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Importance Suicide is a leading cause of death among young people and an escalating public health crisis. Objective To assess the effectiveness and harms of available treatments for suicidal thoughts and behaviors among youths at heightened risk for suicide. Evidence Review A systematic review was conducted searching databases including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and various gray literature sources from January 1, 2000, to September 26, 2024. We included randomized clinical trials, comparative observational studies, and before-after studies of psychosocial interventions, pharmacologic interventions, neurotherapeutics, emerging therapies, and combination therapies. Eligible patients were youths (aged 5-24 years) with heightened risk for suicide, adolescents from racial and ethnic minority groups known to be at increased risk of suicide, or those exposed to crime or violence. Pairs of independent reviewers selected and appraised studies. Findings This review included 65 studies (33 randomized clinical trials, 13 comparative observational studies, and 19 before-after studies) reporting on 14 534 patients (median age, 15.1 years; 75.1% female patients). Psychosocial interventions comprised psychotherapy interventions (33 studies; cognitive behavioral therapy, dialectical behavioral therapy, collaborative assessment and management of suicidality, dynamic deconstructive psychotherapy, attachment-based family therapy, and family-focused therapy), acute (ie, 1-4 sessions or contacts) psychosocial interventions (19 studies; safety planning, family-based crisis management, motivational interviewing crisis interventions, continuity of care after crisis, and brief adjunctive treatments), and school- or community-based psychosocial interventions (13 studies; social network interventions, school-based skills interventions, suicide awareness or gatekeeper programs, and community-based, culturally tailored adjunct programs). Dialectical behavior therapy showed moderate strength of evidence for reducing suicidal ideation. Other categories of psychosocial treatments showed insufficient to low strength of evidence for reducing suicidal outcomes. None of the studies evaluated adverse events. The evidence base on pharmacologic treatment for youths at risk of suicide was largely nonexistent. Conclusions and Relevance This systematic review found that the current evidence on available interventions targeting youths at heightened risk of suicide is uncertain. Medication, neurotherapeutics, and emerging therapies remain unstudied among this population. The limited evidence base calls for the development of novel, developmentally and trauma-informed treatments, as well as multilevel interventions to target the increasing suicide risk among youths.

Background and Aims: Cholangiocarcinoma (CCA) is one of the most lethal cancers, characterized by molecular heterogeneity and treatment resistance. To uncover new biological signals and therapeutic opportunities, we employed multiomic characterization combined with machine learning. Approach and Results: We profiled all anatomical CCA subtypes using whole exome sequencing, mRNA sequencing, and proteome/phosphoproteome analysis. Integrative dimensional reduction revealed RNA, protein, and phosphoprotein features driving tumor heterogeneity, enabling clustering. Machine learning algorithms identified molecular features for each cluster and mapped external datasets and patient-derived xenograft (PDX) models onto these clusters. Kinase enrichment analysis highlighted targetable kinases active in each cluster. In vivo validation was performed in cluster-specific PDX models using the selective TNK1 inhibitor, TP-5801. We identified 3 molecular clusters with distinct pathway characterization: immunomodulatory (cluster 1), metabolic (cluster 2), and gene regulation/cellular fate (cluster 3). Cluster assignment was independent of anatomic subtype but correlated with overall survival following curative-intent resection. We also identified multiomic features and pathways linked to overall survival and lymph node metastases, crucial for patient treatment selection. Kinase enrichment analysis pinpointed TNK1 as a highly active kinase in the metabolic cluster. Treatment with TP-5801 significantly reduced tumor growth in a metabolic PDX model, but not in models representing the other clusters. Combining internal data with publicly available datasets, we identified the immunomodulatory cluster as most responsive to gemcitabine/cisplatin therapy, confirmed in vivo using cluster-specific PDX models. Conclusions: Integrated multiomic characterization provides translational insights by defining unique molecular subtypes associated both with therapeutic response and overall clinical outcomes. This approach identified TNK1 as a previously unrecognized therapeutic target in a defined subset of CCA tumors.

