Journals
2025 EN
Mei Matthew · Palmer Joycelynne · Lee Hun Ju
+15 more
Abstract Nivolumab is an anti‐PD‐1 antibody that is effective in patients with relapsed/refractory (RR) classic Hodgkin lymphoma (cHL). We previously showed PET‐adapted sequential nivolumab ± ifosfamide, carboplatin, and etoposide (ICE) chemotherapy as the first salvage in RR cHL was a safe and effective bridge to autologous stem cell transplant (ASCT) (cohort A). We then tested a non‐PET‐adapted schema where all patients received nivolumab + ICE (cohort B). In this study, we present results from cohort B. Patients with high‐risk RR cHL after frontline treatment received 240 mg nivolumab followed by 2–3 cycles of NICE (240 mg nivolumab day 1, standard doses of ICE). High‐risk disease was defined as having one of the following: primary refractory cHL, relapse within 1 year of completing frontline therapy, B symptoms at relapse, extranodal disease at relapse, or frontline brentuximab vedotin use. PET/CT was performed after nivolumab × 1 and NICE × 2. Responding patients (complete response [CR] or partial response) were intended to proceed to ASCT. The primary endpoint was CR rate per 2014 Lugano classification. A total of 35 patients were enrolled, all of whom were evaluable for safety and efficacy. Overall response rate and CR were 100% and 86%, respectively; 2‐year progression‐free survival (PFS) and overall survival (OS) were 88% and 100%, respectively. Thirty‐two patients proceeded to ASCT directly after NICE; 2‐year post‐ASCT PFS and OS were 94% and 100%, respectively. Immune‐related toxicities were all grades 1–2, and no patient discontinued treatment for toxicity. Nivolumab/NICE is a highly effective salvage regimen and bridges patients effectively to ASCT.
Journals
2025 EN
Treon Steven P. · Sarosiek Shayna · Castillo Jorge J.
ABSTRACT Waldenström macroglobulinemia (WM) is an IgM secreting lymphoplasmacytic lymphoma. Mutations in MYD88 (95%–97%) and CXCR4 (30%–40%) are common in patients with WM. TP53 is also altered in up to 30% of WM patients, particularly those previously treated. Mutated MYD88 triggers the expression and activation of HCK that drives multiple pro‐survival signaling cascades, including BTK. There are over 40 CXCR4 mutation types in WM. WM patients bearing nonsense CXCR4 variants can present with symptomatic hyperviscosity and show greater resistance to covalent BTK inhibitors (cBTK‐i). The cBTK‐i zanubrutinib shows greater response activity and/or improved progression‐free survival in WM patients with wild‐type MYD88, mutated CXCR4, or altered TP53. New or emerging options for patients progressing on c‐BTKi include pirtobrutinib, BGB‐16673, venetoclax, and sonrotoclax. Combinations of BTK inhibitors with chemoimmunotherapy and BCL2 antagonists have advanced. Algorithms for patients with treatment‐naïve and previously treated WM based on genomics, disease characteristics, and co‐morbidities are discussed.
Journals
2025 EN
Beck Tracey · Giese Steven · Khoo Tien K.
Abstract Issue Addressed Health‐related information can often be overwhelming for consumers, frequently infused with complex medical terminology that is difficult to understand and apply. Historically empathic connection, art and narratives have played key roles in communicating with diverse populations however collectively have received little recognition as a modality to improve health literacy. This study aimed to investigate the empathetic connection between art and patient narratives with a view to improve health literacy in the wider community. Methods Nine recently discharged patients and one carer from a regional hospital were paired with 10 tertiary visual arts students for interview. Each narrative was transformed into visual art and exhibited at a community art gallery. The Empathy Quotient (EQ), Medical Outcomes Study 36‐item Short Form Health Survey (SF‐36) and self‐completed questionnaires assessed empathy and functional well‐being. Health literacy was evaluated through community response surveys post‐exhibition exposure. Results Student artist participants' EQ Cognitive Empathy (EQ‐CE) scores were associated with ‘Emotional Reactivity’ (EQ‐ER) ( p = .038). SF‐36 scores revealed that role limitations due to physical health and emotional problems had the greatest impact on patient/carer participant's life at the time. The SF‐36 General Health domain was associated with the EQ‐ER total score ( p = .044). Exhibition surveys revealed that 96.9% of observers had learnt something new about illness or injury. So What? Although a relatively small study, our findings suggest patient/carer narratives and visual art is a simple yet effective modality for health service organisations to facilitate affective learning and improve health literacy when engaging with consumers.
