Excised linear introns regulate growth in yeast.

Spliceosomal introns are ubiquitous non-coding RNAs that are typically destined for rapid debranching and degradation. Here we describe 34 excised introns in Saccharomyces cerevisiae that-despite being rapidly degraded in log-phase growth-accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, which is a key integrator of growth signalling. Introns that become stabilized remain associated with components of the spliceosome and differ from other spliceosomal introns in having a short distance between their lariat branch point and 3' splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates in yeast that are chronically challenged with the TORC1 inhibitor rapamycin. The reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signalling network of S. cerevisiae and, more generally, excised spliceosomal introns can have biological functions.

Classical CD4 T cells as the cornerstone of antimycobacterial immunity.

Tuberculosis is a significant health problem without an effective vaccine to combat it. A thorough understanding of the immune response and correlates of protection is needed to develop a more efficient vaccine. The immune response against Mycobacterium tuberculosis (Mtb) is complex and involves all aspects of the immune system, however, the optimal protective, non-pathogenic T cell response against Mtb is still elusive. This review will focus on discussing CD4 T cell immunity against mycobacteria and its importance in Mtb infection with a primary focus on human studies. We will in particular discuss the large heterogeneity of immune cell subsets that have been revealed by recent immunological investigations at an unprecedented level of detail. These studies have identified specific classical CD4 T cell subsets important for immune responses against Mtb in various states of infection. We further discuss the functional attributes that have been linked to the various subsets such as upregulation of activation markers and cytokine production. Another important topic to be considered is the antigenic targets of Mtb-specific immune responses, and how antigen reactivity is influenced by both disease state and environmental exposure(s). These are key points for both vaccines and immune diagnostics development. Ultimately, these factors are holistically considered in the definition and investigations of what are the correlates on protection and resolution of disease.

Concomitant Cardiac Surgical Procedures in Patients Undergoing HeartMate 3 Left Ventricular Assist Device Implantation.

BACKGROUND: Long-term support with a HeartMate 3 (HM3) left ventricular assist device (LVAD) has improved outcomes of patients with end-stage heart failure. However, there is a paucity of data on the outcomes of patients who underwent concomitant cardiac surgical procedure (CCSP) during HM3-LVAD implantation. OBJECTIVES: To assess our single-center experience with patients who underwent CCSP during the implantation of an HM3-LVAD. METHODS: From December 2016 until April 2022, 131 adult patients underwent HM3-LVAD implantation. A total of 23 patients underwent CCSP during the HM3-LVAD implantation+CCSP, and 108 underwent only HM3-LVAD implantation (HM3-only). RESULTS: The median age was 59 ± 11 years (range 54-67), 82% (n=108) were male, and 76% (n=100) were implanted as a bridge-to-transplant. The concomitant procedures performed during the implantation included 8 aortic valve repairs/replacements, 14 tricuspid valve repairs, 4 patent foramen ovales or atrial septal defect closures, and 3 other cardiac procedures. The mean cardiopulmonary bypass time was 113 ± 58 minutes for the HM3-only group and 155 ± 47 minutes for the HM3+CCSP group (P = 0.007). The mortality rates at 30 days, 6 months, and 12 months post-implantation were 2 (9%), 5 (22%), and 6 (26%) respectively for the HM3+CCSP group, and 7 (6%), 18 (17%), and 30 (28%) for the HM3-only group (P = 0.658, 0.554, and 1.000). CONCLUSIONS: Our experience demonstrated no significant difference in the 30-day, 6-month, and 12-month mortality rates for patients who underwent a CCSP during HM3-LVAD implantation compared to patients who did not undergo CCSP during HM3-LVAD implantation.

Correction: Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

The biochemical basis of mitochondrial dysfunction in Zellweger Spectrum Disorder.

