Rindera graeca (A. DC.) Boiss. & Heldr. (Boraginaceae) In Vitro Cultures Targeting Lithospermic Acid B and Rosmarinic Acid Production.

The in vitro cultures of Rindera graeca, a rare endemic plant, were developed as a sustainable source of phenolic acids. Various shoot and root cultures were established and scaled up in a sprinkle bioreactor. A multiplication rate of 7.2 shoots per explant was achieved. HPLC-PDA-ESI-HRMS analysis revealed the presence of rosmarinic acid (RA) and lithospermic acid B (LAB) as the main secondary metabolites in both the shoot and root cultures. The maximum RA (30.0 ± 3.2 mg/g DW) and LAB (49.3 ± 15.5 mg/g DW) yields were determined in root-regenerated shoots. The strongest free radical scavenging activity (87.4 ± 1.1%), according to 2,2-diphenyl-1-picrylhydrazyl-hydrate assay, was noted for roots cultivated in a DCR medium. The highest reducing power (2.3 µM ± 0.4 TE/g DW), determined by the ferric-reducing antioxidant power assay, was noted for shoots cultivated on an SH medium containing 0.5 mg/L 6-benzylaminopurine. A genetic analysis performed using random amplified polymorphic DNA and start codon targeted markers revealed genetic variation of 62.8% to 96.5% among the investigated shoots and roots. This variability reflects the capacity of cultivated shoots and roots to produce phenolic compounds.

Atrial fibrillation is a predictor of nonobstructive coronary artery disease in elective angiography in old age: a cross-sectional study in Poland and Russia.

BACKGROUND: Significant changes in the coronary vessels are not confirmed in a large proportion of patients undergoing cardiac catheterization. AIMS: The present study aimed to determine correlates and independent predictors of nonobstructive coronary artery disease (CAD) in older adults referred for elective coronary angiography. METHODS: A cross-sectional study was conducted involving 2,214 patients referred to two medical centers (in Poland and Russia) between 2014 and 2016 for elective coronary angiography due to exacerbated angina, despite undergoing optimal therapy for CAD. The median age was 72 years (IQR: 68-76), and 49.5% patients were women. RESULTS: Significant stenosis (defined as stenosis of 50% or more of the diameter of the left main coronary artery stem or stenosis of 70% or more of the diameter of the remaining major epicardial vessels) was diagnosed only in 1135 (51.3%) patients. Female sex (odds ratio [OR], 3.01; 95% confidence interval [CI], 2.44-3.72; p < 0.001) and atrial fibrillation (OR, 1.87; 95% CI 1.45-2.40; p < 0.001) were the main independent predictors of nonobstructive CAD. Significantly lower ORs were observed for diabetes (OR, 0.75; 95% CI 0.59-0.95; p = 0.02), chronic kidney disease (OR, 0.76; 95% CI 0.61-0.96; p = 0.02), and anemia (OR, 0.69; 95% CI 0.50-0.95; p = 0.02) after controlling for age, chronic heart failure, BMI, and study center. DISCUSSION AND CONCLUSIONS: The results confirmed that nonobstructive CAD occurs in a high percentage of older patients referred for elective coronary angiography. This suggests the need to improve patient stratification for invasive diagnosis of CAD, especially for older women and patients with atrial fibrillation. Trial registration number and date of registration: NCT04537507, September 3, 2020.

Biologically Active Diterpenoids in the Clerodendrum Genus-A Review.

One of the key areas of interest in pharmacognosy is that of the diterpenoids; many studies have been performed to identify new sources, their optimal isolation and biological properties. An important source of abietane-, pimarane-, clerodane-type diterpenoids and their derivatives are the members of the genus Clerodendrum, of the Lamiaceae. Due to their diverse chemical nature, and the type of plant material, a range of extraction techniques are needed with various temperatures, solvent types and extraction times, as well as the use of an ultrasound bath. The diterpenoids isolated from Clerodendrum demonstrate a range of cytotoxic, anti-proliferative, antibacterial, anti-parasitic and anti-inflammatory activities. This review describes the various biological activities of the diterpenoids isolated so far from species of Clerodendrum with the indication of the most active ones, as well as those from other plant sources, taking into account their structure in terms of their activity, and summarises the methods for their extraction.

