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Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.
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Bacillus thuringiensis is a Gram-positive entomopathogenic bacterium that produces different pesticidal proteins: vegetative insecticidal proteins (Vpb1/Vpa2, Vip3, and Vpb4) during vegetative growth, which are secreted to the culture medium, and δ-endotoxins (Cry and Cyt) during sporulation, which accumulate into parasporal crystals. Cyt proteins are the smaller subset of δ-endotoxins targeting Diptera species. While Cry and Vip3 proteins undergo positive selection, our analysis suggests that Cyt proteins evolve following a conservative trend driven negative (purifying) selection.
Subject(s)
Bacillus thuringiensis Toxins , Bacillus thuringiensis , Bacterial Proteins , Endotoxins , Hemolysin Proteins , Selection, GeneticABSTRACT
INTRODUCTION: Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. METHODS: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5â months post hospital discharge according to existing risk scores using symptoms, ECG and NT pro-BNP. RESULTS: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month, p=0.252). Of 334 confirmed CTEPD/CTEPH cases, 4 (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further 3 (0.9%) CTEPD without PH. Of 1094 patients (mean age 58â years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. CONCLUSION: A-priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.
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Purpose: To report our experience of performing immediate sequential bilateral cataract surgery (ISBCS) in patients with visually significant cataracts and reduced preoperative corrected distance visual acuity (CDVA). Methods: Data of patients who underwent ISBCS for visually significant cataracts and had preoperative CDVA ≤20/32 (≤0.2 logMAR) in each eye were retrospectively reviewed. Refractive and visual outcomes were evaluated for the last available postoperative visit. Intraoperative and serious postoperative adverse events occurring within the first three months of surgery were reviewed. Results: A total of 1335 patients (2670 eyes) were included in the analysis, with a mean age of 71.9 ± 9.5 years. On the last visit, 50.2% and 89.1% of eyes achieved uncorrected distance visual acuity (UDVA) ≥20/20 (0.0 logMAR) and ≥20/32 (0.2 logMAR), respectively. Of all eyes, 83.8% were within ±0.50D, and 96.4% were within ±1.00 D of emmetropia. Ten patients had postoperative bilateral ametropia of more than 1.00D in each eye, but eight of them still achieved binocular UDVA ≥20/40. Intraoperative events occurred in 14 eyes of 13 patients (per-eye incidence: 0.524% or 1 in 191 eyes). A total of 86 postoperative adverse events occurred in 80 eyes of 53 patients (per-eye incidence 2.996% or 1 in 33 eyes), of which cystoid macular edema was the most common. Only three eyes had CDVA reduced by more than two Snellen lines compared to preoperative CDVA, two of which were not related to cataract surgery. There was no patient with bilateral CDVA loss. Conclusion: In our cohort of patients with visually significant cataracts, ISBCS resulted in good refractive predictability and a low incidence of serious adverse events.
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BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).
Subject(s)
Hypothermia, Induced , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Hypothermia, Induced/methods , Female , Middle Aged , Percutaneous Coronary Intervention/methods , Aged , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/physiopathology , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/surgery , Treatment OutcomeABSTRACT
In this study, secretable Vip3Ag4 protein was encapsulated in Bacillus megaterium and used for quantitative bioassays, in order to determine the UV photoprotective capacity of the cell, for preventing inactivation of the insecticidal activity of the protein. The non-encapsulated and purified protein was exposed to the UV light showing a LC50 of 518 ng/cm2 against Spodoptera littoralis larvae, whereas the exposed encapsulated protein exhibited 479 ng/cm2. In addition to the capability to accumulate Vip3 proteins for the development of novel insecticidal formulates, the B. megaterium cell has demonstrated to provide moderate protection against the deleterious action of UV light.
