Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities.

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time.

The Disease Triangle of Chestnut: A review of host, pathogen, and environmental interactions of chestnuts cultivated in the eastern United States.

Chestnuts, the edible seeds of the genus Castanea, are a perennial food crop closely tied to the global migration of humans throughout history and have recently been gaining popularity in agriculture and forest restoration in eastern North America. Cultivation of chestnuts yields nutritionally balanced food while fostering economic development, food security, and environmental health. However, diseases and insect pests threaten successful ecological restoration and food production. In this review we explore conditions affecting chestnuts in the eastern United States through the lens of the disease triangle. A "host" in the disease triangle is not merely a single tree, but a tree including its constituent population of fungal endophytes. Chestnut trees are rich with microbial life, and the sustainability of chestnuts in forest and cultivated settings may lie in understanding and manipulating microbial communities to improve plant health and control destructive diseases. To benefit from the ecological and economic potential of chestnuts on the landscape, it may be necessary to select locally adapted chestnut trees, regardless of pedigree, that are resilient against cosmopolitan pathogens. With transport of plants and pathogens throughout the globe, and with landscape level environmental changes over the last century, chestnut trees in the eastern United States (U.S.) are in a unique disease landscape compared to their ancestors. Diseases of economic concern from fungi and fungal-like organisms include chestnut blight (Cryphonectria parasitica) and ink disease (Phytophthora cinnamomi) on American and European chestnuts, oak wilt (Bretziella fagacearum) on all chestnut species, and the emerging diseases of brown rot (Gnomoniopsis smithogilvyi) and chestnut anthracnose (Colletotrichum henanense). The eastern U.S. has experienced profound environmental changes over the 20th century and into the early 21st century. These changes happen to coincide with the demise of the American chestnut in the eastern forest, efforts to re-establish chestnut as a forest species, and the rise in cultivation of multiple chestnut species and hybrids as a culinary crop. Chestnut trees growing in the early 21st century face different environmental circumstances than the American chestnuts of pre-colonial times, including changes in forest composition, rainfall changes and acidification, industrialized agriculture's increased chemical inputs, rising global temperatures, and increased levels of carbon dioxide in the atmosphere. We conclude that chestnut tree species for both forestry and agriculture should be considered based on current fitness, adaptability, and economic and ecological value considering continued dynamics in host and pathogens distributions and anthropogenically driven climatic and edaphic conditions.

Comparison of No-Test Telehealth and In-Person Medication Abortion.

Importance: In the US, access to medication abortion using history-based (no-test) eligibility assessment, including through telehealth and mailing of mifepristone, has grown rapidly. Additional evidence on the effectiveness and safety of these models is needed. Objective: To evaluate whether medication abortion with no-test eligibility assessment and mailing of medications is as effective as in-person care with ultrasonography and safe overall. Design, Setting, and Participants: Prospective, observational study with noninferiority analysis. Sites included 4 abortion-providing organizations in Colorado, Illinois, Maryland, Minnesota, Virginia, and Washington from May 2021 to March 2023. Eligible patients were seeking medication abortion up to and including 70 days' gestation, spoke English or Spanish, and were aged 15 years or older. Exposure: Study groups reflected the model of care selected by the patient and clinicians and included: (1) no-test (telehealth) eligibility assessment and mailing of medications (no-test + mail) (n = 228); (2) no-test eligibility assessment and pickup of medications (no-test + pickup) (n = 119); or (3) in-person with ultrasonography (n = 238). Main Outcomes and Measures: Effectiveness, defined as a complete abortion without the need for repeating the mifepristone and misoprostol regimen or a follow-up procedure, and safety, defined as an abortion-related serious adverse event, including overnight hospital admission, surgery, or blood transfusion. Outcomes were derived from patient surveys and medical records. Primary analysis focused on the comparison of the no-test + mail group with the in-person with ultrasonography group. Results: The mean age of the participants (N = 585) was 27.3 years; most identified as non-Hispanic White (48.6%) or non-Hispanic Black (28.1%). Median (IQR) gestational duration was 45 days (39-53) and comparable between study groups (P = .30). Outcome data were available for 91.8% of participants. Overall effectiveness was 94.4% (95% CI, 90.7%-99.2%) in the no-test + mail group and 93.3% (95% CI, 88.3%-98.2%) in the in-person with ultrasonography group in adjusted models (adjusted risk difference, 1.2 [95% CI, -4.1 to 6.4]), meeting the prespecified 5% noninferiority margin. Serious adverse events included overnight hospitalization (n = 4), blood transfusion (n = 2), and emergency surgery (n = 1) and were reported by 1.1% (95% CI, 0.4%-2.4%) of participants, with 3 in the no-test + mail group, 3 in the in-person with ultrasonography group, and none in the no-test + pickup group. Conclusions and Relevance: This prospective, observational study found that medication abortion obtained following no-test telehealth screening and mailing of medications was associated with similar rates of complete abortion compared with in-person care with ultrasonography and met prespecified criteria for noninferiority, with a low prevalence of adverse events.

