The establishment of a multiple myeloma clinical registry in the Asia-Pacific region: The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR).

BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry's design and development, initial data, progress and future plans. METHODS: The APAC MRDR was established in 2018 as a multicentre collaboration across the Asia-Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024. RESULTS: Over 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues. CONCLUSION: The APAC MRDR is providing 'real-world' data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.

Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas.

Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with significant morbidity and can negatively impact functionality and quality of life. OSCCs have significant upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, significantly blocks the growth of several COSCC cell lines established from current patient tumor samples. We further show clinical evidence that the drug is able to cause significant tumor regression in some patients with spontaneously occurring COSCC. Given the limited treatment options available and the high rate of owner rejection of these offered options, these findings provide new hope that more acceptable treatment options may soon enter the veterinary clinic.

Sexual Self Discrepancies, Sexual Satisfaction, and Relationship Satisfaction in a Cross-Sectional Sample of Women Who Experience Chronic Vaginal Pain during Sexual Intercourse.

One out of three women may suffer from chronic vaginal pain during intercourse, a complex health issue that leads to lasting psychological, sexual, emotional, and relational difficulties even after initial relief. Women who experience this pain condition may compare their sexual selves to the societal norm of being pain-free. Comparisons that do not align with one's actual sexual self result in sexual self-discrepancies and may cause emotional distress. Sexual self-discrepancies may hinder sexual and relationship satisfaction for women who experience chronic vaginal pain during sexual intercourse. This mixed-method study examined the sexual self-discrepancies women reported and the degree to which their sexual self-discrepancies were related to their sexual and relationship satisfaction. Results from this cross-sectional study showed that the majority of participants experienced sexual self-discrepancies and that they experienced a significant inverse correlation between sexual self-discrepancies and sexual satisfaction. In multivariate models, sex frequency was the strongest predictor of sexual satisfaction. There were no correlations between sexual self-discrepancies and relationship satisfaction. Future measurement research should examine the role of sex frequency in the experience of sexual satisfaction. Education on maximizing pleasure and minimizing pain may aid women to cope with the negative impact of pain.

An International Survey of Extracorporeal Membrane Oxygenation Education and Credentialing Practices.

Background: The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly over the past decades because of evolving indications, advances in circuit technology, and encouraging results from modern trials. Because ECMO is a complex and highly invasive therapy that requires a multidisciplinary team, optimal education, training, and credentialing remain a challenge. Objective: The primary objectives of this study were to investigate the prevalence and application of ECMO education and ECMO practitioner credentialing at ECMO centers globally. In addition, we explored differences among education and credentialing practices in relation to various ECMO center characteristics. Methods: We conducted an observational study of ECMO centers worldwide using a survey querying participants in two major domains: ECMO education and ECMO practitioner credentialing. Of note, the questionnaire included ECMO program characteristics, such as type and size of hospital and ECMO experience and volume, to explore the association with the two domains. Results: A total of 241 (32%) of the 732 identified ECMO centers responded to the survey, representing 41 countries across the globe. ECMO education was offered at 221 (92%) of the 241 centers. ECMO education was offered at 105 (98.0%) high-ECMO volume centers compared with 136 (87.5%) low-ECMO volume centers (P = 0.005). Credentialing was established at 101 (42%) of the 241 centers. Credentialing processes existed at 52 (49.5%) high-ECMO volume centers compared with 51 (37.5%) low-ECMO volume centers (P = 0.08) and 101 (49.3%) Extracorporeal Life Support Organization centers compared with 1 (2.7%) non-Extracorporeal Life Support Organization center (P < 0.001). Conclusion: We found significant variability in whether ECMO educational curricula are offered at ECMO centers. We also found fewer than half of the ECMO centers surveyed had established credentialing programs for ECMO practitioners. Future studies that assess variability in outcomes among centers with and without standardized educational and credentialing practices are needed.

Venipuncture Site Influences Blood-drop Volume in C57BL/6 Mice.