Peroxisomal biogenesis disorders (PBDs) are genetic disorders of peroxisome biogenesis and metabolism that are characterized by profound developmental and neurological phenotypes. The most severe class of PBDs-Zellweger spectrum disorder (ZSD)-is caused by mutations in peroxin genes that result in both non-functional peroxisomes and mitochondrial dysfunction. It is unclear, however, how defective peroxisomes contribute to mitochondrial impairment. In order to understand the molecular basis of this inter-organellar relationship, we investigated the fate of peroxisomal mRNAs and proteins in ZSD model systems. We found that peroxins were still expressed and a subset of them accumulated on the mitochondrial membrane, which resulted in gross mitochondrial abnormalities and impaired mitochondrial metabolic function. We showed that overexpression of ATAD1, a mitochondrial quality control factor, was sufficient to rescue several aspects of mitochondrial function in human ZSD fibroblasts. Together, these data suggest that aberrant peroxisomal protein localization is necessary and sufficient for the devastating mitochondrial morphological and metabolic phenotypes in ZSDs.

Supervised smoking facility access, harm reduction practices, and substance use changes during the COVID-19 pandemic: a community-engaged cross-sectional study.

BACKGROUND: The potential public health benefits of supervised smoking facilities (SSFs) are considerable, and yet implementation of SSFs in North America has been slow. We conducted this study to respond to significant knowledge gaps surrounding SSF utilization and to characterize substance use, harm reduction practices, and service utilization following the onset of the COVID-19 pandemic. METHODS: A questionnaire was self-administered at a single site by 175 clients using an outdoor SSF in Vancouver, Canada, between October-December 2020. Questionnaire responses were summarized using descriptive statistics. Multinomial logistic regression techniques were used to examine factors associated with increased SSF utilization. RESULTS: Almost all respondents reported daily substance use (93% daily use of opioids; 74% stimulants). Most used opioids (85%) and/or methamphetamine (66%) on the day of their visit to the SSF. Respondents reported drug use practice changes at the onset of COVID-19 to reduce harm, including using supervised consumption sites, not sharing equipment, accessing medically prescribed alternatives, cleaning supplies and surfaces, and stocking up on harm reduction supplies. Importantly, 45% of SSF clients reported using the SSF more often since the start of COVID-19 with 65.2% reporting daily use of the site. Increased substance use was associated with increased use of the SSF, after controlling for covariates. CONCLUSIONS: Clients of the SSF reported increasing not only their substance use, but also their SSF utilization and harm reduction practices following the onset of COVID-19. Increased scope and scale of SSF services to meet these needs are necessary.

Community-Engaged Research Ethics Training (CERET): developing accessible and relevant research ethics training for community-based participatory research with people with lived and living experience using illicit drugs and harm reduction workers.

BACKGROUND: Community-based participatory research (CBPR) can directly involve non-academic community members in the research process. Existing resources for research ethics training can be inaccessible to team members without an academic background and do not attend to the full spectrum of ethical issues that arise through community-engaged research practices. We detail an approach to capacity building and training in research ethics in the context of CBPR with people who use(d) illicit drugs and harm reduction workers in Vancouver's Downtown Eastside neighborhood. METHODS: A project team comprised of academic and community experts in CBPR, research ethics, and harm reduction met over five months to develop the Community-Engaged Research Ethics Training (CERET). The group distilled key principles and content from federal research ethics guidelines in Canada, and developed case examples to situate the principles in the context of research with people who use(d) illicit drugs and harm reduction workers. In addition to content related to federal ethics guidelines, the study team integrated additional content related to ethical issues that arise through community-based research, and ethical principles for research in the Downtown Eastside. Workshops were evaluated using a pre-post questionnaire with attendees. RESULTS: Over the course of six weeks in January-February 2020, we delivered three in-person workshops for twelve attendees, most of whom were onboarding as peer research assistants with a community-based research project. Workshops were structured around key principles of research ethics: respect for persons, concern for welfare, and justice. The discussion-based format we deployed allowed for the bi-directional exchange of information between facilitators and attendees. Evaluation results suggest the CERET approach was effective, and attendees gained confidence and familiarity with workshop content across learning objectives. CONCLUSIONS: The CERET initiative offers an accessible approach to fulfill institutional requirements while building capacity in research ethics for people who use(d) drugs and harm reduction workers. This approach recognizes community members as partners in ethical decision making throughout the research process and is aligned with values of CBPR. Building capacity around intrinsic and extrinsic dimensions of research ethics can prepare all study team members to attend to ethical issues that arise from CBPR.