Journals
2025 EN
Gasavi Nezhad Zeinab · A. Gard Steven · Arazpour Mokhtar
ABSTRACT Background and Aims Hyperkyphosis, which affects 20%–40% of older adults, is characterized by excessive thoracic curvature and is linked to impaired mobility. Age‐related gait changes further complicate this issue, but studies on the relationship between hyperkyphosis and gait parameters have yielded inconsistent results. Focused research is essential to clarify this relationship and develop effective interventions. Methods This systematic review examined the effects of hyperkyphosis on gait in older adults ( ≥ 60 years), adhering to PRISMA 2020 guidelines (PROSPERO registration: CRD42024597304). Observational studies were included, while interventions and studies involving younger populations were excluded. Databases (PubMed, Web of Science, Scopus, CINAHL, Cochrane) were systematically searched. Two independent reviewers screened articles, extracted data, and assessed the risk of bias using validated JBI tools (cohort and cross‐sectional checklists). Studies were categorized as high‐, moderate‐, or low‐quality ( ≥ 75%, 50%–74%, and < 50% scores, respectively). Discrepancies were resolved through consensus. Results were synthesized qualitatively, focusing on methodological strengths and limitations. Results Nineteen studies focusing on older adults with hyperkyphosis were analyzed, highlighting diverse methods for measuring kyphosis and gait parameters. The findings indicated hyperkyphosis adversely affects gait characteristics, including walking speed, step time, and overall mobility. A strong association was found between increased age, reduced muscle mass, and impaired gait performance. Conclusion This review underscores the detrimental impact of hyperkyphosis on gait parameters in older adults, emphasizing the need for standardized measurement protocols and early clinical identification. Targeted interventions are essential to enhance gait performance in this population.
Journals
2025 EN
Ford McKenzie L. · Choh Audrey C. · Gonzalez Brandon
+5 more
ABSTRACT Background and Aims The role of anti‐Müllerian hormone (AMH), a potential marker of the hypothalamic–pituitary–ovarian axis, is not well established in adolescent females. Typical epidemiologic studies use secondary sexual characteristics or chronological age as predictors for AMH. Skeletal maturity, an indicator of bone development, however, has not been examined in association with AMH in adolescent females. This study aimed to examine patterns of change in AMH levels in relation to skeletal maturity in healthy adolescents from the Fels Longitudinal Study. Methods A longitudinal study was conducted on 88 females (212 observations) between the ages of 8 and 18. AMH levels were analyzed using ELISA from stored frozen serum samples. Skeletal age from hand‐wrist radiographs, as well as demographics, anthropometrics, and cardiometabolic risk factors, were included in the analysis. In the stepwise linear mixed‐effects regression models, log‐transformed AMH (AMH log ) was regressed on relative skeletal age, the skeletal maturity indicator calculated as chronological age minus skeletal age. Chronological age modeled as a cubic function, adiposity measures, and cardiometabolic factors such as fasting glucose were included as covariates. Results Skeletal maturity significantly predicted lower AMH log ( β = −0.073, SE = 0.032, p = 0.02). Serum glucose levels were significantly associated with decreases in AMH log ( β = −0.008, SE = 0.004, p = 0.04). Chronological age was not significantly associated with AMH log . Conclusion Our study showed a negative relationship between AMH and skeletal age relative to chronological age. This study highlights that AMH and skeletal maturity provide correlated information on growth and pubertal status in adolescent females.
