bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal and maternal outcomes in patients with tetralogy of Fallot
Authors: Mano T , Ferreira V , Moreira R I , Teixeira B , Agapito A , Rito T , Pinto F , Cruz Ferreira R , De Sousa L
Published: October 2021

Introduction

Women with tetralogy of Fallot (TOF) have an increased risk of adverse cardiac and neonatal events during pregnancy. The aim was to assess fetal and maternal outcomes in patients (pts) with uncorrected and corrected TOF.

Methods

Retrospective analysis of cardiological and obstetric data in women with TOF followed at our institution. Pregnancy and neonatal outcomes were compared in patients (pts) submitted to corrective surgery vs pts with no previous intervention and in pts with or without cyanosis.

Results

51 women (median age 27 years; median number of previous interventions of 2), 22% with cyanosis, who experienced 126 pregnancies resulting in 73 live births A previous corrective surgery was found in 78% (40 pts), while 4% (2 pts) had previous palliative surgery and 18% (9 pts) no previous procedure. We found that women that were not submitted to previous intervention had a significant higher incidence of preterm birth (56% vs 17.5%, p=0.029), spontaneous abortion (56% vs 10%, p=0.006) and stillbirth (22% vs 0%). No difference was found for obstetric complications between groups. Cyanotic pts also demonstrated higher incidence of low birth weight (LBW) (36% vs 7.5%, p=0.031), preterm birth (54% vs 17.5%, p=0.021), spontaneous abortion (55% vs 10%, p=0.004) and stillbirth (18% vs 0%). There were no cardiac complications during pregnancy nor evident deterioration on cardiac status. Congenital heart disease was reported in 2 infants (3% of live births).

Conclusions

Pregnancy is well tolerated in pts with TOF. In our population, even in uncorrected TOF and in pts with cyanosis, there were no cardiac complications during pregnancy, although those pts had worse fetal outcomes. An explanation for the low incidence of cardiac events may be less severe forms of the disease, allowing survival into adulthood without intervention.

Funding Acknowledgement

Type of funding sources: None.
Dose-dependent dynamics of glomerular filtration rate in patients with reduced renal function in the postinfarction period
Authors: Salyamova L , Kvasova O , Tomashevskaya Y , Borisova N
Published: October 2021

Objective

To evaluate the effect of 48-week therapy with atorvastatin at various doses on the glomerular filtration rate (GFR) in patients after acute ST-segment elevation myocardial infarction (STEMI).

Methods

103 STEMI patients aged 52 (45.5; 59) years (92 men and 11 women) were examined. The patients were randomized into three groups: group 1 – 39 patients taking atorvastatin 80 mg; group 2 – 26 patients who received atorvastatin 40 mg; group 3 – 38 people who took atorvastatin 20 mg. The compared subjects were matched by age, sex, height, BMI, and office BP. All patients were receiving STEMI treatment prior to study entry. Initially and after 24, 48 weeks of follow-up, the creatinine level was determined on an Olympus AU400 analyzer (Olympus Corporation, Japan), followed by the calculation of GFR using the CKD-EPI formula.

Results

In group 1, GFR was 86.3 at baseline [95% CI 80.3; 92.3], after 24 weeks – 85.1 [95% CI 80.4; 89.7], after 48 weeks – 85.9 [95% CI 80.4; 91.4] ml/min. In group 2, the following GFR values were found: on days 7–9 – 78.4 [95% CI 73; 83.8], after 24 weeks – 82.2 [95% CI 75.5; 89], and 48 weeks – 78.9 [95% CI 74.1; 83.6] ml/min. In group 3, GFR was 88.2 at baseline [95% CI 80.9; 95.5], at the 24th week – 84.9 [95% CI 80.4; 89.4], after 48 weeks of therapy – 81.1 [95% CI 75.5; 86.7] ml/min. Individuals with a baseline decreased GFR <90 ml/min were identified in each group in accordance with the clinical practice guidelines of KDIGO (2012). At the same time, against the background of therapy with atorvastatin 80 mg, a significant increase in GFR from 71.8 [95% CI 67.9; 75.7] to 79.9 [95% CI 74.2; 85.6] after 24 weeks (p=0.02) and the subsequent increase in GFR to 81.0 [95% CI 74.9; 87.2] ml/min after 48 weeks (p=0.02). Against the background lower doses of atorvastatin, GFR dynamics were not observed: in group 2 – 74.0 [95% CI 69.1; 78.9], 79.3 [95% CI 71.5; 87.1], 77.2 [95% CI 71.7; 82.7] ml/min; in group 3 – 70.9 [95% CI 67.6; 74.1], 79.2 [95% CI 73.1; 85.4], 74.9 [95% CI 65.9; 83.9] ml/min.

Conclusions

In STEMI patients with an initially reduced GFR level, only atorvastatin therapy at a dose of 80 mg for 48 weeks of treatment was accompanied by a significant improvement in renal function.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of myocardial injury and chronic kidney disease in an emergency unit
Authors: Lal-Trehan Estrada N , Carrasquer A , Del Moral V , Sanchez R , Bonet G , Peiro O , Fort I , Bardaji A
Published: October 2021

Background

Cardiac troponin is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Their joint effect is yet to be clarified.

