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2.
Lancet Reg Health Eur ; 7: 100131, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34557840

RESUMEN

Background: Little is known about variations in care and outcomes of patients undergoing surgical repair for type A aortic dissection(TAAD). We aim to investigate decade-long trends in TAAD surgical repair in England. Methods: Retrospective review of the National Adult Cardiac Surgery Audit, which prospectively collects demographic and peri­operative information for all major adult cardiac surgery procedures performed in the UK. We identified patients undergoing surgery for TAAD from January 2009-December 2018, reviewed trends in operative frequency, patient demographics, and mortality. Findings: Over the 10-year period,3,680 TAAD patients underwent surgical repair in England. A doubling in the overall number of operations conducted in England was observed (235 cases in 2009 to 510 in 2018). Number of procedures per hospital per year also doubled(9 in 2009 to 23 in 2018). Overall, in-hospital mortality was 17.4% with a trend toward lower mortality in recent years(23% in 2009 to 14.7% in 2018). There was a significant variation in operative mortality between hospitals and surgeons. We also found that most patients presented towards the middle of the week and during winter. Interpretation: Surgery is the only treatment for acute TAAD but is associated with high mortality. Prompt diagnosis and referral to a specialist center is paramount. The number of operations conducted in England has doubled in 10 years and the associated survival has improved. Variations exist in service provision with a trend towards better survival in high volume centers. Funding: British Heart Foundation and NIHR Biomedical Research center(University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol).

3.
Lancet Reg Health Eur ; 7: 100140, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34557843

RESUMEN

Background: Several studies have suggested a variation of myocardial tolerance to ischaemia depending on the daytime of surgery. To test this hypothesis, we conducted a three-level analysis: metaanalysis, national patient-level dataset analysis and a post-hoc trial analysis. Methods: We first performed a systematic review and metaanalysis of available studies comparing clinical outcomes following cardiac surgery performed in the morning (am) versus afternoon (pm). Then, we interrogated the UK national adult cardiac surgery audit database (NACSA) and analysed the am or pm outcomes of patients undergoing non-emergency aortic valve replacement (AVR) or coronary artery bypass grafting (CABG). In a post-hoc analysis, we further investigated the effect of time of surgery on serum troponin release and ventricular myocardial biopsy adenine nucleotide metabolism. Results: A total of 18377 patients undergoing uncomplicated isolated CABG or isolated AVR on the same day am or pm were included in the metaanalysis. Meta-analytic estimates showed no difference in the risk of MI between patients operated in pm vs am (OR 1.02, 95% CI:0.79-1.32) and in the risk of mortality (OR 1.1, 95% CI:0.85-1.42). Outcomes of 91248 patients from the NACSA dataset were analysed according to the daytime of the procedure. Patient-level analysis showed no significant effect of daytime for both isolated AVR (p=0.094) and isolated CABG (p=0.425). Finally, we performed a post-hoc trial database analysis in 124 patients undergoing isolated AVR or CABG of serial cardiac troponin and nucleotides metabolism on ventricular myocardial biopsies. We found no significant diurnal changes in the perioperative cardiac troponin release or nucleotide metabolism in the AVR (p=0.30) or the CABG cohort (p=0.97). Conclusion: The present three-level analysis found no evidence that daytime influences clinical outcomes and myocardial injury in patients undergoing cardiac surgery.

4.
Int J Cardiol ; 343: 27-34, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34520795

RESUMEN

BACKGROUND: Despite advances in cardiac surgery, observational studies suggest that females have poorer post-operative outcomes than males. This study is the first to review sex related outcomes following both coronary artery bypass graft (CABG) and valve surgery with or without combined CABG. METHODS: We identified 30 primary research articles reporting either short-term mortality (in-hospital/30 day), long-term mortality, and post-operative stroke, sternal wound infection and myocardial infarction (MI) in both sexes following CABG and valve surgery with or without combined CABG. Reported adjusted odds/hazard ratio were pooled using an inverse variance model. RESULTS: Females undergoing CABG and combined valve and CABG surgery were at higher risk of short-term mortality (odds ratio (OR) 1.40; 95% confidence interval (CI) 1.32-1.49; I2 = 79%) and post-operative stroke (OR 1.2; CI 1.07-1.34; I2 = 90%) when compared to males. However, for isolated AVR, there was no difference found (OR 1.19; 95% CI 0.74-1.89). There was no increased risk in long-term mortality (OR 1.04; 95% CI: 0.93-1.16; I2 = 82%), post-operative MI (OR 1.22; 95%CI: 0.89-1.67; I2 = 60%) or deep sternal wound infection (OR 0.92; 95%CI: 0.65-1.03, I2 = 87%). No evidence of publication bias or small study effect was found. CONCLUSION: Females are at a greater risk of short-term mortality and post-operative stroke than males following CABG and valve surgery combined with CABG. However, there is no difference for Isolated AVR. Long-term mortality is equivalent in both sexes. PROSPERO Registration: CRD42021244603.