Journals
2025 EN
Brooks J. Renée · Johnson Henry M. · Johnson Keira
+4 more
ABSTRACT Snowpacks are an important water source for mountainous rivers, worldwide. The timing and volume of streamflow in systems reliant on snowmelt can be affected by changes in snow accumulation and melt time. In the Cascade Range (western USA), seasonal snowpacks are predicted to decrease by over 50% within the next century. During the last decade, Cascade Range snowpacks have varied between 17% and 150% of the median 1981–2023 peak snowpack values. To understand how snowpack variation could affect Willamette River streamflow, we monitored water stable isotopes over 13 years from two sites on the mainstem and 60 streams draining small catchments across the Willamette River Basin. Small catchment water stable isotope values integrated and dampened variation in precipitation isotopes and varied with elevation, providing a marker for determining the mean elevation from which streamflow in the Willamette River was derived. During winter, while snow accumulates in the mountains, most streamflow in the Willamette River originates from rainfall at lower elevations. During summer low‐flow conditions, most streamflow in the river was derived from winter snow that accumulated at elevations above 1200 m, which represents < 12% of the Willamette River Basin area. Peak snow water equivalent from the previous winter was positively correlated with the proportion of Willamette River streamflow derived from > 1200 m during the summer low‐flow period, but both high elevation (> 1200 m) precipitation and temperature trends explained nearly as much variance as snow water equivalent. However, after accounting for climate trends, the estimated amount of high‐elevation streamflow in the Willamette River during summer low‐flow has decreased over the past 13 years. Improved understanding of the origin of, and trends in, summer streamflow in the Willamette River will aid in reconciling human demands with biological instream requirements during periods of low snowpack.
Journals
2025 EN
Blond Kyle · Conrad Steven · Thompson Nathaniel
+1 more
Abstract Aircraft maintenance strategy, execution, and improvement decisions (i.e., solutions) are critical enterprise responses impacting a fleet's sustainment performance. Enterprise maintenance solutions are a key product support activity in the United States Department of Defense that must balance safety, economics, and operations. To guide and regulate enterprise reliability and maintainability decisions, several programs, policies, and standards govern various aspects of a system's product support and sustainment domain. While this body of enterprise knowledge prescribes what to do, it intentionally enables organizations to decide how they want to collaborate and organize to make enterprise‐level reliability and maintainability decisions. In contrast, much of the academic literature focuses on how to make closed form organization‐level reliability and maintainability decisions, but does not address the complexities and implications of involving multiple heterogeneous organizations. To this end, this research seeks to develop enterprise architecture viewpoints and views to characterize the interdependencies, interactions, and integration of reliability and maintainability solutions across organizations. These architectures provide improved traceability and domain understanding of enterprise reliability and maintainability decisions to advance product support and sustainment outcomes. A notional United States Air Force commercial derivative aircraft serves as an exemplar of how these enterprise architectures identify enterprise actors and their exchanges to develop a reliability and maintainability decision‐making framework. Together, this framework and its enterprise context guide the design of a decision support tool for enterprise reliability and maintainability solutions. Finally, applications of enterprise reliability and maintainability architectures are discussed to enable novel Digital Product Support strategies in the United States Department of Defense.
