The Effect of SGLT2 Inhibitor Therapy on Endothelial Progenitor Cell Function in Patients with Heart Failure.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone-marrow derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of the current study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3±10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of VEGFR-2, CD34 and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (IQR 0.10-0.33) vs. 0.55% (IQR 0.28-0.91), P=0.002; 0.12% (IQR 0.07-0.15) vs. 0.24% (IQR 0.15-0.39), P=0.001, respectively]. EPCs-CFU were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) vs. 79.4 (IQR 25.1-110.25) colonies/106 cells, P=0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in circulating EPCs level and function. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in HF patients.

Approaches for identifying and measuring heteroresistance in azole-susceptible Candida isolates.

Heteroresistance to antifungal agents poses a significant challenge in the treatment of fungal infections. Currently, the absence of established methods for detecting and measuring heteroresistance impedes progress in understanding this phenomenon in fungal pathogens. In response to this gap, we present a comprehensive set of new and optimized methods designed to detect and quantify azole heteroresistance in Candida albicans. Here, we define two primary assays for measuring heteroresistance: population analysis profiling, based on growth on solid medium, and single-cell assays, based on growth in liquid culture. We observe good correlations between the measurements obtained with liquid and solid assays, validating their utility for studying azole heteroresistance. We also highlight that disk diffusion assays could serve as an additional tool for the rapid detection of heteroresistance. These methods collectively provide a versatile toolkit for researchers seeking to assess heteroresistance in C. albicans. They also serve as a critical step forward in the characterization of antifungal heteroresistance, providing a framework for investigating this phenomenon in diverse fungal species and in the context of other antifungal agents. Ultimately, these advancements will enhance our ability to effectively measure antifungal drug responses and combat fungal infections.IMPORTANCEHeteroresistance involves varying antimicrobial susceptibility within a clonal population. This phenomenon allows the survival of rare resistant subpopulations during drug treatment, significantly complicating the effective management of infections. However, the absence of established detection methods hampers progress in understanding this phenomenon in human fungal pathogens. We propose a comprehensive toolkit to address this gap in the yeast Candida albicans, encompassing population analysis profiling, single-cell assays, and disk diffusion assays. By providing robust and correlated measurements through both solid and liquid assays, this work will provide a framework for broader applications across clinically relevant Candida species. These methods will enhance our ability to understand this phenomenon and the failure of antifungal therapy.

Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction.

INTRODUCTION: Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. METHODS: Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. RESULTS: Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels ( P  = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients ( P  = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. CONCLUSION: This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.

Differential platelet activation through an interaction with spike proteins of different SARS-CoV-2 variants.

COVID-19 disease is associated with an increased risk of thrombotic complications, which contribute to high short-term mortality. Patients with COVID-19 demonstrate enhanced platelet turnover and reactivity, which may have a role in the development of thrombotic events and disease severity. Evidence has suggested direct interaction between SARS-CoV-2 and platelets, resulting in platelets activation. Here, we compare the effect of various SARS-CoV-2 spike variants on platelet activation. Engineered lentiviral particles were pseudotyped with spike SARS-CoV-2 variants and incubated with Platelet Rich Plasma obtained from healthy individuals. The pseudotyped SARS-CoV-2 exhibiting the wild-type Wuhan-Hu spike protein stimulated platelets to increase expression of the surface CD62P and activated αIIbß3 markers by 3.5 ± 1.2 and 3.3 ± 0.7 fold, respectively (P = 0.004 and 0.003). The Delta variant induced much higher levels of platelet activation; CD62P expression was increased by 6.6 ± 2.2 fold and activated αIIbß3 expression was increased by 5.0 ± 1.5 fold (P = 0.005 and 0.026, respectively). The Omicron BA.1 and the Alpha variants induced the lowest level of activation; CD62P expression was increased by 1.7 ± 0.4 and 1.6 ± 0.9 fold, respectively (P = 0.003 and 0.008), and activated αIIbß3 expression by 1.8 ± 1.1 and 1.6 ± 0.8, respectively (P = 0.003 and 0.001). The Omicron BA.2 variant induced an increase of platelets activation comparable to the Wuhan-Hu (2.8 ± 1.2 and 2.1 ± 1.3 fold for CD62P and activated αIIbß3 markers, respectively). The results obtained for various COVID-19 variants are in correlation with the clinical severity and mortality reported for these variants.