Methyl Jasmonate Activates the 2C Methyl-D-erithrytol 2,4-cyclodiphosphate Synthase Gene and Stimulates Tanshinone Accumulation in Salvia miltiorrhiza Solid Callus Cultures.

The present study characterizes the 5' regulatory region of the SmMEC gene. The isolated fragment is 1559 bp long and consists of a promoter, 5'UTR and 31 nucleotide 5' fragments of the CDS region. In silico bioinformatic analysis found that the promoter region contains repetitions of many potential cis-active elements. Cis-active elements associated with the response to methyl jasmonate (MeJa) were identified in the SmMEC gene promoter. Co-expression studies combined with earlier transcriptomic research suggest the significant role of MeJa in SmMEC gene regulation. These findings were in line with the results of the RT-PCR test showing SmMEC gene expression induction after 72 h of MeJa treatment. Biphasic total tanshinone accumulation was observed following treatment of S. miltiorrhiza solid callus cultures with 50-500 µM methyl jasmonate, with peaks observed after 10-20 and 50-60 days. An early peak of total tanshinone concentration (0.08%) occurred after 20 days of 100 µM MeJa induction, and a second, much lower one, was observed after 50 days of 50 µM MeJa stimulation (0.04%). The dominant tanshinones were cryptotanshinone (CT) and dihydrotanshinone (DHT). To better understand the inducing effect of MeJa treatment on tanshinone biosynthesis, a search was performed for methyl jasmonate-responsive cis-active motifs in the available sequences of gene proximal promoters associated with terpenoid precursor biosynthesis. The results indicate that MeJa has the potential to induce a significant proportion of the presented genes, which is in line with available transcriptomic and RT-PCR data.

The Expression Profiles of the Salvia miltiorrhiza 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase 4 Gene and Its Influence on the Biosynthesis of Tanshinones

Salvia miltiorrhiza is a medicinal plant that synthesises biologically-active tanshinones with numerous therapeutic properties. An important rate-limiting enzyme in the biosynthesis of their precursors is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). This study presents the organ-specific expression profile of the S. miltiorrhiza HMGR4 gene and its sensitivity to potential regulators, viz. gibberellic acid (GA3), indole-3-acetic acid (IAA) and salicylic acid (SA). In addition, it demonstrates the importance of the HMGR4 gene, the hormone used, the plant organ, and the culture environment for the biosynthesis of tanshinones. HMGR4 overexpression was found to significantly boost the accumulation of dihydrotanshinone I (DHTI), cryptotanshinone (CT), tanshinone I (TI) and tanshinone IIA (TIIA) in roots by 0.44 to 5.39 mg/g dry weight (DW), as well as TIIA in stems and leaves. S. miltiorrhiza roots cultivated in soil demonstrated higher concentrations of the examined metabolites than those grown in vitro. GA3 caused a considerable increase in the quantity of CT (by 794.2 µg/g DW) and TIIA (by 88.1 µg/g DW) in roots. In turn, IAA significantly inhibited the biosynthesis of the studied tanshinones in root material.

Impact of short-term air pollution exposure on acute coronary syndrome in two cohorts of industrial and non-industrial areas: A time series regression with 6,000,000 person-years of follow-up (ACS - Air Pollution Study).

