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Сърдечно-съдовата медицина през 2022 г.: най-добрите 10 статии за спешните състояния в кардиологията и исхемичната болест на сърцето

The prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implantation remains a challenge. Recently, risk scores were derived from analysis of the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) data, the EUROMACS-RHF, and the modified postoperative EUROMACS-RHF. The authors assessed the performance characteristics of these 2 risk score formulations in a continuous-flow LVAD cohort at their institution.A retrospective, observational study.At a tertiary-care academic medical center.Adult patients who underwent durable LVAD implantation between 2015 and 2018.None MEASUREMENTS AND MAIN RESULTS: Early post-LVAD RHF was defined as follows: (1) need for right ventricular assist device, or (2) inotropic or inhaled pulmonary vasodilator support for ≥14 postoperative days. The authors used logistic regression and examined receiver operating characteristic (ROC) curves to evaluate the ability of the 2 risk scores to distinguish between outcome groups. A total of 207 patients met the inclusion criteria. Of the patients, 16% developed RHF (33/207). The EUROMACS-RHF score was not predictive of RHF in the authors' cohort (odds ratio [OR] 1.25; 95% CI [0.99-1.60]; p = 0.06), but the postoperative EUROMACS-RHF CPB score was significantly associated (OR 1.38; 95% CI [1.03-1.89]; p = 0.03). The scores had similar ROC curves, with weak discriminatory performance: 0.601 (95% CI [0.509-0.692]) and 0.599 (95% CI [0.505-0.693]) for EUROMACS-RHF and postoperative EUROMACS-RHF, respectively.In the authors' single-center retrospective analysis, the EUROMACS-RHF risk score did not predict early RHF. An optimized risk score for the prediction of RHF after LVAD implantation remains an urgent unmet need.

Delusions are aberrant beliefs that are maintained in the face of conflicting evidence. Promising mechanistic frameworks are suggested by cognitive control theory which delineates detection and resolution stages of conflict processing and an augmented dual-process framework which proposes acquiescence to intuitive beliefs despite awareness that they conflict with rationality. We measured intuitive processes using one-shot decision-making and analytic processes using cognitive reflection (CRT) and Stroop tasks. Higher intuitive strength and lower CRT/Stroop conflict resolution was associated with increased acquiescence. Importantly, those less prone to delusions were more likely to override a strong irrational intuition as their analytic strength (on CRT and Stroop) increased; however, in those high on delusion-proneness, analytic strength predicted an increased likelihood of acquiescing to intuition. These findings highlight an interactive role of intuitive and analytic processes such that those prone to delusions may tend to rally cognitive resources to rationalize their intuitions.

This article examines organizational-level outcomes achieved during a technical assistance (TA) initiative designed to increase the capacity of local health departments (LHDs) to prevent youth violence (YV) via a multisectoral approach. This effort was designed to address the knowledge gap regarding how to provide effective TA to LHDs, specifically in YV. Twelve communities with high rates of YV were selected to participate using a multistage process. TA provided to LHD representatives (and other community partners) included monthly calls with TA specialists, group online learning events, community-of-practice calls, and access to an online portal offering additional resources. Data sources were used to determine the extent to which communities achieved the initiative’s intended outcomes, including increased infrastructure to support youth violence prevention (YVP) at LHDs and the creation of community-wide violence prevention plans. Data sources included an online TA tracking system, annual semistructured group interviews, and point-of-contact surveys. While results indicated variation in TA uptake across sites, several target outcomes were achieved including increased representation and engagement of diverse perspectives in local YVP efforts and strengthened infrastructure and integration of YVP at LHDs. Findings highlight the importance of supporting LHDs to align YVP work with other priorities and funded activities, building a larger role for leadership in providing organizational support for YV, supporting the development of multisector coalitions or partnerships to decrease silos among different sectors focused on similar populations or communities. Implications from this initiative suggest that LHDs can be supported to convene local, multisector YVP efforts, which can be sustained if local YVP infrastructure is enhanced.

Cardiogenic shock (CS) is the final common pathway of impaired cardiovascular performance that results in ineffective forward cardiac output producing clinical and biochemical signs of organ hypoperfusion. CS represents the most common cause of shock in the cardiac intensive care unit (CICU) and accounts for a substantial proportion of CICU patient deaths. Despite significant advances in revascularization techniques, pharmacologic therapeutics and mechanical support devices, CS remains associated with a high mortality rate. Indeed, the prevalence of CS within the CICU appears to be increasing. CS can be differentiated as phenotypes reflecting different metabolic, inflammatory, and hemodynamic profiles, depending also on anatomic substrate and congestion profile. Future prospective studies and clinical trials may further characterize these phenotypes and apply targeted intervention for each phenotype and SCAI SHOCK stage rather than a one-size-fits-all approach. Overall, there are 8 key concepts of CS; 1) the mortality associated with CS; 2) Shock attributed to AMI may be declining in both incidence and associated mortality; 3) providers should think about hemodynamic, metabolic, inflammation and cardiac function in totality to assess CS; 4) CS is a dynamic process; 5) no randomized trials evaluating use of the PAC in patients with CS; 6) most data supporting neosynephrine as first line agent in CS; 7) most registries suggest that almost half of CS patients do not have any mechanical support, and the vast majority of the remainder utilize the IABP; and 8) patients with AMI CS should receive emergent PCI of the culprit vessel.