Abstract Aims The efficacy and safety of vericiguat in patients with chronic heart failure with reduced ejection fraction (HFrEF) on contemporary heart failure (HF) therapies and without recent worsening was investigated in the VICTOR trial, yet some subgroups may be more susceptible to symptomatic hypotension. Methods and results Among VICTOR trial participants that received at least one dose of study drug or placebo, we describe the systolic blood pressure (SBP) trajectories over time (mean change from baseline), symptomatic hypotension events and efficacy of vericiguat in potentially vulnerable patient subgroups: lower baseline blood pressure (SBP ≤110 mmHg), older patients (>75 years) and those taking angiotensin receptor–neprilysin inhibitors (ARNI) or sodium–glucose co-transporter 2 inhibitors (SGLT2i) at baseline. The efficacy outcomes of cardiovascular death and HF hospitalization and cardiovascular death alone across baseline SBP were examined using Cox proportional hazards models. Overall SBP trajectories showed a small initial decline from baseline in vericiguat-treated patients compared with placebo (placebo-corrected differences of −1.17 [−1.84, −0.50], p = 0.0007) that was relatively stable throughout follow-up. This trajectory was similar in those >75 years (vs. younger) as well as those receiving ARNI or SGLT2i (as compared with those not receiving these) or those with SBP ≤110 mmHg at baseline (compared with >110 mmHg). Symptomatic hypotension occurred in 11.3% of vericiguat-treated patients compared with 9.2% of placebo-treated patients with an adjusted hazard ratio of 1.24 (95% confidence interval 1.06–1.46), which was similar across age, SBP, SGLT2i and ARNI groups (all interaction p >0.05). The treatment effect of vericiguat compared with placebo on the efficacy outcomes was similar across the spectrum of baseline SBP (both interaction p >0.15). Conclusions Vericiguat showed a slight adjusted decrease in SBP and resulted in more symptomatic hypotension compared with placebo but was overall well-tolerated in a broad population with HFrEF on contemporary therapy even among those predisposed to hypotension. Treatment effects on efficacy outcomes were consistent regardless of baseline SBP.

AbstractIntroductionThe immune system's inflammatory response, driven by pro-inflammatory proteins, protects against external threats. Fear and disgust-inducing stimuli have been linked to immune responses, yet their specific physiological and inflammatory mechanisms in trypophobia remain unclear. This study aimed to elucidate the inflammatory and physiological responses in relation to natural (non-skin) and skin-related trypophobic images.Material and methodsFifty participants (n = 50) were recruited for the study, and their sensitivity to trypophobia was measured using the trypophobia questionnaire. Then, participants were randomly assigned to either the skin related or non-skin related visual exposure group and viewed trypophobic images from a computer screen. Blood samples were collected pre- and post-exposure to trypophobic images and analyzed for IL-6 and TNF-α using ELISA and RT-qPCR methods.ResultsIL-6 and TNF-α protein levels significantly increased post-exposure, with IL-6 changes varying by stimulus type. mRNA expression showed significant interaction with participants' trypophobia sensitivity scores, suggesting post-transcriptional mechanisms. Heart rate variability (HRV) and heart rate were measured before, during, and after exposure using photoplethysmography. Significant changes in HRV metrics, influenced by stimulus type and trypophobia sensitivity, indicated increased sympathetic and decreased parasympathetic nervous system activity during and after exposure.ConclusionsThese findings highlight the role of physiological and inflammatory responses in trypophobia, suggesting immune activation and autonomic nervous system involvement based on stimulus type and individual sensitivity. These findings not only contribute to phobia literature but also shed light on the physiological and immunological changes that take place in the bodies of individuals with high sensitivity to trypophobia.

Background/Objectives: Multi-cancer detection (MCD) tests have emerged as a promising tool to redefine the landscape of early cancer detection. Implementation of this novel technology will likely fall to primary care clinicians (PCC). The purpose of this study is to characterize and explore differences in PCCs perceptions and preferences towards MCD testing. Methods: Between March and May of 2023, this cross-sectional survey was administered to 281 PCCs, including physicians and advanced care providers practicing within an integrated healthcare system spanning five states. The survey collected data on self-reported characteristics, perceptions of MCD testing, and preferences for learning about MCD testing. Analysis was limited to those with no prior experience with MCD testing (N = 181, response rate 22.8%). Descriptive statistics summarized key variables and chi-square tests assessed differences in perceptions and preferences by key characteristics. Results: Most PCCs were interested in MCD testing (66.3%), but limited knowledge/awareness of MCD testing and confidence to manage patients with a positive test were observed, along with concerns around cost (76.7%) and misuse/poor implementation. The primary preferences for learning about MCD testing were online courses or classroom instruction (64.5%). Significant differences in perceptions and preferences for learning were observed by location, degree, and years in practice. Conclusions: PCCs in our study held positive views towards MCD testing, but gaps and variation in knowledge and confidence towards MCD testing and concerns around the cost and misuse/poor implementation were observed. While efforts to train and educate all PCCs on MCD testing is a critical first step, more research is needed to understand how best to support implementation tailored to individual and system-level needs and characteristics.