BACKGROUND: There is a lack of studies directly comparing the effect of air pollution on acute coronary syndrome (ACS) occurrence in industrial and non-industrial areas. OBJECTIVES: A comparison of association of air pollution exposure with ACS in two cohorts of industrially different areas. MATERIALS AND METHODS: The study covered 6,000,000 person-years of follow-up and five pollutants between 2008 and 2017. A time series regression analysis with 7-lag was used to assess the effects air pollution on ACS. RESULTS: A total of 9046 patients with ACS were included in the analysis, of whom 3895 (43.06%) had ST-elevation myocardial infarction (STEMI) - 45.39% from non-industrial area, and 42.37% from industrial area; and 5151 (56.94%) had non-ST-elevation myocardial infarction (NSTEMI) - 54.61% from non-industrial area and 57.63% from industrial area. The daily concentrations of PM2.5, PM10, NO2, SO2, CO were higher in industrial than in non-industrial area (P < 0.001). In non-industrial area, an increase of 10 µg/m3 of NO2 concentration (Odds Ratio (OR) = 1.126, 95%CI = 1.009-1.257; P = 0.034, lag-0) and an increase of 1 mg/m3 in CO concentration (RR = 1.055, 95%CI = 1.010-1.103; P = 0.017, lag-0) were associated with an increase in the number of hospitalization due to NSTEMI (for industrial area increase of 10 µg/m3 in NO2 (OR = 1.062, 95%CI = 1.020-1.094; P = 0.005, lag-0), SO2 (OR = 1.061, 95%CI = 1.010-1.116; P = 0.018, lag-4), PM10 (OR = 1.010, 95%CI = 1.001-1.030; P = 0.047, lag-6). In STEMI patients in industrial area, an increased hospitalization was found to be associated with an increase of 10 µg/m3 in SO2 (OR = 1.094, 95%CI = 1.030-1.162; P = 0.002, lag-1), PM2.5 (OR = 1.041, 95%CI = 1.020-1.073; P < 0.001, lag-1), PM10 (OR = 1.030, 95%CI = 1.010-1.051; P < 0.001, lag-1). No effects of air pollution on the number of hospitalization due to STEMI were noted from non-industrial area. CONCLUSION: The risk of air pollution-related ACS was higher in industrial over non-industrial area. The effect of NO2 on the incidence of NSTEMI was observed in both areas. In industrial area, the effect of PMs and SO2 on NSTEMI and STEMI were also observed. A clinical effect was more delayed in time in patients with NSTEMI, especially after exposure to PM10. Chronic exposure to air pollution may underlie the differences in the short-term effect between particulate air pollution impact on the incidence of STEMI.

The GRACE Scale in the Prognosis of Patients with Takotsubo Syndrome.

BACKGROUND: The prognosis of Takotsubo syndrome (TTS) is comparable to that of the non-ST-elevation myocardial infarction (NSTEMI). The GRACE scale is used to assess the risk of premature and long-term mortality in patients with NSTEMI in order to select the most favorable treatment strategy. METHODS: 101 patients with TTS hospitalized in four centers of invasive cardiology in Podlaskie Voivodeship during the period 2008-2012 were included in the study. The patients were divided into two groups: I-52 patients (GRACE ≤ 140 points) and II-49 patients (GRACE > 140 points). RESULTS: The mean GRACE score in the study group was 138.66. The in-hospital stay of Takotsubo in the patients with higher GRACE scores was associated with higher incidence of pneumonia (36.7% vs 7.69%, p=0.0004), rhythm abnormalities (17.3% vs 3.85%, p=0.026), and serious complications (cardiogenic shock, pulmonary edema, and sudden cardiac arrest) (30.6% vs 5.77%, p=0.001). The mean observation period was 7.2 years. A significantly higher risk of 6-month (18.37% vs 3.85%, p=0.019), 1-year (22.45 vs 3.85%, p=0.005), 3-year (40.82 vs 3.85%, p < 0.0001), 5-year (42.86% vs 3.85%, p < 0.0001), and 7-year mortalities (53.06% vs 9.62%, p < 0.0001) was observed in the group of patients with a GRACE score ≥140. At multivariate analysis including low BMI, low eGFR, and a higher GRACE score, all these factors were independent predictor of death (p=0.042; p=0.010; p=0.041). The ROC curve presents the discriminatory scores of the GRACE scale for the follow-up prognostication. The area under ROC curve (AUC) for the GRACE scale was 0.805 (95% CI: 0.718-0.892, p < 0.0001), with a cut-off value of 153 points, sensitivity of 74%, and specificity of 77% for TTS. CONCLUSION: The GRACE scale is highly valuable for the prognostication of death risk in patients with TTS in the early and long-term observation.

Impact of renal function on patients with acute coronary syndromes: 15,593 patient-years study.