Asunto(s)
Infarto del Miocardio , Cirugía Torácica , Puente de Arteria Coronaria/efectos adversos , Femenino , Humanos , Masculino , Oportunidad Relativa , Factores de Riesgo , Resultado del Tratamiento
5.
Artículo en Inglés | MEDLINE | ID: mdl-34355735

RESUMEN

OBJECTIVES: Patients presenting with more comorbidities, requiring more complex cardiac surgical procedures and an increase in public scrutiny are impacting on training programme because of the perceived risk of worse outcomes. Hence, we aimed to provide evidence that trainees as the first operator can achieve comparable results to consultants when performing isolated surgical aortic valve replacement. METHODS: From 1996 to 2017, 2919 patients underwent surgical aortic valve replacement at the Bristol Heart Institute, operated on by either a consultant (n = 2220) or a trainee (n = 870) as the first operator. Propensity score matching was used to adjust for imbalance in the baseline characteristics of the 2 groups. RESULTS: Over a 21-year period, the proportion of trainee cases dropped from 41.5% to 25.9%. No differences in the rates and risk of in-hospital mortality, new cerebrovascular accidents, re-exploration for bleeding, deep sternal wound infection and length of stay were found between patients operated on in the 2 groups. Also, there was a comparable risk of late death between the 2 groups (HR 0.88; 95% CI 0.73-1.06; P = 0.27) and this was present regardless of trainees career level and patients surgical risk based on the EuroSCORE. Finally, we showed an increase in patients risk profile in the latest year but, this was not associated with the worst outcomes when trainees performed the operation. CONCLUSIONS: Surgical aortic valve replacement is a safe and reproducible technique and regardless of the patient's risk profile, and no differences in the outcomes between trainees and consultant cases were found.

6.
Artículo en Inglés | MEDLINE | ID: mdl-34392335

RESUMEN

OBJECTIVES: Female sex is an established risk factor for postoperative complications after heart surgery, but the influence of sex on outcomes after minimally invasive cardiac surgery (MICS) for valvular replacement/repair remains controversial. We examined whether the role of sex as a risk factor varies by surgical approach [MICS vs conventional sternotomy (ST)] and further assessed outcomes among female patients including in-hospital mortality and postoperative complications by surgical approach. METHODS: We analysed data from a multicentre registry for patients who underwent isolated aortic valve and mitral surgery with MICS or ST. The primary outcome was in-hospital mortality. Propensity score matching was used to minimize between-group differences. RESULTS: Among the 15 155 patients included in the study, 7674 underwent MICS (50.6%). Female sex was equally distributed in the MICS and ST groups (47.3% vs 47.6%, respectively). Risk for surgery was higher in the ST group than in the MICS group {EuroSCORE II: 4.0 [standard deviation (SD): 6.8] vs 3.7 [SD: 6.4]; P = 0.005}, including among female patients only [ST vs MICS 4.6 (SD: 6.9) vs 4.2 (SD: 6.3); P = 0.04]. Mortality did not significantly vary by procedure among women [MICS vs ST, 2.4% vs 2.8%; hazard ratio 1.09, 95% confidence interval 0.71-1.73; P (surgical approach × sex) = 0.51]. The results also did not vary after adjusting for confounders. CONCLUSIONS: Female sex was associated with higher mortality in patients undergoing valve surgery, regardless of surgical approach. In female patients, MICS did not provide any benefits over ST in terms of in-hospital deaths or postoperative complications. SUBJECT COLLECTION: 117, 125.

