Citations

Abstract The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium’s role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population.

Abstract Background Delirium, an acute brain dysfunction, is proposed to be highly prevalent in clinical care and shown to significantly increase the risk of mortality and dementia. Objectives To report on the global prevalence of clinically documented delirium and delirium-related clinical practices in wards caring for paediatric and adult patients in healthcare facilities. Design A prospective, cross-sectional, 39-question survey completed on World Delirium Awareness Day, 15 March 2023. Participants Clinicians or researchers with access to clinical data. Main Outcome and Measure The primary outcome was the prevalence of clinically documented delirium at 8:00 a.m. (4 h) and 8:00 p.m. (±4 h). Secondary outcomes included delirium-related care practices and barriers to use. Descriptive statistics were calculated and multilevel modelling was completed. Results 1664 wards submitted surveys from 44 countries, reporting on delirium assessments at 8:00 a.m. (n = 36 048) and 8:00 p.m. (n = 32 867); 61% reported use of validated delirium assessment tools. At 8:00 a.m., 18% (n = 2788/15 458) and at 8:00 p.m., 17.7% (n = 2454/13 860) were delirium positive. Top prevention measures were pain management (86.7%), mobilisation (81.4%) and adequate fluids (80.4%). Frequently reported pharmacologic interventions were benzodiazepines (52.7%) and haloperidol (46.2%). Top barriers included the shortage of staff (54.3%), lack of time to educate staff (48.6%) and missing knowledge about delirium (38%). Conclusion and Relevance In this study, approximately one out of five patients were reported as delirious. The reported high use of benzodiazepines needs further evaluation as it is not aligned with best-practice recommendations. Findings provide a benchmark for future quality improvement projects and research.

PURPOSE The outcomes of anti–PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study. PATIENTS AND METHODS Patients had untreated human epidermal growth factor receptor 2–negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m 2 once every 3 weeks, and capecitabine 1,000 mg/m 2 twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS). RESULTS Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%. CONCLUSION DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801 ).

Introduction/Objectives: We aimed to investigate the effect of family structure on depression program outcomes for adolescents enrolled in a depression-focused, primary care-based collaborative care program. Methods: This was a retrospective study of primary care patients ages 12 to 18 years seen at a Midwestern academic center with data obtained by medical record review. We used logistic regression models to assess the effect of family structure on program graduation and achievement of a single Patient Health Questionnaire 9–Modified for Adolescents (PHQ-9M) score <5 at any time while enrolled. Results: Adolescents were divided into 2 groups, Both Parents in Household (n = 179) and Parents Not Together (n = 161). The Both Parents in Household group had higher rates of graduation (38.0% vs 23.6%, P = .005) and achieving single PHQ-9M scores <5 (64.1% vs 46.2%, P = .002) than the Parents Not Together group. Discussion: Youth residing with both parents had higher rates of successful outcomes in a depression-focused collaborative care program.

OBJECTIVE The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors’ objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment. METHODS The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size. RESULTS The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters. CONCLUSIONS This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

Abstract Background The incidence of respiratory syncytial virus (RSV)–acute respiratory infection (ARI) in community-dwelling adults after the Omicron variant of the COVID-19 pandemic is unknown. Our aim was to assess the incidence of RSV-ARI in adults aged 18 to 64 years over 2 consecutive RSV seasons (October–April 2022–2024) in 4 US states. Methods This community-based prospective cohort study comprised 7501 participants in Minnesota, Wisconsin, Florida, and Arizona. We calculated RSV-ARI and RSV–lower respiratory tract disease (LRTD) incidence and attack rates. We reported unadjusted incidence by age group, gender, race and ethnicity, Charlson Comorbidity Index, socioeconomic status, residential state, and rural/urban setting. Results Seasons 1 and 2 had 2250 and 2377 ARI episodes, respectively, with an RSV-ARI positivity rate of 5.5% for season 1 and 5.8% for season 2 among those tested. In season 1, the overall incidence of RSV-ARI was 27.71 (95% CI, 22.82–33.34) per 1000 person-years (1.49% attack rate). Almost half (49.0%) had RSV-LRTD, with an incidence of 13.53 (95% CI, 10.19–17.61) per 1000 person-years (0.73% attack rate). In season 2, the RSV-ARI and RSV-LRTD incidence rates were 26.39 (95% CI, 21.73–31.75) per 1000 person-years (1.51% attack rate) and 12.43 (95% CI, 9.31–16.26) per 1000 person-years (0.72% attack rate). RSV-ARI incidence peaked in November 2022 and December 2023. Conclusions Our observations suggest that RSV-ARI incidence and seasonal pattern are shifting to prepandemic RSV epidemiology.

Abstract Background A retrospective review was performed of 15 adult patients who underwent arthroscopic suture anchor scapholunate capsuloligamentous repair between 2021 and 2023. Materials and Methods There were 12 male and 3 female patients, with a mean age of 44.9 years. Eight patients had European Wrist Arthroscopy Society (EWAS) II (Geissler II), four patients had EWAS IIIC (Geissler III), and three patients had EWAS IV (Geissler IV). After a follow-up of 12 months (12–26), the mean grip strength significantly improved by 131% compared with presurgery. There was a significant improvement in the visual analog scale score from 6 to 1.2, the Mayo Wrist Score from 43.5 to 86.5, and the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire score from 65.9 to 6.5. Two EWAS IV patients had recurrent symptomatic scapholunate diastasis requiring scapholunate ligamentoplasty. Conclusion The arthroscopic dorsal scapholunate capsuloligamentous repair with suture anchors is a reliable and safe technique with minimal complications. It is recommended for reducible acute or chronic injury to the scapholunate ligament complex with suspected avulsion injury. Level of Evidence Level IV