Citations

ABSTRACT Suicidality contributes substantially to global morbidity and mortality, yet despite its heritability, its biological etiology remains largely elusive. We conducted multi-ancestry genome-wide association study meta-analyses of suicidal ideation (259,747 cases), suicide attempt (64,993 cases), suicide death (9,197 cases), and suicidal behavior (suicide attempt/ death, 75,300 cases), across 54 cohorts (e.g., the Psychiatric Genomics Consortium, Million Veteran Program, UK Biobank). We identified 77 significant loci across meta-analyses, including 59 previously unreported for suicidality. SNP-based heritability ranged from 2.0-6.7% and there were strong, yet incomplete, genetic correlations between suicidality phenotypes (0.70-0.88). Fine-mapping prioritized putative causal SNPs and 20 credible genes. Enrichment analyses implicated synaptic pathways and neuronal populations predominantly in subcortical brain regions (e.g., amygdala excitatory, medium spiny, hippocampal CA1-3). Together, these findings establish suicidality as a polygenic set of traits with both shared and distinct genetic influences, providing a foundation for future studies of suicide biology and etiology.

Introduction The rapidly growing population of older adults (individuals aged 65 years and older) presents a new set of challenges for healthcare providers in the emergency department (ED), given the prevalence of severe and life-threatening conditions among this group, such as chronic cancer, Alzheimer’s disease/dementia and congestive heart failure. ED encounters often represent a critical point in an older patient’s trajectory of care and can thus be an important opportunity for various interventions such as palliative care consultation. Therefore, identifying those who will benefit most from palliative care is of high importance, especially in determining the course of future treatment. Thus, we aim to conduct a systematic review assessing the efficacy of palliative care screening in the ED by assessing inpatient length of stay as the primary outcome and quality of life, percentage of hospitalisation and cost of care as secondary outcomes. Methods This study will use Ovid MEDLINE, Embase, EBSCO CINAHL, Web of Science and Cochrane as databases. The study population comprises adults aged 60 years and older, with no focus on any specific clinical specialty or disease. Patients who have not received palliative care screening will serve as the comparator. Only studies with an applicable comparator will be considered. Studies published from 1 January 2000 to 1 July 2025 will be included. All articles will be reviewed independently and in duplicate, and every author will participate in the review, data abstraction and conflict resolution process. Ethics and dissemination Ethical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations. PROSPERO registration number CRD42024562389.

Abstract VanZile, AW, Jones, DD, McHugh, LJ, Clickovich, GL, Morales, MA, Reimschisel, RK, Widenhoefer, TL, Baughman, JT, Urquidi, MD, Conner, DJ, Dobbs, WC, Jagim, AR, Luedke, JA, and Almonroeder, TG. Examining countermovement jump performance and dynamic balance among male high school athletes with varying levels of sports specialization. J Strength Cond Res 39(11): 1163–1168, 2025—Specializing at a young age may limit an athlete's motor development, since focusing on a single sport potentially exposes athletes to less variety of movements and neuromuscular demands. However, there are few studies examining the association between sport specialization and movement performance/control. The purpose of this study was to compare countermovement jump performance and dynamic balance among high school athletes of varying levels of sports specialization. 110 male high school athletes completed countermovement jump testing and the Y-Balance Test (YBT). Ground reaction forces were recorded during countermovement jumps and used to derive peak force, peak velocity, peak power, jump height, and the modified reactive strength index. Y-Balance Test composite scores were calculated to assess dynamic balance across multiple directions, for the dominant and non-dominant limbs. Athletes were grouped into high ( n = 46), moderate ( n = 39), and low ( n = 25) specialization groups based on their sport participation habits. There were no between-group differences for any of the countermovement jump metrics ( p > 0.05). For the YBT composite scores, there was not a group-by-limb interaction effect ( p = 0.28); however, there was a main effect of group ( p = 0.03). Post hoc tests indicated that the high specialization group exhibited lower YBT composite scores compared to the moderate specialization group ( p = 0.01) and a trend toward lower scores compared to the low specialization group ( p = 0.05). In general, highly specialized male athletes exhibited poorer dynamic balance compared to less specialized athletes.

Stereotactic radiosurgery was associated with a higher obliteration rate compared with embolization in patients with eloquent brain arteriovenous malformations, whereas there was no evidence of a difference in functional outcomes or complications after adjustment.