Many experiments require the collection of serial blood samples from mice. However, the size of mice limits the volume of blood that can be safely collected as a survival procedure. In IACUC protocols, investigators may report the amount of blood they collect from mice as a number of drops. Many institutions, including ours, use an anecdotal conversion factor (1 drop of mouse blood = 25 µL) to ensure that blood-collection volumes are compliant with institutional guidelines. To our knowledge, previous work has not experimentally determined the volume of a drop of mouse blood. In this 10-wk crossover experiment, 2 phlebotomists bled 30 C57BL/6J mice from 3 sites (facial, saphenous, and tail) using one or 2 different needle gauge sizes per site. Male and female mice were weighed weekly and divided among 5 groups (n = 6): left and right tail vein, left and right saphenous vein, and facial vein. A single blood drop from each site was weighed, and the volume of each drop was calculated using the average blood density determined from 8 mice terminally bled at the end of the study. Venipuncture site and side significantly influenced blood-drop weight and thus calculated volume. Facial vein puncture produced the largest drop volume (mean: 21.7 µL), followed by the saphenous vein (mean: 9.97 µL) and tail vein (mean: 4.96 µL). Collection from the facial vein was associated with more hemorrhage and morbidity. Left-sided venipuncture was associated with slightly larger-volume blood drops, though the effect size of side was small. The results of this study may be useful in more accurately estimating blood loss via conversion of drops to volume. Our data indicate that blood collection from saphenous and tail veins minimizes blood loss relative to facial vein puncture and may optimize both serial collection of small-volume blood samples and animal welfare.

DNA polymerase ε and δ variants drive mutagenesis in polypurine tracts in human tumors.

Alterations in the exonuclease domain of DNA polymerase ε cause ultramutated cancers. These cancers accumulate AGA>ATA transversions; however, their genomic features beyond the trinucleotide motifs are obscure. We analyze the extended DNA context of ultramutation using whole-exome sequencing data from 524 endometrial and 395 colorectal tumors. We find that G>T transversions in POLE-mutant tumors predominantly affect sequences containing at least six consecutive purines, with a striking preference for certain positions within polypurine tracts. Using this signature, we develop a machine-learning classifier to identify tumors with hitherto unknown POLE drivers and validate two drivers, POLE-E978G and POLE-S461L, by functional assays in yeast. Unlike other pathogenic variants, the E978G substitution affects the polymerase domain of Pol ε. We further show that tumors with POLD1 drivers share the extended signature of POLE ultramutation. These findings expand the understanding of ultramutation mechanisms and highlight peculiar mutagenic properties of polypurine tracts in the human genome.

Designing a Web-Based Navigation Tool to Support Access to Youth Mental Health Services: Qualitative Study.

BACKGROUND: Many young people with mental health problems do not readily seek help or receive treatment and support. One way to address low help-seeking behavior is to improve access to information on mental health services and how to navigate the mental health system via a web-based tool. Seeking input from the end users (young people and parents or caregivers) on key features of the tool is imperative to ensure that it is relevant, engaging, and likely to meet their needs and expectations. OBJECTIVE: This study aims to investigate young person and parent or caregiver views on the design, content, functioning, and user experience of a web-based mental health navigation tool to support connection to mental health services for children and young people aged up to 25 years. METHODS: A total of 4 online focus groups were conducted: 2 with young people aged 16 years and older (total n=15) and 2 with parents or caregivers (total n=13). Focus groups were structured around a series of guiding questions to explore participants' views on content, features, user experience, and design of a mental health navigation website. Focus groups were audio recorded with detailed notes taken. In addition, 53 young people aged 16-25 years and 97 parents or caregivers completed an online survey, comprising closed- and open-ended questions; open-ended responses were included with the focus group data in the qualitative analysis. All qualitative data were analyzed using thematic analysis. RESULTS: A total of 2 topic areas and 7 themes were developed. The first topic area covered the types of information needs of young people and parents. Identified themes concerned the scope of the navigation website, as well as the provision of up-to-date and practical information on how to navigate the whole help-seeking process. The second topic area covered website features that would be beneficial and included the consideration of the website design; search engines; supported navigation; and forums, reviews, and user accounts. CONCLUSIONS: This study provides important insights into the navigation needs of young people and parents or caregivers in seeking mental health services. Key findings identified through this research have directly informed the development of MindMap, a web-based youth navigation tool providing a searchable database of local services, including a clear description, their location, and potential wait times. The website can be navigated independently or with support.

A Qualitative Study of the Social Relationship Experiences Across the Life Course Among Black/African American Women Aging With HIV in the South.