7.
Artículo en Inglés | MEDLINE | ID: mdl-34236801

RESUMEN

INTRODUCTION: This study examines early- and long-term outcomes of mitral valve repairs in a low-volume cardiac surgery centre in the Caribbean. METHODS: Ninety-six consecutive patients underwent mitral valve repair from April 2009 to December 2018. Patients were divided into two groups: functional mitral regurgitation requiring simple mitral annuloplasty (FMR, n=63) or structural degenerative mitral regurgitation requiring more complex repair (DMR, n=33). Data collected prospectively were retrospectively analysed from the unit-maintained cardiac surgery database. RESULTS: Thirty-day mortality in the whole series was 2.1%, with 3% in the FMR group and 0% in the DMR group. Early post-operative echocardiography in the FMR group demonstrated 51 patients (83.6%) without mitral regurgitation, 8 patients (13.1%) with trivial to mild regurgitation, and 2 patients (3.3%) with moderate regurgitation. However, at a mean follow-up of 98.2±50.8, only 21 patients (42.8%) were in NYHA class I, with 7 (14.2%) in class II, 16 (32.6%) in class III, and 5 (10.2%) in class IV. There were 9 cardiacrelated deaths at final follow-up, with freedom from re-operation and survival of 98% and 75.6%, respectively. In the DMR group, early post-operative echocardiography demonstrated 29 patients (87.9%) without mitral regurgitation, 3 patients (9.1%) with trivial regurgitation and 1 patient (3.0%) with mild regurgitation. At a mean follow-up of 114.1±25.4 months, there was a good functional post-operative status in this group with 93.3% in NYHA class I, and 6.7% in class II. No patient required reintervention, 96.3% of patients had mild or no mitral regurgitation and survival was 90.9%. CONCLUSION: Despite challenges of maintaining skills in a lowvolume centre, mitral valve repair can be performed safely with good early- and long-term results.

8.
Perfusion ; : 2676591211029452, 2021 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-34247534

RESUMEN

BACKGROUND: Lack of scientific data on the feasibility and safety of minimally invasive cardiac surgery (MICS) during the COVID-19 pandemic has made clinical decision making challenging. This survey aimed to appraise MICS activity in UK cardiac units and establish a consensus amongst front-line MICS surgeons regarding standard best MICS practise during the pandemic. METHODS: An online questionnaire was designed through the 'googleforms' platform. Responses were received from 24 out of 28 surgeons approached (85.7%), across 17 cardiac units. RESULTS: There was a strong consensus against a higher risk of conversion from minimally invasive to full sternotomy (92%; n = 22) nor there is increased infection (79%; n = 19) or bleeding (96%; n = 23) with MICS compared to full sternotomy during the pandemic. The majority of respondents (67%; n = 16) felt that it was safe to perform MICS during COVID-19, and that it should not be halted (71%; n = 17). London cardiac units experienced a decrease in MICS (60%; n = 6), whereas non-London units saw no reduction. All London MICS surgeons wore an FP3 mask compared to 62% (n = 8) of non-London MICS surgeons, 23% (n = 3) of which only wore a surgical mask. London MICS surgeons felt that routine double gloving should be done (60%; n = 6) whereas non-London MICS surgeons held a strong consensus that it should not (92%; n = 12). CONCLUSION: Whilst more robust evidence on the effect of COVID-19 on MICS is awaited, this survey provides interesting insights for clinical decision-making regarding MICS and aids to facilitate the development of standardised MICS guidelines for an effective response during future pandemics.

9.
Br J Anaesth ; 127(3): 365-375, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34229833

RESUMEN

BACKGROUND: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery. METHODS: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels. RESULTS: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases. CONCLUSIONS: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Inmunidad Innata , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/mortalidad , Citocinas/sangre , Citocinas/inmunología , Femenino , Humanos , Inmunidad Innata/efectos de los fármacos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Resultado del Tratamiento
11.
J Card Surg ; 36(10): 3877-3880, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34143527

RESUMEN

Acute coronary occlusion after surgical replacement of the aortic valve is a rare but potentially fatal event. Due to its rarity, there is no univocal treatment with the percutaneous approach being the most commonly used for its promptness and ease of use. Only a few cases have been treated with coronary artery bypass grafting (CABG) and, to the best of our knowledge, none has been reported with the use of off-pump CABG (OPCABG). Here we describe the case of acute coronary occlusion of the circumflex artery immediately after surgical replacement of the aortic valve in a 79-year-old patient. The occlusion was promptly diagnosed and treated with interval emergency balloon angioplasty followed by OPCABG of the circumflex artery. The patient made a full recovery and was discharged home 12 days after the surgery.