Treating Heparin-Induced Thrombocytopenia in Patients Undergoing HeartMate 3 Left Ventricular Assist Device Implantation.

BACKGROUND: Unfractionated heparin is the preferred anticoagulant used during open heart surgeries, including left ventricular assist device (LVAD) implantation. In cases in which patients are heparin-induced thrombocytopenia positive (HIT+), the accepted practice has been to substitute heparin with bivalirudin. This practice may be associated with significant bleeding and adverse outcomes. OBJECTIVES: To review our experience with HIT+ patients who were heparin-induced thrombocytopenia with thrombosis negative (HITT-) and who underwent HeartMate 3 LVAD implantation using heparin intraoperatively rather than bivalirudin. METHODS: From 2016 to 2022, 144 adult patients were implanted with HeartMate 3 LVAD at our center. Among them, 7 were detected as HIT+ but HITT- and therefore were prescribed intraoperatively with heparin and treated pre- and postoperatively with bivalirudin. We reviewed the preoperative, intraoperative, and postoperative characteristics as well as short-term mortality and the complication rates of these HIT+ patients. RESULTS: The median age of our cohort was 56 years (51-60), 71% were male (n=5), all were INTERMACS Level 1, and most were bridged to transplant (n=6, 86%). The 30-day mortality rate post-implantation was 0%. The average 24-hour chest drain postoperative output was 1502.86 ± 931.34 ml. There were no intraoperative pump thromboses, perioperative thromboses, cerebrovascular accidents, or gastrointestinal bleeding within the first 24 hours postoperative. One patient required a revision due to bleeding. CONCLUSIONS: Intraoperative unfractionated heparin may be administered to patients who are HIT+ and HITT- while undergoing LVAD implantation. However, further investigation is required.

Concurrent inhibition of CDK2 adds to the anti-tumour activity of CDK4/6 inhibition in GIST.

BACKGROUND: Advanced gastrointestinal stromal tumour (GIST) is characterised by genomic perturbations of key cell cycle regulators. Oncogenic activation of CDK4/6 results in RB1 inactivation and cell cycle progression. Given that single-agent CDK4/6 inhibitor therapy failed to show clinical activity in advanced GIST, we evaluated strategies for maximising response to therapeutic CDK4/6 inhibition. METHODS: Targeted next-generation sequencing and multiplexed protein imaging were used to detect cell cycle regulator aberrations in GIST clinical samples. The impact of inhibitors of CDK2, CDK4 and CDK2/4/6 was determined through cell proliferation and protein detection assays. CDK-inhibitor resistance mechanisms were characterised in GIST cell lines after long-term exposure. RESULTS: We identify recurrent genomic aberrations in cell cycle regulators causing co-activation of the CDK2 and CDK4/6 pathways in clinical GIST samples. Therapeutic co-targeting of CDK2 and CDK4/6 is synergistic in GIST cell lines with intact RB1, through inhibition of RB1 hyperphosphorylation and cell proliferation. Moreover, RB1 inactivation and a novel oncogenic cyclin D1 resulting from an intragenic rearrangement (CCND1::chr11.g:70025223) are mechanisms of acquired CDK-inhibitor resistance in GIST. CONCLUSIONS: These studies establish the biological rationale for CDK2 and CDK4/6 co-inhibition as a therapeutic strategy in patients with advanced GIST, including metastatic GIST progressing on tyrosine kinase inhibitors.

Design, Synthesis, and In Vivo Evaluation of C1-Linked 4,5-Epoxymorphinan Haptens for Heroin Vaccines.

