GABA, Aging and Exercise: Functional and Intervention Considerations.

The global growth of an aging population is expected to coincide with an increase in aging-related pathologies, including those related to brain health. Thus, the potential for accelerated cognitive health declines due to adverse aging is expected to have profound social and economic implications. However, the progression to pathological conditions is not an inevitable part of aging. In fact, engaging in activities that improve cardiovascular fitness appears to be a means that offers the benefits of maintaining and/or improving cognitive health in older age. However, to date, the underlying mechanisms responsible for improved central nervous system health and function with exercise are not yet fully elucidated. Consequently, there is considerable interest in studies aimed at understanding the neurophysiological benefits of exercise on aging. One such area of study suggests that the improvements in brain health via exercise are, in part, driven by the recovery of inhibitory processes related to the neurotransmitter gamma-aminobutyric acid (GABA). In the present review, we highlight the opposing effects of aging and exercise on cortical inhibition and the GABAergic system's functional integrity. We highlight these changes in GABA function by reviewing work with in vivo measurements: transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). We also highlight recent and significant technological and methodological advances in assessing the GABAergic system's integrity with TMS and MRS. We then discuss potential future research directions to inform mechanistic GABA study targeted to improve health and function in aging. We conclude by highlighting the significance of understanding the effects of exercise and aging, its influence on GABA levels, and why a better understanding is crucial to allow for more targeted and effective interventions aimed to ultimately improve age-related decline in aging.

Parental Attitudes Towards Palliative Care in Pediatric Oncology: Insights From Bereaved Families.

CONTEXT: Palliative care (PC) has shown significant growth in the US and is associated with improved patient and caregiver experiences. Nevertheless, there are concerns that PC is underutilized in pediatric oncology. Understanding parental attitudes towards PC is crucial to improving PC utilization. OBJECTIVES: This study aimed to explore bereaved parent attitudes towards PC in pediatric oncology. METHODS: This study used data from Alex's Lemonade Stand: My Childhood Cancer Bereavement Survey. The survey included questions regarding bereaved parents' attitudes towards PC. RESULTS: The survey included 72 bereaved families. Parents completed the survey a median of 11 years after their child's death. PC was involved in 71% of cases. These families were more likely to have do not resuscitate (DNR) orders, an advanced care plan, hospice care, a planned death location, and for their child to die outside the hospital. Although most parents (86%) agreed that it is a doctor's obligation to inform all patients with cancer about PC. PC referrals appeared to happen later than parents preferred. Lack of PC involvement was primarily due to PC not being offered or sudden death of the child. CONCLUSIONS: Parental hesitancy should not be viewed as a barrier to PC involvement. Although parents held mixed attitudes about PC, families accepted PC, desired earlier referrals, and believed it was a doctor's obligation to offer PC. These findings highlight the need for timely PC referrals, improved education, and increased awareness of PC services to enhance the integration of PC in pediatric oncology.

Rationale and design of the randomized COmparison of Methods for Pulmonary blood flow Augmentation: Shunt versus Stent (COMPASS) trial: A Pediatric Heart Network study.

Neonates with congenital heart disease (CHD) and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; e.g., Blalock-Thomas-Taussig shunt). However, over the past two decades an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared to SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs. Stent) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization to assess whether one method of palliation demonstrates therapeutic superiority.

Socioeconomic Indices Are Associated With Increased Resource Utilizations, but Not 90-Day Complications Following Total Hip and Knee Arthroplasty.