A novel robotic radiation shielding device for electrophysiologic procedures: A prospective study.

BACKGROUND: A robotic Radiaction Shielding System (RSS) was developed to provide a full-body protection to all medical personnel during fluoroscopy-guided procedures, by encapsulating the imaging beam and blocking scattered radiation. OBJECTIVES: We aimed to evaluate its efficacy in real-world electrophysiologic (EP) laboratory- both during ablations and cardiovascular implantable electronic devices (CIED) procedures. METHODS: A prospective controlled study comparing consecutive real-life EP procedures with and without RSS using highly sensitive sensors in different locations. RESULTS: Thirty-five ablations and 19 CIED procedures were done without RSS installed and 31 ablations and 24 CIED procedures (17 with usage levels ≥70%) were done with RSS. Overall, there was 95% average usage level for ablations and 88% for CIEDs. For all procedures with ≥70% usage level and for all sensors, the radiation with RSS was significantly lower than radiation without RSS. For ablations, there was 87% reduction in radiation with RSS (76%-97% for different sensors). For CIEDs, there was 83% reduction in radiation with RSS (59%-92%). RSS usage did not increase procedure time and radiation time. User feedback showed a high-level of integration in the clinical workflow and safety profile for all types of EP procedures. CONCLUSIONS: For both CIED and ablation procedures the radiation with RSS was significantly lower than without RSS. Higher usage level brings higher reduction rates. Thus, RSS may have an important role in full-body protection to all medical personnel from scattered radiation during EP and CIED procedures. Until more data is available, it is recommended to maintain existing standard shielding.

Testosterone and persistent organic pollutants in East Greenland male polar bears (Ursus maritimus).

Legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) are chemicals that undergo long-range transport to the Arctic. These chemicals possess endocrine disruptive properties raising concerns for development and reproduction. Here, we report the relationship between concentrations of testosterone (T) and persistent organic pollutant (POPs) in 40 East Greenland male polar bears (Ursus maritimus) sampled during January to September 1999-2001. The mean ± standard concentrations of blood T were 0.31 ± 0.49 (mean ± SD) ng/mL in juveniles/subadults (n = 22) and 3.58 ± 7.45 ng/mL in adults (n = 18). The ∑POP concentrations (mean ± SD) in adipose tissue were 8139 ± 2990 ng/g lipid weight (lw) in juveniles/subadults and 11,037 ± 3950 ng/g lw in adult males, respectively, of which Σpolychlorinated biphenyls (ΣPCBs) were found in highest concentrations. The variation in T concentrations explained by sampling date (season), biometrics and adipose tissue POP concentrations was explored using redundancy analysis (RDA). The results showed that age, body length, and adipose lipid content in adult males contributed (p = 0.02) to the variation in POP concentrations. However, although some significant relationships between individual organochlorine contaminants and T concentrations in both juveniles/subadults and adult polar bears were identified, no significant relationships (p = 0.32) between T and POP concentrations were identified by the RDAs. Our results suggest that confounders such as biometrics and reproductive status may mask the endocrine disruptive effects that POPs have on blood T levels in male polar bears, demonstrating why it can be difficult to detect effects on wildlife populations.

Coronary artery disease among patients admitted with atrial fibrillation and chest pain.

