Genetic variability of aquaporin expression in maize: from eQTLs to a MITE insertion regulating PIP2; 5 expression.

Plant aquaporins are involved in numerous physiological processes, such as cellular homeostasis, tissue hydraulics, transpiration, and nutrient supply, and are key players of the response to environmental cues. While varying expression patterns of aquaporin genes have been described across organs, developmental stages and stress conditions, the underlying regulation mechanisms remain elusive. Hence, this work aimed to shed light on the expression variability of four plasma membrane intrinsic protein (PIP) genes in maize (Zea mays) leaves, and its genetic causes, through eQTL (expression quantitative trait locus) mapping across a 252-hybrid diversity panel. Significant genetic variability in PIP transcript abundance was observed to different extents depending on the isoforms. The genome-wide association study mapped numerous eQTLs, both local and distant, thus emphasizing the existing natural diversity of PIP gene expression across the studied panel and the potential to reveal regulatory actors and mechanisms. One eQTL associated with PIP2; 5 expression variation was characterized. Genomic sequence comparison and in vivo reporter assay attributed, at least partly, the local eQTL to a transposon-containing polymorphism in the PIP2; 5 promoter. This work paves the way to the molecular understanding of PIP gene regulation and its possible integration into larger networks regulating physiological and stress-adaptation processes.

Trends in SAVR with biological vs. mechanical valves in middle-aged patients: results from a French large multi-centric survey.

Background/introduction: Currently, despite continued issues with durability ( 1), biological prosthetic valves are increasingly chosen over mechanical valves for surgical aortic valve replacement (SAVR) in adult patients of all ages, at least in Western countries. For younger patients, this choice means assuming the risks associated with a redo SAVR or valve-in-valve procedure. Purpose: To assess the use of mechanical vs. biological valve prostheses for SAVR relative to patient's age and implant time in a large population extracted from the French National Database EPICARD. Methods: Patients in EPICARD undergoing SAVR from 2007 to 2022 were included from 22 participating public or private centers chosen to represent a balanced representation of centre sizes and geographical discrepancies. Patients with associated pathology of the aorta (aneurysm or dissection) and requiring a vascular aortic prosthesis were excluded. Comparisons were made amongst centers, valve choice, implant date range, and patient age. Results: We considered 101,070 valvular heart disease patients and included 72,375 SAVR (mean age 71.4 ± 12.2 years). We observed a mechanical vs. biological prosthesis ratio (MBPR) of 0.14 for the overall population. Before 50 years old (y-o), MBPR was >1.3 (p < 0.001) while patients above 60 years-old received principally biological SAVR (p < 0.0001). Concerning patients between 50 and 60 years-old patients, MPVR was 1.04 (p = 0.03). Patients 50-60 years-old from the first and second study duration quartile (before August 2015) received preferentially mechanical SAVR (p < 0.001). We observed a shift towards more biological SAVR (p < 0.001) for patients from the third and fourth quartile to reach a MBPR at 0.43 during the last years of the series. Incidentally, simultaneous mitral valve replacement were more common in case of mechanical SAVR (p < 0.0001), while associated CABGs were more frequent in case of biological SAVR (p < 0.0001). Conclusion: In a large contemporary French patient population, real world practice showed a recent shift towards a lower age-threshold for biological SAVR as compared to what would suggest contemporary guidelines.

Prosthetic choice in mitral valve replacement for severe chronic ischemic mitral regurgitation: Long-term follow-up.

