Pulsed Field Ablation to Treat Paroxysmal Atrial Fibrillation: Safety and Effectiveness in the ADMIRE Pivotal Trial.

BACKGROUND: Evidence from clinical trials of early pulsed field ablation (PFA) systems in treating atrial fibrillation has demonstrated their promising potential to reduce complications associated with conventional thermal modalities while maintaining efficacy. However, the lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options. A novel variable-loop PFA catheter integrated with an electroanatomic mapping system has been developed that allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity. ADMIRE (Assessment of Safety and Effectiveness in Treatment Management of Atrial Fibrillation With the Bosense-Webster Irreversible Electroporation Ablation System), a multicenter, single-arm, Food and Drug Administration investigational device exemption study, evaluated the long-term safety and effectiveness of this integrated PFA system in a large United States-based drug-refractory symptomatic paroxysmal atrial fibrillation patient population. METHODS: Using the PFA catheter with a compatible electroanatomic mapping system, patients with drug-refractory symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation. The primary safety end point was primary adverse event within 7 days of ablation. The primary effectiveness end point was a composite end point that included 12-month freedom from documented atrial tachyarrhythmia (ie, atrial fibrillation, atrial tachycardia, atrial flutter) episodes, failure to achieve pulmonary vein isolation, use of a nonstudy catheter for pulmonary vein isolation, repeat procedure (except for one redo during blanking), taking a new or previously failed class I or III antiarrhythmic drug at higher dose after blanking, or direct current cardioversion after blanking. RESULTS: At 30 centers, 277 patients with paroxysmal atrial fibrillation (61.5±10.3 years of age; 64.3% male) in the pivotal cohort underwent PFA. More than 25% of the procedures were performed without fluoroscopy. Median (Q1, Q3) pulmonary vein isolation procedure, fluoroscopy, and transpired PFA application times were 81.0 (61.0, 112.0), 7.1 (0.00, 14.3), and 31.0 (24.8, 40.9) minutes, respectively. The primary adverse event rate was 2.9% (8 of 272), with the most common complication being pericardial tamponade. The 12-month primary effectiveness end point was 74.6%. The 1-year freedom from atrial fibrillation, atrial tachycardia, or atrial flutter recurrence rate after blanking was 75.4%. Substantial improvements in quality of life were observed as early as 3 months after the procedure, concurrent with a reduction in multiple health care use measures. CONCLUSIONS: ADMIRE confirmed the safety and effectiveness of the variable-loop PFA catheter, with short procedure and PFA application times and low fluoroscopy exposure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05293639.

Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial.

BACKGROUND: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC. METHODS: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed. FINDINGS: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study. INTERPRETATION: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3. FUNDING: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.

Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.

Ammonia levels are orchestrated by a series of complex interrelated pathways in which the urea cycle has a central role. Liver dysfunction leads to an accumulation of ammonia, which is toxic and is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, hypoxaemia and dysregulation of neurotransmission. Hyperammonaemia is a hallmark of hepatic encephalopathy and has been strongly associated with liver-related outcomes in patients with cirrhosis and liver failure. In addition to the established role of ammonia as a neurotoxin in the pathogenesis of hepatic encephalopathy, an increasing number of studies suggest that it can lead to hepatic fibrosis progression, sarcopenia, immune dysfunction and cancer. However, elevated systemic ammonia levels are uncommon in patients with metabolic dysfunction-associated steatotic liver disease. A clear causal relationship between ammonia-induced immune dysfunction and risk of infection has not yet been definitively proven. In this Review, we discuss the mechanisms by which ammonia produces its diverse deleterious effects and their clinical relevance in liver diseases, the importance of measuring ammonia levels for the diagnosis of hepatic encephalopathy, the prognosis of patients with cirrhosis and liver failure, and how our knowledge of inter-organ ammonia metabolism is leading to the development of novel therapeutic approaches.

Child mental health treatment access and retention in integrated primary care and traditional outpatient services.

INTRODUCTION: There are disparities in child mental health treatment access and treatment retention in terms of race and ethnicity, socioeconomic status (SES), and insurance coverage. Institutions have invested in the integrated primary care (IPC) treatment model with the goal of improving treatment access and promoting child mental health equity. OBJECTIVE: This study compared treatment attendance in an outpatient psychiatry clinic (OPC) versus an IPC clinic to assess whether the IPC was associated with reduced disparities in access to care and treatment retention. METHODS: This study assessed whether there were differences in who is connected to care from the intake appointment to first follow-up appointment. RESULTS: Results showed that the IPC clinic served a more diverse patient population than the OPC clinic in terms of SES, race, and ethnicity. Differences in treatment attendance in the IPC and OPC were also found. After controlling for race, ethnicity, insurance, and distance from patient's home zip code to clinic, the IPC treatment setting was associated with poorer intake and follow-up appointment attendance. CONCLUSIONS: The IPC model may be more accessible to historically underserved youth, but the treatment setting does not inherently eliminate disparities in child mental health treatment retention. Replication of this study has the potential to contribute to the external validity of study findings, improve quality assurance policies, and develop equitable workflow policies. Future research is needed to identify factors that can improve treatment attendance for populations who face greater retention barriers and to shine light on ways that healthcare systems may inadvertently maintain disparity in treatment retention.

Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report from the Pulmonary Embolism Research Collaborative.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes.

Deep Learning for Automated Classification of Hip Hardware on Radiographs.

PURPOSE: To develop a deep learning model for automated classification of orthopedic hardware on pelvic and hip radiographs, which can be clinically implemented to decrease radiologist workload and improve consistency among radiology reports. MATERIALS AND METHODS: Pelvic and hip radiographs from 4279 studies in 1073 patients were retrospectively obtained and reviewed by musculoskeletal radiologists. Two convolutional neural networks, EfficientNet-B4 and NFNet-F3, were trained to perform the image classification task into the following most represented categories: no hardware, total hip arthroplasty (THA), hemiarthroplasty, intramedullary nail, femoral neck cannulated screws, dynamic hip screw, lateral blade/plate, THA with additional femoral fixation, and post-infectious hip. Model performance was assessed on an independent test set of 851 studies from 262 patients and compared to individual performance of five subspecialty-trained radiologists using leave-one-out analysis against an aggregate gold standard label. RESULTS: For multiclass classification, the area under the receiver operating characteristic curve (AUC) for NFNet-F3 was 0.99 or greater for all classes, and EfficientNet-B4 0.99 or greater for all classes except post-infectious hip, with an AUC of 0.97. When compared with human observers, models achieved an accuracy of 97%, which is non-inferior to four out of five radiologists and outperformed one radiologist. Cohen's kappa coefficient for both models ranged from 0.96 to 0.97, indicating excellent inter-reader agreement. CONCLUSION: A deep learning model can be used to classify a range of orthopedic hip hardware with high accuracy and comparable performance to subspecialty-trained radiologists.

Outcomes for Mechanically Ventilated Patients With Acute Myocardial Infarction Admitted to Medical vs Cardiac Intensive Care Units.

Background: Acute myocardial infarction (AMI) remains a common reason for admission to the intensive care unit (ICU). However, there is limited data comparing outcomes for patients with AMI admitted to specific ICUs. Objectives: The purpose of this study was to assess clinical outcomes between patients with AMI requiring invasive mechanical ventilation admitted to the medical ICU (MICU) compared to cardiac (CICU). Methods: We utilized the Vizient Clinical Data Base to identify patients with a primary diagnosis of AMI between October 2015 and December 2019 and requiring invasive mechanical ventilation. Using multivariable logistic regression, we compared clinical outcomes for patients admitted to the MICU vs CICU. Results: We identified 12,639 patients, 25.2% (n = 3,185) of which were admitted to a MICU and 74.8% (n = 9,454) to a CICU. Patients admitted to a CICU were more likely to present with STEMI (57.0% vs 42.8%), cardiogenic shock (46.0% vs 37.4%), and require mechanical circulatory support and vasoactive medications (all, P < 0.001). Median ventilator days were 4 days in both ICUs and not statistically different after multivariable adjustment (P = 0.81). In-hospital mortality was 42.7% compared to 41.3% for MICU vs CICU admissions, respectively (P = 0.15). After multivariable adjustment, CICU admission was associated with lower in-hospital mortality (OR: 0.85, 95% CI: 0.78-0.93, P = 0.001), which persisted when stratified by cardiogenic shock, cardiac arrest, STEMI, largest hospital size (>750 beds), and teaching hospitals (all, P < 0.05). Conclusions: Admission to the CICU, as compared to MICU, was associated with lower in-hospital mortality for patients with AMI. These findings may support optimal triage of critically ill patients with AMI.

Race and Ethnicity Disparities in Management and Outcomes of Critically Ill Adults with Acute Respiratory Failure.

This article reviews the current evidence base for racial and ethnic disparities related to acute respiratory failure. It discusses the prevailing and most studied mechanisms that underlay these disparities, analytical challenges that face the field, and then uses this discussion to frame future directions to outline next steps for developing disparities-mitigating solutions.

Aversion to pragmatic randomised controlled trials: three survey experiments with clinicians and laypeople in the USA.