INTRODUCTION: Coexistence of chronic kidney disease (CKD) in the case of acute coronary syndromes (ACS) significantly worsens the outcomes. AIM: The aim of our study was to assess renal function impact on mortality among patients with ACS. MATERIALS AND METHODS: The study was based on records of 21,985 patients hospitalized in the Medical University of Bialystok in 2009-2015. Inclusion criteria were ACS. Exclusion criteria were: death within 24 h of admission, eGFR <15 ml/min/1.73 m2, hemodialysis. Mean observation time was 2296 days. RESULTS: Criteria were met by 2213 patients. CKD occurred in 24.1% (N = 533) and more often affected those with NSTEMI (26.2 (337) vs. 21.2 (196), p = .006). STEMI patients had higher incidence of post-contrast acute kidney injury (PC-AKI) (5 (46) vs. 4.1 (53), p < .001). During the study, 705 people died (31.9%), more often with NSTEMI (33.2% (428) vs. 29.95% (277), p < .001). However, from a group of patients suffering from PC-AKI 57.6% died. The risk of PC-AKI increased with creatinine concentration (RR: 2.990, 95%CI: 1.567-5.721, p < .001), occurrence of diabetes mellitus (RR: 2.143, 95%CI: 1.029-4.463, p = .042), atrial fibrillation (RR: 2.289, 95%CI: 1.056-4.959, p = .036). Risk of death was greater with an increase in postprocedural creatinine concentration (RR: 2.254, 95%CI: 1.481-3.424, p < .001). CONCLUSION: PC-AKI is a major complication in patients with ACS, occurs more frequently in STEMI and may be a prognostic marker of long-term mortality in patients undergoing percutaneous coronary intervention (PCI). More attention should be given to the prevention and diagnosis of PC-AKI but necessary PCI should not be withheld in fear of PC-AKI.

Transformed Shoots of Dracocephalum forrestii W.W. Smith from Different Bioreactor Systems as a Rich Source of Natural Phenolic Compounds.

Transformed shoots of the Tibetan medicinal plant Dracocephalum forrestii were cultured in temporary immersion bioreactors (RITA and Plantform) and in nutrient sprinkle bioreactor (NSB) for 3 weeks in MS (Murashige and Skoog) liquid medium with 0.5 mg/L BPA (N-benzyl-9-(2-tetrahydropyranyl)-adenine) and 0.2 mg/L IAA (indole-3-acetic acid). The greatest biomass growth index (GI = 52.06 fresh weight (FW) and 55.67 dry weight (DW)) was observed for shoots in the RITA bioreactor, while the highest multiplication rate was found in the NSB (838 shoots per bioreactor). The levels of three phenolic acids and five flavonoid derivatives in the shoot hydromethanolic extract were evaluated using UHPLC (ultra-high performance liquid chromatography). The predominant metabolite was rosmarinic acid (RA)-the highest RA level (18.35 mg/g DW) and total evaluated phenol content (24.15 mg/g DW) were observed in shoots grown in NSB. The NSB culture, i.e., the most productive one, was evaluated for its antioxidant activity on the basis of reduction of ferric ions (ferric reducing antioxidant power, FRAP) and two scavenging radical (O2•- and DPPH, 1,1-diphenyl-2-picrylhydrazyl radical) assays; its antibacterial, antifungal, and antiproliative potential against L929 cells was also tested (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test). The plant material revealed moderate antioxidant and antimicrobial activities and demonstrated high safety in the MTT test-no cytotoxicity at concentrations up to 50 mg/mL was found, and less than a 20% decrease in L929 cell viability was observed at this concentration.

The Increase of Triterpene Saponin Production Induced by Trans-Anethole in Hairy Root Cultures of Panax quinquefolium.

In vitro cultivation is an effective way to increase pharmaceutical production. To increase ginsenoside production in hairy root cultures of American ginseng, the present study uses trans-anethole as an elicitor. The content of nine triterpene saponins was determined: Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, Re and Rf. Trans-anethole was found to stimulate saponin synthesis regardless of exposure time (24 and 72 h). Twenty-four hour exposure to 1 µmol trans-anethole in the culture medium resulted in the highest increase of total saponin content (twice that of untreated roots), and optimum accumulation of Rb-group saponins, with ginsenoside Rc dominating (8.45 mg g-1 d.w.). In contrast, the highest mean content of protopanaxatriol derivatives was obtained for 10 µmol trans-anethole. The Re metabolite predominated, reaching a concentration of 5.72 mg g-1 d.w.: a 3.9-fold increase over untreated roots. Elicitation with use of trans-anethole can therefore be an effective method of increasing ginsenoside production in shake flasks.