BACKGROUND: Prosthetic choice for mitral valve replacement is generally driven by patient age and patient and surgeon preference, and current guidelines do not discriminate between different etiologies of mitral valve disease. Our objective was to assess and compare short- and long-term outcomes after mitral valve replacement among patients with biological or mechanical prostheses in the setting of severe ischemic mitral regurgitation. METHODS: Between 2000 and 2016, 424 patients underwent mitral valve replacement for severe ischemic mitral regurgitation at our institution, using biological prosthesis in 188 (44%) and mechanical prosthesis in 236 (56%). A 1:1 propensity score match (n = 126 per group) and inverse probability of treatment weighting were used to compare groups. Short-term outcomes included in-hospital mortality and other cardiovascular adverse events. Long-term outcomes included survival and hospital readmission for cardiovascular causes, stroke, and major bleeding. RESULTS: In-hospital mortality and early postoperative adverse events were similar between groups in the propensity score match and inverse probability of treatment weighting cohorts. Overall long-term survival was similar at 5 and 9 years, but mechanical prosthesis recipients were more frequently readmitted to hospital for cardiovascular causes, including stroke and non-neurological bleeding in propensity score matching and inverse probability of treatment weighting analyses (all P values < .004). Type of prosthesis did not independently influence all-cause mortality (hazard ratio, 1.01; 95% confidence interval, 0.71-1.43; P = .959), but placement of a mechanical prosthesis was associated with increased risk of readmission for cardiovascular events (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) among matched patients. CONCLUSIONS: The type of prosthesis has no influence on long-term survival among patients with severe ischemic mitral regurgitation undergoing mitral valve replacement. There may be an increased risk of neurologic events and serious bleeding associated with mechanical prostheses.

Surgical Aortic Valve Replacement in the Elderly: It Is Worth It!

To evaluate survival and quality of life of octogenarians after surgical aortic valve replacement (SAVR), up to 10 year of follow-up. Retrospective observational study on octogenarians operated for an isolated or combined SAVR in 2 centers between 2005 and 2011. Preoperative data were collected for each patient and updated regularly with last follow-up on July 2018. Early postoperative course was assessed for all patients. The primary outcome was late survival after discharge. Health-related quality of life was evaluated in all surviving patients using the Short-Form 12 questionnaire. Nine hundred and nine patients were included. The median age was 82 ± 2.6 years, with 400/909 females (44%). Isolated AVR was performed in 452/909 patients (49.7%). Early in-hospital mortality occurred in 71/909 patients (7.8%). Mean follow-up was 5.9 ± 3.4 years. Survival at 2, 5, and 10 years in the overall cohort was 89%, 70%, and 28%, respectively, without significant difference between isolated or combined AVR. Survival was significantly higher in patients with a Euroscore <8% (P< 0.0001). Multivariate analysis found that older age at surgery, diabetes, history of myocardial infarction, atrial fibrillation and chronic renal failure were predictors of long-term mortality. Finally, the SF-12 physical score was 40.7 ± 10.4 and mental and emotional score was 52.7 ± 8.6 at last follow-up, which falls within the expected range for the general population (50 ± 10) with comparable age. SAVR remains an effective treatment for aortic valve disease in octogenarians, not only increasing life expectancy but also conferring a long-standing quality of life with excellent valve durability.

Early to midterm survival of patients with deep sternal wound infection managed with laparoscopically harvested omentum.

OBJECTIVE: The optimal management of deep sternal wound infection (DWSI) remains controversial. Our objective was to evaluate outcomes of patients with DSWI managed with transposition of laparoscopically harvested omentum (LHO). METHODS: Between 2000 and 2020, a total of 38,623 adult patients who underwent full median sternotomy for cardiac surgery were analyzed retrospectively at our institution. DSWI occurred in 455 (1.2%), of whom 364 (93.2%) were managed with pectoralis myocutaneous flap (PMF) and 33 (7.2%) with LHO. Univariate and multivariate analysis models were used to determine predictors of cumulative late mortality and adjusted survival curves were generated. RESULTS: Among patients who received LHO, average age was 65.7 ± 9.7 years and a larger proportion of patients were male. A majority of patients (88%) had coronary bypass surgery, with bilateral internal mammary arteries use in only 21.2%. Mean length of stay (LOS) was 58.90 days and early hospital mortality occurred in 4 patients (12.1%). Patients who received LHO compared to only PMF had larger body mass index and had more heart failure. Furthermore, the hospital LOS was also significantly prolonged in the LHO group (58.9 vs. 27.4 days, p = .002), with a slightly higher in-hospital mortality (12.1% vs. 3.3%, p = .03). Late survival for LHO patients at 5 and 10 years was 71.9% and 44.8%, respectively. CONCLUSION: Use of LHO is a safe and viable alternative to traditional myocutaneous flaps to manage complex DSWI. Early and late survival were favorable in this high-risk population.