OBJECTIVES: Pragmatic randomised controlled trials (pRCTs) are essential for determining the real-world safety and effectiveness of healthcare interventions. However, both laypeople and clinicians often demonstrate experiment aversion: preferring to implement either of two interventions for everyone rather than comparing them to determine which is best. We studied whether clinician and layperson views of pRCTs for COVID-19, as well as non-COVID-19, interventions became more positive during the pandemic, which increased both the urgency and public discussion of pRCTs. DESIGN: Randomised survey experiments. SETTING: Geisinger, a network of hospitals and clinics in central and northeastern Pennsylvania, USA; Amazon Mechanical Turk, a research participant platform used to recruit online participants residing across the USA. Data were collected between August 2020 and February 2021. PARTICIPANTS: 2149 clinicians (the types of people who conduct or make decisions about conducting pRCTs) and 2909 laypeople (the types of people who are included in pRCTs as patients). The clinician sample was primarily female (81%), comprised doctors (15%), physician assistants (9%), registered nurses (54%) and other medical professionals, including other nurses, genetic counsellors and medical students (23%), and the majority of clinicians (62%) had more than 10 years of experience. The layperson sample ranges in age from 18 to 88 years old (mean=38, SD=13) and the majority were white (75%) and female (56%). OUTCOME MEASURES: Participants read vignettes in which a hypothetical decision-maker who sought to improve health could choose to implement intervention A for all, implement intervention B for all, or experimentally compare A and B and implement the superior intervention. Participants rated and ranked the appropriateness of each decision. Experiment aversion was defined as the degree to which a participant rated the experiment below their lowest-rated intervention. RESULTS: In a survey of laypeople administered during the pandemic, we found significant aversion to experiments involving catheterisation checklists and hypertension drugs unrelated to the treatment of COVID-19 (Cohen's d=0.25-0.46, p<0.001). Similarly, among both laypeople and clinicians, we found significant aversion to most (comparing different checklist, proning and mask protocols; Cohen's d=0.17-0.56, p<0.001) but not all (comparing school reopening protocols; Cohen's d=0.03, p=0.64) non-pharmaceutical COVID-19 experiments. Interestingly, we found the lowest experiment aversion to pharmaceutical COVID-19 experiments (comparing new drugs and new vaccine protocols for treating the novel coronavirus; Cohen's d=0.04-0.12, p=0.12-0.55). Across all vignettes and samples, 28%-57% of participants expressed experiment aversion, whereas only 6%-35% expressed experiment appreciation by rating the trial higher than their highest-rated intervention. CONCLUSIONS: Advancing evidence-based medicine through pRCTs will require anticipating and addressing experiment aversion among patients and healthcare professionals. STUDY REGISTRATION: http://osf.io/6p5c7/.

Isolation limits spring pollination in a UK fragmented landscape.

Animal-mediated pollination determines the reproductive success of most flowering plants; this process however can be disrupted by environmental degradation, with habitat loss and fragmentation highlighted as a top driver of pollination deficits. Despite being a pervasive stressor worldwide, we still have rather limited empirical evidence on its effects on pollination services, especially for early spring pollination syndromes. We investigate this using a potted plant phytometry experiment in which we placed English Bluebell (Hyacinthoides non-scripta)-a species largely pollinated in spring-into a fragmented woodland habitat. We selected 51 woodland patches which varied in both size and distance from each other and placed 153 pots of bluebell plants in the patches for c.4 weeks to measure pollination. The woodlands were located in a matrix of grassland, the latter being of low plant species richness and overall in the patches, woodland plants showed a positive species-area relationship. We collected traits on bluebell reproduction, these included the number, size, quality of seeds, the number of seed capsules and the number of flowers that failed to set any seeds. We found that seed traits responded differently to patch area and isolation. Patch isolation negatively affected the number of seeds and capsules, whilst it did not affect the size and quality of seeds. Patch area had no effect on any traits, suggesting that patch area might not necessarily be a factor that affects pollination in this species. The number of flowers that failed to set seed was unaffected by either patch area or isolation. Our study suggests that woodland fragmentation impacts the pollination of understory spring flowering plants. Our results highlight the use of multiple traits of phytometer plants to evaluate pollination and the importance of connectivity in maintaining pollination services in small-fragmented landscapes.

Novel MEN1-associated retroperitoneal pleomorphic liposarcoma.

Soft tissue sarcomas are rarely associated with mutations of the MEN1 gene. We report a patient with a large retroperitoneal pleomorphic liposarcoma harboring a rare mutation of the MEN1 gene not previously reported to be associated with soft tissue sarcomas. This report expands the known spectrum of MEN1-associated cancers.

Evaluating the accuracy of the MBT Lipid Xtract Kit for assessing colistin resistance in comparison to broth microdilution.

Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.

Functional Network Connectivity for Components of Depression-Related Psychological Fragility.