Asunto(s)
Puente de Arteria Coronaria Off-Pump , Oclusión Coronaria , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Puente de Arteria Coronaria , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/cirugía , Humanos , Resultado del Tratamiento
12.
Perfusion ; : 2676591211013730, 2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-33985387

RESUMEN

OBJECTIVES: To establish the impact of the COVID-19 pandemic on adult cardiac surgery by reviewing current data and use this to establish methods for safely continuing to carry out surgery. METHODS: Conduction of a literature search via PubMed using the search terms: '(adult cardiac OR cardiothoracic OR surgery OR minimally invasive OR sternotomy OR hemi-sternotomy OR aortic valve OR mitral valve OR elective OR emergency) AND (COVID-19 or coronavirus OR SARS-CoV-2 OR 2019-nCoV OR 2019 novel coronavirus OR pandemic)'. Thirty-two articles were selected. RESULTS: Cardiac surgery patients have an increased risk of complications from COVID-19 and require vital finite resources such as intensive care beds, also required by COVID-19 patients. Thus reducing their admission and potential hospital-acquired infection with COVID-19 is paramount. During the peak, only emergencies such as acute aortic dissections were treated, triaging patients according to surgical priority and cancelling all elective procedures. Screening and 2-week quarantine prior to admission were essential changes, alongside additional levels of PPE. Focus was on reducing length of stay and switching to day-cases to reduce post-operative transmission risk, whilst several hospitals adopted 'hot' and 'cold' operating theatres for covid-confirmed and covid-negative patients. CONCLUSIONS: This paper suggests a 'CARDIO' approach for reintroducing elective procedures: 'Care, Assess, Re-Evaluate, Develop, Implement, Overcome'; prioritising the mental and physical health of the workforce, learning from and sharing experiences and objectively prioritising patients to improve case load.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33963362

RESUMEN

OBJECTIVES: The risk of brain injury following surgery for type A aortic dissection (TAAD) remains substantial and no consensus has still been reached on which neuroprotective technique should be preferred. We aimed to investigate the association between neuroprotective strategies and clinical outcomes following TAAD repair. METHODS: Using the UK National Adult Cardiac Surgical Audit, we identified 1929 patients undergoing surgery for TAAD (2011-2018). Deep hypothermic circulatory arrest (DHCA) only, unilateral (uACP), bilateral antegrade cerebral perfusion (bACP) and retrograde cerebral perfusion were used in 830, 117, 760 and 222 patients, respectively. The primary end point was a composite of death and/or cerebrovascular accident (CVA). Generalized linear mixed model was used to adjust the effect of neuroprotective strategies for other confounders. RESULTS: The use of bACP was associated with longer circulatory arrest (CA) compared to other strategies. There was a trend towards lower incidence of death and/or CVA using uACP only for shorter CA. In particular, primary end point rate was 27.7% overall and 26.5%, 12.5%, 28.0% and 22.9% for CA <30 min and 28.6%, 30.4%, 33.3% and 33.0% for CA ≥30 min with DHCA only, uACP, bACP and retrograde cerebral perfusion, respectively. The use of DHCA only was associated with five-fold [odds ratio (OR) 5.35, 95% confidence interval (CI) 1.36-21.02] and two-fold (OR 1.77, 95% CI 1.01-3.09) increased risk of death and/or CVA compared to uACP and bACP, respectively, but the effect of uACP was significantly associated with CA duration (hazard ratio 0.97, 95% CI 0.94-0.99; P = 0.04). CONCLUSIONS: In TAAD repair, the use of uACP and bACP was associated with a lower adjusted risk of death and/or CVA when compared to DHCA. uACP can offer some advantage but only for a shorter CA duration.