ABSTRACT: Black/African American women continue to be disproportionately affected by HIV, facing multiple intersecting challenges that influence how they age and effectively manage their health. Supportive social relationships have been shown to help mitigate challenges and improve health in women with HIV, but little is known about Black/African American women's perceptions of social relationships. Guided by Life Course Theory, in-depth life history interviews were conducted with 18 Black/African American women aged 50+ years. In older adulthood, most important relationships among Black/African American women were with their adult children and grandchildren, intimate partners, God, and friends from the community. Factors that influenced relationships over time included: (a) a desire to build a community; (b) a need to empower oneself and give back; (c) yearning to engage the younger generation; and (d) battling HIV stigma. Older Black/African American women with HIV played a critical role in the education of the younger generation.

The photonics and optics workforce: unleashing the potential for greater industry growth-introduction to the feature issue.

This feature issue highlights specific photonics and optics workforce challenges, opportunities for industry support, and state-of-the-art-training methods.

Real-world outcomes in relapsed refractory multiple myeloma patients exposed to three or more prior treatments: an analysis from the ANZ myeloma and related diseases registry.

BACKGROUND: There is no currently available standard of care for triple-class exposed, relapsed refractory myeloma (RRMM) patients in Australia. CARTITUDE-1 (CART-1) was a single-arm, phase 1b/2 study of 97 triple-class exposed RRMM patients, who received BCMA-CAR-T cell therapy with ciltacabtagene autocel. Overall response rate (ORR) was 98%. Median progression free survival (PFS) and overall survival (OS) had not been reached at a median follow-up of 28 months. METHODS: We performed a retrospective analysis on a cohort of CART-1 comparable RRMM patients participating in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR), to compare outcomes in triple-class exposed MM patients treated with currently available therapies, in a real-world context. The CE-MRDR cohort (n = 28) fulfilled CARTITUDE-1 eligibility (CE) criteria: ≥3 lines of therapy (LOT) including an immunomodulatory agent, proteasome inhibitor and CD38-directed monoclonal antibody (CD38mAb) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2 at diagnosis. The modified-CE-MRDR (n = 132) received ≥3 LOT but may not have received a CD38mAb with an ECOG PS score of 3 (0-3). RESULTS: Responses to the first subsequent therapy after eligibility were poor - ORR was 23% and 0% with progressive disease (PD) reported in 61% and 36%, CE-MRDR and m-CE-MRDR respectively. Responses to the second subsequent therapy after eligibility were worse, ORR 0% and 31%, CE-MRDR and m-CE-MRDR respectively, with high rates of PD, particularly in CE-MRDR. Median OS was 5.4 versus 9.5 months, CE-MRDR versus m-CE-MRDR. CONCLUSIONS: This retrospective analysis confirms uniformly poor outcomes for Australian RRMM patients. There remains a critical need for greater accessibility to novel treatments, such as CAR-T, outside clinical trials.

A deep neural network estimation of brain age is sensitive to cognitive impairment and decline.

The greatest known risk factor for Alzheimer's disease (AD) is age. While both normal aging and AD pathology involve structural changes in the brain, their trajectories of atrophy are not the same. Recent developments in artificial intelligence have encouraged studies to leverage neuroimaging-derived measures and deep learning approaches to predict brain age, which has shown promise as a sensitive biomarker in diagnosing and monitoring AD. However, prior efforts primarily involved structural magnetic resonance imaging and conventional diffusion MRI (dMRI) metrics without accounting for partial volume effects. To address this issue, we post-processed our dMRI scans with an advanced free-water (FW) correction technique to compute distinct FW-corrected fractional anisotropy (FAFWcorr) and FW maps that allow for the separation of tissue from fluid in a scan. We built 3 densely connected neural networks from FW-corrected dMRI, T1-weighted MRI, and combined FW+T1 features, respectively, to predict brain age. We then investigated the relationship of actual age and predicted brain ages with cognition. We found that all models accurately predicted actual age in cognitively unimpaired (CU) controls (FW: r=0.66, p=1.62x10-32; T1: r=0.61, p=1.45x10-26, FW+T1: r=0.77, p=6.48x10-50) and distinguished between CU and mild cognitive impairment participants (FW: p=0.006; T1: p=0.048; FW+T1: p=0.003), with FW+T1-derived age showing best performance. Additionally, all predicted brain age models were significantly associated with cross-sectional cognition (memory, FW: ß=-1.094, p=6.32x10-7; T1: ß=-1.331, p=6.52x10-7; FW+T1: ß=-1.476, p=2.53x10-10; executive function, FW: ß=-1.276, p=1.46x10-9; T1: ß=-1.337, p=2.52x10-7; FW+T1: ß=-1.850, p=3.85x10-17) and longitudinal cognition (memory, FW: ß=-0.091, p=4.62x10-11; T1: ß=-0.097, p=1.40x10-8; FW+T1: ß=-0.101, p=1.35x10-11; executive function, FW: ß=-0.125, p=1.20x10-10; T1: ß=-0.163, p=4.25x10-12; FW+T1: ß=-0.158, p=1.65x10-14). Our findings provide evidence that both T1-weighted MRI and dMRI measures improve brain age prediction and support predicted brain age as a sensitive biomarker of cognition and cognitive decline.

