SARS-CoV-2 infection modifies the transcriptome of the megakaryocytes in the bone marrow.

Megakaryocytes, integral to platelet production, predominantly reside in the bone marrow and undergo regulated fragmentation within sinusoid vessels to release platelets into the bloodstream. Inflammatory states and infections influence megakaryocyte transcription, potentially affecting platelet functionality. Notably, COVID-19 has been associated with altered platelet transcriptomes. In this study, we investigated the hypothesis that SARS-CoV-2 infection could impact the transcriptome of bone marrow megakaryocytes. Utilizing spatial transcriptomics to discriminate subpopulations of megakaryocytes based on proximity to bone marrow sinusoids, we identified approximately 19,000 genes in megakaryocytes. Machine learning techniques revealed that the transcriptome of healthy murine bone marrow megakaryocytes exhibited minimal differences based on proximity to sinusoid vessels. Further, at peak SARS-CoV-2 viremia, when the disease primarily affected the lungs, megakaryocytes were not significantly different from those from healthy mice. Conversely, a significant divergence in the megakaryocyte transcriptome was observed during systemic inflammation, although SARS-CoV-2 RNA was never detected in bone marrow and it was no longer detectable in the lungs. Under these conditions, the megakaryocyte transcriptional landscape was enriched in pathways associated with histone modifications, megakaryocyte differentiation, NETosis, and autoimmunity, which could not be explained by cell proximity to sinusoid vessels. Notably, the type-I interferon signature and calprotectin (S100A8/A9) were not induced in megakaryocytes under any condition. However, inflammatory cytokines induced in the blood and lungs of COVID-19 mice were different from those found in the bone marrow, suggesting a discriminating impact of inflammation on this specific subset of cells. Collectively, our data indicate that a new population of bone marrow megakaryocytes may emerge through COVID-19-related pathogenesis.

Serum Neurofilament Light and Postoperative Delirium in Cardiac Surgery: A Preplanned Secondary Analysis of a Prospective Observational Study.

BACKGROUND: Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients' cognitive status and would identify patients at risk of postoperative delirium. METHODS: This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method, and a chart review. RESULTS: A total of 65 of 220 (29.5%) patients developed postoperative delirium. Delirious patients were older (median [25th percentile, 75th percentile], 74 [64, 79] vs. 67 [59, 74] yr; P < 0.001) and had lower cognitive z scores (-0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Postoperative neurofilament light concentrations increased in all patients up to day 5, but did not predict delirium when preoperative concentrations were considered. Baseline neurofilament light values were significantly higher in patients who experienced delirium. They were influenced by age, cognitive z score, renal function, and history of diabetes mellitus. Baselines values were significantly correlated with cognitive z scores (r, 0.49; P < 0.001) and were independently associated with delirium whenever the patient's cognitive status was not considered (hazard ratio, 3.34 [95% CI, 1.07 to 10.4]). CONCLUSIONS: Cardiac surgery is associated with axonal injury, because neurofilament light concentrations increased postoperatively in all patients. However, only baseline neurofilament light values predicted postoperative delirium. Baseline concentrations were correlated with poorer cognitive scores, and they independently predicted postoperative delirium whenever patient's cognitive status was undetermined.

Etiology of severe mastitis in French dairy herds.

Severe clinical mastitis is not so frequent in dairy cows, but it can have a significant economic impact due to its high mortality rate and adverse effects on milk production. Surveys about the cause of mastitis typically provide overall findings without connecting them to a specific medical condition. There are few studies on the specific etiology of severe mastitis. Only etiological results obtained during field studies are available in France, and the number of mastitic milk samples analyzed is always low. In recent years, veterinary clinics have improved their ability to identify bacteria causing bovine mastitis using a widely used method. This in-clinic milk culture made it possible to better understand the etiology of mastitis according to the symptoms observed. Regarding clinical mastitis, veterinarians treat severe cases differently than less severe ones. Based on data from nineteen veterinary clinics in France and over 2000 severe mastitis cases, the current study revealed that Enterobacteriaceae, particularly Escherichia coli, is the most common cause, isolated on average from 53.9% of milk samples. This information is highly reliable for practitioners to quickly and effectively treat the condition, because early and targeted treatment is crucial to avoid the complication of endotoxic shock.