15.
Perfusion ; : 2676591211012571, 2021 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-33899586

RESUMEN

Vascular endothelial cell stimulation is associated with the activation of different signalling pathways and transcription factors. Acute shear stress is known to induce different pro-inflammatory mediators such as IL-8. Nrf2 is activated by prolonged high shear stress promoting an antiinflammatory and athero-protective environment. However, little is known about the impact of acute shear stress on Nrf2 and Keap1 function and its role in IL-8 regulation. We aimed to examine Nrf2-Keap1 complex activation in-vitro and its role in regulating IL-8 transcripts under acute arterial shear stress (12 dyn/cm2) in venous endothelial cells (ECs). We note that acute high shear stress caused a significant upregulation of Nrf2 target genes, HO-1 and GCLM and an increased IL-8 upregulation at 90 and 120 minutes. Mechanistically, acute high shear did not affect Nrf2 nuclear translocation but resulted in reduced nuclear Keap1, suggesting that the reduction in nuclear Keap1 may result in increased free nuclear nrf2 to induce transcription. Consistently, the suppression of Keap1 using shRNA (shKeap1) resulted in significant upregulation of IL-8 transcripts in response to acute shear stress. Interestingly; the over expression of Nrf2 using Nrf2-Ad-WT or Sulforaphane was also associated with significant upregulation of IL-8 compared to controls. This study highlights the role of Keap1 in Nrf2 activation under shear stress and indicates that activation of Nrf2 may be deleterious in ECs in the context of acute haemodynamic injury.

16.
J Card Surg ; 36(7): 2269-2276, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33821500

RESUMEN

BACKGROUND: To investigate the impact of severe patient-prosthesis mismatch (PPM) related to the Edwards Lifesciences Perimount (EP) bioprosthesis in the aortic position on early in-hospital outcomes and long-term survival. METHODS: A total of 5964 consecutive patients underwent aortic valve replacement at the Bristol Heart Institute between 1998 and 2014, 2667 representing the cohort of this study received EP. PPM was defined severe as EOAi < 0.65 cm2 /m2 . To minimize bias, propensity score matching was conducted and two groups A and B (without and with severe PPM) of 320 patients with similar preoperative characteristics were matched. We assessed early in-hospital outcomes including CVA, re-exploration for bleeding, low cardiac output, wound infection, acute renal injury, length of hospital stay, and long-term survival for both groups in unmatched and matched populations. RESULTS: In the unmatched analysis, 18.3% of patients had severe PPM. Severe PPM was not associated with increased in-hospital mortality (4.5% vs. 2.9%, respectively, p = .09) or any other early adverse outcomes except increased length of hospital stay (10.57 ± 8.2 vs. 11.7 ± 9.4, respectively, p = .01). Long-term survival differed significantly between groups at 2 and 8 years (91.8% vs. 91.4% and 60.5% vs. 55.7%, respectively, p = .02). Matched analysis showed no differences between the groups in early health outcomes and overall survival at 2 and 8 years was also similar (89.7% vs. 91% and 57.3% vs. 58%, group A vs. B, respectively p = .9). CONCLUSION: Presence of PPM does not seem to affect early in-hospital outcomes or late survival when using EP in patients undergoing aortic valve replacement.


Asunto(s)
Estenosis de la Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Humanos , Puntaje de Propensión , Diseño de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento
17.
J Card Surg ; 36(6): 1985-1995, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33710658

RESUMEN

BACKGROUND: The success of coronary artery bypass grafting surgery (CABG) is dependent on long-term graft patency, which is negatively related to early wall thickening. Avoiding high-pressure distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening. METHODS: A single-centre, factorial randomized controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial-intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months. RESULTS: Ninety-six eligible participants were recruited. With conventional harvest, low-pressure testing tended to yield a thinner vessel wall compared with high-pressure (mean difference [MD; low minus high] -0.059 mm, 95% confidence interval (CI) -0.12, +0.0039, p = .066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD [pedicle minus conventional] -0.057 mm, 95% CI: -0.12, +0.0037, p = .066, test for interaction p = .07). Lumen diameter was similar across groups (harvest comparison p = .81; pressure comparison p = .24). Low-pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p = .0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p = .0041). CONCLUSIONS: Conventional saphenous vein graft preparation with low-pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events.