BACKGROUND: Socioeconomic disadvantage has been associated with negative outcomes following total hip arthroplasty (THA) and total knee arthroplasty (TKA). The area deprivation index (ADI) and distressed communities index (DCI) are composite rankings that score socioeconomic status (SES) using patients' home addresses. The purpose of this study was to examine the association of ADI and DCI with outcomes following THA and TKA while controlling for potential confounding covariates. METHODS: A series of 4,146 consecutive patients undergoing primary THA and TKA between January 2018 and May 2023 were queried from our institutional total joint registry. The 90-day medical and surgical complications and resource utilization were collected. The ADI and DCI scores were obtained for each patient, and the association between these scores and postoperative outcomes was analyzed. RESULTS: The ADI and DCI were both associated with patient age, sex, race, comorbidity burden, and smoking status. After controlling for these variables, higher ADI and DCI scores were associated with increased length of stay (P = 0.003 and P = 0.008, respectively), but were not associated with the occurrence of any 90-day complication, reoperation, or revision. CONCLUSIONS: The SES, as quantified by ADI and DCI, was associated with multiple known risk factors for complications following THA and TKA, but was not independently associated with complications, reoperations, or revision surgeries at 90 days postoperatively. While convenient metrics for the quantification of SES, in some populations, ADI and DCI may not be independently associated with detrimental outcomes following THA and TKA.

Continuing the conversation about echolalia and gestalt language development: A response to Haydock, Harrison, Baldwin, and Leadbitter.

LAY ABSTRACT: It was recently suggested that a set of ideas known as gestalt language development be embraced as a neurodiversity-affirmative practice. Neurodiversity refers to the idea that people interact with the world in many different ways and that there is not a single right way to do so. Some aspects of gestalt language development, such as embracing autistic communication, are consistent with neurodiversity. However, gestalt language development is also associated with numerous ideas, assertions, and clinical strategies that lack theoretical and empirical support. For this reason, we believe it is premature to embrace gestalt language development as a neurodiversity-affirmative practice. We propose that it is important to make sure we use language that differentiates between delayed echolalia and the broader set of ideas that comprise gestalt language development. We also suggest that it is important to discuss the relationship between neurodiversity-affirmative practices and practices supported by research evidence.

Synthesis, characterization and comparative biological activity of a novel set of Cu(II) complexes containing azole-based ligand frames.

The synthesis and spectroscopic characterization of three complexes containing a substituted 2-(2-pyridyl)benzothiazole (PyBTh) group in the ligand frame are reported along with the comparative biological activity. The ligands have been substituted at the 6-position with either a methoxy (Py(OMe)BTh) or a methyl group (Py(Me)BTh). Reaction of Py(OMe)BTh with either CuCl2 or Cu(NO3)2·2.5 H2O yielded the monomeric [Cu(Py(OMe)BTh))2(NO3)]NO3·1.5 MeOH, (1·1.5 MeOH) complex or the dimeric [Cu(Py(OMe)BTh)Cl2]2 (2), respectively, with the nuclearity of the complex dependent on the starting Cu(II) salt. Reaction between the methyl substituted ligand and Cu(NO3)2·2.5 H2O resulted in the isolation of Cu(Py(Me)BTh)(NO3)2·0.5 THF (3·0.5 THF). Complexes 1-3 were fully characterized. Cyclic voltammetry measurements were performed on all three complexes as well as on [Cu(PyBTh)2(H2O)](BF4)2 (4), a compound previously reported by us which contains the unsubstituted 2-(2-pyridyl)benzothiazole ligand. The biological activity was studied and included concentration dependent DNA binding and cleavage, antibacterial activity, and cancer cell toxicity. All complexes exhibited DNA cleavage activity, however 2 and 4 were found to be the most potent. Mechanistic studies revealed that the nuclease activity is dependent on an oxidative mechanism reliant principally on O2-. Antibacterial studies revealed complex 4 was more potent compared to 1-3. Cancer cell toxicity studies were carried out on HeLa, PC-3, and MCF7 cells with 1-4, Cu(QBTh)(NO3)2(H2O) and Cu(PyBIm)3(BF4)2. The differences in the observed toxicities suggests the importance of the ligand and its substituents in modulating cell death.

Intensive Outpatient Programs for Pediatric Feeding Disorder: A Qualitative Study of Current Challenges and Future Directions.