Does repetitive transcranial magnetic stimulation improve cognitive function in age-related neurodegenerative diseases? A systematic review and meta-analysis.

OBJECTIVE: High-frequency, repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex (DLPFC) is widely used in research to promote neuroplasticity and cognitive enhancement. RTMS is a promising intervention to tackle cognitive decline in people with age-related neurodegenerative diseases. However, there is currently no systematic evidence examining the effects of DLPFC-targeted, high-frequency rTMS on cognitive function in this population. The aim of this systematic review was to evaluate the efficacy and moderators of this treatment intervention. METHODS: A comprehensive literature search of five electronic databases was performed to identify articles published before October, 2022. Following PRISMA guidelines, the identified articles were screened, data was extracted, and the methodological quality was assessed using the Cochrane tool, Risk of Bias 2. Meta-analyses were performed using R Studio (v.4.1.2). RESULTS: Sixteen studies involving 474 participants met the inclusion criteria, of which 8 studies measured global cognitive function. The results from the random-effects meta-analysis showed rTMS significantly improved global cognitive function relative to control groups shown by a large, significant effect size (g = 1.39, 95% CI, 0.34-2.43; p = 0.017). No significant effects were found between subgroups or for individual cognitive domains. CONCLUSIONS: High-frequency rTMS, targeted over the DLPFC, appears to improve global cognitive function in people with age-related neurodegenerative diseases. However, these results should be interpreted with caution due to the small number of studies included, and high between-study heterogeneity.

Role of Serial Phlebotomy in the Management of Blunt Solid Organ Injury in Adults.

BACKGROUND: The management of blunt spleen and liver trauma has become increasingly nonoperative. There is no consensus on timing or duration of serial hemoglobin and hematocrit monitoring in this patient population. OBJECTIVE: This study examined the clinical utility of serial hemoglobin and hematocrit monitoring. We hypothesized that most interventions occur early in the hospital course, based on hemodynamic instability or physical examination findings rather than serial monitoring. METHODS: We conducted a retrospective cohort study of adult trauma patients with blunt spleen or liver injury from November 2014 through June 2019 at our Level II trauma center. Interventions were classified as no intervention, surgical intervention, angioembolization, or packed red blood cell transfusion. Demographics, length of stay, total blood draws, laboratory values, and clinical triggers preceding intervention were reviewed. RESULTS: A total of 143 patients were studied, of whom 73 (51%) received no intervention, 47 (33%) received an intervention within 4 hr of presentation, and 23 (16%) had interventions beyond 4 hr. Of these 23 patients, 13 received an intervention based on phlebotomy results alone. Most of these patients (n = 12, 92%) received blood transfusion without further intervention. Only one patient underwent operative intervention based on serial hemoglobin results on hospital day 2. CONCLUSION: The majority of patients with these injury patterns either require no intervention or declare themselves promptly after arrival. Serial phlebotomy after initial triage and intervention may add little value in the management of blunt solid organ injury.

