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Abstract: Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and natural killer-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In peripheral T-cell lymphoma-not otherwise specified and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL), patients with relapsed lymphoma demonstrated a superior median overall survival (OS) relative to refractory from the time of second-line treatment. We identified several independent predictors of OS for R/R lymphoma including age >60 years, primary refractory disease, histological subtype other than angioimmunoblastic T-cell lymphoma (AITL), extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count less than the lower limit of normal. A multivariable model incorporating these formed the basis for a prognostic index for R/R TCL, in which patients are stratified into low-risk (0-1 risk factor), intermediate-risk (2-3 risk factors), or high-risk (≥4 risk factors) groups, which were associated with 3-year OS of 57.14%, 23.3%, and 7%, respectively. Patients received either a "novel" single agent (SA; 35%) or cytotoxic chemotherapy (CC; 60%) for their second-line treatment. Higher progression-free survival was observed with SA over CC for the entire cohort with a higher 3-year OS in AITL and ALK- ALCL. Among the SA, small-molecule inhibitors demonstrated OS advantage relative to CC in AITL. Our results highlight continued efficacy of novel drugs globally and the potential of a new prediction model in informing heterogeneous prognosis within the R/R population of MTCL and MNKCL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: We analyzed early outcomes regarding the impact of our integrated alcohol-associated liver disease (ALD) clinic on patients with ALD and alcohol use., Methods: We conducted a retrospective study of patients with ALD who were evaluated in our integrated clinic from May 1, 2022, to December 31, 2023. Primary outcomes included differences in baseline clinical/demographic data between patients who accepted versus declined an appointment and changes in the severity of ALD, alcohol consumption, functional status, hospital utilization, and remission in alcohol use disorder for evaluated patients., Results: Patients who declined appointments (n=66) had higher median no-show rates (15.0 [8.0,30.0] vs. 8.5 [3.25,15.0], p<0.001), social vulnerability index (0.53 [0.26,0.79] vs. 0.38 [0.17,0.63], p=0.033), and proportions of cirrhosis (78.8% vs. 59.8%, p=0.017) versus evaluated patients. Comparison of baseline to first follow-up visit for evaluated patients (n=102) demonstrated significant reductions in median AST (59.5 [41.75, 89] vs. 44.5 [33.5, 56.25], p<0.001), alanine-aminotransferase (33.5 [20,45.25] vs. 26.5 [18.75,33.0], p=0.017), total bilirubin (1.6 [0.7,3.3] vs. 1 [0.5,1.9], p=0.001), phosphatidylethanol (263 [35, 784] vs. 0 [0, 163], p<0.001), MELD-3.0 and Sodium scores for patients with alcohol-associated hepatitis and cirrhosis (16 [11, 18.75] vs. 12 [9, 14], p<0.001), 14 [9.25, 17.75] vs. 11 [8.5, 14], p<0.001), and Child-Turcotte-Pugh scores for patients with cirrhosis (9 [6, 10.5] vs. 7 [6, 9], p<0.001). The proportion of patients with active-severe alcohol use disorder significantly decreased (85.2% vs. 51.9%, p<0.001). Additionally, patients had significant reductions in emergency department utilization (incidence rate ratio of 0.64 emergency department visits/month (p=0.002) and 0.71 hospital admissions/month (p=0.025). However, after considering the false discovery rate, the reduction in hospitalization admissions/month was not statistically significant (False Discovery Rate adjusted p=0.056)., Conclusions: Our integrated approach led to reductions in liver injury, degree of liver decompensation, alcohol use, and ED utilization, and remission in AUD in a population of both non-transplant ALD and post-transplant patients., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

1,4-Dicarbonyls are versatile synthons for the construction of diverse pharmacophores and natural products. However, the stereoselective synthesis of densely functionalized 1,4-dicarbonyls is challenging. Here, we report a versatile biocatalytic route to access chiral 2,3-dihydroxy-1,4-diketones in high yields and up to gram scale using d-fructose-6-phosphate aldolase ( Ec FSA). The utility of these compounds as synthons is exemplified in enzyme cascades with subsequent regio- and stereoselective enzymatic transamination to form densely functionalized homochiral 1-pyrrolines followed by chemical or enzymatic reduction to tetrasubstituted pyrrolidines.

Purpose: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs)., Methods: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m 2 , cisplatin 25 mg/m 2 , and nab-paclitaxel 100 mg/m 2 intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 intravenously once per day on days 1 and 8 of a 21-day cycle)., Results: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC. There was no significant difference in overall survival (OS) between GAP versus GC. Median OS with GAP was 14.0 months (95% CI, 12.4 to 16.1) and 13.6 months with GC (95% CI, 9.7 to 16.6); hazard ratio (HR), 0.91 (95% CI, 0.72 to 1.14); P = .41. Median progression-free survival (PFS) was similar between groups with median PFS for GAP being 7.5 months (95% CI, 6.4 to 8.5) versus 6.3 months for GC (95% CI, 4.4 to 8.2); HR, 0.89 (95% CI, 0.71 to 1.12); P = .32. In exploratory subset analyses, the OS and PFS benefits of GAP versus GC treatment were greater in locally advanced disease compared with metastatic disease, although not statistically significant (interaction P = .14 for OS and P = .17 for PFS). Moreover, GAP versus GC showed greater improvement in PFS among participants with GBC than those with ICC or ECC (interaction P = .01), but not OS (interaction P = .28)., Conclusion: The addition of a taxane in the GAP regimen to the standard gemcitabine-cisplatin regimen did not improve OS in newly diagnosed BTC. More toxicity was encountered with GAP versus GC.

Background: Neurological complications in patients with infective endocarditis (IE), such as ischemic and hemorrhagic stroke, are well-described; However, predicting which patients are most likely to experience stroke remains uncertain., Aims: We conducted a systematic review and meta-analysis to identify the factors associated with risk of stroke in patients hospitalized with IE., Methods: A systematic search of Ovid MEDLINE, EMBASE, and Web of Science up to June 27th, 2024 was conducted. Articles evaluating risk of acute ischemic stroke (AIS) or intracranial hemorrhage (ICH) in patients with IE were included. Meta-analysis of odds ratios was feasible for only some predictive factors due to study heterogeneity. Cochrane's Risk of Bias in Non-Randomized Studies of Exposure tool was used for risk-of-bias assessment., Summary of Review: Of 3538 studies identified, 35 were included: 9 prospective and 26 retrospective cohort. Staphylococcus aureus infection (odds ratio, 3.05; 95% CI, 1.96-4.73, I2 = 77.2%; 9 studies), and 1 mm increment in vegetation size (odds ratio, 1.26; 95% CI, 1.02-1.55, I2 = 90.1%; 3 studies) were associated with a higher risk of AIS, after adjusting for other covariates. High intensity signals on transcranial Doppler, and comorbidities such as hypertension, atrial fibrillation, and hyperlipidemia were also found to be associated with a higher risk of AIS. The risk of ICH was increased by thrombocytopenia, mycotic aneurysms, prior ICH or AIS, and cerebral microbleeds., Conclusions: Our study has identified factors which are associated with increased stroke risk in IE, and may help physicians predict risk. While echocardiographic and neuroimaging findings may be particularly informative, underlying comorbidities and various laboratory values may also contribute to predicting IE-associated strokes.

Competing Interests: Declarations. Ethics approval and consent to participate: For this type of study formal consent is not required. Consent for publication: For this type of study consent for publication is not required. Informed consent: For this type of study informed consent is not required. Competing interests: The authors declare that they have no conflict of interest.

Background: A youth mental health crisis is considered one of the great challenges of our time, and research and clinical services in child and adolescent psychiatry have become a priority for governments and funders. Academic leadership is needed to drive forward research. It is not clear how many senior academic leadership posts (professorships) there are in child and adolescent psychiatry, nor how this benchmarks against a similarly sized medical specialty., Aims: This study aimed to determine the number of professorships in child and adolescent psychiatry in the UK and Ireland compared to a similarly sized specialty. A secondary aim was to identify the number of clinical trials registered for mental and behavioural disorders in children., Method: We identified registered specialists in child and adolescent psychiatry and a similarly sized specialty who held full professorships in medical schools. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) and ClinicalTrials.gov for trials., Results: As of 23 March 2023, there were 1725 doctors on the General Medical Council's (GMC) specialist register in child and adolescent psychiatry. The closest specialty in terms of number of registered specialists was neurology ( N = 1724). We identified 24 professors in child and adolescent psychiatry across the UK and Ireland, compared to 124 in neurology. For every intervention trial registered for mental and behavioural disorders in children, there were approximately ten trials registered for diseases of the nervous system., Conclusions: Despite equivalent numbers of medical specialists in child and adolescent psychiatry and neurology, there is a striking disparity in the number of professorship appointments. While young peoples' mental health has, ostensibly, become a priority for policy-makers and funders, this is not reflected in medical professorship appointments. The paucity of senior academic child and adolescent psychiatrists has real-world implications for training, research, innovation and service development in mental health services.