BACKGROUND: Although intensive multidisciplinary interventions (IMIs) provide benefits for patients with pediatric feeding disorders (PFD), access to these programs is limited and challenges faced by the programs remain unclear. OBJECTIVE: To better understand the barriers faced by existing day programs that provide IMI, disparities in patient care, and areas for improvement to better inform policy and improve access to treatment for PFD. METHODS: Semi-structured interviews were conducted with a leader of outpatient programs providing IMI in the United States. Data regarding leader's perspectives on disparities in patient care, barriers faced by the intensive multidisciplinary feeding day programs, and future goals and directions for their programming were collected. Afterward, a qualitative content analysis was conducted to consolidate and categorize information related to patient care, access, and barriers faced by day programs and patients with PFD. RESULTS: Barriers and challenges were identified at the patient, program, and systems levels. Patient-level barriers included familial resources or socioeconomic status, geographic distance from the program site, and difficulty with the time commitment, whereas program-level barriers included limited site personnel and capacity and long wait times. System-level barriers primarily center on insurance, with inconsistent coverage of services and limited payer knowledge about PFD and IMI. CONCLUSION: IMIs are effective in managing PFD; however, a variety of patient-level, program-level, and systems-level factors serve as barriers for patient access to care and program success. Further research, improved reimbursement, and consensus statements on effective treatments can help improve access to and coverage for care, allowing for the development and sustainability of more programs.

Biomarker Discovery in Liver Disease Using Untargeted Metabolomics in Plasma and Saliva.

Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.

Rationale and Design of the Randomized COmparison of Methods for Pulmonary Blood Flow Augmentation: Shunt Versus Stent (COMPASS) Trial: A Pediatric Heart Network Study.

Neonates with congenital heart disease and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; eg, Blalock-Thomas-Taussig shunt). However, over the past two decades, an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared with SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs Stent [COMPASS]) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization in order to assess whether one method of palliation demonstrates therapeutic superiority.

Death in the taste bud: Morphological features of dying taste cells and engulfment by Type I cells.

Taste buds comprise 50-100 epithelial derived cells, which are renewed throughout the life of an organism. Immature cells enter the bud at its base, maturing into one of three distinct cell types. How taste cells die and/or exit the bud, however, remains unclear. Here we present morphological data obtained through Serial Blockface Scanning Electron Microscopy of murine circumvallate taste buds, revealing several taste cells at the end of their life (4-6 per bud). Cells we identify as dying share certain morphological features typical of apoptosis: swollen endoplasmic reticulum, large lysosomes, degrading organelles, distended outer nuclear membranes, heterochromatin reorganization, cell shrinkage, and cell and/or nuclear fragmentation. Based on these features, we divide the cells into "early" and "late" stage dying cells. Most early stage dying cells have Type II cell morphologies, while a few display Type III cell features. Many dying cells maintain contacts with nerve fibers, but those fibers often appear detached from the main trunk of an afferent nerve fiber. Dying cells, like mature Type II and Type III taste cells, are surrounded by Type I taste cells, the glial-like cells of the bud. In many instances Type I cells appear to be engulfing their dying neighbors, suggesting a novel, phagocytic role for Type I cells. Surprisingly, virtually no Type I cells, which have the shortest residence time in taste buds, display features of apoptosis. The ultimate fate of Type I cells therefore remains enigmatic.

Lower Trapezius Tendon Transfer for Restoration of External Rotation in Brachial Plexus Birth Injury.

OBJECTIVE: Patients with brachial plexus birth injuries (BPBIs) are at risk for limitations in shoulder external rotation. The role of lower trapezius tendon transfer to restore shoulder external rotation in this population has not been well characterized. This study aimed to evaluate the utility of lower trapezius tendon transfer for restoration of external rotation in a subset of pediatric patients. METHODS: Seventeen pediatric patients with BPBI were treated with lower trapezius tendon transfer to restore external rotation of the shoulder. Mean age at surgery was 8 years, and 11 were female. Six patients had prior shoulder surgery to restore external rotation, while 1 had prior nerve surgery to restore shoulder function. Range of motion before lower trapezius transfer and at latest follow-up was obtained. Mean follow-up was 36 months. RESULTS: Active forward flexion did not significantly change from preoperative to final follow-up (mean, 147° and 141°; P = 0.46). External rotation in adduction significantly changed from preoperative to final follow-up (mean, 4° and 26°; P < 0.001). External rotation in abduction significantly changed from preoperative to final follow-up (mean, 75° and 84°; P = 0.048). Six patients (35%) had subsequent surgeries at average 17 months from this procedure. Significant univariate associations with subsequent surgery included certain intraoperative concomitant procedures-coracoid osteotomy/excision (P = 0.02) and biceps tenodesis (P = 0.04)-while bony glenoid augmentation/reconstruction trended toward significant association (P = 0.05). CONCLUSIONS: Lower trapezius tendon transfer for BPBI showed a statistically significant but unlikely clinically meaningful improvement in external rotation with a high rate of reoperation.