In our continuing effort to develop effective anti-heroin vaccines as potential medications for the treatment of opioid use disorder, herein we present the design and synthesis of the haptens: 1-AmidoMorHap (1), 1-AmidoMorHap epimer (2), 1 Amido-DihydroMorHap (3), and 1 Amido-DihydroMorHap epimer (4). This is the first report of hydrolytically stable haptenic surrogates of heroin with the attachment site at the C1 position in the 4,5-epoxymorophinan nucleus. We prepared respective tetanus toxoid (TT)-hapten conjugates as heroin vaccine immunogens and evaluated their efficacy in vivo. We showed that all TT-hapten conjugates induced high antibody endpoint titers against the targets but only haptens 2 and 3 can induce protective effects against heroin in vivo. The epimeric analogues of these haptens, 1 and 4, failed to protect mice from the effects of heroin. We also showed that the in vivo efficacy is consistent with the results of the in vitro drug sequestration assay. Attachment of the linker at the C1 position induced antibodies with weak binding to the target drugs. Only TT-2 and TT-3 yielded antibodies that bound heroin and 6-acetyl morphine. None of the TT-hapten conjugates induced antibodies that cross-reacted with morphine, methadone, naloxone, or naltrexone, and only TT-3 interacted weakly with buprenorphine, and that subtle structural difference, especially at the C6 position, can vastly alter the specificity of the induced antibodies. This study is an important contribution in the field of vaccine development against small-molecule targets, providing proof that the chirality at C6 in these epoxymorphinans is a vital key to their effectiveness.

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

Primary intra-abdominal melanoma arising in association with extracutaneous blue naevus: a report of two cases.

AIMS: Blue naevi are uncommon dermal melanocytic neoplasms characterised by GNAQ/GNA11 mutations, which very rarely progress to melanoma. Such melanomas also often have BAP1 mutations, and lack genetic events associated with conventional melanoma. Exceptionally, blue naevi arise in extracutaneous locations; one melanoma arising in this setting has been reported. We report the clinicopathological, immunohistochemical and molecular genetic features of two cases of melanoma arising in extracutaneous blue naevus. METHODS AND RESULTS: Both arose in males, aged 25 and 63 years, with no history of other melanocytic lesions, and presented as large, painful intra-abdominal masses. The tumours were dark-brown/black, multilobulated, involved small intestinal mesentery and consisted of a predominantly fascicular and spindled, but occasionally nested and epithelioid, proliferation of variably pigmented, relatively monotonous cells with pale cytoplasm and ovoid nuclei with mild to moderate atypia. Mitotic activity was variable but generally low. Both cases showed areas of conventional and cellular blue naevus. Recurrent tumour in one case showed predominantly epithelioid morphology and greater cytological atypia and mitotic activity. One case expressed Melan-A, SOX10 and CD117, with absent expression of S100 protein and DOG1; the other expressed Melan-A, HMB45 and S100 protein. Next-generation sequencing identified GNAQ and BAP1 mutations in one case and GNA11 mutation in the other. Both patients developed widespread metastatic disease. CONCLUSION: Exceptionally rare, aggressive melanomas arising in extracutaneous blue naevi should be distinguished from metastatic melanoma, gastrointestinal stromal tumour and malignant melanotic nerve sheath tumour, especially given the significant therapeutic and prognostic differences between these different entities.

XPRESSyourself: Enhancing, standardizing, and automating ribosome profiling computational analyses yields improved insight into data.