Purpose

This study aims to evaluate the prognostic implication of myocardial injury and CKD in patients attended in an emergency room.

Methods

Retrospective study carried out between January 2012 and December 2013 with consecutive patients attended in an emergency room with troponin determination, who were distributed into four cohorts according to positive troponin and/or glomerular filtration rate (GFR) <45ml/min/ 1.7. We analysed their baseline characteristics and the four-year prognosis.

Results

3622 patients were included (median age 68.5 years [IQR 55.5–79.5]; 43% were women). Compared to subjects with normal GFR, the 565 subjects with CKD were significantly older (80.5 vs 66.5 years), with worse cardiovascular profile (arterial hypertension: 87% vs 56%; diabetes mellitus: 46% vs 22%) and greater comorbidity (history of myocardial infarction: 29% vs 18%; heart failure: 17% vs 5%; peripheral vascular disease: 16% vs 5%; cerebrovascular disease: 13% vs 7%%). Myocardial injury was also related to elderly and worse cardiovascular profile and comorbidity, especially in normal GFR subjects. 23.5% (718 subjects) of normal GFR subjects presented with myocardial injury. This percentage was much higher in the presence of renal impairment (331 subjects, 58.6%). Troponin was associated with a higher risk of death (both in-hospital and during follow-up) and of readmission due to infarction or heart failure, regardless of GFR. The reference cohort in the multivariate competing risk mode was that with subjects without myocardial injury or kidney disease. This analysis showed the worst MACE (all-cause death, non-fatal myocardial infarction and heart failure admission) in four-year follow-up in patients with renal impairment and positive troponin (HR 3.94, 95% CI 3.317–4.682), second worst MACE in those with myocardial injury and with normal GFR (HR 2.408, 95% CI 2.064–2.811), and then abnormal GFR patients with negative troponin (HR 1.532, 95% CI 1.220–1.923). Patients with both myocardial injury and renal impairment had the highest mortality (HR 4.633, 95% CI 3.829–5.604) and more readmissions for heart failure (HR 2.163, 95% CI 1.647–2.841). The myocardial-injury-and-normal-GFR cohort showed significantly higher mortality than the renal-impairment-with-negative-troponin cohort (HR 2.669 vs HR 1.794), more heart failure (HR 1.951 vs 1.067) and more myocardial infarctions (HR 2.439 vs 1.235) in the follow-up.

Conclusion

The results suggest that myocardial injury has better predictive power than chronic kidney disease for MACE events and also for individually mortality, readmission for heart failure or myocardial infarction.

Funding Acknowledgement

Type of funding sources: None.
Uncontrolled diabetes predicts anxiety and depression in CAD patients
Authors: Nura L , Hysein K , Beqiri L , Henein M Y , Bytyci I
Published: October 2021

Background and aim

Coronary artery disease (CAD) is a major public health problem worldwide because of high incidence of comorbidity and mortality. Diabetes mellitus (DM) is associated with clustered risk factor for CAD. The aim of this study was to assess the impact of diabetes in CAD and its relationship with depression.

Methods

The study included 77 patients (mean age 64±11 years, 63% female) with CAD. Based on comorbidity patients were classified into CAD with DM (n=49) and CAD without DM (n=28). In this prospective study demographic, clinic, echocardiographic and angiographic indices were collected as well as scale of anxiety and depression.

Results

Patients with CAD and DM were older (p=0.001), had reduced left ventricular ejection fraction-EF (p=0.02), more obese (p=0.03), had higher NYHA class (p=0.04), more prevalent arterial hypertension (p=0.04), and higher anxiety and/or depression scales (p<0.001) compared with patients without DM. Whereas gender was not significantly difference (p=0.11). Diabetes most closely correlated with the scale of depression (r=0.61, p<0. 001).

In multivariate analysis, only diabetes OR=1.099 (95% CI 1.028 to 1.231, p<0.001), predicted depression in patients with CAD. Glycemic >8.9 mmol/L, predicted the scale of depression in patients with CAD (sensitivity 75%, specificity 70%, AUC=0.72, p<0.001).

Conclusions

Diabetes is the most important risk factor for CAD and the uncontrolled levels are related to patient's disturbed mental health. These results constitute important knowledge for nurses serving CAD patients.

Funding Acknowledgement

Type of funding sources: None.
Prevalence of dyspnea and/or chest pain persistence at mid-term after COVID-19 infection: a systematic review and meta-analysis
Authors: Mustafic H , Cekovic D , Yordanov Y , Dinh A , Helft G , Jourdain P
Published: October 2021

Introduction

COVID-19 is a recent infection that affects the whole world. Symptoms such as dyspnea and/or chest pain may persist in some people after the acute infection phase. However, the extent of this phenomenon is not yet well known.

Purpose

To determine the prevalence of dyspnea and/or chest pain at least at one month after COVID-19 infection diagnosis.