Yeast Extract Stimulates Ginsenoside Production in Hairy Root Cultures of American Ginseng Cultivated in Shake Flasks and Nutrient Sprinkle Bioreactors.

One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots cultivated in shake flasks and in a nutrient sprinkle bioreactor after 3 and 7 days of elicitation. The saponin content was determined using HPLC. The maximum yield (20 mg g-1 d.w.) of the sum of six examined ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1) in hairy roots cultivated in shake flasks was achieved after application of YE at 50 mg L-1 concentration and 3 day exposure time. The ginsenoside level was 1.57 times higher than that attained in control medium. The same conditions of elicitation (3 day time of exposure and 50 mg L-1 of YE) also favourably influenced the biosynthesis of studied saponins in bioreactor cultures. The total ginsenoside content was 32.25 mg g-1 d.w. and was higher than that achieved in control medium and in shake flasks cultures. Obtained results indicated that yeast extract can be used to increase ginsenoside production in hairy root cultures of P. quinquefolium.

New biological potential of abietane diterpenoids isolated from Salvia austriaca against microbial virulence factors.

The increasing importance of multi-resistant strains and microbial biofilms in the development of chronic infections has driven the search for more effective alternative therapy including plant-origin preparations. The present study evaluates the broadly-defined antimicrobial activity of two abietane diterpenoids isolated from Salvia austriaca transformed roots: taxodone and 15-deoxy-fuerstione. The direct biostatic/biocidal effect of these phytocompounds and their influence on Staphylococcus aureus and Candida albicans virulence factors/mechanisms (adhesion, biofilm formation, agglutination in human plasma, survival in the blood, germ tube and mycelium formation) were tested using in vitro assays. Both phytocompounds significantly inhibited microbial adhesion and biofilm formation when used at ½ and » MIC. Additionally, taxodone was able to limit staphylococcal survival in human blood, as well as C. albicans germ tube formation and hyphal growth. The tested diterpenoids express significant anti-biofilm activity against both staphylococci and yeast, and adversely affect their virulence factors/mechanisms, which are relevant in the course of the infection in vivo. Therefore, they demonstrate considerable biomedical potential as complements for classic therapy with antibiotics.

Taxodione and Extracts from Salvia austriaca Roots as Human Cholinesterase Inhibitors.

Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti-tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field-grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC50 for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml(-1), respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC50 = 54.84 µg ml(-1)). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC50 = 23.6 µg ml(-1): field-grown plants and 41.6 µg ml(-1): transformed roots) than taxodione (IC50 = 195.9 µg ml(-1)). Taxodione showed significant cytotoxicity against A549 cell line (IC50 = 9.1 µg ml(-1)), whereas the activities for the extracts from S. austriaca roots of field-grown plants (IC50 = 75.7 µg ml(-1)) and hairy roots (IC50 = 86.2 µg ml(-1)) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood-brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities.

Abietane diterpenoids from Salvia sclarea transformed roots as growth inhibitors of pathogenic Acanthamoeba spp.

Amoebae from the genus Acanthamoeba are known agents leading to various diseases such as granulomatous amoebic encephalitis (GAE), a chronic progressive disease of the central nervous system, amoebic keratitis (AK), chronic eye infection, amoebic pneumitis (AP), chronic lung infection, and skin infections. It is known that various synthetic anti-Acanthamoeba substances are ineffective. Therefore, other substances, e.g., natural plant compounds, are the focus of biological investigations regarding anti-parasite activity. In this work, the ability of four abietane diterpenoids (ferruginol, salvipisone, aethiopinone, and 1-oxo-aethiopinone) to inhibit Acanthamoeba growth is reported. All investigated compounds were active against Acanthamoeba growing in vitro. Among them, ferruginol demonstrated the highest activity against Acanthamoeba. This compound inhibited Acanthamoeba growth by about 72% in a 3-day exposure period (IC50 17.45 µM), while aethiopinone and 1-oxo-aethiopinone demonstrated this activity at the level of 55-56%. Salvipisone reduced the growth of Acanthamoeba in vitro culture by 39%. For this compound, the value of IC50 was 701.94 µM after 72 h of exposure.