Ribosome profiling, an application of nucleic acid sequencing for monitoring ribosome activity, has revolutionized our understanding of protein translation dynamics. This technique has been available for a decade, yet the current state and standardization of publicly available computational tools for these data is bleak. We introduce XPRESSyourself, an analytical toolkit that eliminates barriers and bottlenecks associated with this specialized data type by filling gaps in the computational toolset for both experts and non-experts of ribosome profiling. XPRESSyourself automates and standardizes analysis procedures, decreasing time-to-discovery and increasing reproducibility. This toolkit acts as a reference implementation of current best practices in ribosome profiling analysis. We demonstrate this toolkit's performance on publicly available ribosome profiling data by rapidly identifying hypothetical mechanisms related to neurodegenerative phenotypes and neuroprotective mechanisms of the small-molecule ISRIB during acute cellular stress. XPRESSyourself brings robust, rapid analysis of ribosome-profiling data to a broad and ever-expanding audience and will lead to more reproducible and accessible measurements of translation regulation. XPRESSyourself software is perpetually open-source under the GPL-3.0 license and is hosted at https://github.com/XPRESSyourself, where users can access additional documentation and report software issues.

Community-Based Participatory Approaches to Knowledge Translation: HIV Prevention Case Study of the Investigaytors Program.

Approaches to knowledge translation (KT) that engage community stakeholders in the research cycle have been identified as particularly promising for addressing the "know-do" gap. Using the case study of a long-standing community-based participatory research (CBPR) project known as the "Investigaytors," this article describes the development and implementation of a KT intervention aimed at facilitating access to HIV pre-exposure prophylaxis for gay, bisexual, and other sexual minority men in British Columbia, Canada, through a publicly funded program. In doing so, we offer a model of CBPR for KT that is highly participatory, driven by community members, and centered around capacity building. We also present findings from a focus group with eight volunteer co-researchers to capture the perspectives of community members involved in the CBPR process and to evaluate the strengths and challenges associated with the use of a CBPR framework for KT. Findings from the focus group reveal how the inclusion of multiple perspectives from community, academic, and healthcare partners contributes to the perceived strength and credibility of the KT intervention opportunities for improving the CBPR process and how the CBPR process itself can be a form of integrated KT. This work has implications for future KT that deploys a CBPR framework, including an expanded understanding of reciprocity that can include benefits such as training and professional development, as well as introducing a novel approach to KT that is driven by community and integrates multiple perspectives. We conclude with reflections on implementing CBPR practices for KT in different settings.

The Effect of Chest Compression Location and Occlusion of the Aorta in a Traumatic Arrest Model.

BACKGROUND: Recent evidence demonstrates that closed chest compressions directly over the left ventricle (LV) in a traumatic cardiac arrest (TCA) model improve hemodynamics and return of spontaneous circulation (ROSC) when compared with traditional compressions. Resuscitative endovascular balloon occlusion of the aorta (REBOA) also improves hemodynamics and controls hemorrhage in TCA. We hypothesized that chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCA using REBOA. MATERIALS AND METHODS: Transthoracic echo was used to mark the location of the aortic root (traditional location) and the center of the LV on animals (n = 26), which were randomized to receive chest compressions in one of the two locations. After hemorrhage, ventricular fibrillation was induced to simulate TCA. After a period of 10 min of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support for an additional 10 min. REBOA balloons were inflated at 6 min into BLS. Hemodynamic variables were averaged during the final 2 min of the BLS and advanced life support periods. Survival was compared between this REBOA cohort and a control group without REBOA (no-REBOA cohort) (n = 26). RESULTS: There was no significant difference in ROSC between the two REBOA groups (P = 0.24). Survival was higher with REBOA group versus no-REBOA group (P = 0.02). CONCLUSIONS: There was no difference in ROSC between LV and traditional compressions when REBOA was used in this swine model of TCA. REBOA conferred a survival benefit regardless of compression location.

Substance use patterns and awareness of biomedical HIV prevention strategies among sexual and gender minority men in Canada.