Methods

EMBASE, Ovid MEDLINE in-process and other nonindexed citations, and Ovid MEDLINE (between 1948 and January 15, 2021), and EBM Reviews-Cochrane Central Register of Controlled Trials and EBM Reviews-Cochrane Database of Systematic Reviews (between 2005 and January 15, 2021) were searched for a combination of keywords related to the type of exposure (COVID-19 infection) and to the type of outcomes (dyspnea persistence and/or chest pain persistence at least one month after COVID-19 infection diagnosis). Two independent reviewers selected studies of any design and in any language, using original data. Descriptive and quantitative information was extracted from each selected study and study quality was also assessed. We estimated prevalence in percentage and 95% Cis for each outcome, using a random-effects model. Statistical heterogeneity across the studies was calculated by the I2 statistic to quantify inconsistencies between studies. To assess the potential for publication bias, we visually inspected funnel plots and added the Egger's regression test p-value for funnel symmetry.

Results

After an exhaustive screening of 1287 citations in title and abstract, 31 studies were reviewed from entire article and 10 studies with 2004 patients were finally selected for meta-analysis. Interrater agreements were very high (0.91 and 1 respectively for the two selection steps). The pooled dyspnea persistence prevalence from 10 studies was of 39%; 95% Ci [29%-49%], p<0.01, I2=91%, Egger's regression test p=0.19. The pooled chest pain persistence prevalence from 6 studies was of 18%; 95% Ci [11%-24%], p<0.01, I2=89%, Egger's regression test p=0.12).

Conclusion

Dyspnea and/or chest pain persistence prevalences after COVID-19 infection diagnosis are unexpectedly high, at least at one month. We have to take into account high heterogeneity due to subjects characteristics, various COVID-19 infection severities and study methodologies but there were no statistical argument for a publication bias. Nevertheless, this phenomenon requires more research to determine the long-term prevalence of these symptoms persistence and the mechanisms involved.

Funding Acknowledgement

Type of funding sources: None.
Inhibition of RAS components attenuates progression of heart failure and its adverse consequences on myocardial remodeling in both normotensive and hypertensive rats
Authors: Sykora M , Kratky V , Tribulova N , Kopkan L , Szeiffova Bacova B
Published: October 2021

Rationale and purpose

Prevention or attenuation of heart failure (HF) is persistent task in clinic as well as challenge for progress in research. Both, intercellular connexin-43 (Cx43) channels and extracellular matrix (ECM) exert high impact on heart function. Thus, we aimed to explore whether HF due to volume overload (VO) induces alterations in myocardial Cx43, ECM proteins MMP2, SMAD2/3, TGFβ1 and PKC signaling as well as changes that may be revealed by enzyme histochemistry. Moreover, we tested the impact of treatment suppressing RAS on examined targeted proteins.

Methods

VO-HF was induced in male normotensive Hannover Sprague- Dawley (HSD) and mRen-2 transgenic hypertensive (TGR) rats by creating an aorto-caval fistula (ACF) and heart response was examined 20-weeks later. Sham-rats were compared with non-treated rats with ACF and those treated for 15-weeks with ACEI (trandolapril, 6mg/l, p.o.) or ARB (losartan (200mg/l, p.o.). Left ventricular heart (LV) tissue was analyzed using western blot, zymography and enzyme histochemistry.

Key results

Echocardiography confirmed an increase in cardiac output and a decrease in ejection fraction in both strains of rats. BW was higher in TGR vs HSD and it was not affected by VO. HW and LVW were higher in TGR vs HSD and VO increased both parameters regardless the strain while ACEI>ARB attenuated it. In parallel, myocardial pro-hypertrophic PKCd expression was higher in TGR vs HSD and increased in both strains due to VO while both drugs prevent it. Glycogen phosphorylase and capillary associated 5-nucleotidase, alkaline phospatase and dipeptidyl peptidase IV activities were reduced due to VO in HSD and TGR and it was attenuated by treatment. Cx43 expression and its functional phosphorylation status were lower in TGR vs HSD and suppressed in both strains due to VO but ACEI>ARB prevented it. Similar trend of changes was observed in PKCe expression, which phosphorylates Cx43. Profibrotic TGFβ1-Smad2/3 pathway was suppressed along with reduced MMP2 activity in TGR comparing to HSD. VO reduced SMAD2/3 in HSD and TGFβ1 in TGR as well as MMP2 expression in both strains, whereby treatment abolished these changes. VO decreased MMP2 (63kDa) activity only in TGR and ARB prevented it. VO did not affect collagen deposition in either strain vs sham rats.

Conclusions

Hypertrophic and hypofibrotic phenotypes are induced by volume overload in both rat strains. Together with deterioration of Cx43 mediated intercellular coupling it may contribute to heart dysfunction. Inhibition of RAS components attenuates progression of VO and its adverse consequences.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20
Telomerase and myocardin co-expressing mesenchymal cells increase survival and induce cardiac and vascular markers in cardiac stromal cells undergoing simulated ischemia/reperfusion
Authors: Madonna R , Guarnieri S , Csenger Kovacshazi C , Gorbe A , Giricz Z , Geng Y J , Mariggio M A , Ferdinandy P , De Caterina R
Published: October 2021

Background

Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favoring their paracrine activities.

Aim

To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs).

Methods and results

Murine CSCs were isolated with the cardiosphere (CSps) isolation technique.

T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28±4 vs 10±3%, p=0.02). Pretreatment with CM (15±2, p=0.02) or with the EV-enriched fraction (10±1%, p=0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more prononunced with CM (7±1%, p=0.01) or the EV-enriched fraction (2±1%, p=0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin.

Conclusions

The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.