Failure of Passive Immunity Transfer Is Not a Risk Factor for Omphalitis in Beef Calves.

Omphalitis is the third most frequent disease in newborn calves after neonatal diarrhea and bovine respiratory disease (BRD), but limited data on the prevalence and risk factors are available in the literature. Failure of passive immunity transfer (FPIT) is recognized as a major risk factor for diseases and mortality in calves. However, the association between omphalitis and FPIT remains poorly described. To assess this association, 964 suckler beef calves from 22 farms were included in a longitudinal cohort study for 5 months. Each calf was examined twice (mean ages: 4.4 and 11.1 days old) to diagnose omphalitis through clinical examination and ultrasonographic evaluation (USE) if necessary. Measurements of the total solids percentage (TS-%Brix) and total protein (TP) were performed on the serum during the first visit to evaluate the calves' passive immunity status. FPIT (fair and poor) was defined as serum %Brix < 8.1 or TP < 5.1 g/dL; among calves with omphalitis, 14% had FPIT and among calves without omphalitis 12% had FPIT. The omphalitis prevalence was 32.3% in calves without any other disease (overall prevalence of 30.9%). No statistical association between the prevalence of omphalitis and FPIT was observed. Further research is needed to identify the risk factors and promote the prevention measures for omphalitis in cow-calf systems, such as calving difficulty, hygiene of housing, and navel disinfection.

Echocardiography of the aortic root: a practical approach for aortic valve-sparing surgery.

Owing to its excellent long-term results, aortic valve-sparing surgery is increasingly used in patients with aortic regurgitation and/or ascending aortic aneurysm. Moreover, in patients with a bicuspid valve who meet the criteria for replacement of the aortic sinuses or aortic regurgitation surgery, valve-sparing surgery may be considered if performed at a comprehensive valve center (Class 2b indication in both the American and European guidelines). Reconstructive valve surgery aims at restoring a normal aortic valve function and a normal aortic root shape as well. Echocardiography plays a central role in defining abnormal valve morphologies, in quantifying aortic regurgitation and mechanisms, and in appreciating tissue valve quality and surgical results. Therefore, despite the emergence of other tomographic techniques, 2D and 3D echocardiography represents the cornerstone for patient selection and prediction of the probability of a reliable repair. The present review focuses on echocardiographic evaluation to detect aortic valve and aortic root abnormalities, to quantify aortic valve regurgitation, to predict aortic valve reparability, and to assess immediate postoperative results in the operating room. Echocardiographic predictors of successful valve and root repair are presented in a practical way.

Late results of aortic valve repair for isolated severe aortic regurgitation.

OBJECTIVES: The objectives were to analyze the long-term outcomes of tricuspid aortic valve repair for isolated severe aortic regurgitation and the impact of different annuloplasty techniques. METHODS: The study cohort consists of 127 consecutive patients who received aortic valve repair for isolated severe aortic regurgitation in the tricuspid aortic valve between 1996 and 2019 in our institution. Exclusion criteria were aorta dilatation (≥45 mm), connective tissue disease, active endocarditis, type A dissection, and rheumatic disease. Mean age of patients was 55.6 ± 16 years, and 80% were male. Median follow-up was 6.4 years. Time-to-event analysis was performed, as well as risk of death, reoperation, and aortic regurgitation recurrence. RESULTS: Cusp repair was performed in 117 patients (92%), and annuloplasty was performed in 126 patients (99%) with Cabrol stitch (73%), reimplantation technique (19.7%), or ring annuloplasty (6.3%). There was no hospital mortality. At 10 and 14 years, overall survival was 81% ± 5% and 71% ± 6%, respectively, and freedom from reoperation was 80% ± 5% and 73% ± 6%, respectively. Age and left coronary cusp repair were independent predictors of reoperation. Freedom from recurrent severe aortic regurgitation (>2+) was 73% ± 5% and 66% ± 7% at 10 and 12 years, respectively. Age, left ventricular end-diastolic diameter, and patch repair were independent predictors of recurrent aortic regurgitation. Type of annuloplasty had no impact on survival or reoperation. CONCLUSIONS: Aortic valve repair for isolated severe aortic regurgitation in the tricuspid aortic valve is a safe procedure, and durability at 14 years is acceptable. In this study, the annuloplasty technique did not influence repair durability as was found in bicuspid aortic valve repair or aortic valve-sparing surgery. Severity of cusp pathology seems to be the main determinant of repair durability.