Adult cardiac surgery during COVID-19 lockdown: Impact on activity and outcomes in a high-volume centre.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak had a direct impact on adult cardiac surgery activity, which systematically necessitates a postoperative stay in intensive care. AIM: To study the effect of the COVID-19 lockdown on cardiac surgery activity and outcomes, by making a comparison with the corresponding period in 2019. METHODS: This prospective observational cohort study compared adult cardiac surgery activity in our high-volume referral university hospital from 9 March to 10 May 2020 versus 9 March to 10 May 2019. Data were collected in our local certified database and a national database sponsored by the French society of thoracic and cardiovascular surgery. The primary study endpoints were operative mortality and postoperative complications. RESULTS: With 105 interventions in 2020, our activity dropped by 57% compared with the same period in 2019. Patients were at higher risk, with a significantly higher EuroSCORE II score (3.8±4.5% vs. 2.0±1.8%; P<0.001) and higher rates of active endocarditis (7.6% vs. 2.9%; P=0.047) and recent myocardial infarction (9.5% vs. 0%; P<0.001). The weight and priority of the interventions were significantly different in 2020 (P=0.019 and P<0.001, respectively). The rate of acute aortic syndromes was also significantly higher in 2020 (P<0.001). Operative mortality was higher during the lockdown period (5.7% vs. 1.7%; P=0.038). The postoperative course was more complicated in 2020, with more postoperative bleeding (P=0.003), mechanical circulatory support (P=0.032) and prolonged mechanical ventilation (P=0.005). Only two patients (1.8%) developed a positive status for severe acute respiratory syndrome coronavirus 2 after discharge. CONCLUSIONS: Adult cardiac surgery was heavily affected by the COVID-19 lockdown. A further modulation plan is necessary to improve outcomes and reduce postponed operations to decrease operative mortality and morbidity.

Frozen elephant trunk infection: to defrost or to debranch?

Infections of frozen elephant trunk hybrid prosthesis (HP) are not well documented in the literature and their management is not standardized yet. We report herein the case of a 59-year-old patient who benefited from a Thoraflex™ HP aortic arch replacement for an acute type A aortic dissection. He presented a year later with a Staphylococcus aureus infection of the proximal part of this prosthesis. We performed a replacement of the proximal compound of the HP accompanied by a complete debranching of the 3 supra-aortic vessels with an inter-carotidal retro-oesophageal bypass. As we left in situ the endovascular graft within the descending aorta, a life-long antibiotic therapy was introduced. The postoperative follow-up was uneventful, and the patient discharged home 2 weeks after his surgery. As an alternative to a more radical redo surgery with major risk, a hybrid medical and surgical treatment of infected frozen elephant trunk could be considered.

Long-term outcome of the in situ versus free internal thoracic artery as the second arterial graft.

OBJECTIVES: The study objective was to determine the impact on outcome associated with using the second internal thoracic artery as a free compared with an in situ graft among patients who received the first internal thoracic artery as an in situ internal thoracic artery to the left anterior descending artery. METHODS: Among 2600 patients who underwent bilateral internal thoracic artery with an in situ internal thoracic artery to the left anterior descending artery, the second internal thoracic artery was used as a free graft bilateral internal thoracic artery in 136 patients and as an in situ graft (in situ bilateral internal thoracic artery) in 2464 patients. One-to-many propensity score matching was performed to produce a cohort of 134 patients with a second free graft internal thoracic artery matched to 2359 patients with a second in situ internal thoracic artery. Early and long-term outcomes including survival, hospital readmission, and repeat revascularization up to a maximum of 25.8 years were compared. RESULTS: There were no differences between the 2 matched groups' preoperative baseline characteristics and early adverse events. Long-term survival at 5, 10, and 15 years was significantly higher among patients with an in situ bilateral internal thoracic artery compared with patients with a free graft bilateral internal thoracic artery (hazard ratio free graft bilateral internal thoracic artery vs in situ bilateral internal thoracic artery, 1.53; 95% confidence interval, 1.14-2.10; P = .004). However, the long-term risk of readmission to the hospital for cardiovascular reasons and need for repeat revascularization were not significantly different between the 2 matched groups. CONCLUSIONS: In a small, propensity-matched cohort of patients undergoing coronary artery bypass grafting, the use of a second in situ internal thoracic artery was associated with an increase in late survival compared with the use of a second internal thoracic artery as a free graft. However, the risk of late hospital readmission and the need for repeat revascularization were similar.

