Continuum of Preshock to Classic Cardiogenic Shock in the Critical Care Cardiology Trials Network Registry.

BACKGROUND: The prognostic implications of phenotypes along the preshock to cardiogenic shock (CS) continuum remain uncertain. OBJECTIVES: This study sought to better characterize pre- or early shock and normotensive CS phenotypes and examine outcomes compared to those with conventional CS. METHODS: The CCCTN (Critical Care Cardiology Trials Network) is a registry of contemporary cardiac intensive care units. Consecutive admissions (N = 28,703 across 47 sites) meeting specific criteria based on hemodynamic variables, perfusion parameters, and investigator-reported CS were classified into 1 of 4 groups or none: isolated low cardiac output (CO), heart failure with isolated hypotension, normotensive CS, or SCAI (Society of Cardiovascular Angiography and Intervention) stage C CS. Outcomes of interest were in-hospital mortality and incidence of subsequent hypoperfusion among pre- and early shock states. RESULTS: A total of 2,498 admissions were assigned to the 4 groups with the following distribution: 4.8% isolated low CO, 4.4% isolated hypotension, 12.1% normotensive CS, and 78.7% SCAI stage C CS. Overall in-hospital mortality was 21.3% (95% CI: 19.7%-23.0%), with a gradient across phenotypes (isolated low CO 3.6% [95% CI: 1.0%-9.0%]; isolated hypotension 11.0% [95% CI: 6.9%-16.6%]; normotensive CS 17.0% [95% CI 13.0%-21.8%]; SCAI stage C CS 24.0% [95% CI: 22.1%-26.0%]; global P < 0.001). Among those with an isolated low CO and isolated hypotension on admission, 47 (42.3%) and 56 (30.9%) subsequently developed hypoperfusion. CONCLUSIONS: In a large contemporary registry of cardiac critical illness, there exists a gradient of mortality for phenotypes along the preshock to CS continuum with risk for subsequent worsening of preshock states. These data may inform refinement of CS definitions and severity staging.

American Association of Neurological Surgeons/Congress of the Neurological Surgeons Section on Tumors Guidelines: Assessing Their Impact on Brain Tumor Clinical Practice.

Clinical guidelines direct healthcare professionals toward evidence-based practices. Evaluating guideline impact can elucidate information penetration, relevance, effectiveness, and alignment with evolving medical knowledge and technological advancements. As the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors marks its 40th anniversary in 2024, this article reflects on the tumor guidelines established by the Section over the past decade and explores their impact on other publications, patents, and information dissemination. Six tumor guideline categories were reviewed: low-grade glioma, newly diagnosed glioblastoma, progressive glioblastoma, metastatic brain tumors, vestibular schwannoma, and pituitary adenomas. Citation data were collected from Google Scholar and PubMed. Further online statistics, such as social media reach, and features in policy, news, and patents were sourced from Altmetric. Online engagement was assessed through website and CNS+ mobile application visits. Data were normalized to time since publication. Metastatic Tumor guidelines (2019) had the highest PubMed citation rate at 26.1 per year and webpage visits (29 100 page views 1/1/2019-9/30/2023). Notably, this guideline had two endorsement publications by partner societies, the Society of Neuro-Oncology and American Society of Clinical Oncology, concerning antiepileptic prophylaxis and steroid use, and the greatest reach on X (19.7 mentions/y). Citation rates on Google Scholar were led by Vestibular Schwannoma (2018). Non-Functioning Pituitary Adenoma led Mendeley reads. News, patent, or policy publications were led by low-grade glioma at 1.5/year. Our study shows that the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors guidelines go beyond citations in peer-reviewed publications to include patents, online engagement, and information dissemination to the public.

A methylation risk score for chronic kidney disease: a HyperGEN study.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Risk of new-onset diabetes and efficacy of pharmacological weight loss therapy.

AIMS: To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy. MATERIALS AND METHODS: A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes. RESULTS: During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027). CONCLUSIONS: The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making.

Working mechanisms of the use and acceptability of ecological momentary interventions: a realist evaluation of a guided self-help ecological momentary intervention targeting self-esteem.