The cancer nursing workforce in Australia: a national survey exploring determinants of job satisfaction.

BACKGROUND: To maintain and improve the quality of the cancer nursing workforce, it is crucial to understand the factors that influence retention and job satisfaction. We aimed to investigate the characteristics of cancer nurses in Australia and identify predictors of job satisfaction. METHODS: We analysed data from an anonymous cross-sectional survey distributed through the Cancer Nurses Society Australia membership and social media platforms from October 2021 to February 2022. The survey was compared to national nursing registration data. Data were analysed with non-parametric tests, and a stepwise, linear regression model was developed to best predict job satisfaction. RESULTS: Responses were received from 930 cancer nurses. Most respondents (85%) described themselves as experienced nurses, and more than half had post-graduate qualifications. We identified individual, organizational, and systemic factors that contribute to job satisfaction and can impact in workforce shortages. The findings include strategies to address and prioritize workforce challenges. There were 89 different titles for advanced practice nursing roles. Managing high workload was a reported challenge by 88%. Intention to stay less than 10 years was reported by nearly 60%; this was significantly correlated with job satisfaction and age. Significantly higher scores for job satisfaction were associated with those who had career progression opportunities, career development opportunities, adequate peer support and a clearly defined scope of role. Conversely, job satisfaction scores decreased the more people agreed there was a lack of leadership and they had insufficient resources to provide quality care. CONCLUSION: Cancer nurses are critical to the delivery of cancer care however, the workforce faces multiple challenges. This study provides an understanding of the Australian cancer nursing workforce characteristics, their roles and activities, and highlights important considerations for retaining nurses in the profession.

Adaptable middle-skilled labor: a neglected roadblock to photonics industry growth.

A roadblock to long-term growth of the photonics industry is the availability of well-trained, adaptable middle-skilled workers. This research characterizes the middle-skilled workforce gap, including the quantity required and skills needed. We estimate that 42,000 new technical middle-skilled workers are needed by 2030, requiring another 100 technician programs nationwide. Training skills along the supply chain are critical; programs must emphasize testing, troubleshooting, and process design. Middle-skilled workers trained in critical thinking will enable an adaptable workforce capable of handling technology evolution. Finally, recommendations for the academia, industry, and middle-skilled training ecosystem are included to ensure that the latter evolves with technology development.

Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

Social Connectivity and Coping Among Vulnerable Veterans During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic dramatically changed how people socialized. However, little is known about the extent to which the pandemic changed the social connections of people with tenuous interpersonal relationships at baseline, including homeless-experienced people and people with psychotic disorders. We sought to understand how these populations experienced changes in their social connectivity and to identify coping strategies employed. We conducted 43 semi-structured interviews with 27 vulnerable participants (11 homeless-experienced people and 16 people with psychotic disorders) and 16 comparison group participants, all of whom used services at the Department of Veterans Affairs (VA). Vulnerable participants in both groups had sparse prepandemic social connectedness; few perceived pandemic-related social network changes. While many homeless-experienced participants struggled with transitioning to technology to communicate, participants with psychotic disorders used technology to stay connected. Resilience derived from military service experiences was adaptive during the pandemic, complemented by VA services that provided supports.

Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.

Leveraging longitudinal diffusion MRI data to quantify differences in white matter microstructural decline in normal and abnormal aging.

Introduction: It is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging. Methods: Diffusion MRI data from several well-established longitudinal cohorts of aging (Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], Vanderbilt Memory & Aging Project [VMAP]) were free-water corrected and harmonized. This dataset included 1723 participants (age at baseline: 72.8 ± 8.87 years, 49.5% male) and 4605 imaging sessions (follow-up time: 2.97 ± 2.09 years, follow-up range: 1-13 years, mean number of visits: 4.42 ± 1.98). Differences in white matter microstructural decline in normal and abnormal agers was assessed. Results: While we found a global decline in white matter in normal/abnormal aging, we found that several white matter tracts (e.g., cingulum bundle) were vulnerable to abnormal aging. Conclusions: There is a prevalent role of white matter microstructural decline in aging, and future large-scale studies in this area may further refine our understanding of the underlying neurodegenerative processes. HIGHLIGHTS: Longitudinal data were free-water corrected and harmonized.Global effects of white matter decline were seen in normal and abnormal aging.The free-water metric was most vulnerable to abnormal aging.Cingulum free-water was the most vulnerable to abnormal aging.