Funding Acknowledgement

Type of funding sources: None.
Genetic predisposition in pediatric acute myocarditis: a pilot study
Authors: Gourzi P , Pantou M P , Vagenakis G , Tsoutsinos A , Vatsellas G , Makrythanasis P , Rammos S , Degiannis D
Published: October 2021

Background

Myocarditis is an inflammatory disease of the heart muscle with a wide range of clinical presentations, from asymptomatic to cardiogenic shock and death. Although acute myocarditis is rare in pediatric population, it is caused by common viral infections, like parvovirus B19 or enteroviruses. Limited scientific evidence supports the existence of a genetic background that could underlay the susceptibility to virus-induced myocarditis.

Purpose

The aim of the present study was to identify mutations in genes associated with cardiomyopathies, that could possibly underly acute myocarditis in pediatric patients with biopsy-proven parvovirus B19 infection, verified by real time PCR.

Methods

Nine pediatric patients presented in our center with acute myocarditis were genotyped with next generation sequencing using Clinical Exome Solution kit (Sophia Genetics) covering 4493 disease-related genes. Variant pathogenicity was accessed according to guidelines by American College of Medical Genetics (2015).

Results

Genetic analysis revealed that three of the nine patients were found positive for pathogenic/likely pathogenic mutations in TTR, ABCC6 and SLC22A5 genes. The patient that carried the SLC22A5 variant initially received telbivudine and her ejection fraction was improved from 20% to 45%. Genetic test results suggested that the patient may suffer from mild L-carnitine deficiency. Oral supplementation with high dose of L-carnitine during one month period improved dramatically her EF to normal (65%). The patient that carried the ABCC6 mutation, also carried a variant of unknown significance in MYH7 gene. Four patients carried variants of unknown significance. The variants of unknown significance detected in MYBPC3, SCN5A, and MYH7 genes are of particular interest since they accumulate evidence of pathogenicity. Two patients did not harbor any mutations.

Conclusion

A significant proportion of rare variants in genes associated with cardiomyopathies has been identified in a small cohort of pediatric patients with parvovirus-induced acute myocarditis. The findings of our study, although limited, support the existence of a genetic background that could function as a predisposing factor influencing the clinical course of the disease.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Onassis Foundation
Interleukin 6 –174 G/C polymorphism: its relation to coronary artery disease and circulating IL-6 levels – a systematic review and meta-analysis
Authors: Rai H , Colleran R , Cassese S , Joner M , Kastrati A , Byrne R A
Published: October 2021

Introduction

Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 –174 G/C, rs1800795) have been found to be independently associated with coronary artery disease (CAD). However, the association status of this polymorphism with CAD remains unclear.

Purpose

We conducted a systematic review and updated meta-analysis to comprehensively ascertain the association status of IL6 –174 G/C with CAD and its effect on the levels of circulating IL-6 in humans.

Methods

Comprehensive online search was undertaken to find relevant case-control/cohort studies investigating the association of IL6 –174 G/C with CAD. The association status of –174 G/C with CAD amongst pooled sample as well as separately amongst different ancestral populations was assessed. Association of –174 G/C with circulating IL-6 levels was also assessed amongst pooled sample as well as separately for CAD cases and CAD-free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled by Mantel-Haenszel fixed-effects models.

Results

Quantitative synthesis for assessing the role of this polymorphic variant in CAD was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases / 32,053 controls). The pooled association of –174 G/C with CAD was found to be statistically significant through dominant (OR= 1.15, 95% CI= 1.05–1.25, p=0.002) as well as allelic genetic model comparisons (OR= 1.13, 95% CI= 1.06–1.21, p=0.0003). Asian and Asian-Indian ancestral subgroups showed significant association with CAD in both genetic model comparisons (OR range= 1.29 to 1.53, p value range ≤0.02). Other ancestral subgroups did not show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the “C” allele carriers in the pooled sample (Standard mean difference, SMD= 0.31, 95% CI= 0.01–0.22 pg/ml, p=0.009) as well as the CAD-free control subgroup (SMD= 0.10, 95% CI= 0.02–0.17 pg/ml, p=0.009). CAD case subgroup did not show any significant association (p=0.12).

Conclusions

The present systematic review and meta-analysis confirms an association between IL6 –174 G/C polymorphism residing in the IL6 gene and CAD, especially amongst Asian and Asian-Indian ancestral groups. Upregulation of plasma IL-6 levels in the “C” allele carriers seem to be at least partly responsible for the observed association. Further investigations with large structured case-control studies amongst these ancestral groups are warranted.

Funding Acknowledgement

Type of funding sources: None.
Circadian dependence of the acute immune response to myocardial infarction
Authors: Kilgallen A B , Crnko S , Feyen D A M , Van Der Akker F , Gremmels H , Du Pre B C , Sampiao Pinto V M , Reijers R , Doevendans P A , De Jager S C A , Sluijter J P G , Van Laake L W
Published: October 2021

Aim

Circadian rhythms control many physiological processes, including numerous aspects of the immune system. Whether these immunological oscillations play a role in the pathophysiology after ischemic injury, such as myocardial infarction (MI), remains unclear. In this study, we aimed to characterize circadian rhythms during the acute inflammatory responses after MI.