Purpose: Treatment courts, such as drug court, have been part of the criminal justice system since 1989. While treatment courts have played an important role in justice reform, they have also been plagued by inequities where programs tend to be more effective for White participants than African Americans., Materials and Methods: To the best of our knowledge, this is the first qualitative study to explore the experiences of African American men ( n  = 11) who are in treatment courts and participate in the Habilitation Empowerment Accountability Therapy (HEAT) program. HEAT is a curriculum-based therapy that addresses Afrocentric topics, such as racial trauma., Results: Three themes emerged from the data: (1) Limiting the amount of clinical information shared from HEAT to treatment court increases participant honesty, engagement, and satisfaction with counseling; (2) Appreciating an Afrocentric approach to support substance use disorder recovery; and (3) Expanding Afrocentrism in the criminal justice system to promote equality in treatment court outcomes., Discussion: Positive outcomes seem to be associated with integrating practices that contribute to safety and trust, such as limiting disclosure between counselors and courts, incorporating Afrocentric approaches into substance use disorder treatment, and creating a therapeutic environment that is person-centered and free from stigmatizing language., Conclusion: Implications for future research and treatment court practice are discussed, particularly around revisiting how substance use disorder counselors share information with treatment court and the importance of Afrocentric training for treatment court professionals.

The capacity of the brain to process input across temporal scales is exemplified in human narrative, which requires integration of information ranging from words, over sentences to long paragraphs. It has been shown that this processing is distributed in a hierarchy across multiple areas in the brain with areas close to the sensory cortex, processing on a faster time scale than areas in associative cortex. In this study we used reservoir computing with human derived connectivity to investigate the effect of the structural connectivity on time scales across brain regions during a narrative task paradigm. We systematically tested the effect of removal of selected fibre bundles (IFO, ILF, MLF, SLF I/II/III, UF, AF) on the processing time scales across brain regions. We show that long distance pathways such as the IFO provide a form of shortcut whereby input driven activation in the visual cortex can directly impact distant frontal areas. To validate our model we demonstrated significant correlation of our predicted time scale ordering with empirical results from the intact/scrambled narrative fMRI task paradigm. This study emphasizes structural connectivity's role in brain temporal processing hierarchies, providing a framework for future research on structure and neural dynamics across cognitive tasks., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for controlling bTB. A key requirement for vaccination strategies using BCG is the validation of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in a natural setting. The cattle were tested every 4 months with a skin test and every 2 months with interferon-gamma (IFN-γ) release assays (IGRA) over a year of exposure. Before exposure, the DIVA skin, DIVA IGRA, and tuberculin tests showed 100% specificity in unvaccinated control calves. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had comparable sensitivities of 46% (95% CI 36, 56), 45% (95% CI 35, 55), and 47 (95% CI 37, 57), respectively, when assessed against animals positive by M. bovis culture PCR. The results suggest that test-and-slaughter control strategies using tests with low sensitivity are not expected to be effective in controlling bTB in high-prevalence herds, and highlight an urgent need to improve the sensitivity of diagnostic tests for bTB in these settings., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. Crown.)

Introduction: The evolving landscape of general practice (GP)/family medicine (FM) in the post-COVID-19 era, focussing on integrating telemedicine and remote consultations requires a new definition for this specialty. Hence, a broader consensus-based definition of post-COVID-19 GP/FM is warranted., Methods: This study involved a modified electronic Delphi technique involving 27 specialists working in primary care recruited via convenient and snowball sampling. The Delphi survey was conducted online between August 2022 and April 2023, utilizing the Google Forms platform. Descriptive statistics were employed to analyse consensus across Delphi rounds., Results: Twenty-six international experts participated in the survey. The retention rate through the second and third Delphi rounds was 96.2% (n = 25). The broader consensus definition emphasizes person-centred care, collaborative patient-physician partnerships, and a holistic approach to health, including managing acute and chronic conditions through in-person or remote access based on patient preferences, medical needs, and local health system organization., Conclusion: The study highlights the importance of continuity of care, prevention, and coordination with other healthcare professionals as core values of primary care. It also reflects the role of GP/FM in addressing new challenges post-pandemic, such as healthcare delivery beyond standard face-to-face care (e.g. remote consultations) and an increasingly important role in the prevention of infectious diseases. This underscores the need for ongoing research and patient involvement to continually refine and improve primary healthcare delivery in response to changing healthcare landscapes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The impact of the COVID-19 pandemic on recruitment has been significant, including the recruitment of pregnant individuals with behavioral health risk factors. The objective of this manuscript is to highlight our response to the methodological challenges created by the pandemic and how we leveraged technology to adapt and expand our recruitment procedures for the Health Check-up for Expectant Moms, a technology-delivered behavioral skills intervention aimed at empowering and motivating pregnant women engaging in substance use and sexual health risks (e.g., condomless sex, multiple partners) to reduce their likelihood of STIs and substance use during pregnancy. After the onset of the pandemic, we transitioned from in-person recruitment to remote clinic recruitment (e.g., by phone, text messaging, and e-mail) as well as social media campaigns via Facebook® and Instagram® with a confidential web-based screening questionnaire for our study targeting pregnant women in 27 counties of Michigan. For remote recruitment, we contacted 6238 women; 1360 completed the study screening questionnaire (mean age = 31.5; SD = 4.6), 90 were eligible, and 73 were enrolled (6% eligibility). For social media recruitment, we had 2512 completing the pre-screening questionnaire. Of these, 501 (mean age = 31.9; SD = 4.6) went on to complete the full study screening questionnaire, 25 women were eligible, and 20 were enrolled (5%). Our 5% eligibility rate from our social media campaign is on par with our remote and in-clinic recruitment methods yet took far less time (15 weeks vs. 150 weeks vs. 48 weeks, respectively). Despite study recruitment challenges related to the pandemic, remote recruitment-particularly social media-was found to be a successful approach, may have a broader reach, and a cost-effective alternative to active recruitment., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board (IRB) of the Michigan Medicine (HUM00143896). Consent to Participate: Informed consent was obtained from all participants included in the study. Competing Interests: The authors declare no competing interests., (© 2025. Society for Prevention Research.)