First report of Colletotrichum henanense causing anthracnose on Chinese chestnut in the United States.

Culinary chestnut production in the United States (US) is a rapidly growing industry supporting fresh market and value-added industries. An estimated 200-400 new acres of chestnuts are planted every year in the US, with most growers east of the Rocky Mountains planting Chinese chestnut (Castanea mollissima) or Chinese chestnut hybrids. In 2018, Ohio producers of Chinese chestnut reported losses of up to 80% to blossom end rot. Symptoms were like those reported by Fowler and Berry (1958), including black spots on the chestnut shell, often at the stylar end, and blackening of the kernels. Spots covered 1-100% of the kernel, however, no signs of any pathogen were present on the shell or kernel. In 2020, cankers that were brown/black in color, sunken, and ~1 cm in length were observed on 1-yr twigs of chestnut seedlings from a nursery operation on the same farm from which the symptomatic kernels were observed. In some seedlings, distal portions of the twigs died, while in other seedlings only shoots and leaves within the cankered areas died. Black acervuli were observed erupting from the cankers. Colletotrichum spp. were isolated and cultured on potato dextrose agar from surface-sterilized tissue from kernel lesions (MLI246-21 to MLI249-21) and twig cankers (MLI250-21 and MLI251-21). All isolates produced grey aerial mycelia, pink sporodochia, and cylindrical conidia with rounded ends ranging in size from 12-20 um long by 5-8 um wide. Isolates were preliminarily identified as belonging to the Colletotrichum gloeosporioides species complex (CGSC). The glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, ß-tubulin (TUB2) gene, and the intergenic spacer ApMat were amplified from genomic DNA and sequenced (Dowling et al. 2020). These genes are suitable for identifying species within the CGSC (Eaton et al. 2021). Sequences were submitted to the GenBank database (GAPDH OL687148 to OL687153, TUB2 OL741624 to OL741629 and ApMAT OL695914 to OL695919). BLASTn queries of NCBI GenBank showed that the GAPDH, TUB2, and ApMat sequences from all isolates had 98%, 98% and 99% identity with C. henanense isolates MT513015.1, MT513080.1, and MT512917.1 from apple (Martin et al. 2021). Representative isolates were used to demonstrate Koch's postulates and confirm pathogenicity on kernels (MLI246-21 and MLI249-21) and twigs (MLI250-21). Developing chestnuts in burs (n=4 per isolate) were gathered from the field and surface-sterilized with 70% ethanol. Nuts (n=12 per isolate) inside burs were inoculated by injecting 50uL of inoculum (~1.0 x 106 conidia/mL) directly into each kernel with a hypodermic needle and sterile syringe. Burs were incubated at room temperature in a moist chamber for 14 days. One-year-old seedlings (n=6) grown in containers were used for twig inoculations. Twig nodes (one/seedling) were surface sterilized with 70% ethanol and inoculated by wounding the stem with a sterile probe and dropping 100uL of inoculum into each wound. Seedlings were incubated in a glass house for 60 days and monitored daily for symptom development. Nuts (n=9) and twigs (n=3) were inoculated with sterile water using the same inoculation and incubation conditions to serve as negative controls. Inoculated kernels developed characteristic brown/black lesions at the wound site and inoculated twigs developed brown/black, slightly sunken cankers with acervuli. No symptoms developed on the control kernels or twigs. Fungi with the same colony, conidial, and molecular characteristics as C. henanense were re-isolated from inoculated kernels and twigs. Blossom end rot caused by Glomerella cingulata has been reported on chestnut kernels in Georgia (Fowler and Berry 1958), but this is the first report of C. henanense causing rot on kernels and twigs in the US. Since 2018, C. henanense has been isolated from infected nuts received from commercial orchards in Pennsylvania, Missouri, and Alabama. We propose to retire the name "blossom end rot" for the symptoms found in kernels and replace it with the name "chestnut anthracnose" for this disease that affects both twigs and kernels of Chinese chestnut.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Harmonizing Cigar Survey Data Across Tobacco Centers of Regulatory Science, Center for Tobacco Products, and Population Assessment of Tobacco and Health Studies: The Cigar Collaborative Research Group.