Methods and results

Balb/c mice were operated at Zeitgeber Time (ZT) 2, 8, 14 and 20. Three hours after MI, animals were terminated and blood and hearts were collected to assess immunological status and damage. We observed diurnal fluctuation in leukocyte numbers in the blood, peaking during the rest-phase (ZT2 and 8) of the circadian cycle. Interestingly, the homing and infiltration of neutrophils to the injured myocardium was more pronounced during the active-phase of the mice (ZT14 and 20), at which time higher levels of Troponin-T were measured in the serum. Higher neutrophil extravasation during the active phase (especially the sleep-to-wake transition, ZT14) was also correlated to greater chemokine release in the blood and adhesion molecule expression in the heart.

Conclusion

The occurrence of a myocardial infarction during the early-morning hours leads to greater myocardial damage in patients. In the present study, we showed that the neutrophil response in the first hours after MI is stronger during the sleep-to-wake transition, thereby potentially playing a role in the worse clinical outcome observed during this time period.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research received funding from the EU's H2020 research and innovation programme under Marie S. Curie cofund RESCUE grant agreement No 801540.
Enhancement of engineered cardiac tissues by promotion of hiPSC-cardiomyocyte proliferation
Authors: Hesselbarth R , Esser T U , Roshanbinfar K , Struefer S , Schubert D W , Engel F B
Published: October 2021

Background/Introduction

Cardiac tissue engineering is a promising strategy to generate human cardiac tissues for modelling cardiac diseases, screening for therapeutic drugs, and repairing the injured heart. Yet, several issues remain to be resolved including the generation of tissues with high cardiomyocyte density.

Purpose

Determining the effects of the induction of human-induced pluripotent stem cell-derived (hiPSC) cardiomyocyte proliferation post-fabrication.

Methods

hiPSCs were differentiated into cardiomyocytes, embedded with or without CHIR990121 at three concentrations in a collagen pre-gel, and cast. The engineered cardiac tissues were then cultured in the absence or presence of CHIR99021 for up to 35 days. Hydrogels and engineered cardiac tissues were analysed utilizing rheology and assays to determine viability, proliferation, calcium flow, and contractility.

Results

Here, we show that the integration of CHIR99021 in collagen I hydrogels promotes proliferation of hiPSC-cardiomyocytes post-fabrication improving contractility of and calcium flow in engineered cardiac tissues. Presence of CHIR99021 has no effect on the gelation kinetic or the mechanical properties of collagen I hydrogels. Analysis of cell density and proliferation based on Ki-67 staining indicates that integration of CHIR99021 together with external CHIR99021 stimulation increases hiPSC-cardiomyocyte number by ∼2-fold within 7 days post-fabrication. Analysis of the contractility of engineered cardiac tissues after another 3 days in the absence of external CHIR99021 shows that CHIR99021-induced hiPSC-cardiomyocyte proliferation results in synchronized calcium flow, rhythmic beating, increases speed of contraction and contraction amplitude, and reduces peak-to-peak time. The CHIR99021-stimulated engineered cardiac tissues exhibited spontaneous rhythmic contractions for at least 35 days.

Conclusion

Collectively, our data demonstrate the potential of induced cardiomyocyte proliferation to enhance engineered cardiac tissues by increasing cardiomyocyte density and reducing arrhythmia.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft
Activation of adenosine receptors improved cardiac dysfunction induced by myocardial infarction
Authors: Beltrame F , Da Silva J S , Montagnoli T L , Maia R , Fraga C A M , Barreiro E J , Zapata-Sudo G
Published: October 2021

Introduction

Acute myocardial infarction (MI) is characterized by an intense inflammatory response leading to cardiac remodeling and subsequent cardiac dysfunction.

Purpose

Activation of adenosine A2A and A3 receptors induced by LASSBio-1027 could improve cardiac function, through the reduction of the inflammatory response and the activated cardiac fibroblasts (CF).

Methods

The Animal Care and Use Committee approved the experimental protocols. MI was induced in male Wistar rats by ligation of the anterior descending coronary artery and confirmed by transthoracic echocardiography. The experimental groups were Sham and MI treated orally with either vehicle or LASSBio-1027 (30 or 70 μmol/kg) during 7 days. At the endpoint, hemodynamic parameters were evaluated and hearts were prepared for histological and immunohistochemical analysis for fibrosis and cellular infiltrate detection and for α-SMA, TNF-α, iNOs, c-fos, p38MAPK expression, respectively. Production of reactive oxygen species and collagen in CF with H2O2–induced oxidative stress was observed in the presence or absence of LASSBio-1027 (10 μM).

Results

Diastolic dysfunction was detected in MI group because the filling pressure (E/e') and the left ventricular end diastolic pressure (LVEDP) were increased from 22.9±1.6 to 37.0±3.7 and from 3.2±0.9 to 18.2±2.2 mmHg (p<0.01), respectively. LASSBio-1027 (70 μmol/kg) prevented diastolic dysfunction since E/e' and LVEDP reduced to 23.8±5.3 and 6.4±1.6 mmHg (p<0.01). Adenosine receptor agonist improved systolic dysfunction in MI group with increase of ejection fraction from of 30.1±3.1 to 48.4±4.8% (p<0.05). As shown in figure 1, MI promoted an increase in collagen deposition, cellular infiltrate, expression of SMA-α, TNF-α, iNOs, c-fos and p38MAPK which confirmed the intense fibrosis, cell proliferation and inflammation. Oral administration of LASSBio-1027 reduced those parameters in a dose dependent manner. LASSBio-1027 reduced H2O2-induced fibroblast-myofibroblast transformation with the decrease of stain density of α-SMA from 1794.4 to 574.4 staining area/cell and collagen production from 33.7±9.6 to 22.1±18.9% (p<0.05). Effects of LASSBio-1027 were inhibited by the antagonists of A2A (ZM-241385) and A3 (MRE3008F20) receptors.