Research with 3-month-old infants from the general population has shown benefits to their exploratory behavior from play involving 'sticky mittens'. Sticky mittens are Velcro-covered mittens that are used with Velcro-covered toys to enable pre-reaching infants to grab and move toys simply by swatting at them. Our randomized controlled trial examined whether sticky mittens play, supervised by parents in the home environment, could similarly improve the exploratory behavior and later development of preterm infants. Participants (N = 62, 25-33 weeks of gestation) were recruited at 3 months of age corrected for prematurity and assigned randomly to either an intervention or active control group. For up to 5-10 min per day for three weeks, the intervention group used sticky mittens regularly while the control group instead watched their caregiver move the toys. Object-oriented exploratory behavior was evaluated immediately before and after the intervention, and caregivers completed questionnaires about their infant's development until 15 months' corrected age. Results showed that the intervention group made significantly greater gains than the control group in mouthing, F = 9.24, p = .004, η p 2  = 0.13, and bimanual exploration of the toys at or near the mouth, F = 8.07, p = .006, η p 2  = 0.12. However, the groups showed equivalent development over the next year as gauged by parent-report questionnaires p's > 0.05. While the sticky mittens intervention has immediate benefits for preterm infants' exploratory behavior, more research is needed before conclusions can be drawn regarding the longer-term impact on their development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Racial and ethnic disparities in cardiovascular disease (CVD) risk factors are well-documented. However, racial and ethnic differences in the longitudinal changes among multiple CVD risk factors are unknown., Methods: We used prospective cohort data of U.S. adults aged ≥50 in the 2006-2016 Health and Retirement Study. Group-based multi-trajectory models characterized age-related trajectories of systolic blood pressure ([BP] mmHg), non-HDL cholesterol (mg/dL), diabetes mellitus (DM), and smoking. Racial and ethnic differences in the multi-trajectory profiles were examined using multinomial logistic regression. Karlson-Holm-Breen methods were used to assess factors contributing to these associations., Results: Among 10,292 participants (median age: 61), approximately 32% had an overall favorable profile of CVD risk factors. Compared with non-Hispanic White adults, non-Hispanic Black adults were more likely to exhibit elevated systolic BP with high risks of DM (relative risk ratio [RRR] = 3.36; 95% CI, 2.69-4.21; P < .001) and with low risks of DM (RRR = 3.23; 95% CI, 2.38-4.38; P < .001). Non-Hispanic Black adults were also more likely to exhibit high rates of smoking with and without other co-occurring risk factors. Hispanic adults were most likely to exhibit high risks of DM with elevated systolic BP (RRR = 1.74; 95% CI, 1.28-2.38; P < .001) and without elevated systolic BP (RRR = 1.90; 95% CI, 1.50-2.40; P < .001). Education, income, and country-of-origin were significantly associated with the excess CVD risks observed among racial and ethnic minority groups., Conclusions: Significant racial and ethnic disparities were observed in trajectories of CVD risk factors in U.S. adults. Social determinants largely contributed to these associations in non-Hispanic Black adults and Hispanic adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Dupre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Post-traumatic stress (PTS) symptoms are highly comorbid with substance use (i.e., alcohol, tobacco, and cannabis). Few studies have investigated potential individual-, household-, and neighborhood-level socioeconomic effect modifiers of this comorbidity in longitudinal analyses. We aim to examine interactions between this multi-level environment and PTS symptoms on future substance use behaviors., Methods: Data were drawn from the Advancing Understanding of RecOvery afteR traumA (AURORA) study, including 2943 individuals who presented to the emergency department (ED) within 72 h of a traumatic event. Frequency of tobacco, alcohol, cannabis use, and PTS symptoms were reported at 6 timepoints. Mixed effect Poisson models, clustered by state, were used to generate incidence rate ratios (IRRs) substance use, both cross-sectionally and prospectively. Moderation analysis of PTS and substance use, stratified by household income and area deprivation index (ADI), was conducted using mixed effect models and parallel process growth curves., Results: Significant associations were observed between PTS with tobacco, alcohol, and cannabis use frequency cross-sectionally, and for tobacco and alcohol and PTS exposure prospectively. Lower income (P < 0.001) and higher deprivation (P < 0.001) were associated with tobacco use, while higher income (P < 0.001) and less deprivation (P = 0.01) were associated with increased alcohol use. We found modest modification by household income for alcohol and tobacco, and little evidence of modification by neighborhood ADI., Conclusions: Household income had greater evidence of effect modification for substance use, compared to neighborhood-level ADI. Our findings demonstrate that household indicators of socioeconomic status likely modify the relationship between PTS and substance use., Competing Interests: Declarations. Conflict of interest: Dr. Koenen’s has been a paid scientific consultant for the US Department of Justice and Covington Burling, LLP over the last three years. She receives royalties from Guilford Press and Oxford University Press. Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, and the Rett Research Foundation. Dr. Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical with significant stock. These relationships are unconnected to the current work. Dr. Jovanovic receives support from the National Institute of Mental Health, R01 MH129495. Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Her family also has equity in Intelerad Medical Systems, Inc. Dr. Rauch reported serving as secretary of the Society of Biological Psychiatry; serving as a board member of Community Psychiatry and Mindpath Health; serving as a board member of National Association of Behavioral Healthcare; serving as secretary and a board member for the Anxiety and Depression Association of America; serving as a board member of the National Network of Depression Centers; receiving royalties from Oxford University Press, American Psychiatric Publishing Inc, and Springer Publishing; and receiving personal fees from the Society of Biological Psychiatry, Community Psychiatry and Mindpath Health, and National Association of Behavioral Healthcare outside the submitted work. Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. Dr. McLean has served as a consultant for Walter Reed Army Institute for Research, Arbor Medical Innovations, and BioXcel Therapeutics, Inc. The authors declare no competing interests directly related to this work. Ethical statement: This research was a secondary data analysis of de-identified data, and therefore determined not human subjects research by the Harvard Longwood Campus Institutional Review Board. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Glioblastoma (GBM) tumors exhibit extensive genomic, epigenomic, and transcriptional diversity, with significant intratumoral heterogeneity, complicating standard treatment approaches involving radiation (RT) and the DNA-alkylating agent temozolomide (TMZ). In this study, we employed an integrative multi-omics approach, including targeted proteomics, transcriptomics, genomics, and DNA methylation profiling, to investigate the response of a representative panel of GBM patient-derived cancer stem cells (CSCs) to astrocytic differentiation and RT and TMZ treatments. Differentiated CSC progenies retained the expression of key stemness genes and survival pathways, while activating the BMP-Smad signaling pathway and upregulating extracellular matrix components. This was associated with increased resistance to TMZ, though not to RT, across all models. We identified TP53 status as a critical determinant of transcriptional response to both RT and TMZ, which was also modulated by the differentiation state and treatment modality in wildtype (wt) p53 GBM cells. Both mutant and wt p53 models exhibited significant activation of the DNA-damage associated interferon (IFN) response in CSCs and differentiated cells, implicating this pathway in the GBM response to therapy. We observed that activation of NF-κB was positively correlated with the levels of O-6-methylguanine-DNA methyltransferase (MGMT) protein, a direct DNA repair enzyme leading to TMZ resistance, regardless of MGMT promoter methylation status, further supporting the clinical potential for inhibition of NF-kB signaling in GBM treatment. Our integrative analysis of the impact of GBM cell developmental states, in the context of genomic and molecular diversity of patient-derived models, provides valuable insights for pre-clinical studies aimed at optimizing treatment strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Berezovsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Case: Three cases of pediatric patients with knee injuries from cactus thorns are included. These cases are variable in presentation ranging from acute inflammatory responses to permanent limb deformity secondary to growth arrest. Definitive treatment also varied widely from nonoperative conservative management to multiple arthroscopic and open surgeries., Conclusion: Pediatric cactus thorn injuries have varied presentations, requiring a high level of clinical suspicion for diagnosis and treatment to prevent permanent damage., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C543)., (Copyright © 2025 by The Journal of Bone and Joint Surgery, Incorporated.)

Purpose: The purpose of this study was to evaluate the safety and efficacy of a bioinductive patch augmentation following arthroscopic rotator cuff repair (RCR) in terms of patient-reported outcomes, motion, and complications stratified by tear size., Methods: A retrospective review of patients undergoing primary RCR with and without bioinductive bovine collagen patch augmentation for supraspinatus/infraspinatus tears from 2014 to 2022 at two centers was performed. Exclusion criteria included: age <18 years, revisions, or lack of 6-month postoperative follow-up. Patients were propensity-score matched 2:1 to patch-augmented patients based on age, sex, BMI, and tear size. Outcomes were compared between the patch and control groups after being stratified by tear size., Results: A total of 125 patients patch augmented RCRs were matched to 250 controls. No significant differences in demographics or comorbidities between groups. Following stratification by tear size, VAS for partial and small/medium tears in the patch cohorts were lower ( p  = 0.02) at 3 months. Functional scores were not statistically different. Patch-augmented partial and small/medium tears showed increased forward elevation ( p  < 0.05) at 1-year follow-up. Retear rates were statistically similar., Conclusions: Bioinductive patch augmentation demonstrates equivalent outcomes for pain and function, retear rate, but is associated with improved forward elevation up to 1-year for partial and small/medium tears., Level of Evidence: Level III, retrospective cohort study., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shariff K. Bishai reports a relationship with Smith and Nephew Inc that includes: consulting or advisory. Shariff K. Bishai reports a relationship with DePuy Synthes Mitek Sports Medicine that includes: consulting or advisory. Shariff K. Bishai reports a relationship with CONMED Corporation that includes: consulting or advisory. Shariff K. Bishai reports a relationship with Shoulder Innovations that includes:. Shariff K. Bishai reports a relationship with Pacira BioSciences Inc that includes: consulting or advisory. Stephanie Muh reports a relationship with Smith and Nephew Inc that includes: funding grants. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2025.)