Sexual and gender minority men (SGMM) who use drugs are frequently cited as at-risk for HIV. Fortunately, biomedical prevention can greatly reduce transmission, provided individuals are aware of and interested in the uptake of these strategies. We examined associations between substance use patterns and biomedical prevention among SGMM in Canada. Latent class analysis identified patterns of substance use. Demographic-adjusted logistic regression models assessed the associations between latent classes and key biomedical prevention indicators. Among 669 participants living with HIV (PLWH) and 7,184 HIV-negative participants, six substance use classes characterized "limited" (46.0%; infrequent/low use of drugs), "common" (31.9%; alcohol, cannabis, and tobacco), "club" (5.2%; alcohol, cocaine, and psychedelics), "sex" (4.8%; alcohol, crystal methamphetamine, GHB, poppers, and erectile drugs), "prescription" (11.0%; alcohol and prescription drugs), and "polydrug" (1.1%; most drugs) use. HIV-negative men in the "prescription" and "sex" substance use classes were more likely to know about the preventive benefits of HIV treatment. All non-"limited use" HIV-negative men were more likely to report interest in taking pre-exposure prophylaxis (PrEP). For PLWH, substance use patterns were not associated with detectable viral loads or treatment awareness. While PLWH exhibited high levels of undetectability and treatment awareness regardless of substance use class, a variety of substance use patterns were associated with increased awareness, interest, and uptake of risk management strategies among HIV-negative participants.

Acute Kidney Injury With Ventricular Assist Device Placement: National Estimates of Trends and Outcomes.

RATIONALE & OBJECTIVE: Ventricular assist devices (VADs) are used for end-stage heart failure not amenable to medical therapy. Acute kidney injury (AKI) in this setting is common due to heart failure decompensation, surgical stress, and other factors. Little is known about national trends in AKI diagnosis and AKI requiring dialysis (AKI-D) and associated outcomes with VAD implantation. We investigated national estimates and trends for diagnosed AKI, AKI-D, and associated patient and resource utilization outcomes in hospitalizations in which implantable VADs were placed. STUDY DESIGN: Cohort study of 20% stratified sample of US hospitalizations. SETTING & PARTICIPANTS: Patients who underwent implantable VAD placement in 2006 to 2015. EXPOSURE: No AKI diagnosis, AKI without dialysis, AKI-D. OUTCOMES: In-hospital mortality, length of stay, estimated hospitalization costs. ANALYTICAL APPROACH: Multivariate logistic and linear regression using survey design methods to account for stratification, clustering, and weighting. RESULTS: An estimated 24,140 implantable VADs were placed, increasing from 853 in 2006 to 3,945 in 2015. AKI was diagnosed in 56.1% of hospitalizations and AKI-D occurred in 6.5%. AKI diagnosis increased from 44.0% in 2006 to 2007 to 61.7% in 2014 to 2015; AKI-D declined from 9.3% in 2006 to 2007 to 5.2% in 2014 to 2015. Mortality declined in all AKI categories but this varied by category: those with AKI-D had the smallest decline. Adjusted hospitalization costs were 19.1% higher in those with diagnosed AKI and 39.6% higher in those with AKI-D, compared to no AKI. LIMITATIONS: Administrative data; timing of AKI with respect to VAD implantation cannot be determined; limited pre-existing chronic kidney disease ascertainment; discharge weights not derived for subpopulation of interest. CONCLUSIONS: A decreasing proportion of patients undergoing VAD implantation experience AKI-D, but mortality among these patients remains high. AKI diagnosis with VAD implantation is increasing, possibly reflecting changes in AKI surveillance, awareness, and coding.

A Traumatic Pulseless Electrical Activity Model: Mortality Increases With Hypovolemia Time.