BACKGROUND: Technology improves accessibility of psychological interventions for youth. An ecological momentary intervention (EMI) is a digital intervention geared toward intervening in daily life to enhance the generalizability and ecological validity, and to be able to intervene in moments most needed. Identifying working mechanisms of the use of ecological momentary interventions might generate insights to improve interventions. METHODS: The present study investigates the working mechanisms of the use and acceptability of an ecological momentary intervention, named SELFIE, targeting self-esteem in youth exposed to childhood trauma, and evaluates under what circumstances these mechanisms of use and acceptability do or do not come into play. A realist evaluation approach was used for developing initial program theories (data: expert interviews and a stakeholders focus group), and subsequently testing (data: 15 interviews with participants, a focus group with therapists, debriefing questionnaire), and refining them. RESULTS: The SELFIE intervention is offered through a smartphone application enabling constant availability of the intervention and thereby increasing accessibility and feasibility. When the intervention was offered on their personal smartphone, this enhanced a sense of privacy and less hesitance in engaging with the app, leading to increased disclosure and active participation. Further, the smartphone application facilitates the practice of skills in daily life, supporting the repeated practice of exercises in different situations leading to the generalizability of the effect. Buffering against technical malfunction seemed important to decrease its possible negative effects. CONCLUSIONS: This study enhanced our understanding of possible working mechanisms in EMIs, such as the constant availability supporting increased accessibility and feasibility, for which the use of the personal smartphone was experienced as a facilitating context. Hereby, the current study contributes to relatively limited research in this field. For the field to move forward, mechanisms of use, and acceptability of EMIs need to be understood. It is strongly recommended that alongside efficacy trials of an EMI on specific target mechanisms, a process evaluation is conducted investigating the working mechanisms of use. TRIAL REGISTRATION: The current paper reports on a realist evaluation within the SELFIE trial (Netherlands Trial Register NL7129 (NTR7475)).

Sex Differences in Characteristics, Resource Utilization, and Outcomes of Cardiogenic Shock: Data From the Critical Care Cardiology Trials Network (CCCTN) Registry.

BACKGROUND: Sex disparities exist in the management and outcomes of various cardiovascular diseases. However, little is known about sex differences in cardiogenic shock (CS). We sought to assess sex-related differences in the characteristics, resource utilization, and outcomes of patients with CS. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of advanced cardiac intensive care units (CICUs) in North America. Between 2018 and 2022, each center (N=35) contributed annual 2-month snapshots of consecutive CICU admissions. Patients with CS were stratified as either CS after acute myocardial infarction or heart failure-related CS (HF-CS). Multivariable logistic regression was used for analyses. RESULTS: Of the 22 869 admissions in the overall population, 4505 (20%) had CS. Among 3923 patients with CS due to ventricular failure (32% female), 1235 (31%) had CS after acute myocardial infarction and 2688 (69%) had HF-CS. Median sequential organ failure assessment scores did not differ by sex. Women with HF-CS had shorter CICU lengths of stay (4.5 versus 5.4 days; P<0.0001) and shorter overall lengths of hospital stay (10.9 versus 12.8 days; P<0.0001) than men. Women with HF-CS were less likely to receive pulmonary artery catheters (50% versus 55%; P<0.01) and mechanical circulatory support (26% versus 34%; P<0.0001) compared with men. Women with HF-CS had higher in-hospital mortality than men, even after adjusting for age, illness severity, and comorbidities (34% versus 23%; odds ratio, 1.76 [95% CI, 1.42-2.17]). In contrast, there were no significant sex differences in utilization of advanced CICU monitoring and interventions, or mortality, among patients with CS after acute myocardial infarction. CONCLUSIONS: Women with HF-CS had lower use of pulmonary artery catheters and mechanical circulatory support, shorter CICU lengths of stay, and higher in-hospital mortality than men, even after accounting for age, illness severity, and comorbidities. These data highlight the need to identify underlying reasons driving the differences in treatment decisions, so outcomes gaps in HF-CS can be understood and eliminated.

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context.

BACKGROUND: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. AIMS: The aim of this study was to generate an experts' consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. METHOD: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. RESULTS: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. CONCLUSION: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

Targeted proteomic profiling of cardiogenic shock in the cardiac intensive care unit.

AIMS: We sought to characterize circulating protein biomarkers associated with cardiogenic shock (CS) using highly multiplex proteomic profiling. METHODS AND RESULTS: This analysis employed a cross-sectional case-control study design using a biorepository of patients admitted to a cardiac intensive care unit between 2017 and 2020. Cases were patients adjudicated to have CS, and controls were those presenting for cardiac critical care without shock, including subsets of patients with isolated hypotension or heart failure (HF). The Olink platform was used to analyse 359 biomarkers with Bonferroni correction. The analysis included 239 patients presenting for cardiac critical care (69 cases with CS, 170 non-shock controls). A total of 63 biomarkers (17.7%) were significantly associated with CS after Bonferroni correction compared with all controls. Of these, nine biomarkers remained significantly associated with CS when separately cross-validated in subsets of controls presenting with isolated hypotension and HF: cathepsin D, fibroblast growth factor (FGF)-21 and -23, growth differentiation factor (GDF)-15, insulin-like growth factor-binding protein-1, N-terminal pro-B-type natriuretic peptide, osteopontin, oncostatin-M-specific receptor subunit beta (OSMR), and soluble ST2 protein (sST2). Four biomarkers were identified as providing complementary information for CS diagnosis with development of a multi-marker model: sST2, FGF-23, CTSD, and GDF-15. CONCLUSION: In this pilot study of targeted proteomic profiling in CS, we identified nine biomarkers significantly associated with CS when cross-validated against non-shock controls including those with HF or isolated hypotension, illustrating the potential application of a targeted proteomic approach to identify novel candidates that may support the diagnosis of CS.