(1) Background: Cranial neuropathy is a commonly encountered condition with various underlying etiologies. While carotid artery dissection (CAD) is a well-recognized cause of ischemic stroke, CAD-related cranial neuropathy is rare and poorly characterized. We have conducted a comprehensive review of the published literature to better characterize its clinical course and outcomes. (2) Methods: We systematically reviewed the PubMed, CENTRAL, Ovid MEDLINE, and Embase literature for CAD-related cranial neuropathy. Data extracted included demographics, affected cranial nerves, symptoms, time course, diagnostic approach, and therapeutic interventions. (3) Results: From 635 screened studies, 97 met the inclusion criteria, yielding data on 108 patients with CAD- or dissecting pseudoaneurysm (dPSA)-related cranial neuropathy. The hypoglossal nerve (CN XII) was most commonly affected (76%), and the distal cervical internal carotid artery was the most frequently involved segment (89%). Most patients (90%) were treated with antithrombotic therapy which included either antiplatelets (47%) or anticoagulants (43%). Thirteen patients (12%) underwent endovascular intervention, nearly all with a diagnosed dPSA (mean size, 14.8 mm). Outcomes were favorable, with 94% experiencing symptom improvement. (4) Conclusions: Despite inherent limitations, our study demonstrates that CAD-related cranial neuropathy is typically a benign condition that has excellent outcomes with medical management. Endovascular treatment is rarely performed and is primarily reserved for cases involving diagnosed dPSA.

Background: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) that is prevalent worldwide. It can affect any segment of the gastrointestinal tract, from the mouth to the anus. When CD affects the anus, perianal fistulizing disease develops. The management of perianal CD is challenging and may require morbid surgery when there is no response to medical therapy. The emergence of novel biologic therapies, namely tumor necrosis alpha (TNF-α) inhibitors, has proven to provide long-term relief and prevent disease-related complications. Perianal CD is, however, refractory or recurrent in up to 80% of patients. One of the reported options to manage perianal CD is hyperbaric oxygen therapy (HBOT), which aims at increasing tissue oxygen saturation in an attempt to promote repair and reverse local inflammation. Data on this approach is scant. Methods: A retrospective review was performed to identify patients with CD at the Mayo Clinic in Rochester who underwent HBOT for perianal disease between 2014 and 2023. Demographic and clinical data were reviewed, including the history of the disease, concomitant medical and surgical therapy and the need for fecal diversion. The HBOT regimen, including the number of sessions and clinical response, were reviewed. Results: Six patients aged from 19 to 60 years underwent HBOT for perianal CD. Two patients had a history of total proctocolectomy with ileal-anal pouch anastomosis (IPAA). All patients except one were on immunosuppressive medication including biologic agents. Four patients had fecal diversion with an ileostomy or colostomy. Patients received between 10 and 40 sessions of HBOT. Four patients reported symptomatic improvement. On physical examination and/or imaging assessment, improvement was noted in one patient. Progression of the perianal disease was noted in all other patients, with all except one requiring an operation in the following year. Conclusions: HBOT may provide symptomatic relief in some patients with refractory perianal CD, but data on its long-term efficacy remains limited.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, largely due to delayed diagnosis in its early stages. While conventional diagnostic tools like low-dose CT and tissue biopsy are routinely used, they suffer from limitations including invasiveness, radiation exposure, cost, and limited sensitivity for early-stage detection. Liquid biopsy, a minimally invasive alternative that captures circulating tumor-derived biomarkers such as ctDNA, cfRNA, and exosomes from body fluids, offers promising diagnostic potential—yet its sensitivity in early disease remains suboptimal. Recent advances in Artificial Intelligence (AI) and radiomics are poised to bridge this gap. Objective: This review aims to explore how AI, in combination with radiomics, enhances the diagnostic capabilities of liquid biopsy for early detection of lung cancer and facilitates personalized monitoring strategies. Content Overview: We begin by outlining the molecular heterogeneity of lung cancer, emphasizing the need for earlier, more accurate detection strategies. The discussion then transitions into liquid biopsy and its key analytes, followed by an in-depth overview of AI techniques—including machine learning (e.g., SVMs, Random Forest) and deep learning models (e.g., CNNs, RNNs, GANs)—that enable robust pattern recognition across multi-omics datasets. The role of radiomics, which quantitatively extracts spatial and morphological features from imaging modalities such as CT and PET, is explored in conjunction with AI to provide an integrative, multimodal approach. This convergence supports the broader vision of precision medicine by integrating omics data, imaging, and electronic health records. Discussion: The synergy between AI, liquid biopsy, and radiomics signifies a shift from traditional diagnostics toward dynamic, patient-specific decision-making. Radiomics contributes spatial information, while AI improves pattern detection and predictive modeling. Despite these advancements, challenges remain—including data standardization, limited annotated datasets, the interpretability of deep learning models, and ethical considerations. A push toward rigorous validation and multimodal AI frameworks is necessary to facilitate clinical adoption. Conclusion: The integration of AI with liquid biopsy and radiomics holds transformative potential for early lung cancer detection. This non-invasive, scalable, and individualized diagnostic paradigm could significantly reduce lung cancer mortality through timely and targeted interventions. As technology and regulatory pathways mature, collaborative research is crucial to standardize methodologies and translate this innovation into routine clinical practice.