INTRODUCTION: Cigars are a popular tobacco product of choice for youth and young adults. Despite growing interest in cigar research, there are gaps in the available literature limiting an ability to set evidence-based policies. Too small research samples, the heterogeneity of types of cigars when asking a single question about use, makes analyzing data difficult. Given the Food and Drug Administration's (FDA's) authority granted in 2016 to regulate cigars, and its popularity, data to better understand use and preference for cigars will help FDA set appropriate regulatory policies. METHODS: We harmonized cigar survey data previously collected by five independent tobacco regulatory science survey research projects. Data supplying participants included three Tobacco Centers of Regulatory Science, one Center for Tobacco Products grantee, and data from Population Assessment of Tobacco and Health (PATH) study's public use dataset. RESULTS: Analyzing 92 data variables from across five studies, and applying a rigorous data harmonization protocol, we report findings on 24 key cigar use variables. The step by step protocol for harmonizing is presented. Selected findings showing strict reproducibility across all five studies reveal youth 17-19 years at highest risk for cigar initiation; relative reproducibility shows males more likely to try cigars than females but with significant differences in magnitude across studies; and areas of inconsistent reproducibility are revealed when evaluating brand preferences. CONCLUSION: Harmonizing data from multiple sources fosters a broader view of the robustness and generalizability of survey data than that from a single source. These observations raise awareness to look for the highest degree of reproducibility among and across data sources to inform policy. IMPLICATIONS: Harmonizing data from discrete datasets provides insights into cigar initiation and use and is presented showing opportunities, challenges, and solutions. Comparing observational data from PATH and four independent research studies provides a best-practices approach and example of data synthesis for the tobacco research community. The dataset of five studies offers a look at the degree of confidence in analyzing harmonized survey results. Variable conclusions raise the need to strive for the highest degree of reproducibility, to best understand the behaviors of cigar users, and allow for the future development of the most effective interventions to alter tobacco use patterns.

Low-dose whole thorax radiation therapy for COVID-19 pneumonia: inpatient onboarding process for a randomized controlled trial.

BACKGROUND: The mortality of the SARS-CoV-2 virus (COVID-19) has been associated with a pulmonary inflammatory response resulting in hypoxemia and rapid clinical decline. PREVENT is an ongoing prospective multicenter Phase II randomized controlled trial where patients hospitalized with COVID-19 pneumonia are randomized to low dose radiation therapy (RT) versus control (clinicaltrials.gov, NCT04466683). We describe the inpatient onboarding process of the center contributing the largest number of patients to this trial. MATERIALS AND METHODS: COVID-19 hospital admissions were attained by the clinical research manager and radiation oncologist daily. Text message contact was made with infectious disease, critical care, and nursing staff with reciprocal discussion of the trial protocol and approval for virtual consulting of the patient. Witnessed informed consent was obtained first by telephone and later in person. Simulation and treatment (performed without a computer plan) was performed on a linear accelerator with one personal protective equipment-protected therapist moving in and out of the treatment room, and a second therapist manning the console. Following on-site dose calculation by physics, the radiation oncologist approved the fields prior to treatment delivery. RESULTS: Between August 28, 2020 and October 6, 2020, the first 10 enrolled patients on this multicenter trial were randomized and treated at our institution; no team member (research staff, radiation oncology) contracted COVID-19 while employing this protocol. CONCLUSION: This represents the first published protocol to address efficient and safe recruitment of COVID-19 patients for a radiation oncology trial, serving as a model for conducting recruitment of COVID-19 patients for clinical trials.

Evaluation of Region of Interest Digital Cytology Compared to Light Microscopy for Veterinary Medicine.