Background: Neuregulin 1 ( NRG1 ) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with NRG1 fusion-positive solid tumors are unclear., Methods: In this registrational, phase 2 clinical study, we assigned patients with advanced NRG1 fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall response (complete or partial response) according to investigator assessment. Secondary end points included duration of response, progression-free survival, and safety., Results: A total of 204 patients with 12 tumor types were enrolled and treated. Among 158 patients who had measurable disease and were enrolled at least 24 weeks before the data-cutoff date, a response occurred in 30% (95% confidence interval [CI], 23 to 37). The median duration of response was 11.1 months (95% CI, 7.4 to 12.9); 19% of responses were ongoing at the data-cutoff date. Responses were observed in multiple tumor types - including in 27 of 93 patients (29%; 95% CI, 20 to 39) with non-small-cell lung cancer (NSCLC) and 15 of 36 patients (42%; 95% CI, 25 to 59) with pancreatic cancer - and across multiple NRG1 fusion partners. The median progression-free survival was 6.8 months (95% CI, 5.5 to 9.1). Adverse events were primarily grade 1 or 2. The most common adverse events that were considered by the investigator to be related to zenocutuzumab were diarrhea (in 18% of the patients), fatigue (in 12%), and nausea (in 11%). Infusion-related reactions (composite term) were observed in 14% of the patients. One patient discontinued zenocutuzumab owing to a treatment-related adverse event., Conclusions: Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, notably NSCLC and pancreatic cancer, with mainly low-grade adverse events. (Funded by Merus; eNRGy ClinicalTrials.gov number, NCT02912949.)., (Copyright © 2025 Massachusetts Medical Society.)

Abstract: The transcription factor GATA-binding protein 3 (GATA-3) and the transcriptional program it regulates have emerged as oncogenic drivers across diverse T-cell lymphomas (TCLs), many of which are resistant to conventional chemotherapeutic agents and characterized by recurrent losses of key tumor suppressor genes, including TP53 and PTEN, both of which are clients of the nuclear export protein XPO1. Here, we demonstrated that XPO1 is highly expressed by malignant T cells expressing GATA-3 and by lymphoma-associated macrophages (LAMs) within their tumor microenvironment (TME). Using complementary genetically engineered mouse models, we demonstrated that TP53- and/or phosphate and tensin homolog (PTEN)-deficient TCLs, and LAMs within their TME, are sensitive to the selective exportin-1 (XPO1) antagonist selinexor. In an effort to identify TP53- and PTEN-independent mechanisms, we used complementary and orthogonal approaches to investigate the role of eIF4E and XPO1-dependent messenger RNA nuclear export in these TCLs. We identified a novel role for eIF4E/XPO1 in exporting GATA-3 and GATA-3-dependent transcripts from the nucleus in TCLs, and in the export of therapeutically relevant transcripts, including colony-stimulating factor-1 receptor, from LAMs. Therefore, XPO1 antagonism, by impairing oncogenic transcriptional programs in TCLs and depleting LAMs from their TME, is a novel approach to target 2 independent dependencies in a group of therapeutically challenging TCLs., (© 2025 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

At the 2023 Global Vaccine and Immunization Research Forum (GVIRF), researchers from around the world gathered in the Republic of Korea to discuss advances and opportunities in vaccines and immunization. Many stakeholders are applying the lessons of Covid-19 to future emergencies, by advancing early-stage development of prototype vaccines to accelerate response to the next emerging infectious disease, and by building regional vaccine research, development, and manufacturing capacity to speed equitable access to vaccines in the next emergency. Recent vaccine licensures include: respiratory syncytial virus vaccines, both for the elderly and to protect infants through maternal immunization; a new dengue virus vaccine; and licensure of Covid-19 vaccines previously marketed under emergency use authorizations. Malaria vaccine implementation is expanding and a second malaria vaccine has been recommended by the World Health Organization. In a setback for human immunodeficiency virus vaccine development, the only remaining Phase 3 trial has been discontinued. In immunization, greater clarity is emerging on the challenges of achieving access and equity, along with strategies to address those challenges. A better understanding of behavioral and social determinants of vaccine uptake and a validated toolkit for measuring and modifying the drivers of vaccination is informing program design and service delivery, contributing to improved uptake. Implementation research, which has been essential for human papillomavirus and malaria vaccine delivery, will be critical for delivering the new respiratory syncytial virus vaccines and for many other vaccines currently in development. The growing diversity of vaccines and complexity of immunization programs are leading to greater interest in simplified regimens, combination vaccines, and other innovations to facilitate delivery. Collaboration emerged as the unifying theme of GVIRF 2023, underscoring that the combined efforts of many contributors have enabled progress thus far, and going forward will continue to be essential to ensure equitable access to vaccines for all., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Birgitte Giersing and Martin Friede report financial support was provided by Bill & Melinda Gates Foundation. Angela Hwang reports financial support and travel were provided by Bill & Melinda Gates Foundation. Annie X. Mo, Shahida Baqar, Andrew Ford, Carolyn Deal, and B. Fenton Hall report relationships with the National Institute of Allergy and Infectious Diseases that include: employment and travel reimbursement. Birgitte Giersing and Martin Friede report relationships with the World Health Organization that include: employment and travel reimbursement. Kristen Earle and Peter Dull report relationships with the Bill & Melinda Gates Foundation that include: employment and travel reimbursement. Angela Hwang reports a relationship with World Health Organization that includes: consulting or advisory and travel reimbursement. WHO receives grant funding related to developing guidance for a number of vaccines referred to in the manuscript. (BG and MF) NIAID is a leading supporter of vaccine R&D, however the co-authors employed by NIAID have no conflicts of interest in their routine course of employment. (AXM, SB, AF, CD, BFH)., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Human papillomavirus (HPV) vaccination uptake has increased in the United States yet continues to fall short of the Healthy People 2030 goal. Cost of care is a known barrier. The Affordable Care Act (ACA) aimed to enhance access to preventive healthcare services, including HPV vaccination. Our study examined the association between the ACA and known vaccination-enabling factors in the United States., Methods: We analyzed data from 29,216 adults aged 18-26 in the National Health Interview Survey from 2011 to 2017. Changes in vaccination-enabling factors (regular physician visitation and changes in health insurance status) and HPV vaccination status pre- (2011-2013; n = 13,494) to post-ACA (2014-2017; n = 15,722) were assessed using logistic regression models adjusted for poverty, education, marital status, comorbidities, sex, and geography., Results: A total of 13,494 and 15,722 eligible individuals were identified pre- and post-ACA, respectively. Post-ACA, the proportion of individuals reporting receipt of one dose of the HPV vaccine increased by 43 % (3.9 % to 5.5 %; OR 1.45, 95 % CI 1.24, 1.70; p < .001), with significant gains among non-Hispanic White (OR 1.55, 95 % CI 1.24, 1.94) and Black individuals (OR 1.59, 95 % CI 1.12, 2.29). Completion of ≥2 doses rose from 12.5 % to 17.8 % (OR 1.62, 95 % CI 1.47, 1.79), notably among Hispanic individuals (7.6 % to 14.7 %, OR interaction  = 1.36, 95 % CI 1.05, 1.77; p = .020). Post-ACA, there was a significant decrease in uninsured rates and an increase in vaccination completion odds among individuals privately insured (OR 1.36, 95 % CI 1.22, 1.52; p < .001) and those insured by Medicaid (OR 1.81, 95 % CI 1.35, 2.43; p < .001). Regular physician visits also rose pre- to post-ACA (53.1 % to 57.1 %, OR 1.17, 95 % CI 1.09, 1.25; p < .001)., Conclusion: The ACA has been associated with increased HPV vaccination uptake, especially among racial/ethnic minorities, gains likely driven by an increase in vaccination-enabling factors such as decreased uninsurance and increased access to physician visits., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory D. Zimet has served as an external advisory board member for Merck, Pfizer, and Moderna and as a consultant to Merck; has received investigator-initiated research funding from Merck administered through Indiana University and serves as an unpaid member of the Board of Directors for the Unity Consortium, a nonprofit organization that supports adolescent health through vaccination. Dr. Osazuwa-Peters is a scientific advisor to Navigating Cancer. All other authors have no conflict of interest to report., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: To perform a systematic review and meta-analysis assessing the diversity and representation of diabetic retinopathy (DR) patients in clinical trials conducted in the United States from January 1, 2018, to December 31, 2023., Methods: A comprehensive search strategy was conducted on May 28th, 2024 using MEDLINE (PubMed) and Embase (Elsevier) to identify relevant clinical trials. Inclusion criteria included trials published between January 1, 2018 and December 31, 2023, focusing on interventions for DR that were conducted in the United States. Screening and data extraction were independently performed by three reviewers., Results: Eleven clinical trials met the inclusion criteria and were analyzed for participant representation based on sex, age, and race/ethnicity. Sex representation was rated as good in 9 of the 11 studies. However, age representation was rarely reported (only 1/11 studies) and race/ethnicity representation was poor in 6 of the 11 studies. The findings highlight significant underrepresentation of Asian and Black populations., Conclusion: This study reveals substantial disparities in the demographic representation within DR clinical trials in the United States, emphasizing the critical need for improved inclusion strategies. Enhancing diversity in these trials is essential for producing research findings that are more applicable to the broader population affected by DR, ultimately contributing to more equitable healthcare outcomes and advancing the effectiveness of treatments across diverse demographic groups.

