Limited versus full sternotomy for aortic valve replacement

Copyright \ua9 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. BACKGROUND: Aortic valve disease is a common condition easily treatable with cardiac surgery. This is conventionally performed by opening the sternum (\u27median sternotomy\u27) and replacing the valve under cardiopulmonary bypass. Median sternotomy is well tolerated, but as less invasive options become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access have raised safety concerns with regard to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. This is an update of a Cochrane review first published in 2017, with seven new studies. OBJECTIVES: To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement. SEARCH METHODS: We performed searches of CENTRAL, MEDLINE and Embase from inception to August 2021, with no language limitations. We also searched two clinical trials registries and manufacturers\u27 websites. We reviewed references of primary studies to identify any further studies of relevance. SELECTION CRITERIA: We included randomised controlled trials comparing aortic valve replacement via a median sternotomy versus aortic valve replacement via a limited sternotomy. We excluded trials that performed other minimally invasive incisions such as mini-thoracotomies, port access, transapical, transfemoral or robotic procedures. Although some well-conducted prospective and retrospective case-control and cohort studies exist, these were not included in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial papers to extract data, assess quality, and identify risk of bias. A third review author provided arbitration where required. We determined the certainty of evidence using the GRADE methodology and summarised results of patient-relevant outcomes in a summary of findings table. MAIN RESULTS: The review included 14 trials with 1395 participants. Most studies had at least two domains at high risk of bias. We analysed 14 outcomes investigating the effects of minimally invasive limited upper hemi-sternotomy on aortic valve replacement as compared to surgery performed via full median sternotomy. Upper hemi-sternotomy may have little to no effect on mortality versus full median sternotomy (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.45 to 1.94; 10 studies, 985 participants; low-certainty evidence). Upper hemi-sternotomy for aortic valve replacement may increase cardiopulmonary bypass time slightly, although the evidence is very uncertain (mean difference (MD) 10.63 minutes, 95% CI 3.39 to 17.88; 10 studies, 1043 participants; very low-certainty evidence) and may increase aortic cross-clamp time slightly (MD 6.07 minutes, 95% CI 0.79 to 11.35; 12 studies, 1235 participants; very low-certainty evidence), although the evidence is very uncertain. Most studies had at least two domains at high risk of bias. Postoperative blood loss was probably lower in the upper hemi-sternotomy group (MD -153 mL, 95% CI -246 to -60; 8 studies, 767 participants; moderate-certainty evidence). Low-certainty evidence suggested that there may be no change in pain scores by upper hemi-sternotomy (standardised mean difference (SMD) -0.19, 95% CI -0.43 to 0.04; 5 studies, 649 participants). Upper hemi-sternotomy may result in little to no difference in quality of life (MD 0.03 higher, 95% CI 0 to 0.06 higher; 4 studies, 624 participants; low-certainty evidence). Two studies reporting index admission costs concluded that limited sternotomy may be more costly at index admission in the UK National Health Service (MD 1190 GBP more, 95% CI 420 GBP to 1970 GBP, 2 studies, 492 participants; low-certainty evidence). AUTHORS\u27 CONCLUSIONS: The evidence was of very low to moderate certainty. Sample sizes were small and underpowered to demonstrate differences in some outcomes. Clinical heterogeneity was also noted. Considering these limitations, there may be little to no effect on mortality. Differences in extracorporeal support times are uncertain, comparing upper hemi-sternotomy to full sternotomy for aortic valve replacement. Before widespread adoption of the minimally invasive approach can be recommended, there is a need for a well-designed and adequately powered prospective randomised controlled trial. Such a study would benefit from also performing a robust cost analysis. Growing patient preference for minimally invasive techniques merits thorough quality of life analyses to be included as end points, as well as quantitative measures of physiological reserve

Does Comorbidity Index Predict OPAT Readmission?