INTRODUCTION: Patients who present to the emergency department with chest pain during an episode of atrial fibrillation (AF) impose a clinical challenge regarding the source of pain - being coronary artery disease (CAD) or AF in origin. The aim of this study was to identify clinical, imaging or laboratory markers which can predict significant CAD among patients with an AF episode and chest pain. METHODS: We included 57 consecutive patients admitted to our hospital with AF and chest pain. All patients underwent coronary evaluation. Significant CAD was defined as >50% stenosis in a major coronary artery by coronary angiography or cardiac CT. We compared CAD and non-CAD groups and analyzed risk factorsby regression analysis. RESULTS: Twenty-four patients (42%) were diagnosed with- and 33 patients (58%) without obstructive CAD. In a multivariate analysis of regional wall motion abnormality (RWMA), elevated troponin and hypertension were found to be predictors for CAD [odds ratio (OR), 22.4 (confidence interval (CI), 1.8-272.4; P = 0.02); OR, 5.6 (CI, 1-31.0; P = 0.05) and OR, 21.4 (CI, 1.6-284.6; P = 0.02), respectively]. There were no significant differences regarding the rate of typical chest pain at presentation in the CAD vs. the non-CAD group [13 (54%) vs. 20 (60%), P = 0.374], or in ECG ST-changes [12 (50%) vs.9 (27%), respectively; P = 0.08]. CONCLUSION: In patients who present acutely with chest pain and AF, troponin elevation and RWMA appear to be highly predictive of obstructive CAD, whereas clinical symptoms and ECG changes are not predictive. These findings may be helpful for guiding the management of patients admitted with AF and chest pain.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

BACKGROUND: Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. METHODS: We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. RESULTS: Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. CONCLUSION: Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Simultaneous Noninvasive Detection and Therapy of Atherosclerosis Using HDL Coated Gold Nanorods.

Cardiovascular disease (CVD) is a major cause of death and disability worldwide. A real need exists in the development of new, improved therapeutic methods for treating CVD, while major advances in nanotechnology have opened new avenues in this field. In this paper, we report the use of gold nanoparticles (GNPs) coated with high-density lipoprotein (HDL) (GNP-HDL) for the simultaneous detection and therapy of unstable plaques. Based on the well-known HDL cardiovascular protection, by promoting the reverse cholesterol transport (RCT), injured rat carotids, as a model for unstable plaques, were injected with the GNP-HDL. Noninvasive detection of the plaques 24 h post the GNP injection was enabled using the diffusion reflection (DR) method, indicating that the GNP-HDL particles had accumulated in the injured site. Pathology and noninvasive CT measurements proved the recovery of the injured artery treated with the GNP-HDL. The DR of the GNP-HDL presented a simple and highly sensitive method at a low cost, resulting in simultaneous specific unstable plaque diagnosis and recovery.

Comparison of Factors Associated with Inflammation, Thrombosis, and Platelet Reactivity as well as Turnover between Patients with High versus Low CHA2DS2-VASc without Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF). OBJECTIVES: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA2DS2-VASc score in SR. METHODS: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA. RESULTS: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA2DS2-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA2DS2-VASc group (45, interquartile ratio [IQR] 36-49) vs. 37 (IQR 28-46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7-9.3) vs. 1.6 (IQR 0.78-5.4), P < 0.001; NLR 2.7 (IQR 2.1-3.8) vs. 2.1 (IQR 1.6-2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups. CONCLUSIONS: Patients in SR with high CHA2DS2-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score.

Intravascular leiomyomatosis with cardiac extension: a case report.

BACKGROUND: Intravascular leiomyomatosis (IVL) with intracardiac extension is a rare benign tumour seen exclusively in women, characterized by proliferation of uterine smooth muscle cells through the venous circulation into the inferior vena cava (IVC) and the right heart chambers. CASE SUMMARY: A 47 years old women with history of previous hysterectomy due to myomatosis, presented with nausea, anorexia, and bilateral lower limb swelling over the preceding 2 months. An outpatient abdominal ultrasound discovered a mass in the IVC. Echocardiogram and computed tomography demonstrated a large intravascular mass extending from the pelvis to the right heart chambers. The tumour was completely removed in a concomitant open-heart surgery and laparotomy. Post-operative course was uncomplicated. A month later, the patient was feeling well and in good clinical condition. The histological analysis consisted with IVL. DISCUSSION: Intracardiac leiomyomatosis is a rare clinical condition which requires high index of suspicion. Multimodality imaging is usually required to establish the preoperative diagnosis, although the final diagnosis is achieved with tissue investigation. Complete surgical resection of the tumour is curative and associated with good long-term prognosis.