Objective: To develop a patient-specific algorithm to better guide clinical decision-making when considering between single port (SP) and multi-port (MP) robotic partial nephrectomy (RPN). Materials and Methods: A retrospective review was performed on the institutional review board-approved, prospectively maintained multi-institutional database of the Single Port Advanced Research Consortium to identify all consecutive patients who underwent SP and MP-RPN between 2019 and 2023. Baseline clinicodemographic variables were used to identify the significant predictors of SP-RPN. The significant variables were used to construct a nomogram to predict the likelihood of SP vs MP-RPN. Results: Of the 1021 patients included in our analysis, 189 (18.5%) and 832 (81.5%) underwent SP and MP-RPN, respectively. Statistically significant predictors of SP-RPN included a lower comorbidity profile, a significant abdominal surgical history as characterized by a higher Hostile Abdomen Index, as well as tumors of lower complexity. The nomogram generated using the aforementioned variables demonstrated a reasonable performance with an area under the curve of 0.79. An optimal cutoff point was determined, with likelihood ratios above 0.12 indicating a preference for SP-RPN. Of note, all SP-RPN cases that scored above the 0.12 cutoff exhibited improved perioperative outcomes, including shorter ischemia time and less intraoperative blood loss. Conclusions: In this study, we have devised a novel patient selection nomogram aimed at enhancing clinical decision-making within the expanding repertoire of RPN approaches. The findings highlighted in this study offer valuable guidance to facilitate appropriate patient selection and thereby ensuring favorable perioperative outcomes associated with RPN procedures.

Importance: The advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood., Observations: In December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies., Conclusions and Relevance: Ten key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.

Purpose: Research on adolescent social media use focuses on negative mental health outcomes, with less attention on potential positive outcomes. The current study addresses this limitation by investigating associations between adolescent social media use and both psychological well-being and psychopathology., Methods: Three US-based pediatric cohort sites participating in the National Institutes of Health Environmental influences on Child Health Outcomes study contributed cross-sectional survey data. Adolescents (13-18 years) self-reported the time spent and type of (active, passive) social media use, and their psychological well-being (Patient-Reported Outcome Measurement Information System [PROMIS] Life Satisfaction and Meaning and Purpose), psychopathology (Strengths and Difficulties Questionnaire and PROMIS Depressive Symptoms), and peer relationship quality (PROMIS Peer Relationships). We estimated associations between social media use and 4 mental health groups aligned to the dual factor model of mental health (high well-being/low psychopathology; high well-being/high psychopathology; low well-being/low psychopathology; low well-being/high psychopathology), and tested interactions with peer relationships. Models were adjusted for age, sex, race, ethnicity, and family income., Results: Participants (N = 963) were sociodemographically diverse (22% income ≤130% federal poverty level; 42% adolescents of color). Elastic net regressions revealed more hours using social media increased the probability of being in the high psychopathology/low well-being group; adolescents with poor peer relationships spending ≥7 hours/day on social media had the greatest risk of poor mental health. Positive peer relationships were the strongest predictor of positive mental health., Discussion: Peer relationships were the most meaningful contribution to adolescent mental health, and quality of social media use had little influence., (Copyright © 2025 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Isoform sequencing (Iso-Seq) uses long-read technology to produce highly accurate full-length reads of mRNA transcripts. Visualization of individual mRNA molecules can reveal new details of transcript variation within understudied portions of mRNA, such as the 5' untranslated region (UTR). Differential 5' UTRs may contain motifs, upstream open reading frames (uORFs), and secondary structures that can serve to regulate translation or further indicate changes in promoter usage, where transcriptional control may impact protein expression levels. To begin to explore isoform variation during T-cell activation, we generated the first Iso-Seq reference transcriptome of activated human CD4 T cells. Within this dataset, we discovered many novel splice- and end-variant transcripts. Remarkably, one in every eight genes expressed in our dataset was found to have a notable proportion of transcripts with 5' UTR lengthened by over 100 bp compared to the longest corresponding UTR within the Gencode dataset. Among these end-variant transcripts, two novel isoforms were identified for CXCR5, a chemokine receptor associated with T follicular helper cell (Tfh) function and differentiation. When investigated in a model cell system, these lengthened UTR conferred reduced transcript stability and, for one of these isoforms, short uORFs introduced by the added length altered protein expression kinetics. This study highlights instances in which current reference databases are incomplete relative to the information obtained by long-read sequencing of intact mRNA. Iso-Seq is thus a promising approach to better understanding the plasticity of promoter usage, alternative splicing, and UTR sequences that influence RNA stability and translation efficiency., (© 2025. The Author(s).)

Altered brain connectivity and atypical neural oscillations have been observed in autism, yet their relationship with autistic traits in nonclinical populations remains underexplored. Here, we employ electroencephalography to examine functional connectivity, oscillatory power, and broadband aperiodic activity during a dynamic facial emotion processing task in 101 typically developing children aged 4 to 12 years. We investigate associations between these electrophysiological measures of brain dynamics and autistic traits as assessed by the Social Responsiveness Scale, 2nd Edition (SRS-2). Our results revealed that increased facial emotion processing-related connectivity across theta (4 to 7 Hz) and beta (13 to 30 Hz) frequencies correlated positively with higher SRS-2 scores, predominantly in right-lateralized (theta) and bilateral (beta) cortical networks. Additionally, a steeper 1/f-like aperiodic slope (spectral exponent) across fronto-central electrodes was associated with higher SRS-2 scores. Greater aperiodic-adjusted theta and alpha oscillatory power further correlated with both higher SRS-2 scores and steeper aperiodic slopes. These findings underscore important links between facial emotion processing-related brain dynamics and autistic traits in typically developing children. Future work could extend these findings to assess these electroencephalography-derived markers as potential mechanisms underlying behavioral difficulties in autism., (© The Author(s) 2025. Published by Oxford University Press.)