Background Global efforts to raise delirium awareness have been made over the past years, such as the formation of the iDelirium group and the institution, in 2017, of the annual World Delirium Awareness Day (WDAD) in March. In 2023, our group and researchers from around the world conducted a global one-day point prevalence study of delirium on WDAD. These strategies appear to improve delirium recognition and management. Objective To assess participants’ perceived impact of participating in the WDAD 2023 one-day point prevalence study and to gather feedback on the survey process to inform future campaigns. Methods An online survey was administered to multiple national and clinical collaborators from 44 countries participating in the one-day global point delirium prevalence study on WDAD 2023. Using SurveyMonkey®, the survey was distributed via a snowball system, with participants’ consent implied through their involvement. The survey, developed iteratively to balance time and detail, consisted of six core questions, including closed and open formats. Data were collected from September 9th to October 9th, 2023, and qualitative and quantitative analyses were performed using Excel®. Quantitative data underwent statistical analysis using IBM® SPSS Statistics28. Results 49 out of 53 (93.45%) healthcare professionals responded to the survey: 71.43% reported increased awareness, and responses were almost equally divided between those who initiated projects (46.94%) and those who did not (53.06%). Most participants (93.88%) did not find the WDAD 2023 one-day point prevalence study in March burdensome, and all expressed interest in future participation. The WDAD 2023 one-day point prevalence study highlighted diverse projects, primarily focused on delirium awareness and education. The survey found suggestions for future improvements emphasizing more efficient, digital, and engaging research methods and a clear need for educational resources, particularly in ICU delirium. Conclusions Our survey finds that participation in WDAD 2023 one-day point prevalence study boosted delirium visibility, leading to ongoing awareness, interest in future studies, and practice changes that benefit patients and the healthcare system. Further evidence-based research is needed to assess the impact of these campaigns on delirium recognition and management.

ABSTRACT Following a routine screening colonoscopy, a 54-year-old man underwent colon resection for adenocarcinoma, which revealed neoplastic B-cells in the lymph nodes surrounding the colon suggestive of chronic lymphocytic leukemia (CLL). Further evaluation identified a monoclonal B-cell population, and he was diagnosed with monoclonal B-cell lymphocytosis without meeting CLL diagnostic criteria. The patient had no clinical signs of leukemia and did not need acute treatment but was placed under annual surveillance. This case highlights the incidental discovery of neoplastic B-cells, emphasizing the importance of comprehensive histopathological evaluation and clinical correlation to guide management and monitoring for potential progression to CLL.