A deep neural network estimation of brain age is sensitive to cognitive impairment and decline.

The greatest known risk factor for Alzheimer's disease (AD) is age. While both normal aging and AD pathology involve structural changes in the brain, their trajectories of atrophy are not the same. Recent developments in artificial intelligence have encouraged studies to leverage neuroimaging-derived measures and deep learning approaches to predict brain age, which has shown promise as a sensitive biomarker in diagnosing and monitoring AD. However, prior efforts primarily involved structural magnetic resonance imaging and conventional diffusion MRI (dMRI) metrics without accounting for partial volume effects. To address this issue, we post-processed our dMRI scans with an advanced free-water (FW) correction technique to compute distinct FW-corrected fractional anisotropy (FAFWcorr) and FW maps that allow for the separation of tissue from fluid in a scan. We built 3 densely connected neural networks from FW-corrected dMRI, T1-weighted MRI, and combined FW+T1 features, respectively, to predict brain age. We then investigated the relationship of actual age and predicted brain ages with cognition. We found that all models accurately predicted actual age in cognitively unimpaired (CU) controls (FW: r=0.66, p=1.62×10-32; T1: r=0.61, p=1.45×10-26, FW+T1: r=0.77, p=6.48×10-50) and distinguished between CU and mild cognitive impairment participants (FW: p=0.006; T1: p=0.048; FW+T1: p=0.003), with FW+T1-derived age showing best performance. Additionally, all predicted brain age models were significantly associated with cross-sectional cognition (memory, FW: ß=-1.094, p=6.32×10-7; T1: ß=-1.331, p=6.52×10-7; FW+T1: ß=-1.476, p=2.53×10-10; executive function, FW: ß=-1.276, p=1.46×10-9; T1: ß=-1.337, p=2.52×10-7; FW+T1: ß=-1.850, p=3.85×10-17) and longitudinal cognition (memory, FW: ß=-0.091, p=4.62×10-11; T1: ß=-0.097, p=1.40×10-8; FW+T1: ß=-0.101, p=1.35×10-11; executive function, FW: ß=-0.125, p=1.20×10-10; T1: ß=-0.163, p=4.25×10-12; FW+T1: ß=-0.158, p=1.65×10-14). Our findings provide evidence that both T1-weighted MRI and dMRI measures improve brain age prediction and support predicted brain age as a sensitive biomarker of cognition and cognitive decline.

The prognostic impact of t(11;14) in multiple myeloma: A real-world analysis from the Australian Lymphoma Leukaemia Group (ALLG) and the Australian Myeloma and Related Diseases Registry (MRDR).

The prognostic impact of t(11;14) in multiple myeloma (MM) needs to be better understood to inform future treatment decisions. The Australian Lymphoma Leukaemia Group embarked on a retrospective, observational cohort study using real-world data to interrogate treatment patterns and outcomes in 74 MM patients with t(11;14) [t(11;14)-MM] diagnosed over 10 years. This was compared to 159 and 111 MM patients with high-risk IgH translocations (IgH HR-MM) and hyperdiploidy (Hyperdiploid-MM), respectively, from the Australian Myeloma and Related Diseases Registry. No appreciable differences in age, gender, ISS, LDH levels, 1q21 or del(17p) status, or treatment patterns were observed between groups. Median PFS-1 was not different between groups but both t(11;14)-MM and IgH HR-MM had an inferior PFS-2 vs. Hyperdiploid-MM: median PFS-2 8.2 months, 10.0 months, and 19.8 months (p = 0.002), respectively. The 3-year OS were 69%, 71%, and 82% (p = 0.026), respectively. In the t(11;14)-MM group, gain or amplification of 1q21 at diagnosis predicted for poorer OS (HR 3.46, p = 0.002). Eleven patients had received venetoclax with 45% achieving better than a very good partial response. Results suggest that t(11;14) MM may confer an unfavorable risk profile and that the use of targeted therapies such as venetoclax earlier in the treatment algorithm should be explored.