Subject(s)
Bacillus megaterium , Bacterial Proteins , Insecticides , Spodoptera , Ultraviolet Rays , Bacillus megaterium/drug effects , Animals , Spodoptera/drug effects , Insecticides/pharmacology , Bacterial Proteins/pharmacology , Larva/drug effectsABSTRACT
The traditional approach to management of cardiovascular disease relies on grouping clinical presentations with common signs and symptoms into pre-specified disease pathways, all uniformly treated according to evidence-based guidelines ("one-size-fits-all"). The goal of precision medicine is to provide the right treatment to the right patients at the right time, combining data from time honoured sources (e.g., history, physical examination, imaging, laboratory) and those provided by multi-omics technologies. In patients with ischemic heart disease, biomarkers and intravascular assessment can be used to identify endotypes with different pathophysiology who may benefit from distinct treatments. This review discusses strategies for the application of stratified management to patients with acute and chronic coronary syndromes.
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Purpose: To compare the outcomes of the Tecnis Eyhance ICB00 IOL, designed to enhance intermediate vision, to a conventional Tecnis Monofocal ZCB00 IOL. Methods: This retrospective analysis compared two cohorts of patients undergoing lens replacement surgery with bilateral implantation of the Tecnis ICB00 or the Tecnis ZCB00 IOL (383 patients in each group). Monocular and binocular uncorrected distance (UDVA), intermediate (UIVA; 66cm), and near (UNVA; 40cm) visual acuities, refractive predictability, and patient-reported outcomes were compared. A sub-analysis of patients with the Eyhance IOL was performed to compare patients who achieved bilateral emmetropia to those with mini-monovision. One-month postoperative outcomes were analyzed. Results: Both groups had comparable UDVA outcomes. On average, both monocular and binocular UIVAs were approximately one Snellen line better in patients implanted with Eyhance IOL (monocular UIVA: ICB00 0.23 ± 0.18 logMAR, ZCB00 0.33 ± 0.19 logMAR; binocular UIVA: ICB00 0.18 ± 0.18 logMAR, ZCB00 0.26 ± 0.20 logMAR, p < 0.01). Likewise, the mean UNVA was also one Snellen line better with the ICB00 model (monocular UNVA: ICB00 0.51 ± 0.20 logMAR, ZCB00 0.61 ± 0.18 logMAR; binocular UNVA: ICB00 0.42 ± 0.19 logMAR, ZCB00 0.51 ± 0.22 logMAR, p < 0.01). There was no difference between the two groups in overall satisfaction or visual phenomena. A subgroup of patients who achieved mini-monovision with Eyhance IOL had, on average, one Snellen line better UIVA and UNVA compared to patients with bilateral emmetropia. Conclusion: Patients receiving the enhanced monofocal IOL had better intermediate and near vision compared to those receiving the conventional monofocal IOL, with similar levels of patient-reported photic phenomena in both groups.
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BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.
Subject(s)
Magnetic Resonance Imaging, Cine , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/diagnostic imaging , Male , Female , Middle Aged , Magnetic Resonance Imaging, Cine/methods , Prospective Studies , Aged , Prognosis , Microcirculation , Microvessels/diagnostic imaging , Microvessels/injuries , Microvessels/pathologyABSTRACT
BACKGROUND: The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. METHODS: From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n = 1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. RESULTS: Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95% CI: 2.31-7.50; P < 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. CONCLUSIONS: MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.
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BACKGROUND AND AIMS: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Eligible studies were RCTs of routine invasive vs. a conservative or selective invasive strategy in patients presenting with NSTE-ACS that included patients with previous CABG. Summary data were collected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Summary data were obtained from 11 RCTs, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477 routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40). CONCLUSIONS: This is the first meta-analysis assessing the effect of a routine invasive strategy in patients with prior CABG who present with NSTE-ACS. The results confirm the under-representation of this patient group in RCTs of invasive management in NSTE-ACS and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered RCT.
Subject(s)
Acute Coronary Syndrome , Conservative Treatment , Coronary Artery Bypass , Randomized Controlled Trials as Topic , Humans , Acute Coronary Syndrome/therapy , Acute Coronary Syndrome/surgery , Conservative Treatment/methods , Non-ST Elevated Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/mortality , Percutaneous Coronary Intervention/methodsABSTRACT
In this study we analysed the effect of the temperature, diverse strains of Bacillus thuringiensis, Lysinibacillus sphaericus and nanoformulations with essential plant oils (EONP) on the survival of Sarcoptes scabiei mites derived from naturally-infested Iberian ibex (Capra pyrenaica). In general, mites maintained at 12ºC survived more than those maintained at 35ºC (40.7â¯hr and 31.2â¯hr, respectively). Mites with no treatment survived 27.6â¯h on average. Mites treated with B. thuringiensis serovar. konkukian and geranium EONP showed significant reduction in their survival. Despite the fact that these agents seem to be promising candidates for controlling sarcoptic mange in the field, further research is still needed to get stable, efficient and eco-friendly acaricides.