BACKGROUND AND OBJECTIVES: It is not clear whether changes in lesion volume might represent a clinically relevant and statistically advantageous outcome parameter in early phase trials aimed at preventing bleeding in cerebral cavernous malformations (CCM). METHODS: We examined prospective changes in CCM lesion volume in the double-blinded AT CASH EPOC trial (clinicaltrials.gov NCT02603328). We correlated these with symptomatic hemorrhage (SH) events, contemporaneously assessed changes in lesional iron content by quantitative susceptibility mapping (QSM) on MRI, and objective (modified Rankin Scale (mRS)) and subjective (Euro-QoL Visual Analog Scale [EQ-VAS]) functional status. We also simulated sample sizes needed to detect potential effects on lesion volume. RESULTS: There was excellent correlation between independently assessed maximum lesion diameter and CCM lesion volume (R 2 = 0.68, P < .0001). The mean (SD) percentage change in lesion volume per year was +6 (65) and +18 (94) in atorvastatin and placebo patients, respectively ( P = .43). All cases with SH had increases in lesion volume and increases in mean lesional iron content by QSM, and most had declines in functional status on mRS and EQ-VAS, but there were no overall meaningful correlations of changes in lesion volume with concomitant changes in mean lesional QSM, mRS, or EQ-VAS (all R/R 2 < 0.5 and Bonferroni corrected P > .05), including in brainstem lesions analyzed separately. Sample size simulations indicate larger case numbers needed to demonstrate an effect on change in lesion volume than those needed to detect an effect on QSM change with α = 0.05 and β = 0.8, and even larger samples to detect effects on the number of cases with increased or decreased lesion volume. CONCLUSION: Changes in lesion volume occur frequently in CCM lesions after recent SH, but do not correlate with biomarkers of lesional bleeding, nor reflect functional changes, and are not statistically advantageous compared with QSM measures in detecting potential drug effects.

BACKGROUND: Pelvic exenteration is the treatment of choice for selected patients with locally advanced primary and recurrent rectal cancer. Involvement of major pelvic neurovascular structures and bone was historically considered a contraindication due to unacceptably high rates of morbidity and low R0 resection rates. OBJECTIVE: To compare the outcomes of these “high-complexity” exenterative resections to those of “conventional” pelvic exenteration. DESIGN: International multicenter retrospective cohort study. SETTINGS: Sixteen specialized exenteration centers. PATIENTS: Those who underwent total pelvic exenteration for locally advanced primary and recurrent rectal cancer between 2018 and 2023 at participating centers. MAIN OUTCOME MEASURES: Perioperative resource utilization, morbidity, mortality, and R0 resection rates were reported. RESULTS: Seven hundred sixty-three patients underwent total pelvic exenteration, of whom 478 (63%) and 285 (37%) required conventional and high-complexity procedures, respectively. High-complexity pelvic exenteration was associated with longer operating time (600 vs 480 minutes, p < 0.001 for locally advanced primary rectal cancer, 623 vs 480 minutes, p < 0.001 for locally recurrent rectal cancer), intensive care stay (2 vs 1 day, p < 0.001 and 3 vs 1 day, p < 0.001), hospital stay (19 vs 15 days, p = 0.008 and 23 vs 15 days, p < 0.001), and higher blood loss (2000 vs 1236 mL, p < 0.001 and 3000 vs 1600 mL, p < 0.001). Morbidity and mortality outcomes and R0 resection rates were similar between the groups. LIMITATIONS: Generalizability of findings outside of expert units. CONCLUSIONS: High-complexity pelvic exenteration for the treatment of rectal cancer is associated with similar morbidity, mortality, and R0 resection rates, but it has a significantly higher operative time, blood loss, and hospital resource utilization compared to conventional pelvic exenteration. In high-volume, specialized centers, these techniques are considered the standard of care for appropriately selected patients with tumors that involve major pelvic bone or neurovascular structures. See Video Abstract . EXENTERACIÓN PÉLVICA TOTAL CONVENCIONAL FRENTE A EXENTERACIÓN PÉLVICA TOTAL DE ALTA COMPLEJIDAD PARA EL CÁNCER RECTAL LOCALMENTE AVANZADO Y LOCALMENTE RECURRENTE: UN ESTUDIO MULTICÉNTRICO INTERNACIONAL ANTECEDENTES: La exenteración pélvica es el tratamiento de elección para determinados pacientes con cáncer rectal primario y recurrente localmente avanzado. La afectación de las principales estructuras neurovasculares y óseas pélvicas se consideraba históricamente una contraindicación debido a las tasas inaceptablemente altas de morbilidad y a las bajas tasas de resección R0. OBJETIVO: Comparar los resultados de estas resecciones exenteración «de alta complejidad» con los de la exenteración pélvica «convencional». DISEÑO: Estudio de cohorte retrospectivo multicéntrico internacional. ENTORNOS: Dieciséis centros especializados en exenteración. PACIENTES: Aquellos que se sometieron a una exenteración pélvica total por cáncer rectal primario y recurrente localmente avanzado entre 2018 y 2023 en los centros participantes. PRINCIPALES MEDIDAS DE RESULTADOS: Se informaron la utilización de recursos perioperatorios, la morbilidad, la mortalidad y las tasas de resección R0. RESULTADOS: 763 pacientes se sometieron a una exenteración pélvica total, de los cuales 478 (63 %) y 285 pacientes (37 %) requirieron procedimientos convencionales y de alta complejidad, respectivamente. La exenteración pélvica de alta complejidad se asoció con un tiempo quirúrgico más prolongado (600 frente a 480 minutos, p < 0,001 para el cáncer rectal primario localmente avanzado, 623 frente a 480 minutos, p < 0,001 para el cáncer rectal localmente recurrente), estancia en cuidados intensivos (2 frente a 1 día, p < 0,001 y 3 frente a 1 día, p < 0,001), estancia hospitalaria (19 frente a 15 días, p = 0,008 y 23 frente a 15 días, p < 0,001) y mayor pérdida de sangre (2000 frente a 1236 ml, p < 0,001 y 3000 frente a 1600 ml, p < 0,001). Los resultados de morbilidad y mortalidad, así como las tasas de resección R0, fueron similares entre los grupos. LIMITACIONES: Generalización de los resultados fuera de las unidades especializadas CONCLUSIONES: La exenteración pélvica de alta complejidad para el tratamiento del cáncer de recto se asocia con tasas similares de morbilidad, mortalidad y resección R0, pero con un tiempo quirúrgico, una pérdida de sangre y una utilización de recursos hospitalarios significativamente mayores en comparación con la exenteración pélvica convencional. En centros especializados con un gran volumen de casos, estas técnicas se consideran el tratamiento estándar para pacientes adecuadamente seleccionados con tumores que afectan a los huesos pélvicos principales o a las estructuras neurovasculares. ( AI-generated translation )