Asunto(s)
Puente de Arteria Coronaria , Vena Safena , Humanos , Vena Safena/diagnóstico por imagen , Recolección de Tejidos y Órganos , Ultrasonografía , Grado de Desobstrucción Vascular
18.
Mol Ther ; 29(7): 2239-2252, 2021 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-33744469

RESUMEN

MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.

19.
Mol Cell Endocrinol ; 526: 111195, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33571577

RESUMEN

The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to re-establish homeostasis during periods of stress, including critical illness and major surgery. During critical illness, evidence suggests that locally induced inflammation of the adrenal gland could facilitate immune-adrenal cross-talk and, in turn, modulate cortisol secretion. It has been hypothesized that immune cells are necessary to mediate the effect of inflammatory stimuli on the steroidogenic pathway that has been observed in vivo. To test this hypothesis, we developed and characterized a trans-well co-culture model of THP1 (human monocytic cell)-derived macrophages and ATC7 murine zona fasciculata adrenocortical cells. We found that co-culture of ATC7 and THP1 cells results in a significant increase in the basal levels of IL-6 mRNA in ATC7 cells, and this effect was potentiated by treatment with LPS. Addition of LPS to co-cultures of ATC7 and THP1 significantly decreased the expression of key adrenal steroidogenic enzymes (including StAR and DAX-1), and this was also found in ATC7 cells treated with pro-inflammatory cytokines. Moreover, 24-h treatment with the synthetic glucocorticoid dexamethasone prevented the effects of LPS stimulation on IL-6, StAR and DAX-1 mRNA in ATC7 cells co-cultured with THP1 cells. Our data suggest that the expression of IL-6 and steroidogenic genes in response to LPS depends on the activation of intra-adrenal immune cells. Moreover, we also show that the effects of LPS can be modulated by glucocorticoids in a time- and dose-dependent manner with potential implications for clinical practice.


Asunto(s)
Sistema Inmunológico/metabolismo , Modelos Biológicos , Monocitos/citología , Zona Fascicular/citología , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Dexametasona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Ratones , Monocitos/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Esteroides/metabolismo , Células THP-1 , Factores de Tiempo
20.
Eur J Cardiothorac Surg ; 60(1): 34-46, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-33517391

RESUMEN

OBJECTIVES: We sought to provide further evidence on the safety and efficacy of aortic valve neocuspidization (AVNeo) using autologous pericardium in adult patients with aortic valve disease by reporting clinical and echocardiographic results from the first UK experience and performing a meta-analytic comparison with other biological valve substitutes. METHODS: We reported clinical and echocardiographic outcomes of 55 patients (mean age 58 ± 15 years) undergoing AVNeo with autologous pericardium in 2 UK centres from 2018 to 2020. These results were included in a meta-analytic comparison between series on AVNeo (7 studies, 1205 patients, mean weighted follow-up 3.6 years) versus Trifecta (10 studies, 8705 patients, 3.8 years), Magna Ease (3 studies, 3137 patients, 4.1 years), Freedom Solo (4 studies, 1869 patients, 4.4 years), Freestyle (4 studies, 4307 patients, 7 years), Mitroflow (4 studies, 4760 patients, 4.1 years) and autograft aortic valve (7 papers, 3839 patients, 9.1 years). RESULTS: In the present series no patients required intraoperative conversion. After mean follow-up of 12.5 ± 0.9 months, 3 patients presented with endocarditis and 1 required reintervention. The remaining patients had absent or mild aortic valve insufficiency with very low peak and mean transvalvular gradients (16 ± 3.7 and 9 ± 2.2 mmHg, respectively). Meta-analytic estimates showed non-significant difference between AVNeo and all but Magna Ease valves with regards to structural valve degeneration, reintervention and endocarditis. When compared Magna Ease valve, AVNeo and other valve substitutes showed an excess of valve-related events. CONCLUSIONS: AVNeo is safe, associated with excellent haemodynamic profile. Its midterm risk of valve-related events is comparable to most biological valve substitutes. Magna Ease is potentially the best biological choice as far as risk of reintervention is concerned.


Asunto(s)
Estenosis de la Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Adulto , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Hemodinámica , Humanos , Persona de Mediana Edad , Pericardio/cirugía , Pericardio/trasplante , Diseño de Prótesis , Resultado del Tratamiento , Reino Unido/epidemiología
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