Mausolates: Large-Cavity Chelates with Potential as Delivery Vehicles in Nuclear Medicine.

A new type of diborate clathrochelate (cage) ligand featuring nine inwardly pointing nitrogen donors that form a large, rigid cavity, termed a mausolate, is presented. The cavity size and high denticity make this an attractive delivery vehicle for large radionuclides in nuclear medicine. Metal mausolate complexes are stable to air and water (neutral pH) and display extremely high thermal stability (>400 °C). Lanthanide uptake by the mausolate ligand occurs rapidly in solution at room temperature and once complexed, the lanthanide ions are not displaced by a 250-fold excess of a competitive lanthanide salt over more than one week.

The associations between daily reports of loneliness and psychotic experiences in the early risk stages for psychosis.

AIM: Bi-directional associations between loneliness and psychotic experiences (PEs) have been reported, but the mechanisms underlying these associations are unknown. This study aims to explore associations between daily reports of loneliness and PEs, and test differences in this association across young adult individuals at different levels of risk for psychosis. METHODS: We analysed 90-day diary data on loneliness and PEs from N = 96 participants (mean age 24.7, range 18-35, 77% female) divided into 4 subgroups, each indexing increased levels of risk for psychosis according to the clinical staging model: 'psychometric' (n = 25), 'low' (n = 27), 'mild' (n = 24), and 'ultra-high'(n = 20) risk. Multilevel vector autoregressive models examined within-day (contemporaneous) and between-day (temporal) associations between loneliness and PEs for the total sample. Next, these associations were compared across subgroups. RESULTS: Loneliness and PEs were significantly associated contemporaneously (partial correlation B = 0.14) but not temporally. Subgroup membership moderated both contemporaneous and temporal associations. The contemporaneous association between loneliness and PEs was stronger in the low-risk subgroup compared to the mild-risk (B = -0.35, p < .01) and ultra-high-risk (B = -0.36, p < .01) subgroups. The temporal association between loneliness on the previous day and PEs on the current day was stronger in mild-risk subgroup compared to the ultra-high-risk subgroup (B = -0.03, p = .03). After adjusting for multiple testing, only the contemporaneous-but not the temporal-associations remained statistically significant. CONCLUSIONS: Loneliness is associated with PEs in individuals at risk for psychosis, particularly in those with low to mild symptoms. Our findings tentatively suggest that especially individuals with low expressions of PEs may be more sensitive to social context, but future studies are needed to replicate and further unravel the potentially stage-specific interplay between social context and PEs.

Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018-2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status. RESULTS: Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%-45% and 11%-73% for VIS <10 to ≥40, respectively; Ptrend <0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS (Ptrend <0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70-0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69-0.74] to 0.76 [95% CI, 0.74-0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70-0.74] to 0.77 [95% CI, 0.75-0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23-1.49] versus 1.84 [95% CI, 1.69-2.01]; Pinteraction <0.0001). CONCLUSIONS: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.

Need for a Cardiogenic Shock Team Collaborative-Promoting a Team-Based Model of Care to Improve Outcomes and Identify Best Practices.

Cardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time-sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well-resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team-based approach to care (the "shock team") has been advocated by professional societies and implemented at select high-volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative-akin to the successful Pulmonary Embolism Response Team Consortium-with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care.

Pulmonary Artery Diastolic Pressure as a Surrogate for Pulmonary Capillary Wedge Pressure in Cardiogenic Shock.

BACKGROUND: It is common for clinicians to use the pulmonary artery diastolic pressure (PADP) as a surrogate for the pulmonary capillary wedge pressure (PCWP). Here, we determine the validity of this relationship in patients with various phenotypes of cardiogenic shock (CS). METHODS AND RESULTS: In this analysis of the Critical Care Cardiology Trials Network registry, we identified 1225 people admitted with CS who received pulmonary artery catheters. Linear regression, Bland-Altman and receiver operator characteristic analyses were performed to determine the strength of the association between PADP and PCWP in patients with left-, right-, biventricular, and other non-myocardia phenotypes of CS (eg, arrhythmia, valvular stenosis, tamponade). There was a moderately strong correlation between PADP and PCWP in the total population (r = 0.64, n = 1225) and in each CS phenotype, except for right ventricular CS, for which the correlation was weak (r = 0.43, n = 71). Additionally, we found that a PADP ≥ 24 mmHg can be used to infer a PCWP ≥ 18 mmHg with ≥ 90% confidence in all but the right ventricular CS phenotype. CONCLUSIONS: This analysis validates the practice of using PADP as a surrogate for PCWP in most patients with CS; however, it should generally be avoided in cases of right ventricular-predominant CS.