The syndrome of cardiogenic shock (CS) manifests with a spectrum of severity. Categorizing CS into clinical stages may enable improved risk stratification and patient selection for therapies. We sought to determine whether the new 2019 Society for Cardiovascular Angiography and Interventions (SCAI)

The updated UNOS heart transplantation allocation system, implemented in 10/2018, gives priority to pts treated with non-dischargeable mechanical circulatory support (MCS) devices while awaiting heart transplant. Whether there has been a change in temporary MCS use in cardiac intensive care units (

The prevalence and prognosis of NSTEMI patients who require invasive mechanical ventilation (IMV) and non-invasive ventilation (NIV) are unknown We conducted a retrospective cohort study of patients with NSTEMI using the National Inpatient Sample between 2002 and 2014. The exposure variable was IMV

We leveraged a clinical pharmacokinetic (PK)/pharmacodynamics (PD)/efficacy relationship established with an oral phosphatidylinositol 3-kinase (PI3K)

There are many challenges when an innovation (i.e., a program, process, or policy that is new to an organization) is actively introduced into an organization. One critical component for successful implementation is the organization's readiness for the innovation. In this article, we propose a practical implementation science heuristic, abbreviated as R= MC2 . We propose that organizational readiness involves: 1) the motivation to implement an innovation, 2) the general capacities of an organization, and 3) the innovation-specific capacities needed for a particular innovation. Each of these components can be assessed independently and be used formatively. The heuristic can be used by organizations to assess readiness to implement and by training and technical assistance providers to help build organizational readiness. We present an illustration of the heuristic by showing how behavioral health organizations differ in readiness to implement a peer specialist initiative. Implications for research and practice of organizational readiness are discussed.

Clinical investigations of shock in CICUs have focused on cardiogenic shock (CS) in pts with acute MI. Few studies have evaluated the full spectrum of shock admitted to contemporary CICUs. The CCCTN is an investigator-initiated multicenter network of 16 advanced CICUs in the US & Canada. During a 2

With improvements in acute coronary syndromes (ACS) treatment, routine triage of many pts with ACS to the cardiac intensive care unit (CICU) may no longer be necessary. The Critical Care Cardiology Trials Network (CCCTN) is an investigator-initiated multicenter network of 16 advanced CICUs in the

Historically, there has been considerable variability in how formative evaluation has been conceptualized and practiced. FORmative Evaluation Consultation And Systems Technique (FORECAST) is a formative evaluation approach that develops a set of models and processes that can be used across settings and times, while allowing for local adaptations and innovations. FORECAST integrates specific models and tools to improve limitations in program theory, implementation, and evaluation. In the period since its initial use in a federally funded community prevention project in the early 1990s, evaluators have incorporated important formative evaluation innovations into FORECAST, including the integration of feedback loops and proximal outcome evaluation. In addition, FORECAST has been applied in a randomized community research trial. In this article, we describe updates to FORECAST and the implications of FORECAST for ameliorating failures in program theory, implementation, and evaluation.

Sense of community may play an important role in the undergraduate transfer student experience by encouraging academic and social success. This cross-sectional study assessed sense of community in the transfer experiences of 53 students majoring in science, technology, engineering, math (STEM) subjects. Sense of community, participation, and GPA were analyzed using moderated regression analysis, t tests, and cross-tabulations. Results suggest that students who reported high participation in STEM activities and strong sense of community performed better academically than students who reported high participation and low sense of community. Further, results highlight discrepancies between students’ actual and ideal sense of community (particularly for female and non-White students), as well as greater importance placed upon sense of community at the post-transfer institution compared to the pre-transfer institution. This study suggests the need to examine sense of community in the transfer process. Results have implications for higher education literatures and for research and practice aimed at helping individuals engage with environments.