The frozen elephant trunk technique in an emergency: THORAFLEX French National Registry offers new insights.

OBJECTIVES: Our goal was to study the immediate outcome after an emergency frozen elephant trunk procedure with a Thoraflex™ Hybrid prosthesis (THP) in patients included in the EPI-Flex national registry and operated on in 21 French centres. METHODS: All patients operated on in France between April 2016 and April 2019 for acute aortic syndromes and who had an frozen elephant trunk procedure with a THP were included in the study. The main end point was in-hospital mortality. The secondary end point was neuromorbidity, including paraplegia. The evolution of the main end point was monitored using a variable life-adjusted display graph with cumulative sum derivatives in order to stop inclusions in case the observed mortality became out of range compared to an expected mortality between 15% and 20%. RESULTS: Enrolment ended on the scheduled date and included 109 patients. Most cases (54%) were performed at 3 centres, where more than 10 THP each were implanted (10-26). The observed mortality in the large-volume centres (22%) was comparable to that observed in the low-volume centres (20%). The individually risk-adjusted cumulative sum revealed that observed in-hospital mortality was statistically in line with that predicted by the log EuroSCORE. Analysis of the secondary end point revealed 8% cases of paraplegia, all of which appeared after treatment of the thoracic type A aortic dissection. CONCLUSIONS: In France, THP for emergency frozen elephant trunk surgery outside high-volume centres did not result in excessive in-hospital deaths. However, a word of caution must be expressed regarding the prevention of medullar ischaemia even in emergency aortic surgery.

Aortic valve calcification in the era of non-coding RNAs: The revolution to come in aortic stenosis management?

Aortic valve stenosis remains the most frequent structural heart disease, especially in the elderly. During the last decade, we noticed an important consideration and a huge number of publications related to the medical and surgical treatment of this disease. However, the molecular aspect of this degenerative issue has also been more widely studied recently. As evidenced in oncologic but also cardiac research fields, the emergence of microRNAs in the molecular screening and follow-up makes them potential biomarkers in the future, for the diagnosis, follow-up and treatment of aortic stenosis. Herein, we present a review on the implication of microRNAs in the aortic valve disease management. After listing and describing the main miRNAs of interest in the field, we provide an outline to develop miRNAs as innovative biomarkers and innovative therapeutic strategies, and describe a groundbreaking pre-clinical study using inhibitors of miR-34a in a pre-clinical model of aortic valve stenosis.

Exploring the N-Glycosylation Profile of Glycoprotein B from Human Cytomegalovirus Expressed in CHO and Nicotiana tabacum BY-2 Cells.

The ability to control the glycosylation pattern of recombinant viral glycoproteins represents a major prerequisite before their use as vaccines. The aim of this study consisted of expressing the large soluble ectodomain of glycoprotein B (gB) from Human Cytomegalovirus (HMCV) in Nicotiana tabacum Bright Yellow-2 (BY-2) suspension cells and of comparing its glycosylation profile with that of gB produced in Chinese hamster ovary (CHO) cells. gB was secreted in the BY-2 culture medium at a concentration of 20 mg/L and directly purified by ammonium sulfate precipitation and size exclusion chromatography. We then measured the relative abundance of N-glycans present on 15 (BY-2) and 17 (CHO) out of the 18 N-sites by multienzymatic proteolysis and mass spectrometry. The glycosylation profile differed at each N-site, some sites being occupied exclusively by oligomannosidic type N-glycans and others by complex N-glycans processed in some cases with additional Lewis A structures (BY-2) or with beta-1,4-galactose and sialic acid (CHO). The profiles were strikingly comparable between BY-2- and CHO-produced gB. These results suggest a similar gB conformation when glycoproteins are expressed in plant cells as site accessibility influences the glycosylation profile at each site. These data thus strengthen the BY-2 suspension cultures as an alternative expression system.

Transcatheter Aortic Valve Replacement for a Failed Mechanical Aortic Prosthesis.

The options for reoperation for a dysfunctional mechanical aortic prosthesis in a small aortic root may be limited for high-risk patients. This report describes a case in which transcatheter aortic valve replacement was used through the open aorta on cardiopulmonary bypass to minimize operative duration and reduce the risk of prosthesis-patient mismatch in a patient who was a Jehovah's Witness with a failed 17-mm mechanical aortic prosthesis.