Purpose: Effective measurement of positive child health is critical in improving public health. A proposed measure of positive health, a positive child health index (PCHI), is based on how many of 11 specific physical, developmental, and mental health conditions a child has (ranging from 0 to 11). Accepted measures of positive health, Patient-Reported Outcome Measurement Information System (PROMIS®) measures of global health, meaning and purpose, and life satisfaction, are based on child and caregiver perceptions., Methods: The sample comprised 3713 children aged 5 to 17 years from the NIH Environmental influences on Child Health Outcomes (ECHO) Cohort with data to calculate PCHI and at least 1 child- or caregiver-reported PROMIS measure. Linear regressions were performed to test the associations between each PROMIS measure T-score and the PCHI, adjusting for gestational age, child sex, child age, and maternal factors (age, education, income)., Results: The PROMIS measure associated most strongly with PCHI was caregiver-reported global health, followed by child-reported global health. Caregiver-reported life satisfaction and child-reported meaning and purpose were higher for children with a PCHI = 0 compared with children with 3 or more health conditions but not when compared with children with only 1 or 2 conditions. Among children with 4 or more conditions, girls reported lower global health than boys. Sex differences were not found for caregiver-reported measures., Conclusion: PROMIS measures and PCHI offer complementary information on positive child health. PROMIS measures are intended as measures of a person's perception of their health, whereas PCHI reflects a cumulative impact of chronic health conditions from the perspective of health care systems. Both viewpoints are informative in public health promotion., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The University of North Carolina and each cohort’s home institutional review board approve data collection and sharing. Consent to participate: Each cohort followed local procedures to obtain informed consent from all individual participants or their legal guardians., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Young adults experiencing homelessness often suffer from adverse mental health outcomes and suicide is a leading cause of death. The objective of this study is to examine service use and psychosocial risk factors for suicide, in relation to suicide risk assessment, to inform strategies for engaging youth in suicide prevention services., Methods: A cross-sectional analysis of youth enrolled in a supportive housing randomized clinical trial. We categorized suicide risk into three groups (low-, moderate-, and high-risk) based on suicidal ideation and past-year suicide attempt. The service use patterns across these groups are described, as well as other psychosocial risk factors (psychiatric comorbidity, depressive symptoms, substance use, and sleep impairment)., Results: Among 193 enrolled youth, 126 (65.3%), 32 (16.6%), and 35 (18.1%) were categorized as low-risk, moderate-risk, and high-risk for suicide, respectively. A high proportion of youth reported ever having been diagnosed with a psychiatric disorder (57.5%) and cannabis was the most heavily used substance. However, only a minority of youth received medical care or mental health services in the past 3 months, 40% and 34%, respectively. Even fewer youth received mental/emotional health services in the past 3 months (15%), though use was highest among the high-risk group (34%)., Conclusion: Understanding the needs of youth experiencing homelessness who are at risk for suicide is critical to developing interventions to alleviate their risk for suicide. Given that the use of medical and mental health care is low among this population, more active outreach strategies may be warranted to deliver prevention interventions., Competing Interests: Declarations. Ethics approval and consent to participate: The study was reviewed and approved by the Ohio State University Institutional Review Board. The study obtained written informed consent from all research participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: The year 2023 marked the 10-year anniversary of the launch of direct-acting antivirals (DAAs) for the treatment of the hepatitis C virus (HCV). HCV treatment trends by country, region, and globally are important to monitor progress toward the World Health Organization's 2030 elimination targets. Additionally, the historical patterns can help predict the treatment uptake for future therapies for other liver diseases., Methods: The number of people living with HCV (PLHCV) treated between 2014-2023 across 119 countries was estimated using national HCV registries, reported DAA sales data, pharmaceutical companies' reports, and estimates provided by national experts. For the countries with no available data, the average estimate of the corresponding Global Burden of Disease region was used., Results: An estimated 13,816,000 (95% uncertainty intervals (UI): 13,221,000-16,415,000) PLHCV were treated, of whom 12,748,000 (12,226,000-15,231,000) were treated with DAAs, of which 11,081,000 (10,542,000-13,338,000) were sofosbuvir-based DAA regimens. Country-level data accounted for 97% of these estimates. In high-income countries, there was a 41% drop in treatment from its peak, and reimbursement was a large predictor of treatment. In low- and middle-income countries, price played an important role in expanding treatment access through the public and private markets, and treatment continues to increase slowly after a sharp drop at the end of the Egyptian national program., Conclusions: In the last 10 years, 21% of all HCV infections were treated with DAAs. Regional and temporal variations highlight the importance of active screening strategies. Without program enhancements, the number of treated PLHCV stalled in every country/region which may not reflect a lower prevalence but may instead reflect the diminishing returns of the existing strategies., Impact and Implications: Long-term hepatitis C virus (HCV) infection can lead to cirrhosis and liver cancer. Since 2014, these infections can be effectively treated with 8-12 weeks of oral therapies. In 2015, the World Health Organization (WHO) established targets to eliminate HCV by 2030, which included treatment targets for member countries. The current study examines HCV treatment patterns across 119 countries and regions from 2014 to 2023 to assess the impact of national programs. This study can assist physicians and policymakers in understanding treatment patterns within similar regions or income groups and in utilizing historical data to refine their strategies in the future., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Trauma exposure poses a risk for diagnoses beyond trauma and stressor-related disorders listed in current psychological taxonomies. Alternative models, such as the Hierarchical Taxonomy of Psychopathology, posit that psychological phenomena are better organized in a hierarchical manner, with broader dimensions accounting for the covariation among lower order syndromes. Thus, the present study investigated the relationships between trauma exposure and internalizing syndromes through higher order psychological dimensions., Method: Undergraduates (N = 585) at a large midwestern university completed questionnaires, which included the Life Events Checklist for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), the Inventory for Depression and Anxiety Symptoms (2nd ed.), and the Childhood Trauma Questionnaire. Three structural equation models with stressors congruent and incongruent with Criterion A listed as predictors were used to examine the total, indirect, and direct effects for all internalizing indicators and first-order factors., Results: After accounting for higher order dimensions, only insomnia and panic maintained a unique portion of variance explained by trauma variety. Trauma variety and interpersonal index traumas explained unique proportions of posttraumatic stress symptoms, but not distress or fear., Conclusions: Findings support the utility of assessing stressors through shared mechanisms within a hierarchical framework and substantiate trauma-induced insomnia theories through a novel relationship between trauma variety and insomnia. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Introduction: Healthcare institutions have sought to standardize opioid prescribing after elective total joint arthroplasty. The purpose of this study was (1) to compare opioid prescriptions at discharge with perceived opioid prescribing patterns and (2) to determine the relationship between preoperative adjunctive treatments and opioids prescribed at discharge., Methods: All surgeons who performed total joint arthroplasty of the shoulder, hip, or knee from January 1, 2021, to October 4, 2023, at a single academic institution were included. Surgeons completed a survey assessing perceived opioid prescriptions at discharge and perioperative pain protocols. Actual prescriptions were captured using our institutional opioid database. All opioid prescriptions were converted to morphine milligram equivalents (MMEs)., Results: Orthopaedic surgeons prescribed on average 594.2 MMEs more than they perceived as their postoperative protocol. They prescribed an additional 60.9 MMEs for every 10 MMEs that they perceived they were prescribing. Patients receiving liposomal bupivacaine were prescribed on average 597 fewer MMEs and had fewer opioid prescriptions (P < 0.001). Genicular nerve blocks and cryoneurolysis were associated with fewer prescribed MMEs (P < 0.001)., Conclusion: Orthopaedic surgeons prescribe substantially more opioids than intended. This study underscores the need for standardized opioid prescribing practices and the potential of adjunctive treatments in reducing opioid prescribing., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Radioresistance is thought to be a major consequence of tumor milieu acidification resulting from the Warburg effect. Previously, using ogremorphin (OGM), a small molecule inhibitor of GPR68, an extracellular proton sensing receptor, we demonstrated that GPR68 is a key pro-survival pathway in glioblastoma cells. Here, we demonstrate that GPR68 inhibition also induces ferroptosis in lung cell carcinoma (A549) and pancreatic ductal adenocarcinoma (Panc02) cells. Moreover, OGM synergized with ionizing radiation to induce lipid peroxidation, a hallmark of ferroptosis, as well as reduce colony size in 2D and 3D cell culture. GPR68 inhibition is not acutely detrimental but increases intracellular free ferrous iron, which is known to trigger reactive oxygen species (ROS) generation. In summary, GPR68 inhibition induces lipid peroxidation in cancer cells and sensitizes them to ionizing radiation in part through the mobilization of intracellular free ferrous iron. Our results suggest that GPR68 is a key mediator of cancer cell radioresistance activated by acidic tumor microenvironment., Competing Interests: Declarations. Competing interests: LRN, JC, SR, CHW and CCH are inventors on a patent application related to this manuscript. DTF and CdAF declare no conflicts of interest., (© 2025. The Author(s).)

Murine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies. Herein, we report a 51-year-old female with MDM2-amplified, TP53-wild type adenoid cystic carcinoma who was treated with a MDM2 inhibitor and developed persistent pancytopenia despite drug discontinuation. Her pancytopenia was associated with 20 distinct pathogenic TP53 mutations in peripheral blood and bone marrow not present in drug-resistant tumor tissue. Plasma TP53 mutations were similarly detected among 4 other patients treated at our institution, with the number of mutations correlating strongly with duration of treatment. This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may confer a risk of subsequent myeloid malignancy. As multiple MDM2 inhibitor trials are ongoing, our findings underscore the need for further investigation into the potential long-term deleterious effects of these inhibitors in the hematopoietic stem and progenitor compartment., Competing Interests: Competing interests: C.C. has received research grants (to his institution) from the following: Cholangiocarcinoma Foundation, ADC Therapeutics, Oric Pharmaceuticals, Seattle Genetics, Rain Therapeutics, Kinnate, Gilead, Mersana Therapeutics, Riboscience, Takeda, Palleon, Merus, Revolution Medicines, Tango Therapeutics, and Genentech-Roche, and has received consulting fees from Boxer Capital and Guidepoint Global Advisors. The remaining authors report no competing interests., (© 2025. The Author(s).)