EVALUATION OF ANTIOXIDANT PROPERTIES OF METHANOLIC EXTRACTS FROM LEAVES AND ROOTS OF REHMANNIA GLUTINOSA LIBOSCH. IN HUMAN BLOOD.

Compounds with antioxidant activity may protect different elements of blood from damaging effects of oxidative stress. The present in vitro study was designed to examine the antioxidant activity of methanolic extracts from leaves and roots of R. glutinosa plants against damages induced by oxidative stress. Oxidative stress was stimulated in human plasma and human blood platelet samples by the strong biological oxidant--hydrogen peroxide (H2O2) or H2O2/Fe (the donor of hydroxyl radicals). In experimental trials, the level of biomarker of lipid peroxidation--TBARS was significantly decreased by the action of methanolic extracts from R. glutinosa leaves. Therefore, it seems that the methanolic extract from leaves of the plants may be a new source of bioactive antioxidant natural compounds. It may be also an active pharmacological agent or a food supplement for healthy subjects and for people with different diseases (cardiovascular diseases and cancer) induced by oxidative stress.

Surgical ablation, left atrial appendage occlusion or both? Nationwide registry analysis of cardiac surgery patients with underlying atrial fibrillation.

OBJECTIVES: The aim of this study was to evaluate in-hospital outcomes and long-term survival of patients undergoing cardiac surgery with preoperative atrial fibrillation (AF). We compared different strategies, including no-AF treatment, left atrial appendage occlusion (LAAO) alone, concomitant surgical ablation (SA) alone or both. METHODS: A retrospective analysis using the KROK registry included all patients with preoperative diagnosis of AF who underwent cardiac surgery in Poland between between January 2012 and December 2022. Risk adjustment was performed using regression analysis with inverse probability weighting of propensity scores. We assessed 6-year survival with Cox proportional hazards models. Sensitivity analysis was performed based on index cardiac procedure. RESULTS: Initially, 42 510 patients with preoperative AF were identified, and, after exclusion, 33 949 included in the final analysis. A total of 1107 (3.26%) received both SA and LAAO, 1484 (4.37%) received LAAO alone, 3921 (11.55%) SA alone and the remaining 27 437 (80.82%) had no AF-directed treatment. As compared to no treatment, all strategies were associated with survival benefit over 6-year follow-up. A gradient of treatment was observed with the highest benefit associated with SA + LAAO followed by SA alone and LAAO alone (log-rank P < 0.001). Mortality benefits were reflected when stratified by surgery type with the exception of aortic valve surgery where LAAO alone fare worse than no treatment. CONCLUSIONS: Among patients with preoperative AF undergoing cardiac surgery, surgical management of AF, particularly SA + LAAO, was associated with lower 6-year mortality. These findings support the benefits of incorporating SA and LAAO in the management of AF during cardiac surgery.

Effect of air pollution exposure on risk of acute coronary syndromes in Poland: a nationwide population-based study (EP-PARTICLES study).

Background: Air pollution (AP) is linked up to 20% of cardiovascular deaths. The aim of this nationwide study was to investigate subpopulations vulnerable to AP for non-ST- (NSTEMI) and ST-elevation myocardial infarction (STEMI) incidence. Methods: We analysed short- (lags up to seven days) and mid-term (0-30 days moving average) influence of particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2) and benzo(a)pyrene (BaP) on hospitalizations due NSTEMI and STEMI in 2011-2020. Data on AP concentrations were derived using GEM-AQ model. Study included residents of five voivodeships in eastern Poland, inhabited by over 8,000,000 individuals. Findings: Higher NO2 and PM2.5 concentrations increased mid-term risk of NSTEMI in patients aged < 65 years by 1.3-5.7%. Increased SO2 and PM2.5 concentration triggered STEMI in the short- (SO2, PM2.5) and mid-term (PM2.5) amongst those aged ≥ 65 years. In the short- and mid-term, women were more susceptible to PM2.5 and BaP influence resulting in increased STEMI incidence. In rural regions, STEMI risk was triggered by SO2, PM2.5 and BaP. Income-based stratification showed disproportions regarding influence of BaP concentrations on NSTEMI incidence based on gross domestic product (up to 1.4%). Interpretation: There are significant disparities in the influence of air pollution depending on the demographic and socio-economic factors. AP exposure is associated with the threat of a higher risks of NSTEMI and STEMI, especially to younger people, women, residents of rural areas and those with lower income. Funding: National Science Center and Medical University of Bialystok, Poland.