Subject(s)
Acaricides , Goats , Sarcoptes scabiei , Animals , Acaricides/pharmacology , Sarcoptes scabiei/drug effects , Scabies/drug therapy , Scabies/veterinary , Biological Products/pharmacology , Goat Diseases/drug therapy , Goat Diseases/parasitology , Bacillus thuringiensis/drug effects , Oils, Volatile/pharmacologyABSTRACT
BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.
Subject(s)
COVID-19 , Cardiovascular Diseases , Humans , COVID-19/epidemiology , COVID-19/complications , COVID-19/diagnosis , Male , Female , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/diagnosis , Prospective Studies , Middle Aged , Aged , Risk Factors , Hospitalization/statistics & numerical data , Time Factors , SARS-CoV-2 , Recovery of FunctionSubject(s)
Adenosine , Coronary Circulation , Microcirculation , Vascular Resistance , Humans , Adenosine/administration & dosage , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Male , Fractional Flow Reserve, Myocardial , Middle Aged , Vasodilator Agents/administration & dosage , Coronary AngiographyABSTRACT
BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.
Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Coronary Artery Disease/physiopathology , Coronary Artery Disease/therapy , Female , Male , Aged , Middle Aged , Prospective Studies , Treatment OutcomeSubject(s)
Coronary Vessels , Fractional Flow Reserve, Myocardial , Thermodilution , Humans , Thermodilution/methods , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Fractional Flow Reserve, Myocardial/physiology , Male , Female , Middle Aged , Coronary Circulation/physiology , Blood Pressure/physiology , Coronary AngiographyABSTRACT
AIMS: Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. METHODS AND RESULTS: EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10 mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24 weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers. CONCLUSIONS: EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI.
Subject(s)
Benzhydryl Compounds , Glucosides , Magnetic Resonance Imaging, Cine , Myocardial Infarction , Sodium-Glucose Transporter 2 Inhibitors , Ventricular Function, Left , Ventricular Remodeling , Humans , Benzhydryl Compounds/therapeutic use , Myocardial Infarction/drug therapy , Ventricular Remodeling/drug effects , Glucosides/therapeutic use , Glucosides/pharmacology , Double-Blind Method , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Magnetic Resonance Imaging, Cine/methods , Male , Female , Ventricular Function, Left/physiology , Ventricular Function, Left/drug effects , Stroke Volume/physiology , Stroke Volume/drug effects , Middle Aged , Aged , Disease Progression , Follow-Up StudiesABSTRACT
BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.
Subject(s)
Coronary Sinus , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Coronary Sinus/diagnostic imaging , Coronary Circulation , Treatment Outcome , Prospective Studies , Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Hemorrhage/etiologyABSTRACT
Mosquitoes, males and females, rely on sugar-rich resources, including floral nectar as a primary source of sugar to meet their energy and nutritional needs. Despite advancements in understanding mosquito host-seeking and blood-feeding preferences, significant gaps in our knowledge of the chemical ecology mediating mosquito-nectar associations remain. The influence of such association with nectar on mosquito behavior and the resulting effects on their fitness are also not totally understood. It is significant that floral nectar frequently acts as a natural habitat for various microbes (e.g. bacteria and yeast), which substantially alter nectar characteristics, influencing the nutritional ecology of flower-visiting insects, such as mosquitoes. The role of nectar-inhabiting microbes in shaping the nectar-mosquito interactions remains, however, under-researched. This review explores recent advances in understanding the role of such multitrophic interactions on the fitness and life history traits of mosquitoes and outlines future directions for research toward their control as disease vectors.