Effects on voice hearing distress and social functioning of unguided application of a smartphone app - A randomized controlled trial.

Background: Temstem is a smartphone app developed with and for clinical voice hearing individuals with the aim to reduce their voice hearing distress and improve social functioning. Methods: A randomized controlled trial with adult outpatients suffering from distressing and frequent auditory verbal hallucinations (AVH) was conducted. Participants were randomized to unguided 'Temstem+AVH monitoring' or unguided 'AVH monitoring only' (control condition). Assessments were performed at baseline, post-intervention (week 5-6), and follow-up (week 9-10). Primary outcomes were voice hearing distress and social functioning, as measured with Experience Sampling Method (ESM), consisting of multiple daily questionnaires during six days. In addition, voices and mood were self-monitored with help of a daily reflective questionnaire. Analyses were linear regression models (intention-to-treat). Results: 44 Participants were allocated to Temstem and 45 to the control condition. No significant differences between the groups were found on both primary outcomes. Conclusion: Our results do not support the effectiveness of stand-alone use of Temstem versus symptom monitoring on voice hearing distress or social functioning in voice hearing individuals. In order to potentially improve effectiveness of an mHealth tool in a population of people with frequent and distressing voices, we recommend to involve persons with lived experience in all stages of development and research; to thoroughly test the (technological) usability before performing an RCT; to test whether guidance of a therapist is needed to optimize effectiveness; and to provide prompts to remind the user to actually use the tool.

Development of a Tool to Measure Student Perceptions of Equity and Inclusion in Medical Schools.

Importance: Creating an inclusive and equitable learning environment is a national priority. Nevertheless, data reflecting medical students' perception of the climate of equity and inclusion are limited. Objective: To develop and validate an instrument to measure students' perceptions of the climate of equity and inclusion in medical school using data collected annually by the Association of American Medical Colleges (AAMC). Design, Setting, and Participants: The Promoting Diversity, Group Inclusion, and Equity tool was developed in 3 stages. A Delphi panel of 9 members identified survey items from preexisting AAMC data sources. Exploratory and confirmatory factor analysis was performed on student responses to AAMC surveys to construct the tool, which underwent rigorous psychometric validation. Participants were undergraduate medical students at Liaison Committee on Medical Education-accredited medical schools in the US who completed the 2015 to 2019 AAMC Year 2 Questionnaire (Y2Q), the administrations of 2016 to 2020 AAMC Graduation Questionnaire (GQ), or both. Data were analyzed from August 2020 to November 2023. Exposures: Student race and ethnicity, sex, sexual orientation, and socioeconomic status. Main Outcomes and Measures: Development and psychometric validation of the tool, including construct validity, internal consistency, and criterion validity. Results: Delphi panel members identified 146 survey items from the Y2Q and GQ reflecting students' perception of the climate of equity and inclusion, and responses to these survey items were obtained from 54 906 students for the Y2Q cohort (median [IQR] age, 24 [23-26] years; 29 208 [52.75%] were female, 11 389 [20.57%] were Asian, 4089 [7.39%] were multiracial, and 33 373 [60.28%] were White) and 61 998 for the GQ cohort (median [IQR] age, 27 [26-28] years; 30 793 [49.67%] were female, 13 049 [21.05%] were Asian, 4136 [6.67%] were multiracial, and 38 215 [61.64%] were White). Exploratory and confirmatory factor analyses of student responses identified 8 factors for the Y2Q model (faculty role modeling; student empowerment; student fellowship; cultural humility; faculty support for students; fostering a collaborative and safe environment; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation) and 5 factors for the GQ model (faculty role modeling; student empowerment; faculty support for students; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation). Confirmatory factor analysis indicated acceptable model fit (root mean square error of approximation of 0.05 [Y2Q] and 0.06 [GQ] and comparative fit indices of 0.95 [Y2Q] and 0.94 [GQ]). Cronbach α for individual factors demonstrated internal consistency ranging from 0.69 to 0.92 (Y2Q) and 0.76 to 0.95 (GQ). Conclusions and Relevance: This study found that the new tool is a reliable and psychometrically valid measure of medical students' perceptions of equity and inclusion in the learning environment.

Modes of Death in Patients with Cardiogenic Shock in the Cardiac Intensive Care Unit: A Report from the Critical Care Cardiology Trials Network.

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects.

Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.