Psychological resilience (PR) is known to be inversely associated with depression. While there is a growing body of research examining how depression alters activity across multiple functional neural networks, how differences in PR affect these networks is largely unexplored. This study examines the relationship between PR and functional connectivity in the alpha and beta bands within (and between) eighteen established cortical nodes in the default mode network, the central executive network, and the salience network. Resting-state EEG data from 99 adult participants (32 depressed, 67 non-depressed) were used to measure the correlation between the five factors of PR sourced from the Connor-Davidson Resilience Scale and eLORETA-based measures of coherence and phase synchronisation. Distinct functional connectivity patterns were seen across each resilience factor, with a notable absence of overlapping positive results across the depressed and non-depressed samples. These results indicate that depression may modulate how resilience is expressed in terms of fundamental neural activity.

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.

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.

Small versus large-bore thoracostomy for traumatic hemothorax: A systematic review and meta-analysis.

BACKGROUND: Traumatic hemothorax (HTX) is common, and while it is recommended to drain it with a tube thoracostomy, there is no consensus on the optimal catheter size. We performed a systematic review to test the hypothesis that small bore tube thoracostomy (SBTT) (≤14 F) is as effective as large-bore tube thoracostomy (LBTT) (≥20F) for the treatment of HTX. METHODS: Pubmed, EMBASE, Scopus, and Cochrane review were searched from inception to November 2022 for randomized controlled trials or cohort studies that included adult trauma patients with HTX who received a tube thoracostomy. Data was extracted and Critical Appraisal Skills Program checklists were used for study appraisal. The primary outcome was failure rate, defined as incompletely drained or retained HTX requiring a second intervention. Cumulative analysis was performed with χ2 test for dichotomous variables and an unpaired t-test for continuous variables. Meta-analysis was performed using a random effects model. RESULTS: There were 2,008 articles screened, of which nine were included in the analysis. The studies included 1,847 patients (714 SBTT and 1,233 LBTT). The mean age of patients was 46 years, 75% were male, average ISS was 20, and 81% had blunt trauma. Failure rate was not significantly different between SBTT (17.8%) and LBTT (21.5%) (p = 0.166). Additionally, there were no significant differences between SBTT vs. LBTT in mortality (2.9% vs. 6.1%, p = 0.062) or complication rate (12.3% vs. 12.5%, p = 0.941), however SBTT had significantly higher initial drainage volumes (753 vs. 398 mL, p < 0.001) and fewer tube days (4.3 vs. 6.2, p < 0.001). There are several limitations. Some studies did not report all the outcomes of interest, and many of the studies are subject to selection bias. CONCLUSION: SBTT may be as effective as LBTT for the treatment of traumatic HTX. LEVEL OF EVIDENCE: SR/MA with more than two negative criteria; Level IV.

Neurological Validation of ASD Diagnostic Criteria Using Frontal Alpha and Theta Asymmetry.

Background/Objectives: Diagnosis of Autism Spectrum Disorder (ASD) relies on the observation of difficulties in social communication and interaction, plus the presence of repetitive and restrictive behaviors. The identification of neurological correlates of these symptoms remains a high priority for clinical research, and has the potential to increase the validity of diagnosis of ASD as well as provide greater understanding of how the autistic brain functions. This study focused on two neurological phenomena that have been previously associated with psychiatric disorders (alpha- and theta-wave asymmetry across the frontal region of the brain), and tested for their association with the major diagnostic criteria for ASD. Methods: A total of 41 male autistic youth underwent assessment with the Autism Diagnostic Observation Schedule (ADOS-2) and 3 min of eyes-closed resting EEG to collect alpha- and theta-wave data from right and left frontal brain sites. Results: Different associations were found for theta versus alpha asymmetry and the ADOS-2 subscales, across different brain regions responsible for a varying range of cognitive functions. In general, theta asymmetry was associated with conversation with others, sharing of enjoyment, and making social overtures, whereas alpha asymmetry was linked with making eye contact, reporting events to others, and engaging in reciprocal social communication. Specific brain regions involved are identified, as well as implications for clinical practice. Conclusions: Specific autism symptoms may be associated with selected brain region activity, providing a neurological basis for diagnosis and treatment.

In vivooptogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity.

Objective.Optogenetics allows the manipulation of neural circuitsin vivowith high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models).Approach.Here, we have developed, optimised, and testedin vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181µLEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies.Main results.Thinning the combinedµLED and needle backplane of the device from 300µm to 230µm improved the efficiency of light delivery to tissue by 80%, allowing lowerµLED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1 °C. The device was testedin vivoin the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons.Significance.It was shown that the UOA produced the strongest optogenetic response in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling-demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential activity.