Surgical Coronary Revascularization in Patients With Underlying Atrial Fibrillation: State-of-the-Art Review.

The number of individuals referred for coronary artery bypass grafting (CABG) with preoperative atrial fibrillation (AF) is reported to be 8% to 20%. Atrial fibrillation is a known marker of high-risk patients as it was repeatedly found to negatively influence survival. Therefore, when performing surgical revascularization, consideration should be given to the concomitant treatment of the arrhythmia, the clinical consequences of the arrhythmia itself, and the selection of adequate surgical techniques. This state-of-the-art review aimed to provide a comprehensive analysis of the current understanding of, advancements in, and optimal strategies for CABG in patients with underlying AF. The following topics are considered: stroke prevention, prophylaxis and occurrence of postoperative AF, the role of surgical ablation and left atrial appendage occlusion, and an on-pump vs off-pump strategy. Multiple acute complications can occur in patients with preexisting AF undergoing CABG, each of which can have a significant effect on patient outcomes. Long-term results in these patients and the future perspectives of this scientific area were also addressed. Preoperative arrhythmia should always be considered for surgical ablation because such an approach improves prognosis without increasing perioperative risk. While planning a revascularization strategy, it should be noted that although off-pump coronary artery bypass provides better short-term outcomes, conventional on-pump approach may be beneficial at long-term follow-up. By collecting the current evidence, addressing knowledge gaps, and offering practical recommendations, this state-of-the-art review serves as a valuable resource for clinicians involved in the management of patients with AF undergoing CABG, ultimately contributing to improved outcomes and enhanced patient care.

Regional antibiotic delivery for sternal wound infection prophylaxis a systematic review and meta-analysis of randomized controlled trials.

Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35-0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18-0.64]; p < 0.001) and gentamicin (0.58 [0.39-0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32-0.65]; p < 0.001 and 0.60 [0.44-0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43-0.83]; p = 0.003) and superficial SWIs (0.54 [0.32-0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations' activity: vancomycin against gram-negative strains: 0.20 (0.01-4.18) and gentamicin against gram-positive strains: 0.42 (0.28-0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.

Additional bypass graft or concomitant surgical ablation? Insights from the HEIST registry.

BACKGROUND: Surgical ablation for atrial fibrillation at the time of isolated coronary artery bypass grafting is reluctantly attempted. Meanwhile, complete revascularization is not always possible in these patients. We attempted to counterbalance the long-term benefits of surgical ablation against the risks of incomplete revascularization. METHODS: Atrial fibrillation patients undergoing isolated coronary artery bypass grafting for multivessel disease between 2012 to 2022 and included in the HEart surgery In atrial fibrillation and Supraventricular Tachycardia registry were divided into complete revascularization, complete revascularization with additional grafts, and incomplete revascularization cohorts; these were further split into surgical ablation and non-surgical ablation subgroups. RESULTS: A total of 8,405 patients (78% men; age 69.3 ± 7.9) were included; of those, 5,918 (70.4%) had complete revascularization, and 556 (6.6%) had surgical ablation performed. Number of anastomoses was 2.7 ± 1.2. The median follow-up was 5.1 [interquartile range 2.1-8.8] years. In patients in whom complete revascularization was achieved, surgical ablation was associated with long-term survival benefit: hazard ratio 0.69; 95% confidence intervals (0.50-0.94); P = .020 compared with grafting additional lesions. Similarly, in patients in whom complete revascularization was not achieved, surgical ablation was associated with a long-term survival benefit of 0.68 (0.49-0.94); P = .019. When comparing surgical ablation on top of incomplete revascularization against complete revascularization without additional grafts or surgical ablation, there was no difference between the 2: 0.84 (0.61-1.17); P = .307, which was also consistent in the propensity score-matched analysis: 0.75 (0.39-1.43); P = .379. CONCLUSION: To achieve complete revascularization is of utmost importance. However, when facing incomplete revascularization at the time of coronary artery bypass grafting in a patient with underlying atrial fibrillation, concomitant surgical ablation on top of incomplete revascularization is associated with similar long-term survival as complete revascularization without surgical ablation.