Bringing evidence based programs to scale was a major initial impetus for the development of the Interactive Systems Framework for Dissemination and Implementation (ISF). The ISF demonstrates the importance of the Support System in facilitating the uptake of innovations in the community (the Delivery System). Two strategies that members of the Support System commonly use are training-of-trainers (TOT) models and technical assistance (TA). In this article, we focus on the role of the Support System in bringing evidence-based programs (EBPs) to scale in the Delivery System using a case example, with special attention on two strategies employed by Support Systems-training-of-trainers (TOT) and proactive technical assistance. We then report on findings from a case example from the Promoting Science Based Approaches to Teen Pregnancy Prevention project that furthers our conceptualization of these strategies and the evidence base for them. We also report on the limitations in the literature regarding research on TOTs and proactive TA and provide suggestions for future research on TOTs and proactive TA that will enhance the science and practice of support in the ISF.

OBJECTIVE Certified Peer Specialist training initiatives leading to paid peer support positions are increasing nationally. This longitudinal study examines a comprehensive set of outcomes associated with such an initiative undertaken in Pennsylvania beginning in 2004. METHODS Certified Peer Specialist Training participants in three regions of Pennsylvania responded to a 60-item, multiple choice knowledge test based on the Certified Peer Specialist training curriculum. Additionally, these individuals were asked to provide permission to be contacted up to one year after completing the program to obtain employment information related to their experience as a certified peer specialist. RESULTS Ninety-seven percent of the trainees successfully completed the program with a 22% increase in knowledge. Eighty-two percent were working one year later. Peer specialists were very satisfied with their employment; felt accepted by co-workers and reported receiving good, but infrequent supervision. CONCLUSIONS The results suggest that these initiatives can be successfully implemented, although greater attention is needed to ensure that new jobs are being created for trainees and that they are being properly supervised like all other employees.

Despite the availability of many evidence-based prevention interventions (EBIs), gaps exist in bringing these programs into widespread practice. Technical assistance (TA) is a strategy for enhancing the readiness of practitioners to implement EBIs. Although many millions of dollars are spent on TA each year, there is little consensus about what the essential features of TA are and how to provide TA with quality. A broad-based research synthesis methodology was used for analyzing the current evidence base for TA using three frames: (1) applying the Getting To Outcomes (GTO) model for categorizing evidence on TA that specifies tasks for planning, implementing, and evaluating TA; (2) understanding the relevance of a successful relationship between the TA provider and TA recipient; and (3) considering the extent to which TA fits the life cycle needs of the preventive intervention. Results indicated that an explicit model or organizing framework is rarely used to plan, implement, and/or evaluate TA; specific TA tasks performed vary widely across studies; TA is rarely delivered to recipients who are seeking to sustain innovations subsequent to adoption and implementation; however, there is systematic attention to relationships and relationship-building. Overall, this synthesis indicates that the extent to which TA is being delivered systematically is limited. We suggest that funders and other stakeholders develop and implement standards for TA quality in order to ensure that many of these limitations are addressed. Electronic supplementary material The online version of this article (doi:10.1007/s11121-016-0636-5) contains supplementary material, which is available to authorized users.

Our policy of conducting biotransformation studies with extended chromatography prior to pharmacokinetic bioanalyses allowed us to quickly detect an unusual, cis/trans metabolite in rat plasma that was inseparable using a short chromatographic method. We caution investigators that short methods invite unknown isobaric metabolites to cause inaccuracies in plasma concentration measurements.

Introduction and hypothesis: Recent data have indicated an increase in the rate of early, confirmed pump thrombosis of the HeartMate II (HMII) left ventricular assist device. Factors related to this increase were not known, but one of the hypotheses was change in clinical management over time. The PREVENT ( PREVEN tion of Heartmate II Pump T hrombosis through Clinical Management) study was designed to evaluate the impact of clinical practices developed to reduce the risk of HMII pump thrombosis. Methods: PREVENT is a prospective, multi-center, single-arm, non-randomized study of up to 300 patients at up to 25 sites. Patient and pump management, including implant technique, anticoagulation, and pump settings are guided by protocol (Table 1). Primary endpoint is incidence of confirmed pump thrombosis at 3 months, with a total follow-up of 6 months. Presented here are the preliminary results from the first 100 subjects enrolled. Results: Median age was 61 years [25-79], 87% were male, and 79% were destination therapy. At implant, 9% were in INTERMACS Profile1, 68% Profiles 2-3, and 22% Profiles 4-7. Preliminary analysis of 90-day outcomes demonstrated an incidence of 1% for confirmed and 2% for suspected thrombosis with a 38% incidence of INTERMACS-defined bleeding. Adherence to the protocol recommendations was as follows: 91% of the pumps were anchored, 97% of the patients were bridged with heparin, median pump speed at 1 month was 9190 [range: 8400-10000], with 93% of the patients having a pump speed > 8600, and 78% of the patients having pump speeds > 9000. Median INR per patient was 2.2 [IQR: 2.0-2.4]. Overall Kaplan-Meier survival was 93%. Conclusions: Preliminary results are encouraging and suggest good adherence to the PREVENT protocol and low rates of pump thrombosis without a resultant increase in bleeding complications. Overall survival after HM II implantation remains excellent.