Conclusions

Activation of adenosine A2A and A3 receptors by LASSBio-1027 improved cardiac function and remodeling induced by MI.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): CNPq. CAPES, FAPERJ Histological AnalysisImmunohistochemistry analysis
Physical exertion at work and addictive behaviors: tobacco, cannabis, alcohol, sugar and fat intake
Authors: Hamieh N , Descatha A , Zins M , Goldberg M , Czernichow S , Plessz M , Roquelaure Y , Lemogne C , Matta J , Airagnes G
Published: October 2021

Background

This study examined the prospective association of physical exertion at work with risk of tobacco, cannabis, alcohol use and sugar and fat consumption.

Methods

Volunteers of the French population-based CONSTANCES cohort currently employed were included from 2012 to 2017 for tobacco and cannabis outcomes (n = 100,612), and from 2012 to 2016 for alcohol and sugar and fat outcomes (n = 75,414). High level of physical exertion was defined as a score ≥12 at the Rating Perceived Exertion Borg scale. Substance use was self-reported and patterns of sugar and fat intakes were obtained from principal component analysis and used in quartiles. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to baseline physical exertion at work, while adjusting for sociodemographic factors, depressive symptoms and baseline level of consumption.

Results

High physical exertion was associated with tobacco use, i.e.: increased odd of relapse in former smokers (OR = 1.13, 95% confidence interval (CI):1.02-1.24), and increased number of cigarettes per day in current smokers (OR = 1.54, 95%CI:1.33-1.78) with dose-dependent relationships (P for trend<0.001). It was also associated with increased odd of cannabis use at least once per month compared to no use in the past year (OR = 1.31, 95%CI:1.03-1.66) and with increased odds of sugar and fat consumption (OR = 1.06, 95%CI:1.01-1.11 and OR = 1.13, 95%CI:1.07-1.18, for third and fourth quartiles compared to the first, respectively).

Conclusions

The associations between physical exertion at work and subsequent tobacco and cannabis use and sugar and fat consumption should be taken into account for information and prevention strategies.

Key messages

The associations between physical exertion at work and subsequent tobacco and cannabis use and sugar and fat consumption should be taken into account for information and prevention strategies. High physical exertion at work was positively associated with subsequent tobacco and cannabis use and sugar and fat consumption.
Assessment of glycemic control among Tunisian diabetic adults
Authors: Cherif I , Rejaibi S , Ben Mansour N , Zoghlami N , Saidi O , Skhiri A , Ben Slama F , Ben Romthane H , Turki Z , Aounallah-Skhiri H
Published: October 2021

Background

Diabetes, a major public health issue in Tunisia, is responsible of an increased burden of morbidity and premature mortality. Achieving a good glycemic control is essential for reducing the morbidity-mortality associated with this disease. The purpose of our study was to assess the proportion of uncontrolled diabetes (UD) among Tunisian diabetic adults and assess associated factors.

Methods

A national household survey, stratified at three degrees, was conducted in 2016. As part of this study, we included previously diagnosed diabetic adults aged 20 years or above. Sociodemographic data and medical history were collected using an individual questionnaire, and glycated hemoglobin (HbA1C) was measured using the “A1C Now +” device. The UD was defined based on the American Diabetes Association criteria for the year 2016 (HbA1c ≥7%). Multiple logistic regression model was used to determine factors associated with UD. Adjusted Odds Ratios (AOR) were presented with 95% confidence intervals (CI). All data analysis was performed using SPSS software.

Results

A total of 873 subjects were included with a median age of 61 years and a sex-ratio equal to 0.9. The proportion of UD was (72.8%, 95% CI: [69.1-76.3]). In multivariate analysis, UD was more frequent among rural areas residents (AOR=1.8 [1.1-2.7]), those who had never seen a doctor within the year preceding the survey (AOR=2.2 [1.1-4.2]) and among those on oral antidiabetics (AOR=6.1 [1.9-18.9]) or insulin (AOR=23.8 [7.1-79.8]) compared to those who were following a diabetic diet.

Conclusions

This study highlighted a very high proportion of UD in diabetic Tunisian adults. A better involvement of primary care physicians in overall patient care, and improved availability of antidiabetic drugs for patients, are strongly recommended.