ABSTRACT The World Health Organization (WHO) 5th Edition and International Consensus Classification (ICC) have continued to delineate more genetically defined acute leukemias. Both recognize genetic aberrations associated with myelodysplastic syndromes/neoplasms (MDS) as defining MDS‐related AML (AML‐MR). Mutations in RUNX1 are included in this category in the ICC, but not WHO. The current classifications are unclear on how acute leukemias with ambiguous lineage (ALAL), including those of mixed lineage (MPAL) and those without a defined lineage (AUL), should be categorized in the presence of such mutations. Our multi‐institutional study aims to determine the significance of RUNX1 mutation in ALAL compared to de novo AML. Newly diagnosed MPAL, AUL, and AML with RUNX1 mutations were collected. ALAL with MDS‐related cytogenetics, BCR::ABL1 , KMT2A rearrangements, or ZNF384 or BCL11b abnormalities were excluded. We analyzed 17 cases of ALAL and 71 cases of AML that met inclusion criteria. ALAL‐ RUNX1 and AML‐ RUNX1 showed overlapping mutational landscapes with frequent comutations in MDS‐associated genes. No ALAL‐ RUNX1 or AML‐ RUNX1 cases showed concomitant TP53 mutation. ALAL‐ RUNX1 had more bone marrow blasts and more karyotypic abnormalities; however, neither impacted survival, nor did RUNX1 variant allele frequency (VAF). Survival analysis revealed similarly poor outcomes between them. AML‐directed therapies and allogeneic hematopoietic stem cell transplant trended toward improved survival in ALAL‐ RUNX1; however, it did not reach significance. Our results suggest ALAL‐ RUNX1 is associated with younger age, higher blasts, and more karyotypic abnormalities, but has similar clinical and genetic features and outcomes to AML‐ RUNX1 . Our findings suggest, like other MR mutations, RUNX1 ‐mutated ALALs should be included within AML‐MR.

Background: Early detection and prediction of arterial hypertension (HTN) are vital to reduce cardiovascular morbidity and mortality. AI has enhanced ECG diagnostic capabilities, enabling detection of latent cardiovascular abnormalities. Aims: This systematic review evaluates current evidence on AI-enhanced ECG for detection and prediction of HTN in in both clinical and subclinical populations. Methods: A search was conducted on April 28, 2025, in PubMed, Scopus, and Web of Science. Gray literature and study reference lists, plus the first 10 pages of Google Scholar, were screened. The review followed PRISMA 2020 guidelines. Bias risk was assessed using PROBAST (for prediction models) and QUADAS-2 (for diagnostic studies). Two reviewers independently performed study selection and data extraction after pilot training. Results: A total of 26 studies were included: 16 focused on detection and 10 on prediction of HTN using AI-enhanced ECG. Overall, 96% reported successful outcomes, underscoring the strong diagnostic and prognostic potential of this approach. Among detection studies, 94% successfully identified hypertensive individuals, classified blood pressure (BP) levels, or evaluated cardiovascular risk. Most were retrospective in design (75%), with internal validation in 44% and external validation in 19%. Sample sizes ranged from 100 to over 120,000, including healthy and cardiovascular patients. Commonly used algorithms included deep Learning, random forest, and ensemble methods, often using single-lead ECG data, highlighting the feasibility of wearable technologies. QUADAS-2 identified 56% of studies had low risk of bias. All prediction studies achieved accurate estimation of systolic/diastolic BP or predicted future HTN onset. Designs were 40% experimental and 50% retrospective. All studies reported internal validation, and 50% included external validation. AI models such as CNNs, ResNet-LSTM, and U-Net were used across clinical and community-based populations, with follow-up periods of up to 6.8 years. Populations were predominantly normotensive or mixed. PROBAST assessments showed 60% low and 40% moderate risk of bias. Conclusion: AI-enhanced ECG is a promising, non-invasive tool for early detection and prediction of HTN. However, external validation and clinical trials are needed to support integration and generalizability.