Predictors of long-term stenosis in bicuspid aortic valve repair.

OBJECTIVES: The use of modern techniques for bicuspid aortic valve repair has been shown to provide safe and durable results against recurrent regurgitation. However, an emerging body of evidence is indicating that aortic stenosis might be an additional late complication of these procedures. To date, the pathogenesis and clinical impact of aortic stenosis after bicuspid aortic valve repair are poorly understood. METHODS: A retrospective analysis of 367 patients with bicuspid aortic valve repair was performed to identify predictors of reoperation for stenosis. Bicuspid aortic valve repair was performed using a combination of procedures on the leaflet, annulus, and aortic root. RESULTS: During a median follow-up of 8 years, reoperation for stenosis was required in 33 patients (9.0%). Freedom from reoperation for stenosis was 100%, 99.6%, 91.7%, and 74.9% at 1, 5, 10, and 15 years, respectively. The following factors were independently associated with reoperation for aortic stenosis: Leaflet or raphe resection with shaving was a protective factor (hazard ratio, 0.34; 95% confidence interval, 0.16-0.71; P = .004), whereas the use of expanded polytetrafluoroethylene for free-edge running suture (hazard ratio, 2.55; 95% confidence interval, 1.16-5.57; P = .019), supracoronary replacement of the ascending aorta in combination with valve repair (hazard ratio, 5.41; 95% confidence interval, 2.11-13.85; P = .001), and the need for a second aortic crossclamp (hazard ratio, 10.95; 95% confidence interval, 2.80-42.80; P = .001) were associated with increased risk of reoperation for aortic stenosis. CONCLUSIONS: While confirming previous findings, our analysis suggests that the inability to restore leaflet mobility and polytetrafluoroethylene for free-edge running suture are risk factors for stenosis. The so-called ascending phenotypes are probably more prone to stenosis. If the first attempt to repair is unsuccessful, the risk of late reoperation for aortic stenosis is high.

Robotic mitral valve repair: A single center experience over a 7-year period.

BACKGROUND: We report the clinical and echocardiographic results of our experience in robotic mitral valve repair over a 7-year period. The outcomes of the earliest and the latest patients will be compared. METHODS: Between March 2012 and October 2019, 226 patients underwent robotic mitral valve repair for severe mitral regurgitation in a single institution. The first 113 patients (Group 1) were operated between March 2012 and September 2015 and the last 113 patients (Group 2) between October 2015 and October 2019. Conventional techniques employed in open surgery were used. Clinical and echographic follow-up were 96.0% and 94.2% complete, respectively. RESULTS: Successful mitral repair was achieved in all cases with no hospital mortality. The overall survival rate was 92.7 ± 2.8% and 91.0 ± 3.2% at 3 and 7 years, respectively, with no in between groups difference (p = 0.513). The overall freedom from mitral reoperation was 97.4 ± 1.2% at 3 and 7 years and was similar in both groups (p = 0.276). Freedom from mitral regurgitation Grade 2+ at 3 and 7 years were 89.1 ± 2.6% and 87.9 ± 2.8%, respectively, with no significant difference between groups (p = 0.056). CONCLUSIONS: Developing a robotic mitral repair program can be done without compromising the safety and efficacy of repair. After a well-conducted training, robotic approach allows to perform simple and complex mitral repair using similar techniques as in conventional approach and without additional risk for the patient.