Journals
2025 EN
Gao Weiman · Karsa Mawar · Xiao Lin
+17 more
Abstract Cancer cells are addicted to polyamines, polycations essential for cellular function. While dual targeting of cellular polyamine biosynthesis and polyamine uptake is under clinical investigation in solid cancers, preclinical and clinical studies into its potential in haematological malignancies are lacking. Here we investigated the preclinical efficacy of polyamine depletion in acute leukaemia. The polyamine biosynthesis inhibitor difluoromethylornithine (DFMO) inhibited growth of a molecularly diverse panel of acute leukaemia cell lines, while non‐malignant cells were unaffected. Responsiveness to DFMO was linked to decreased levels of its molecular target, the rate‐limiting polyamine biosynthesis enzyme ODC1, and of the polyamine transporters ATP13A2 and ATP13A3. DFMO increased polyamine uptake and upregulated expression of polyamine transporters in acute leukaemia cells, a compensatory effect abolished by treatment with the polyamine transport inhibitor AMXT 1501. This drug, currently in a phase 1 clinical trial in solid tumours in combination with DFMO, potentiated the inhibitory effects of DFMO, and their combination synergistically inhibited the growth of acute leukaemia cell lines by inducing apoptosis. DFMO and AMXT 1501 limited disease progression in highly aggressive xenograft models of infant KMT2A ‐rearranged leukaemia, even when treatment was initiated at high disease burden. Increased expression of c‐MYC was associated with enhanced sensitivity to the combination of DFMO and AMXT 1501, suggesting this oncoprotein as a potential predictive marker of response to the drug combination. In conclusion, targeting polyamine biosynthesis and polyamine uptake limits disease progression in models of acute leukaemia, supporting further preclinical and clinical investigation into this approach for acute leukaemia.
Journals
2025 EN
Nitschke Christine · Phan Charline · Souto Yara
+13 more
Abstract Pancreatic ductal adenocarcinoma (PDAC) ranks among the most lethal cancers, with only 20% of patients qualifying for curative treatment at diagnosis. Three‐dimensional tumor organoids capturing patient‐specific features of PDAC serve as a valuable disease model. We employed this technology to assess drug sensitivities of patient‐derived tumor organoids to clinically relevant drugs and combinations, evaluated culture success rates, and correlated in vitro data with clinicopathological and follow‐up information. Tumor organoid cultures were established from PDAC patients undergoing surgical resection (or liver biopsy) and follow‐up at a single medical center. Patient‐derived cultures displaying sustained growth were analyzed regarding their molecular subtype and utilized for functional drug sensitivity testing (f‐DST). Correlative analyses of our PDAC patient cohort ( n = 67; n = 42 patients with curative tumor resection and n = 25 palliative patients) revealed a link between tumor organoid growth and reduced patient survival. Furthermore, drug sensitivity profiles (obtained of 10 patient‐derived cultures) revealed notable inter‐individual differences and mirrored clinical responses to administered drug therapies. f‐DST was applicable across tumor organoid cultures of both classical and basal subtype, according to the Purity Independent Subtyping of Tumors (PurIST) classifier. This pilot study confirms the feasibility of deriving and maintaining tumor organoid cultures from heterogeneous samples. Cultures displaying sustained proliferation correlated positively with advanced‐stage tumors (Tumour, Node, Metastasis (UICC) stages III and IV). Individual patient case analyses integrating in vitro drug sensitivity profiles with clinical follow‐up data suggest that f‐DST using tumor organoids could guide future therapeutic strategies. In summary, tumor organoids offer insights into patient‐specific responses to treatment, highlighting the potential of precision medicine in managing this challenging cancer.
Journals
2025 EN
Louwen Frank · Deuster Eileen · McAuliffe Fionnuala M.
+4 more
Abstract Recent political statements linking paracetamol (acetaminophen) use during pregnancy to autism spectrum disorders have created concern among patients and healthcare providers worldwide. This editorial critically examines the scientific evidence, highlighting that the largest and most methodologically rigorous population‐based studies employing sibling control analyses demonstrate no causal association between prenatal paracetamol exposure and neurodevelopmental disorders. While some observational studies have suggested potential weak associations, these findings likely reflect confounding by indication and familial genetic factors rather than actual causal relationships. The most robust evidence comes from a Swedish population‐based study of 2.48 million children, which found no increased risk when controlling for familial confounding. Major international medical organizations including ACOG, RCOG, and FIGO, and regulatory agencies including the European Medicines Agency continue to recommend paracetamol as the safest analgesic option during pregnancy when clinically indicated. The established risks of untreated pain and fever during pregnancy significantly outweigh theoretical concerns based on methodologically limited studies. Healthcare providers should continue evidence‐based counseling while avoiding unnecessary anxiety about this essential medication in obstetric practice.