[COMPLETE ATRIOVENTRICULAR BLOCK DUE TO PULMONARY EMBOLISM].

INTRODUCTION: Pulmonary embolism, a common and potentially fatal clinical condition, occurs when a blood thrombus becomes lodged in the pulmonary vasculature and creates an acute increment in the pulmonary vascular resistance, which, in turn, creates a right ventricular strain. Among the more familiar electrocardiographic manifestations in acute pulmonary embolism is sinus tachycardia, right bundle branch block and ST-T abnormalities in the right precordium leads. Complete heart block or any type of bradycardia is uncommon. In our case report we present an 81 years old woman who was admitted to our institution with acute pulmonary embolism and complete atrioventricular block, which later resolved with appropriate anticoagulation therapy.

Effects of electret coating technology on coronary stent thrombogenicity.

Stent thrombosis (ST) is a catastrophic event and efforts to reduce its incidence by altering blood-stent interactions are longstanding. A new electret coating technology that produces long-lasting negative charge on stent surface could make them intrinsically resistant to thrombosis. We assessed the thrombogenicity of stents using an annular perfusion model with confocal microscopy, and determined the efficacy of electret coating technology to confer thrombo-resistant properties to standard stents. Using an annular perfusion chamber, Bare Metal Stent (BMS), standard uncoated DES (DES), and Electret-coated DES (e-DES) were exposed to human blood under arterial flow conditions. Deposits of fibrinogen and platelets on the stent surface were analyzed using immunofluorescence staining and confocal microscopy. Surface coverage by fibrinogen and platelets and the deposit/aggregate size were quantified using computerized morphometric analysis. The experimental methodology produced consistent, quantifiable results. Area of stent surface covered by fibrinogen and platelets and the average size of the deposits/aggregates were lowest for e-DES and highest on BMS, with DES in the middle. The size of fibrinogen-deposits showed no differences between the stents. The testing methodology used in our study successfully demonstrated that electret coating confers significant antithrombotic property to DES stents. These findings warrant confirmation in a larger study.

Immature platelets in patients with Covid-19: association with disease severity.

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9-8.7) vs. 4.2 (2.73-6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03-21.56), vs 10.9 (IQR 6.79-15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.

Circulating Endothelial Progenitor Cells in Patients with Heart Failure with Preserved versus Reduced Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with a mechanism that appears to involve endothelial dysfunction of the cardiac microcirculation. Endothelial progenitor cells (EPC) are bone marrow derived cells that are able to differentiate into functional endothelial cells and participate in endothelial surface repair. OBJECTIVES: To compare the level and function of EPCs in patients with HFpEF compared with heart failure with reduced ejection fraction (HFrEF) and control subjects. METHODS: We enrolled 21 patients with HFpEF (LVEF ≥ 50%, age 74.5 ± 9.9 years, 43% men, 48% diabetes), 20 patients with HFrEF (LVEF < 40%, age 70 ± 11.5 years, 90% men, 60% diabetes), and 11 control subjects with cardiovascular risk factors (age 53.3 ± 6.1years, 90% men, 64% diabetes). Circulating EPC levels were evaluated by expression of vascular endothelial growth factor receptor-2 (VEGFR-2), CD34, and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. RESULTS: The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was similar among the HFpEF and HFrEF groups, and significantly lower than in the control group. The number of EPC-CFUs was also similar among the two heart failure groups and significantly lower than the control group. CONCLUSIONS: Patients with HFpEF, like HFrEF, have significant reduction in EPC level and function.

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials.

BACKGROUND: THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention. OBJECTIVES: In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors. METHODS: Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications. RESULTS: In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications. CONCLUSION: Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.

(Mis)Understanding scientific disagreement: Success versus pursuit-worthiness in theory choice.