Digital microscopy (DM) has been employed for primary diagnosis in human medicine and for research and teaching applications in veterinary medicine, but there are few veterinary DM validation studies. Region of interest (ROI) digital cytology is a subset of DM that uses image-stitching software to create a low-magnification image of a slide, then selected ROI at higher magnification, and stitches the images into a relatively small file of the embedded magnifications. This study evaluated the concordance of ROI-DM compared to traditional light microscopy (LM) between 2 blinded clinical pathologists. Sixty canine and feline cytology samples from a variety of anatomic sites, including 31 cases of malignant neoplasia, 15 cases of hyperplastic or benign neoplastic lesions, and 14 infectious/inflammatory lesions, were evaluated. Two separate nonblinded adjudicating clinical pathologists evaluated the reports and diagnoses and scored each paired case as fully concordant, partially concordant, or discordant. The average overall concordance (full and partial concordance) for both pathologists was 92%. Full concordance was significantly higher for malignant lesions than benign. For the 40 neoplastic lesions, ROI-DM and LM agreed on general category of tumor type in 78 of 80 cases (98%). ROI-DM cytology showed robust concordance with the current gold standard of LM cytology and is potentially a viable alternative to current LM cytology techniques.

Stress Mitigation Strategies for Trauma Nurses: A Case Study.

Trauma nurses encounter multiple intense stressors on a regular basis. These nurses not only treat the injured patient following a traumatic event but then interact with family members who are also impacted by the event. Repeated experiences with significant trauma can have cumulative effects and negatively impact these nurses and the entire trauma team. Professional nursing associations make recommendations promoting wellness, and health care organizations implement wellness programs that foster and support mind, body, and spirit health. Individuals cope with and respond to stress in different ways, dependent on their unique backgrounds, beliefs, and support systems. Because of these differences, it is important for organizations to offer various ways for nurses and team members to process their reactions and use effective strategies to effectively manage stress. The organization highlighted in this case study offers several stress mitigation programs and techniques designed to support the overall health of trauma nurses and restore their emotional well-being, so that they are best able to care for their injured patients.

Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

OBJECTIVES: To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope. METHODS: MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest. RESULTS: Of 3188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder. CONCLUSIONS: There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.

Reassessment of Cardiac Function and Implantable Cardioverter-Defibrillator Use Among Medicare Patients With Low Ejection Fraction After Myocardial Infarction.

BACKGROUND: Guidelines recommend that patients with low ejection fraction (EF) after myocardial infarction (MI) have their EF reassessed 40 days after MI for implantable cardioverter-defibrillator (ICD) candidacy. This study examines rates of EF reassessment and their association with 1-year ICD implantation in post-MI patients with low EF. METHODS: We examined rates of postdischarge EF reassessment and ICD implantation among 10 289 Medicare-insured patients ≥65 years of age with an EF≤35% during the index MI admission from January 2007 through September 2010 in ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines). Multivariable Cox models tested the association between time-dependent EF reassessment and 1-year ICD implantation, stratified by revascularization status during the index MI admission. RESULTS: Among patients with EF ≤35% during the index MI admission, 66.8% (95% confidence interval [CI], 65.9-67.8) had EF reassessment within the next year. Revascularized patients were more likely to have EF reassessment (76.9% [95% CI, 75.8-78.0)] versus 53.7% [95% CI, 52.2-55.2]; P<0.001) and had shorter times to EF reassessment (median, 67 versus 84 days; P<0.001) than nonrevascularized patients. Among patients with EF reassessment, only 11% received an ICD within 1 year. Reassessment of EF was associated with a higher likelihood of ICD implantation for both revascularized (unadjusted, 12.1% versus 2.4%, P<0.001; adjusted hazard ratio, 10.6, 95% CI, 7.7-14.8) and nonrevascularized (unadjusted, 10.0% versus 1.7%, P<0.001; adjusted hazard ratio, 6.1, 95% CI, 4.1-9.2) patients. CONCLUSIONS: In US practice, EF reassessments are commonly performed among patients with MI with an initially reduced EF. Although 1-year EF reassessment is associated with increased likelihood of ICD implantation, 1-year ICD implantation rates remain very low even among patients with EF reassessment, regardless of revascularization status.