Two decades of valve-sparing root reimplantation in tricuspid aortic valve: impact of aortic regurgitation and cusp repair.

OBJECTIVES: Our goal was to analyse the influence of preoperative aortic regurgitation (AR) on the necessity of cusp repair during valve-sparing reimplantation (VSR). We focused on patients with tricuspid aortic valves (TAV) and evaluated the impact of AR and cusp repair on long-term outcomes. METHODS: From March 1998 to December 2018, a total of 512 consecutive patients underwent VSR at our institution; of these, 303 had a TAV. The mean age was 53 ± 15 years, and the median follow-up was 6.12 years. The rate and type of cusp repair were analysed based on preoperative AR. Time-to-event analysis was performed, as well as risk of death, reoperation and AR recurrence. RESULTS: Cusp repair was necessary in 168 (55.4%) patients; the rate rose significantly as AR grade increased (P < 0.001). In-hospital mortality was 1% (n = 3). At 5 and 10 years, overall survival was 92 ± 2% and 75 ± 5%, respectively. Freedom from valve reoperation was 95 ± 2% and 90 ± 3%. Freedom from AR >2+ and AR >1+ at 10 years was 88 ± 4% and 70.4 ± 4.6%, respectively. Independent predictors of death included age, New York Heart Association functional class and type-A aortic dissection. Predictors of AR greater than mild included previous cardiac surgery and severe preoperative AR. CONCLUSION: In patients with TAV receiving VSR, the necessity of cusp repair increased with the degree of preoperative AR. Preoperative AR and cusp repair do not impact long-term survival and aortic valve reoperation, but severe preoperative AR and multiple cusp repair increase the risk of recurrent moderate-to-severe AR. Overall, cusp repair seems to attenuate the negative impact of preoperative AR for at least 1 decade in a majority of patients.

Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery.

BACKGROUND: Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo. METHODS: In this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 µg kg-1 h-1) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method. RESULTS: POD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52-1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital. CONCLUSIONS: Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study. CLINICAL TRIAL REGISTRATION: NCT03388541.

Predicting postoperative delirium and postoperative cognitive decline with combined intraoperative electroencephalogram monitoring and cerebral near-infrared spectroscopy in patients undergoing cardiac interventions.

Studies have associated electroencephalogram (EEG) suppression with postoperative delirium (POD) and postoperative cognitive decline (POCD). Otherwise, improving cerebral tissue oxygen saturation (rScO2) seems beneficial. No study has evaluated the impact of EEG suppression and decreased rScO2 on the incidence of POD and POCD when the intraoperative management of patients is performed with a depth-of-anesthesia (DOA) monitor and a cerebral oximetry. In this prospective study patients undergoing cardiac interventions were monitored with the NeuroSENSE® DOA monitor and bilateral cerebral oximetry. An algorithm was used to optimize cerebral oxygenation. EEG suppression was presented as total area under the curve (AUC) of suppression ratio (SR) > 0 s (AUCEEGSR>0s). Cerebral desaturation was defined as AUC of 25% drop of oximetry values as compared to baseline. POD was evaluated by the chart review method. POCD was defined as a Z-score ≤ 2 based on Mini Mental State Examination at baseline and day 5 or if the patient reported any cognitive decline at 3 and at 6 months postoperatively. Among the 1616 patients, 1513 underwent normothermic surgery and were further analyzed. POD and POCD were respectively evaluated in 1504 and 1350 patients of whom 303 (20%) and 270 (20%) were respectively diagnosed positive. Having experienced high magnitudes of EEG suppression (fourth quartile of AUCEEGSR>0s) was significantly associated with POD (OR = 2.247; 95% CI = 1.414-3.571; P = 0.001). Low rScO2 at the end of surgery was statistically associated with POCD (OR = 0.981; 95% CI = 0.965-0.997; P = 0.018). The results of our study show that the degree of intraoperative EEG suppression on one hand, and low rScO2 at the end of procedure on the other hand, are associated with respectively POD and POCD in patients undergoing cardiac interventions.