BACKGROUND: There currently are no well-defined animal models for traumatic pulseless electrical activity (PEA). Our objective was to develop a swine model of traumatic PEA that would be useful for laboratory research where mortality is an outcome of interest. In this pilot study, we hypothesized that animals that remained in PEA without intervention for a longer period would have increased mortality. MATERIALS AND METHODS: Sixteen Yorkshire swine were alternately allocated to either 5 or 10 min of traumatic PEA without intervention. After the nonintervention period, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support (ALS) for an additional 10 min. Hemodynamic and laboratory values are reported for baseline, posthemorrhage, end of BLS, and end of ALS periods. RESULTS: Mortality in the 10-min PEA group (100%) was higher than the 5-min group (38%) (P = 0.03). Animals in the 5-min group had improved aortic diastolic blood pressure, coronary perfusion pressure, and end-tidal CO2 at the end of both the BLS (P = 0.02, 0.002, and 0.02, respectively) and ALS (P = 0.009, 0.005, and 0.008, respectively). The 10-min animals had increased hyperkalemia at the end of the BLS (P = 0.004) and ALS (P = 0.005) periods. All animals in the 10-min group developed ventricular fibrillation (VF) and 38% of the 5-min animals developed VF (P = 0.03). CONCLUSIONS: In our pilot study of traumatic PEA in a swine model, a shorter period of nonintervention resulted in increased survival, improved hemodynamics during resuscitation, decreased hyperkalemia, and less incidence of conversion to VF arrest.

Effect of concomitant mitral valve procedures for severe mitral regurgitation during left ventricular assist device implantation.

The effect of performing a concomitant mitral valve procedure (MVP) during continuous-flow left ventricular assist device (CF-LVAD) implantation has been reported for patients with moderate-to-severe mitral regurgitation (MR), but moderate MR is less of a clinical concern for CF-LVAD patients. There is a paucity of reports focusing on patients with severe MR. Thus, the purpose of this study was to analyze the effect of performing a concomitant MVP during CF-LVAD implantation in patients with severe preoperative MR. Between November 2003 and March 2016, 526 patients underwent primary implantation of a CF-LVAD at our center. Patients with severe MR who underwent a concomitant MVP were compared to those who did not in regard to overall survival, perioperative complications, postoperative echocardiography data, bridge-to-transplantation success, and CF-LVAD explantation. Of the 108 patients with severe MR, 26 underwent a concomitant MVP and 82 did not. These groups showed no difference in survival (p = 0.61). Additionally, the two groups had similar rates of postoperative right heart failure (p = 0.69) and readmissions (p = 0.42). The 24-month follow-up echocardiography results were also similar. Furthermore, the groups showed no difference in bridge-to-cardiac transplantation success (30.0% vs 25.0%, p = 0.80) or CF-LVAD explantation rates (0.0% vs 0.0%. p = 1.0). Our findings suggest that patients with severe MR who undergo a MVP during CF-LVAD implantation do not have superior outcomes to those who do not. However, assessments of other outcomes may show some benefits to performing concomitant MVPs.

Outcomes in patients who underwent a concomitant tricuspid valve procedure during left ventricular assist device implantation.

BACKGROUND: Study findings have been inconsistent regarding whether a concomitant tricuspid valve replacement or repair performed concurrently with continuous-flow left ventricular assist device (CF-LVAD) implantation has additive clinical benefit in patients with severe tricuspid valve regurgitation (TR). AIM OF STUDY: To determine the effect of performing a concomitant tricuspid valve procedure (TVP) at the time of CF-LVAD implantation on patient outcomes. METHODS: We retrospectively reviewed our single-institution experience in 526 patients who underwent primary implantation of a CF-LVAD between November 2003 and March 2016. We identified 59 (11.2%) patients who had severe TR at the time of implantation and analyzed the effect of performing a concomitant TVP at the time of CF-LVAD implantation on the rate of survival, incidence of postoperative right heart failure (RHF), recurrence of TR, and incidence of 30-day readmission. RESULTS: We did not observe a significant difference in the overall survival rate (P = .51), incidence of postoperative RHF (P = .26), or recurrence of TR (P = .73) between patients with severe TR who underwent a TVP and those who did not at the time of CF-LVAD implantation. However, the incidence of 30-day readmission was significantly lower in patients who underwent a TVP than in those who did not (P = .002). CONCLUSIONS: Performing a concomitant TVP at the time of CF-LVAD implantation did not improve patient outcomes but reduced the incidence of 30-day readmission.