Evaluation of dermal exposure to phthalates and parabens resulting from the use of hair relaxers.

Hair relaxers have been suggested as a source of exposure to parabens and phthalates. However, dermally absorbed doses of these chemicals resulting from consumer use of hair relaxers have yet to be quantified, and results from epidemiological studies have consistently demonstrated that there is no increased risk for hormone-sensitive, reproductive cancers associated with use of hair relaxers among Black women. Therefore, dermal absorption of parabens and phthalates associated with hair relaxer use for several commercially available hair relaxer kits was modeled using IH SkinPerm™. The chemicals detected in the hair relaxer kits included methylparaben (MP), ethylparaben (EP), butylparaben (BP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and the phthalate substitute bis(2-ethylhexyl) adipate (DEHA). The daily absorbed dose ranges (mg/kg/day), standardized over a year of product use, were as follows: 8.64 × 10-5-0.00116 MP, 2.30 × 10-8-3.07 × 10-6 EP, 3.24 × 10-8-4.33 × 10-6 BP, 8.65 × 10-9-1.15 × 10-6 DEP, and 8.94 × 10-7-0.000119 DEHP for Kit #1; 8.44 × 10-5-0.00113 MP and 7.91 × 10-5-0.00106 DEP for Kit #2; and 2.49 × 10-6-3.33 × 10-5 MP, 1.52 × 10-8-2.03 × 10-6 EP, 3.29 × 10-9-4.39 × 10-7 DEP, and 3.11 × 10-6-4.14 × 10-5 DEHA for Kit #3. These absorbed doses were well below applicable health-based guidance values, indicating consumer exposure from product use is not expected to pose a health risk. These results provide valuable information for health risk evaluations for hair relaxer use.

Health-Related Quality of Life After Neonatal Treatment of Symptomatic Tetralogy of Fallot: Insights from the Congenital Cardiac Research Collaborative.

To evaluate the association between initial management strategy of neonatal symptomatic Tetralogy of Fallot (sTOF) and later health-related quality of life (HRQOL) outcomes. We performed a multicenter, cross-sectional evaluation of a previously assembled cohort of infants with sTOF who underwent initial intervention at ≤ 30 days of age, between 2005 and 2017. Eligible patients' parents/guardians completed an age-appropriate Pediatric Quality of Life Inventory, a Pediatric Quality of Life Inventory Cardiac Module Heart Disease Symptoms Scale, and a parental survey. The association between treatment strategy and HRQOL was evaluated, and the entire sTOF cohort was compared to published values for the healthy pediatric population and to children with complex congenital heart disease and other chronic illness. The study cohort included 143 sTOF subjects, of which 59 underwent a primary repair, and 84 had a staged repair approach. There was no association between initial management strategy and lower HRQOL. For the entire cohort, in general, individual domain scores decreased as age sequentially increased. Across domain measurements, mean scores for the sTOF cohort were significantly lower than the healthy pediatric population and comparable to those with other forms of complex CHD and other chronic health conditions. The presence of a genetic syndrome was significantly associated with a poor HRQOL (p = 0.003). Initial treatment strategy for sTOF was not associated with differences in late HRQOL outcomes, though the overall HRQOL in this sTOF cohort was significantly lower than the general population, and comparable to others with chronic illness.

A dendritic mechanism for balancing synaptic flexibility and stability.