Background: Research has linked postcode-level sociodemographic, food and built environment factors to maternal and perinatal outcomes like overweight (BMI > 25 kg/m 2 ), gestational diabetes mellitus (GDM) and large for gestational age (LGA) birthweight. However, little is known about how these factors were influenced by the COVID-19 pandemic. We examine how postcode-level indicators and lockdown conditions are associated with the prevalence of maternal overweight, GDM and LGA., Materials and Methods: We analysed birth records from 12 public maternity hospitals in Melbourne, integrating postcode-level environmental indicators. Spatial regression models assessed associations between these indicators and maternal health outcomes, distinguishing between (a) the COVID-19 lockdown and (b) post-lockdown periods., Results: We included 31 083 singleton birth records from 2020 to 2023 across 235 postcodes in Greater Melbourne. The prevalence of maternal overweight, GDM and LGA were 496, 178 and 103 per 1000 births, respectively. Maternal overweight was less prevalent in postcodes with higher median ages and socioeconomic scores, with disparities intensifying during lockdowns. GDM was more common in areas with younger, overseas-born populations, while LGA correlated with higher median age and fewer overseas-born residents. Notably, maternal overweight mediated the effect of socioeconomic status on GDM and LGA., Conclusions: The prevalence of maternal overweight, GDM and LGA varies significantly across Melbourne, shaped by postcode-level factors. The pandemic lockdown amplified existing health disparities. The food and built-environment factors independently influence maternal and perinatal outcomes., (© 2025 The Author(s). Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Surrogate endpoints such as laboratory parameters that are not direct measurements of, but predict, clinical benefit are approved by regulatory agencies for initial proof of efficacy. No surrogate endpoints are approved for disorders of gut-brain interaction., Aim: To assess the correlation of scintigraphic colonic transit (CT) with response rates according to patient-reported symptom-based endpoints (composite/global symptoms, abdominal pain or stool frequency/consistency) in irritable bowel syndrome (IBS) or chronic idiopathic constipation (CIC)., Methods: We reviewed available data from, randomised controlled trials (RCTs) reporting effects on CT at 24 h and 48 h with drug versus placebo and extracted the difference in the proportions responding to drug or placebo, using rates from individual RCTs or from meta-analyses when more than one RCT existed for a drug. We analysed associations between differences (drug vs. placebo) in CT and in response rates using Spearman correlation. Additional analyses of CT at 24 h with composite/global symptom or pain endpoints were performed with exclusion of alosetron (the only drug slowing CT)., Results: CT at 24 h correlated significantly with composite/global symptom endpoints (Rs = -0.755, p = 0.021). CT correlated with stool frequency or consistency (at 24 h, Rs = 0.506, p = 0.074; at 48 h, Rs = 0.631, p = 0.026). CT at 24 h did not correlate with abdominal pain (Rs = -0.054, p = 0.843). With the exclusion of alosetron data, CT at 24 h was non-significantly correlated with the composite/global symptom endpoint (Rs = -0.667, p = 0.073), but not with abdominal pain (Rs = 0.377, p = 0.419)., Conclusion: Scintigraphic CT measurement fulfils the expectation of a surrogate endpoint for symptom-based outcomes, particularly in IBS-D or IBS-C and CIC., (© 2025 John Wiley & Sons Ltd.)

Background: Reduced reward positivity (RewP), an electroencephalography marker elicited by feedback indicating reward, has been associated with an increased risk for depression during adolescence. However, the ability of the RewP to predict the first-lifetime onset of depressive disorders, as opposed to anxiety and suicidal ideation in high-risk populations, has not been thoroughly investigated. In this study, we examined whether the RewP predicts the first-lifetime onset of depression, anxiety, and suicidal ideation over 18 months in familial high-risk adolescents., Methods: The sample included 145 adolescents (64.8% female), ages 11 to 17 years, who had at least 1 parent with a history of mood or anxiety disorders and completed baseline and at least 1 follow-up measurement. At baseline, the RewP was measured using a simple gambling task; current internalizing symptoms were assessed using self-report questionnaires; and the adolescent's psychiatric diagnoses were evaluated with diagnostic interviews. The same interview was administered to the adolescents again 9 months and 18 months later., Results: Logistic regression models showed that higher RewP scores significantly predicted a lower likelihood of developing a first onset of major depressive disorder over 18 months, even after controlling for sex, age, and baseline internalizing symptoms. In contrast, the RewP did not significantly predict the first onset of anxiety disorders or suicidal ideation., Conclusions: A reduced RewP precedes the first onset of depression in high-risk adolescents, highlighting the RewP's predictive capability for depression risk in predisposed populations. A blunted RewP could complement self-reported symptoms in screening and prevention., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Lung cancer is the leading cause of cancer-related death. The percentage of people who have never smoked with lung cancer has risen recently, but alternative risk factors require further study. Our goal was to determine the influence of air quality on incidence of lung cancer in people who have smoked or never smoked., Methods: The cancer registry from a large urban medical center was queried to include every new diagnosis of lung cancer from 2013 to 2021. Air quality and pollution data for the county were obtained from the US Environmental Protection Agency from 1980 to 2018. Patient demographics, location of residence, smoking history, and tumor stage were recorded. Bivariate comparison analyses were conducted in R (R Foundation for Statistical Computing)., Results: A total of 2223 new cases of lung cancer were identified. Mean age was 69.2 years. There was a nonsmoking rate of 8.1%. A total of 37% of patients identified as a racial minority. People who have never smoked were more likely to be diagnosed at an advanced stage. When analyzing geographic distribution, incidence of lung cancer among people who have never smoked was more closely associated with highly polluted areas. People who have never smoked with lung cancer had significantly higher exposure levels of multiple pollutants., Conclusions: Newly diagnosed lung cancer appears to be more related to poor air quality among people who have never smoked than people who have smoked. Future studies are needed to examine the associations of specific pollutants with lung cancer incidence., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Itch is a prominent symptom in many cutaneous disorders, including atopic dermatitis (AD), prurigo nodularis, and psoriasis. Itch is also a common but overlooked concern in patients with hidradenitis suppurativa (HS). Currently, the mechanisms underlying itch in HS remain unclear. To gain a better understanding, we reviewed the literature on pruritus in HS and other itch-predominant disorders, AD, and psoriasis. In HS, psoriasis, and AD, we found that itch often co-localized with pain and occurred more frequently at night. Furthermore, itch was found to negatively affect sleep and increase the risk for comorbid psychiatric disorders in HS, psoriasis, and AD. However, HS-, psoriasis-, and AD-related itch differ in temporality. Itch in AD is often described as chronic, while itch in HS and psoriasis is often described as episodic. HS-associated itch is likely multifactorial, and several mechanisms have been proposed including peripheral sensitization, central sensitization, and neuroinflammation. Prior studies in HS highlight enhanced IgE production and a dense infiltration of mast cells, along with a variety of cytokines and chemokines. Furthermore, alterations in the skin microbiome may contribute to itch in HS. To date, few therapies have been studied to treat itch in HS. Given the efficacy of several biologics and small molecules in treating itch in AD and psoriasis, similar agents may be explored in future HS studies. Alternative therapies to target neurological and psychiatric contributions to itch may include anticonvulsants, cannabinoids, and nonpharmacological treatments. In conclusion, pathomechanisms of itch in HS remain to be fully elucidated. However, we can draw on lessons from other pruritic disorders to begin addressing the symptom of it and identify important questions for future study., (© 2025 Japanese Dermatological Association.)