According to the Interactive Systems Framework for Dissemination and Implementation, implementation is a major mechanism and concern in bridging research and practice. The growing number of implementation frameworks need to be synthesized and translated so that the science and practice of quality implementation can be furthered. In this article, we: (1) use the synthesis of frameworks developed by Meyers et al. (Am J Commun Psychol, 2012) and translate the results into a practical implementation science tool to use for improving quality of implementation (i.e., the Quality Implementation Tool; QIT), and (2) present some of the benefits and limitations of the tool by describing how the QIT was implemented in two different pilot projects. We discuss how the QIT can be used to guide collaborative planning, monitoring, and evaluation of how an innovation is implemented.

An individual or organization that sets out to implement an innovation (e.g., a new technology, program, or policy) generally requires support. In the Interactive Systems Framework for Dissemination and Implementation, a Support System should work with Delivery Systems (national, state and/or local entities such as health and human service organizations, community-based organizations, schools) to enhance their capacity for quality implementation of innovations. The literature on the Support System [corrected] has been underresearched and under-developedThis article begins to conceptualize theory, research, and action for an evidence-based system for innovation support (EBSIS). EBSIS describes key priorities for strengthening the science and practice of support. The major goal of EBSIS is to enhance the research and practice of support in order to build capacity in the Delivery System for implementing innovations with quality, and thereby, help the Delivery System achieve outcomes. EBSIS is guided by a logic model that includes four key support components: tools, training, technical assistance, and quality assurance/quality improvement. EBSIS uses the Getting To Outcomes approach to accountability to aid the identification and synthesis of concepts, tools, and evidence for support. We conclude with some discussion of the current status of EBSIS and possible next steps, including the development of collaborative researcher-practitioner-funder-consumer partnerships to accelerate accumulation of knowledge on the Support System.

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

The serine/threonine specific protein kinase B-Raf is part of the MAPK pathway and is an interesting oncology target. We have identified thieno[2,3-d]pyrimidines as a core scaffold of small molecule B-Raf inhibitors. The SAR of analogs in this series will be described.

CC-223 is an orally active selective mammalian target of rapamycin (mTOR) kinase inhibitor which is currently in clinical development. In biochemical assays CC-223 was highly selective to mTOR over 249 kinases. In cellular assays CC-223 inhibited both mTORC1 and mTORC2 as evidenced by inhibition of pS6RP(Ser 235/236) and pAkt(Ser 473). The current study was aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship, antitumor activity, and mechanism of action of CC-223 in mice with PC3 human prostate cancer tumors. In PK/PD studies with PC3 tumor-bearing mice, CC-223 exhibited a dose-dependent inhibition mTOR pathway biomarkers, pS6RP, and pAkt, which correlated with plasma exposure. Antitumor activity of CC-223 was tested in mice with PC3 tumors of approximately 100-150 mm3 in size. CC-223 consistently exhibited dose-dependent tumor growth inhibition. The minimum dose required to obtain >65% tumor volume reduction compared with vehicle control was 5 mg/kg BID. In addition to showing antitumor activity in smaller tumors, CC-223 also caused the regression or growth delay of larger PC3 tumors. At 10 mg/kg BID, CC-223 caused the regression of tumors, whereas 5 and 1 mg/kg BID slowed tumor growth compared to the vehicle control. The mechanism of action of CC-223 on PC3 tumors was characterized by analyzing tumors for functional markers (proliferation, apoptosis, and blood vessel markers). The number of proliferating cells in CC-223-treated tumors was significantly reduced compared to vehicle control. A significant increase in the number of apoptotic cells and a significant decrease in blood vessel density was observed in CC-223-treated tumors. In conclusion, treatment with the mTOR kinase inhibitor CC-223 significantly inhibited PC3 prostate tumor growth. Significant inhibition of mTOR pathway markers pS6RP and pAkt in CC-223-treated tumors suggests that the observed antitumor activity of CC-223 was mediated through inhibition of both mTORC1 and mTORC2. Maintenance of >80% and >60% biomarker inhibition for pS6 and pAkt, respectively, and plasma levels greater than 0.2 μM through 8 hours twice daily confers good antitumor efficacy in PC3 tumors. Further immunohistochemical data demonstrated that the antitumor activity of CC-223 was not only due to the inhibition of tumor cell proliferation but also due to the increase in apoptosis and antiangiogenic activity of CC-223. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A165. Citation Format: Rama Krishna Narla, Sophie Peng, Jim Gamez, Jason Katz, Julius Apuy, Mehran Moghaddam, Kimberly E. Fultz, Sabita Sankar, Deborah S. Mortensen, Heather K. Raymon. Antitumor activity of mTOR kinase inhibitor CC-223 in a mouse model of prostate cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A165.