Biological and artificial neural networks learn by modifying synaptic weights, but it is unclear how these systems retain previous knowledge and also acquire new information. Here, we show that cortical pyramidal neurons can solve this plasticity-versus-stability dilemma by differentially regulating synaptic plasticity at distinct dendritic compartments. Oblique dendrites of adult mouse layer 5 cortical pyramidal neurons selectively receive monosynaptic thalamic input, integrate linearly, and lack burst-timing synaptic potentiation. In contrast, basal dendrites, which do not receive thalamic input, exhibit conventional NMDA receptor (NMDAR)-mediated supralinear integration and synaptic potentiation. Congruently, spiny synapses on oblique branches show decreased structural plasticity in vivo. The selective decline in NMDAR activity and expression at synapses on oblique dendrites is controlled by a critical period of visual experience. Our results demonstrate a biological mechanism for how single neurons can safeguard a set of inputs from ongoing plasticity by altering synaptic properties at distinct dendritic domains.

Diagnosis and Management of Hypertension in Adolescents with Obesity.

Purpose of Review: Hypertension (HTN) and obesity are increasing in prevalence and severity in adolescents and have significant implications for long term morbidity and mortality. This review focuses on the diagnosis and management of HTN in adolescents with obesity with an emphasis on co-management of the two conditions. Recent Findings: Recent studies affirm the increasing prevalence of abnormal blood pressures and diagnoses of HTN associated with increased adiposity. Current guidelines recommend routine screening with proper technique for HTN in patients with obesity. Additionally, obesity and HTN related co-occurring medical conditions should be evaluated as there is frequently a bidirectional impact on risk and outcomes. Importantly, advances in adolescent obesity management have subsequently led to positive implications for the management of obesity-related comorbidities such as HTN. The co-management of obesity and HTN is an emerging strategy for treatment and prevention of additional morbidity and mortality as patients progress to adulthood. Summary: In adolescent patients with obesity, prompt recognition and appropriate diagnosis of HTN as well as related co-occurring conditions are necessary first steps in management. Co-management of obesity and HTN is likely to lead to improved outcomes. While lifestyle interventions serve as the foundation to this management, adjunctive and emerging therapies should be considered to adequately treat both conditions.

Multimodal Imaging in Mycobacterium Chimaera Cardiovascular Infections: The Mayo Clinic Experience.

Objective: To review the salient features of multimodality cardiovascular imaging in patients with disseminated Mycobacterium chimaera (MC) infections after exposure to contaminated heater-cooler units during cardiopulmonary bypass. Patients and Methods: Twelve patients with confirmed MC infection were retrospectively identified after a review from January 1, 2010, to April 30, 2021. The electronic medical records were examined with a focus on transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance imaging, and positron emission tomography-CT. Results: Three (27.3%) patients had diagnostic findings of endocarditis on transthoracic echocardiography, with most patients having nonspecific abnormalities including elevated prosthetic valve gradients or prosthetic leaflet thickening. Transesophageal echocardiography identified 4 (36.7%) patients with vegetations and 3 (27.3%) with aortic root abscess or pseudoaneurysm, with more common findings such as mild aortic root or prosthetic leaflet thickening. Six (50%) patients underwent cardiac CT imaging, which found aortic root pseudoaneurysms or abscesses, prosthetic ring dehiscence, and leaflet thickening. Three (25%) patients underwent cardiac magnetic resonance imaging demonstrating prosthetic valve vegetations, leaflet thickening, and abnormal myocardial delayed enhancement in a noncoronary distribution, suggesting myocarditis. Ten (83%) patients underwent positron emission tomography-CT, 4 (40%) had an abnormal fluorodeoxyglucose uptake around the cardiac prosthetic material, and 7 (70%) had a fluorodeoxyglucose uptake in other organs, suggesting concomitant multiorgan involvement. Conclusion: Multimodality cardiovascular imaging is central to the management of patients with disseminated MC and can help establish a preliminary diagnosis while awaiting confirmatory microbiological data, potentially reducing the time to diagnosis. Imaging findings are subtle and atypical, not always meeting classically modified Duke's criteria for infectious endocarditis. Clinicians should have a high index of suspicion for the disease and a low threshold for repeat imaging when initial testing is equivocal.

Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice.

Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection-endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein-specific CD8+ T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8+ T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.

APPROACH e-PROM system: a user-centered development and evaluation of an electronic patient-reported outcomes measurement system for management of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) confers increased risks of premature mortality, non-fatal morbidity, and significant impairment in functional status and health-related quality of life. Routine administration of electronic patient-reported outcome measures (PROMs) and its real time delivery to care providers is known to have the potential to inform routine cardiac care and to improve quality of care and patient outcomes. This study describes a user-centered development and evaluation of the Alberta Provincial Project for Outcomes Assessment (APPROACH) electronic Patient Reported Outcomes Measurement (e-PROM) system. This e-PROM system is an electronic system for the administration of PROMs to patients with CAD and the delivery of the summarized information to their care providers to facilitate patient-physician communication and shared decision-making. This electronic platform was designed to be accessible via web-based and hand-held devices. Heuristic and user acceptance evaluation were conducted with patients and attending care providers. RESULTS: The APPROACH e-PROM system was co-developed with patients and care providers, research investigators, informaticians and information technology experts. Five PROMs were selected for inclusion in the online platform after consultations with patient partners, care providers, and PROMs experts: the Seattle Angina Questionnaire, Patient Health Questionnaire, EuroQOL, and Medical Outcomes Study Social Support Survey, and Self-Care of Coronary Heart Disease Inventory. The heuristic evaluation was completed by four design experts who examined the usability of the prototype interfaces. User acceptance testing was completed with 13 patients and 10 cardiologists who evaluated prototype user interfaces of the e-PROM system. CONCLUSION: Both patients and physicians found the APPROACH e-PROM system to be easy to use, understandable, and acceptable. The APPROACH e-PROM system provides a user-informed electronic platform designed to incorporate PROMs into the delivery of individualized cardiac care for persons with CAD.

Epidemiology of Cardiogenic Shock Using the Shock Academic Research Consortium (SHARC) Consensus Definitions.

BACKGROUND: The Shock Academic Research Consortium (SHARC) recently proposed pragmatic consensus definitions to standardize classification of cardiogenic shock (CS) in registries and clinical trials. We aimed to describe contemporary CS epidemiology using the SHARC definitions in a cardiac intensive care unit (CICU) population. METHODS: The Critical Care Cardiology Trials Network (CCCTN) is a multinational research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). CS was defined as a cardiac disorder resulting in SBP<90mmHg for ≥30 minutes (or the need for vasopressors, inotropes, or mechanical circulatory support [MCS] to maintain SBP ≥90mmHg) with evidence of hypoperfusion. Primary etiologic categories included acute myocardial infarction-related CS (AMI-CS), heart failure-related CS (HF-CS), and non-myocardial (secondary) CS. Post-cardiotomy CS was not included. HF-CS was further subcategorized as de novo vs. acute-on-chronic HF-CS. Patients with both cardiogenic and non-cardiogenic components of shock were classified separately as mixed CS. RESULTS: Of 8,974 patients meeting shock criteria (2017-2023), 65% had isolated CS and 17% had mixed shock. Among patients with CS (n=5,869), 27% had AMI-CS (65% STEMI), 59% HF-CS (72% acute-on-chronic, 28% de novo), and 14% secondary CS. Patients with AMI-CS and de novo HF-CS were most likely to have had concomitant cardiac arrest (p<0.001). Patients with AMI-CS and mixed CS were most likely to present in more severe shock stages (SCAI D or E; p<0.001). Temporary MCS use was highest in AMI-CS (59%). In-hospital mortality was highest in mixed CS (48%), followed by AMI-CS (41%), similar in de novo HF-CS (31%) and secondary CS (31%), and lowest in acute-on-chronic HF-CS (25%; p<0.001). CONCLUSIONS: SHARC consensus definitions for CS classification can be pragmatically applied in contemporary registries and reveal discrete subpopulations of CS with distinct phenotypes and outcomes that may be relevant to clinical practice and future research.