Key messages

Majority of Tunisian diabetic adults aged 20 years or older had an uncontrolled diabetes. Improving patient education and the availability of antidiabetic drugs for diabetic individuals in primary healthcare facilities is essential.
“Missed a vaccine?” Survey on vaccine hesitancy of high-risk categories in Bologna
Authors: Montalti M , Rallo F , Kregel J , Po G , Stillo M , Musti M , Pandolfi P , Fantini MP , Resi D , Gori D
Published: October 2021

Background

Vaccine Hesitancy (VH) is considered by the WHO to be one of the ten threats of the 21st century. The Italian National Plan for Vaccine Prevention, as well as the European Action Plan, have among their objectives that of increasing the adherence to vaccinations both in general population and in categories at higher risk. It is precisely to these latter groups that the action of the Bologna Local Health Authority (LHA) has addressed targeted vaccination campaigns in recent years (e.g., DTP, HepB, PCV/PPV, RZV). Aim of our study was to investigate adherence to the proposed vaccination campaigns.

Methods

An anonymous QR-code scanned survey was administered to adults during the COVID-19 vaccine campaign in February in Bologna, a city in Northern Italy.

Results

A total of 2,321 participants were enrolled, 59% of whom were female. Among healthcare workers (n = 1,417), VH was 45.6% for Hib in 2020, 60.3% in 2019, and 68.3% in 2018; and 14.9% for HepB. Among people with chronic conditions (n = 149), 36.6% did not get the PCV/PPV vaccine. Among RZV vaccine recipients (n = 406), only 11.1% reported having been vaccinated. Women who were at least once pregnant in the last 5 years (n = 124), did not get the anti-pertussis vaccine in 41.9% of cases, and 71.8% of them refused the Hib vaccine. In general, the reasons most often given for missed vaccinations were ‘I did not inform myself enough about this specific vaccine' (ranging from 16.0% for Hib for healthcare workers to 44.8% for RZV), ‘I am not informed about the vaccinations I am entitled to' (27.3% for RZV, 31.8% for PCV/PPV), and ‘I do not find it useful' (46.2% for Hib in healthcare workers).

Conclusions

Our findings show that even in those who accept the COVID-19 vaccine, VH is high for other vaccinations campaigns run by the Bologna LHA. Targeted awareness and designed catch-up actions are needed, especially regarding this group that does not totally stand in the ranks of the so-called ‘no vax'.

Key messages

Vaccine Hesitancy toward other vaccines remains high among those who accept the anti-COVID-19 vaccination. A large number of hesitant respondents report either not being aware of the possibility of vaccination or not being adequately informed about the specific vaccine.
A dynamic GIS space-time diffusion model to tackle COVID-19 emergency
Authors: De Vito C , Pesaresi C , Villari P , Migliara G , Pavia D , Di Rosa E , Barbara A , Cerabona V
Published: October 2021

Background

Surveillance and containment of the spread of COVID-19 requires the use of advanced geographic information science and technology (GIS&T) to map the spread and eventually to guide interventions. A dynamic space-time diffusion model in a GIS environment was developed and succesfully tested in Rome, Italy.

Methods

Information on cases of SARS-CoV-2 infection confirmed by molecular diagnostics from Feb 25 to Sep 26 2020 (collected by a large Local Health Unit of Rome, Italy) was used to test a GIS simulator model able to monitor the spatial diffusion and temporal evolution of the spread of the disease. Data included information on: sex, date and place of birth, healthcare facility of hospitalization, date of notification, start date and end date of isolation, date of recovery (both clinical and laboratory confirmed), residence address.

Results

Globally, 3,056 cases were geocoded and analysed. The spatio-temporal analysis of the first 45 days since 25 Feb 2020 shows that the spread of COVID-19 was very fast (1,230 cases recorded on 11 Apr) and spatially widespread. Number of cases was highest in the city centre with clusters, thickets and axes in different sub-municipal areas. A slowdown occurred the following month, confirming the positive effect of the lockdown. This effect continued until 11 Jun with a small increase in the number of cases (+10.9%). The period up to 26 Sep is paradigmatic of the second wave, with a continuous increase in cases that spread from the city centre to the suburbs.

Conclusions

Using geocoding process and a detailed GIS mapping it is possible to identify streets, buildings and census sections where the number of cases is high and tends to increase rapidly and, at the same time, it is possible to distinguish clusters and axes that should be kept immediately under special observation as potential pools of super-diffusion. Development of its use in near-real time could bring significant advantages in controlling the spread of COVID-19.

Key messages

The use of GIS technology is fundamental for mapping the spread of COVID-19. A greater effort should be made by institutions to increase the digitisation of health data and the possibility of using them for both research and surveillance purposes.
Promoting food literacy in type 2 diabetes: a systematic review
Authors: Riccardi MT , Savarese M , Acquati G , Nurchis MC , Sapienza M , Mastrilli V , Graps EA , Guendalina G , Damiani G
Published: October 2021

Background

Diabetes is one of the major global health threats whose burden is sharply increasing. Food literacy is proved to be relevant to optimize self-management in diabetic patients. The present review aims to map the current literature on educational interventions to promote food literacy in type 2 diabetes, with a particular focus on the concept of patient engagement.

Methods

Five databases were queried using the Population-Intervention-Context-Outcome (PICO) model. Individual study quality was assessed using the Quality Criteria Checklist for primary research provided by the American Diabetes Association. Data were summarized using descriptive statistic and a comparison between intervention carried out by a multidisciplinary team versus a single professionist was performed adopting a Chi-square test (p < 0.05 was deemed as statistically significant).