Background: Primary care data in the UK are widely used for cancer research, but the reliability of recording key events like diagnoses remains uncertain. Although data linkage can improve reliability, its costs, time requirements, and sample size constraints may discourage its use. We evaluated accuracy, completeness, and date concordance of prostate cancer (PCa) diagnosis recording in Clinical Practice Research Datalink (CPRD) GOLD and Aurum compared to linked Cancer Registry (CR) and Hospital Episode Statistics (HES) Admitted Patient Care (APC) in England., Methods: Incident PCa diagnoses (2000-2016) for males aged ≥46 at diagnosis who remained registered with their General Practitioner (GP) by age 65 and were recorded in at least one data source were analysed. Accuracy was the proportion of diagnoses recorded in GOLD or Aurum with a corresponding record in CR or HES. Completeness was the proportion of CR or HES diagnoses with a corresponding record in GOLD or Aurum., Results: The final cohorts for comparisons included 29,500 records for GOLD and 26,475 for Aurum. Compared to CR, GOLD was 86 % accurate and 65 % complete, while Aurum was 87 % accurate and 77 % complete. Compared to HES, GOLD was 76 % accurate and 60 % complete, and Aurum was 79 % accurate and 70 % complete. Concordance in diagnosis dates improved over time in both GOLD and Aurum, with 93 % of diagnoses recorded within a year compared to CR, and 66 % (GOLD) and 71 % (Aurum) compared to HES. Delays of 2-3 weeks in primary care diagnosis recording were observed compared to CR, whereas most diagnoses appeared at least 3 months earlier in primary care than in HES., Conclusions: Aurum demonstrated better accuracy and completeness for PCa diagnosis recording than GOLD. However, linkage to HES or CR is recommended for improved case capture. Researchers should address the limitations of each data source to ensure research validity., Competing Interests: Declaration of Competing Interest All authors confirm that they are not involved in any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Low post-operative day (POD) 1 Factor V has been retrospectively associated with graft loss after liver transplantation when stratified by a cutoff of 0.36 U/mL. We aimed to validate this prospectively., Methods: Patients transplanted at Toronto General Hospital were recruited (May 2018-March 2021). Factor V measurements were obtained on POD1-3, 5, and 7. Graft and patient survival at 3, 6, and 12 months were primary and secondary outcomes, respectively. We identified an optimal cutoff through receiver operating characteristic (ROC) analysis and the Youden index. Kaplan-Meier method and Log-rank tests were used to assess/compare survival., Results: One hundred and twenty-nine patients were included. One hundred and eight had Factor V >0.36 and 21 had ≤0.36 U/mL. This cutoff was predictive of 6- and 12-month graft survival and 12-month patient survival. With an optimal cutoff of 0.46 U/mL on POD1, 87 patients had Factor V >0.46 and 42 had ≤0.46 U/mL. Three-, 6-, and 12-month graft survival rates were 100%, 98.8%, and 98.8%, for patients with Factor V >0.46 U/mL, and 92.9%, 87.7%, and 87.7% for Factor V ≤0.46 U/mL. Similarly, 3-, 6-, and 12-month patient survival rates were 98.8%, 96.4%, and 95.0% for patients with Factor V >0.46 U/mL, and 92.9%, 88.0%, and 82.9% for Factor V ≤0.46 U/mL. Stratification below the novel cutoff was associated with decreased graft survival at months 3 (p = 0.012), 6 (p = 0.006), and 12 (p = 0.006), and decreased patient survival at 12 months (p = 0.022)., Conclusions: Factor V serves as an early biomarker for graft loss, with an optimal predictive cutoff of 0.46 U/mL in this prospective population. Validation of this new cutoff is necessary., (© 2025 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)

Background: The severity of hip dysplasia is characterized by radiographic measurements that require user definition of the acetabular sourcil edge, a bony landmark for which the corresponding three-dimensional (3D) anatomy is not well defined in any imaging plane., Questions/purposes: To use digitally reconstructed radiographs to determine: (1) What 3D anatomy is contributing to the "acetabular sourcil" location used to make lateral center-edge angle (LCEA) and anterior center-edge angle (ACEA) measurements in standing AP and false-profile radiographic views, respectively? (2) How do intraobserver and interobserver agreement in LCEA and ACEA translate into agreement of the 3D anatomy being evaluated? (3) How distinct are regions around the acetabular rim circumference that are evaluated by LCEA and ACEA measurements on radiographs?, Methods: Between January 2018 and May 2019, 72 patients were indicated for periacetabular osteotomy to treat hip dysplasia or acetabular retroversion at our institution. From these patients, a series of 10 patients were identified of the first 12 patients in 2018 who were treated with periacetabular osteotomy, excluding two with missing or low-quality clinical imaging. A second series of 10 patients was identified of the first 11 patients in 2019 who were treated with periacetabular osteotomy and concurrent hip arthroscopy, excluding one who was missing clinical imaging. Pelvis and femoral bone surface models were generated from CT scans of these two series of 10 patients. There were 15 female and five male patients, with a median patient age of 18 years (IQR 17 to 23 years), a preoperative LCEA of 22° (IQR 18° to 24°), and a preoperative ACEA of 23° (IQR 18° to 27°). Exclusion criteria included missing preoperative CT or standard clinical radiographic imaging or severe joint incongruity. To address our first study question, digitally reconstructed radiographs matching each patient's standing AP and false-profile clinical radiographs were created from the segmented CT volumes. A board-certified orthopaedic surgeon and three trained researchers measured LCEA and ACEA on the digitally reconstructed radiographs, and the selected sourcil points were projected back into coordinates in the 3D anatomic space. To address our second study question, intraobserver and interobserver agreement in radiographic coverage angles were related to variations in 3D coordinates of the selected bony anatomy. Lastly, to address our third study question, 3D locations around the acetabular rim identified as contributing to the lateral and anterior sourcil points were summarized across patients in a clockface coordinate system, and statistical analysis of the "time" separating the 3D acetabular contributions of the sourcil edges was performed., Results: The 3D anatomy contributing to the lateral sourcil was a variable length (27 mm [IQR 15 to 34 mm]) span of the laterosuperior acetabular edges, with contributions by the anterior inferior iliac spine in 35% (7 of 20) of hips. The anterior sourcil reflected a 28-mm (IQR 25 to 31 mm) span of bone from the medial ilium (posterior-medial to the anterior-inferior iliac spine and anterior-lateral to the arcuate line) to the anterior and lateral edges of the acetabulum. Interobserver variability was good for LCEA (intraclass correlation coefficient [ICC] 0.82 to 0.83) and moderate to good for ACEA (ICC 0.73 to 0.79), whereas the agreement in identified 3D sourcil locations varied widely (ICC 0.32 to 0.95). The acetabular edge of the 3D anatomy contributing to the anterior sourcil overlapped the circumferential range of the acetabular rim contributing to the lateral sourcil., Conclusion: Projection of two-dimensional radiographic landmarks contributing to the diagnosis of structural hip deformity into 3D allowed for the identification of the overlapping bony anatomy contributing to radiographically visible anterior and lateral sourcil edges., Clinical Relevance: This work leveraging digitally reconstructed radiographs and 3D pelvis anatomy has found that bone outside the joint contributes to the radiographic appearance of the sourcil and may variably confound estimates of joint coverage. Furthermore, the substantial overlap between the acetabular bone contributing to measurement of the LCEA and ACEA would indicate that these angles measure similar acetabular deformity, and that additional measures are needed to assess anterior coverage independent of lateral coverage., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Background: 37.5% of deaths in our area occur in hospital. There are known high unmet needs of adult patients dying in hospital, this unmet need can be reduced by using an individualised care plan and specialist palliative care review. Intervention: In 2022 UHSussex developed an electronic comfort observation chart and individualised care plan, with a centralised dashboard allowing Palliative Care Teams (SPCT) to view trends, target interventions, and a rolling prospective audit. Results: 3000 patients have had their care supported with electronic comfort observations (e-comfort obs). Over 72% of all deaths in the Trust in the last 3 months have been on e-comfort obs, with 2/3 of all deaths in the first 12 months on e-comfort obs. The average length of time on e-comfort obs is 4 days resulting in 70,000 sets of e-comfort obs recorded since launch. Seven percent of e-comfort obs record moderate or severe symptoms. We have identified benefits to people who are dying, those important to them, ward staff, SPCT and on a systems level. Conclusion: E-comfort obs can be successfully embedded in a large acute Trust. This development should improve quality of end of life care in our hospitals both for individuals and for future patients, through on-going targeted education and intervention. Further work is needed to develop the system further including integrating data from electronic prescribing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Robotic-assisted devices help provide precise component positioning in conversion of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA). A few studies offer surgical techniques for computed tomography (CT) based robotic-assisted conversion of UKA to TKA; however, no studies to date detail this procedure utilizing a non-CT-based robotic-assisted device. This article introduces a novel technique employing a non-CT-based robotic-assisted device (ROSA Knee System, Zimmer Biomet, Warsaw, IN) for converting UKA to TKA with a focus on its efficacy in gap balancing. We present three patients (ages 46-66 years) who were evaluated for conversion of UKA to TKA for aseptic loosening, stress fracture, and progressive osteoarthritis. Each patient underwent robotic-assisted conversion to TKA. Postoperative assessments at 6 months revealed improved pain, function, and radiographic stability. Preoperative planning included biplanar long leg radiographs to determine the anatomic and mechanical axis of the leg. After arthrotomy with a standard medial parapatellar approach, infrared reflectors were pinned into the femur and tibia, followed by topographical mapping of the knee with the UKA in situ. The intraoperative software was utilized to evaluate flexion and extension balancing and plan bony resections. Then, the robotic arm guided placement of the femoral and tibial guide pins and the UKA components were removed. After bony resection of the distal femur and proximal tibia, the intraoperative software was used to reassess the extension gap, and plan posterior condylar resection to have the flexion gap match the extension gap. The use of a non-CT-based robotic-assisted device in conversion of UKA to TKA is a novel technique and a good option for surgeons familiar with robotic-assisted arthroplasty, resulting in excellent outcomes at 6 months., Competing Interests: M.A.C. and W.T.N. receive compensation for consulting and research support from Zimmer-Biomet. All other authors do not have any disclosures at this time., (Thieme. All rights reserved.)