacific affinities in the Arctic, especially in the Chukchi, Beaufort and East Siberian Seas of the Eastern Arctic, which receive direct inputs of northward-flowing Pacific waters. In contrast, animal species with Pacific affinities are found throughout the nearshore regions of the Arctic, reaching their highest frequency in the marginal seas between the New Siberian Islands and the Canadian Archipelago. Organization of published and unpublished data, additional field collections, and the use of cladistics and molecular DNA techniques by systematists are a high priority for future research in reconstructing the evolution of the arctic biotic assemblage.