Biological scoring system for early prediction of acute bowel ischemia after cardiac surgery: the PALM score.

BACKGROUND: Bowel ischemia is a life-threatening emergency defined as an inadequate vascular perfusion leading to bowel inflammation resulting from impaired colonic/small bowel blood supply. Main issue for physicians regarding bowel ischemia diagnosis lies in the absence of informative and specific clinical or biological signs leading to delayed management, resulting in a poorer prognosis, especially after cardiac surgery. The aim of the present series was to propose a simple scoring system based on biological data for the diagnosis of bowel ischemia. METHODS: In a retrospective monocentric study, patients admitted in cardiac ICU, after cardiovascular surgery, were screened for inclusion. According to a 1:2 ratio (case-control), matching between two groups was based on sex, type of cardiovascular surgery, and the operative period (per month). Patients were divided into two groups: "ischemic group" which corresponds to patients with confirmed bowel ischemia and "non-ischemic group" which corresponds to patients without bowel ischemia. Primary objective was the conception of a scoring system for the diagnosis of bowel ischemia. Secondary objectives were to detail the postoperative morbidity and the diagnostic features for the distinction between acute mesenteric ischemia and ischemic colitis. RESULTS: Forty-eight patients (1.3%) had confirmed bowel ischemia ("ischemic group"). According to the 2:1 matching, 96 patients were included in the "non-ischemic group." Aspartate aminotransferase > 449 UI/L, lactate > 4 mmol/L, procalcitonin > 4.7 µg/L, and myoglobin > 1882 µg/L were found to be independently associated with bowel ischemia. Based on their respective odds ratios, points were assigned to each item ranging from 4 to 8. AUROCC [95% confidence interval] of the scoring system to diagnose bowel ischemia was 0.93 [0.91-0.95], p < 0.001. The optimal threshold after bootstrapping was ≥ 14 points; this yielded a sensitivity of 85.4%, a specificity of 94.8%, a positive likelihood ratio of 16.42, a negative likelihood ratio of 0.15, a Youden's index of 0.802, and a diagnostic odds ratio of 106.62. CONCLUSIONS: A biological scoring system based on PCT, ASAT, lactate, and myoglobin measurement allows the diagnosis of bowel ischemia after cardiac surgery with high accuracy. This score could help clinician to propose an early diagnosis and an early treatment in this high mortality disease.

miR-92a: A Novel Potential Biomarker of Rapid Aortic Valve Calcification.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare the tissular expression of microRNAs (miRs) in bicuspid and tricuspid valves, and to evaluate their use as potential novel biomarkers of aortic valve calcification in bicuspid valves. METHODS: A prospective single-center observational study was conducted on stenotic bicuspid and tricuspid human aortic valves. According to their potential role in valve vascular and valvular calcification, a decision was taken to include miR- 92a, miR-141, and miR-223 in this analysis. A real-time quantitative polymerase chain reaction was used to measure the expression of each miR, using U6 and Cel-miR-39 as endogenous and exogenous gene controls, respectively. RESULTS: Among a total of 47 human calcified aortic valves collected, 30 (63.8%) were tricuspid valves. The mean preoperative transvalvular gradient was 50.8 mmHg (range: 37-89 mmHg), with no significant difference between bicuspid and tricuspid valves (50 mmHg versus 51.2 mmHg; p = 0.729). The mean aortic valve area was 0.79 cm2 (range: 0.33-1.3 cm2), again with no significant difference between the two groups (p = 0.34). The level of miR-92a expression was twofold higher in bicuspid valves compared to tricuspid valves (0.38 versus 0.17; p = 0.016), but no significant difference in miR-141 and miR-223 expression was observed between the two groups (p = 0.68 and p = 0.35, respectively). A positive correlation was observed between miR-92a expression and mean preoperative transvalvular gradient (r = 0.3257, p = 0.04). CONCLUSIONS: miR-92a is overexpressed in calcified bicuspid aortic valves, and may serve as a potential biomarker of rapid aortic valve calcification. Further studies based on these results may be designed to correlate the relative expression of miR-92a in the serum with its tissular expression in AS.