Results

Of 1580 articles, 28 were finally included. Outcome categories were narratively labelled as “clinical”, “psychological”, “behavioural” and “literacy”. When the provider was a multidisciplinary team (25% of studies) improvement in self-management occurred in 86% of cases while in single-provider intervention the percentage was 71%, but the difference was not significant (p = 0.45). In the 10.7% of articles the use of technologies was reported, but generically descripted as the use of webpages, email or social media. Globally, an improvement in food literacy was reported in 75% of the interventions.

Conclusions

Nowadays, the use of a technology proxy is recognized as an efficient support in boosting patients' education, but the evidence in improving food literacy is scarce and difficult to compare. Public health programs improving food literacy are effective at different levels. These findings should encourage decision makers to allocate resources in this kind of programs.

Key messages

Engaging people in the management of their disease by increasing food literacy level may represent a first step to reach the “health in all policies” approach. When planning a public health intervention, allocating resources for improving individual’s education is essential to achieve better health outcomes.
Diabetes screening among School Teachers: Exploring the Ignored Dimension of School Health Program
Authors: Ketata N , Ben Ayed H , Baklouti M , Masmoudi I , Yaich S , Maamri H , Jdidi J , Kassis M , Feki H , Damak J
Published: October 2021

Introduction

The rising prevalence of diabetes is a serious public health concern globally, with its complications and associated health expenditures. The school teachers have chronic stress, predisposing them to many chronic diseases. The aim of this survey was to assess the prevalence and the predisposing factors influencing diabetes among secondary school teachers.

Methods

A cross-sectional analytical study was carried out on a three-stage randomized sample of 258 secondary school teachers of 12 public schools on march 2021. A self-administered and pretested questionnaire was performed to assess sociodemographic characteristics and a Glucometer using glucose sticks was used to measure fasting blood sugar level. Diabetes and pre-diabetes were defined according to the International Diabetes Federation.

Results

Overall, 136 participants were females (52.7%) giving a male to female ratio of 0.9. The median age was 49 years (Interquartile range (IQR) = [43-53]). Of all teachers, 228 cases (88.4%) were married, 190 cases (73.6%) were from urban areas and 63 cases (24.4%) had a chronic disease. There were 29 (11.2%) active smokers. We noted that 23 participants were diabetics, giving a prevalence of fortuitous discovery diabetes of 8.9%. The prevalence of pre-diabetes was 10.5%. In multivariate logistic regression, higher prevalence of diabetes was independently associated with daily consumption of coffee (Adjusted odds ratio (AOR)=1.8; p = 0.048); frequently pasta consumption (>3 times/week) (AOR=1.8; p = 0.012); family history of diabetes (AOR=2.5; p = 0.032), work seniority >30 years (AOR= 2.2; p = 0.041) and higher body mass index (AOR=3.2; p = 0.02)

Conclusions

Our study results indicated that the prevalence of diabetes was relatively high among school teachers, addressing the urgent need for adopting healthy lifestyle. The School health program can be utilized as an effective tool to screen non-communicable diseases and to strengthen primary preventive care in school.

Key messages

Diabetes screening and associated factors. School teachers.
Non-communicable diseases in Southern Tunisia: morbidity, mortality profile and chronological trends
Authors: Ketata N , Ben Ayed H , Jedidi J , Yaich S , Maamri H , Baklouti M , Karray R , Kassis M , Feki H , Damak J
Published: October 2021

Introduction

Non-communicable diseases (NCDs) represent a major public health problem worldwide. Giving their impact on the morbidity and mortality burden, understanding their chronological trends over time is a priority for epidemiological surveillance. We aimed to determine the epidemiological specificities of NCDs and to study their chronological trends over the period 2010-2015.

Methods

We retrospectively collected data of hospitalized patients from the regional registry of morbidity and mortality in the Southern University Hospital of Tunisia during the period 2010-2015.

Results

We included 18081 patients with NCDs aged ≥ 25 years, with an annual number of 3013 cases/year. The median age of patients was 60 years(Interquartile range IQR = [43-80 years)]). There were 10288 males(57%), with a sex ratio (male/female)of 1.3. The distribution of NCDs was characterized by the predominance of cardiovascular disease(CVD)(10346 cases, 57.2%), then cancers(3034 cases; 16.8%),diabetes(2489 cases; 13.8%) and chronic respiratory tract diseases(2212 cases; 12.2%). Chronological trends analysis of NCDs showed that they remained globally stable between 2010 and 2015. The same result was applied to the group of cancers, chronic respiratory diseases and diabetes mellitus. However, there was a sharp rise for CVD between 2010 and 2015(ρ = 0.84; p = 0.036). The proportion of CVD increased significantly among men(ρ = 0.87; p = 0.019) and elderly(ρ = 0.88; p = 0.019). During the study period, 234 deaths were due to NCDs, with hospital mortality and lethality rates of 5.2/1000 hospitalizations and 1.29%, respectively. CVD were the main cause of deaths(60%). The hospital mortality rate of NCDs increased significantly from 2010 to 2015(ρ = 0.85; p = 0.031), notably for CVDs(ρ = 0.94; p = 0.005).

Conclusions

Chronological trends analysis revealed a significant rise in the morbidity and mortality burden ofCVDs during the period 2010-2015. It is imperative, therefore, to strengthen health care for these patients.

Key messages

Non-communicable diseases. Morbidity and mortality.