Scientists often diverge widely when choosing between research programs. This can seem to be rooted in disagreements about which of several theories, competing to address shared questions or phenomena, is currently the most epistemically or explanatorily valuable-i.e. most successful. But many such cases are actually more directly rooted in differing judgments of pursuit-worthiness, concerning which theory will be best down the line, or which addresses the most significant data or questions. Using case studies from 16th-century astronomy and 20th-century geology and biology, I argue that divergent theory choice is thus often driven by considerations of scientific process, even where direct epistemic or explanatory evaluation of its final products appears more relevant. Broadly following Kuhn's analysis of theoretical virtues, I suggest that widely shared criteria for pursuit-worthiness function as imprecise, mutually-conflicting values. However, even Kuhn and others sensitive to pragmatic dimensions of theory 'acceptance', including the virtue of fruitfulness, still commonly understate the role of pursuit-worthiness-especially by exaggerating the impact of more present-oriented virtues, or failing to stress how 'competing' theories excel at addressing different questions or data. This framework clarifies the nature of the choice and competition involved in theory choice, and the role of alternative theoretical virtues.

Immature platelet fraction over time and clinical outcomes in patients with acute myocardial infarction.

BACKGROUND: Immature platelets in the circulation can be measured as immature platelet fraction (IPF). Limited data exist regarding IPF during the course of an acute myocardial infarction (AMI), the association between IPF and extent of cardiac damage, and the long-term prognostic implications of IPF in patients with AMI. AIMS: To examine the temporal course of IPF during the first month after AMI, the association between IPF and extent of cardiac damage, and the long-term prognostic effect of IPF in AMI patients. METHODS: Patients with AMI treated with percutaneous coronary intervention (PCI) were examined. IPF was evaluated by a Sysmex XN-3000 autoanalyzer, at 4 time points: baseline; one day post-PCI; 3 days post-PCI, and 30 days post-PCI. The association between peak troponin-T levels and IPF was evaluated. One-year clinical outcomes (cardiac hospitalization, urgent revascularization, or death) were assessed. RESULTS: One hundred patients were included, mean age was 59.5 ± 11.3 years, 82 were men, 27 had diabetes, and 54 were hospitalized with ST-segment elevation myocardial infarction (STEMI) and 46 with non-ST segment elevation myocardial infarction (NSTEMI). The levels of IPF modestly decreased a day after PCI but did not change in subsequent measurements. Peak troponin-T level was significantly associated with the levels of IPF at all 4 time points. IPF levels three days post-PCI were associated with the composite clinical outcome at 1 year. CONCLUSIONS: The levels of IPF following AMI remain relatively stable over a one-month period. Higher levels of IPF during the acute phase of AMI appear to be associated with worse cardiac outcomes at 1 year.

Immature platelets in patients hospitalized with Covid-19.

Coronavirus disease 2019 (Covid-19) is associated with high incidence of venous and arterial thromboembolic events. Currently, there are no markers to guide antithrombotic therapy in Covid-19. Immature platelets represent a population of hyper-reactive platelets associated with arterial events. This prospective study compared consecutive Covid-19 patients (n = 47, median age = 56 years) to patients with acute myocardial infarction (AMI, n = 100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n = 64, median age = 68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPF% on admission was higher in Covid-19 than the stable group and similar to the AMI group (4.8% [IQR 3.4-6.9], 3.5% [2.7-5.1], 4.55% [3.0-6.75], respectively, p = 0.0053). IPC on admission was also higher in Covid-19 than the stable group and similar to the AMI group (10.8 × 109/L [8.3-18.1], 7.35 × 109/L [5.3-10.5], 10.7 × 109/L [7.7-16.8], respectively, P < 0.0001). The maximal IPF% among the Covid-19 group was higher than the stable group and similar to the AMI group. The maximal IPC in Covid-19 was higher than the maximal IPC in both the stable and AMI groups (COVID-19: 14.4 × 109/L [9.4-20.9], AMI: 10.9 × 109/L [7.6-15.2], P = 0.0035, Stable: 7.55 × 109/L [5.55-10.5], P < 0.0001). Patients with Covid-19 have increased immature platelets indices compared to stable patients with cardiovascular risk factors, and as the disease progresses also compared to AMI patients. The enhanced platelet turnover and reactivity may have a role in the development of thrombotic events in Covid-19 patients.