The Involvement of miRNA in Carotid-Related Stroke.

Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Stroke is associated with a marked disability burden and has a major economic impact; this is especially true for carotid artery stroke. Major advances in primary and secondary prevention during the last few decades have helped to tackle this public health problem. However, better knowledge of the physiopathology of stroke and its underlying genetic mechanisms is needed to improve diagnosis and therapy. miRNAs are an important, recently identified class of post-transcriptional regulators of gene expression and are known to be involved in cerebrovascular disease. These endogenous, small, noncoding RNAs may have applications as noninvasive biomarkers and therapeutic tools in practice. Here, we review the involvement of several miRNAs in cell-based and whole-animal models of stroke, with a focus on human miRNA profiling studies of carotid artery stroke. Lastly, we describe the miRNAs' potential role as a biomarker of stroke.

N-Glycosylation of an IgG antibody secreted by Nicotiana tabacum BY-2 cells can be modulated through co-expression of human ß-1,4-galactosyltransferase.

Nicotiana tabacum BY-2 suspension cells have several advantages that make them suitable for the production of full-size monoclonal antibodies which can be purified directly from the culture medium. Carbohydrate characterization of an antibody (Lo-BM2) expressed in N. tabacum BY-2 cells showed that the purified Lo-BM2 displays N-glycan homogeneity with a high proportion (>70%) of the complex GnGnXF glycoform. The stable co-expression of a human ß-1,4-galactosyltransferase targeted to different Golgi sub-compartments altered Lo-BM2N-glycosylation and resulted in the production of an antibody that exhibited either hybrid structures containing a low abundance of the plant epitopes (α-1,3-fucose and ß-1,2-xylose), or a large amount of galactose-extended N-glycan structures. These results demonstrate the suitability of stable N-glycoengineered N. tabacum BY-2 cell lines for the production of human-like antibodies.

Unusual Gastrointestinal Bleeding After Sutureless Aortic Valve Replacement: A Word of Caution.

We report the clinical case of a male patient who presented, after an aortic valve replacement with a rapid deployment bioprosthesis, a Heyde-like syndrome, secondary to a moderate aortic paravalvular leakage. All the digestive and hematologic investigations confirmed the diagnosis. A redo surgery to fill the paravalvular gap was accomplished and the postoperative course was uneventful, with a normalization of the biological parameters. To our knowledge, this is the first described case of such a complication with the new generation of sutureless bioprosthesis.

Monitoring dynamic arterial elastance as a means of decreasing the duration of norepinephrine treatment in vasoplegic syndrome following cardiac surgery: a prospective, randomized trial.

PURPOSE: To evaluate the ability of an algorithm based on dynamic arterial elastance to decrease the duration of norepinephrine treatment. METHODS: We performed a prospective, open-label, randomized study in patients requiring norepinephrine for vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass. Patients were randomized to an algorithm-based intervention group or a control group. The primary outcome was the duration of norepinephrine treatment. The secondary outcomes included the total dose of norepinephrine, the length of stay (LOS) in the ICU, central venous oxygen saturation, arterial lactate levels, arrhythmia and diuresis. RESULTS: Of 130 included patients, 118 were analysed on an intention-to-treat basis (intervention group: n = 59; control group: n = 59). On inclusion, the intervention and control groups did not differ significantly in terms of demographic characteristics, surgical data or the prior duration of norepinephrine treatment [5 h (4-10) vs. 5 h (5-7), respectively; P = 0.543]. The cumulative duration of norepinephrine treatment after inclusion was shorter in the intervention group than in the control group [17 h (13-26)] vs. 39 h (19-58), respectively; (P < 0.001). The cumulative dose of norepinephrine and the LOS in the ICU were also lower in the intervention group (P < 0.05). There were no intergroup differences for other outcomes (the sepsis-related organ failure score, central venous oxygen saturation, arrhythmia, and arterial lactate levels). CONCLUSION: A haemodynamic algorithm based on dynamic arterial elastance was associated with a shorter duration of norepinephrine treatment and a shorter LOS in the ICU. Use of the algorithm did not alter perfusion parameters or increase the volume of fluid infused. ClinicalTrials.gov Identifier: NCT02479529.