Objectives – To determine if the Charlson Comorbidity Index (CCI) is an accurate predictor of unplanned readmissions for patients using Outpatient Parenteral Antimicrobial Therapy (OPAT) services. Methods – Retrospective analysis of patients > 16 years of age who had received OPAT at Lancashire Teaching Hospitals between 2019 and 2021. The number of unplanned hospitalisations was measured and categorised as OPAT related or non-OPAT related. The CCI for each patient group was calculated using an online tool and multivariate analysis was used for each group of readmitted patients. Results – The cohort consisted of 741 patients. Unplanned readmission was seen in 112 patients (15.1%). The mean CCI score for patients with OPAT related readmissions was 4.22, 0.92 higher than the mean for patients who were not readmitted (3.30). The mean CCI score for patients with non-OPAT related readmissions was higher still, 4.89. Multivariate analysis showed that increased CCI, age, male gender and home location compared with clinic were associated with increased odds of readmission, although these effects did not meet statistical significance. Conclusions – These results suggest that a higher CCI score is associated with a non-statistically significant increased risk of unplanned hospitalisation. We concluded that the CCI may therefore be used in future decision making regarding the acceptance of patients to OPAT and requires further investigation

Optimisation of ex vivo memory B cell expansion/differentiation for interrogation of rare peripheral memory B cell subset responses

Background: Human memory B cells play a vital role in the long-term protection of the host from pathogenic re-challenge. In recent years the importance of a number of different memory B cell subsets that can be formed in response to vaccination or infection has started to become clear. To study memory B cell responses, cells can be cultured ex vivo, allowing for an increase in cell number and activation of these quiescent cells, providing sufficient quantities of each memory subset to enable full investigation of functionality. However, despite numerous papers being published demonstrating bulk memory B cell culture, we could find no literature on optimised conditions for the study of memory B cell subsets, such as IgM + memory B cells. Methods: Following a literature review, we carried out a large screen of memory B cell expansion conditions to identify the combination that induced the highest levels of memory B cell expansion. We subsequently used a novel Design of Experiments approach to finely tune the optimal memory B cell expansion and differentiation conditions for human memory B cell subsets. Finally, we characterised the resultant memory B cell subpopulations by IgH sequencing and flow cytometry. Results: The application of specific optimised conditions induce multiple rounds of memory B cell proliferation equally across Ig isotypes, differentiation of memory B cells to antibody secreting cells, and importantly do not alter the Ig genotype of the stimulated cells.  Conclusions: Overall, our data identify a memory B cell culture system that offers a robust platform for investigating the functionality of rare memory B cell subsets to infection and/or vaccination

Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?

In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

A Cretaceous origin for fire adaptations in the Cape flora

Fire has had a profound effect on the evolution of worldwide biotas. The Cape Floristic Region is one of the world's most species-rich regions, yet it is highly prone to recurrent fires and fire-adapted species contribute strongly to the overall flora. It is hypothesized that the current fire regimes in the Cape could be as old as 6-8 million years (My), while indirect evidence indicates that the onset of fire could have reached 18 million years ago (Ma). Here, we trace the origin of fire-dependent traits in two monocot families that are significant elements in the fire-prone Cape flora. Our analysis shows that fire-stimulated flowering originated in the Cape Haemodoraceae 81 Ma, while fire-stimulated germination arose in the African Restionaceae at least 70 Ma, implying that wildfires have been a significant force in the evolution of the Cape flora at least 60 My earlier than previous estimates. Our results provide strong evidence for the presence of fire adaptations in the Cape from the Cretaceous, leading to the extraordinary persistence of a fire-adapted flora in this biodiversity hotspot, and giving support to the hypothesis that Cretaceous fire was a global phenomenon that shaped the evolution of terrestrial floras

Exploring Species Limits in Two Closely Related Chinese Oaks

Background. The species status of two closely related Chinese oaks, Quercus liaotungensis and Q. mongolica, has been called into question. The objective of this study was to investigate the species status and to estimate the degree of introgression between the two taxa using different approaches. [br/] Methodology/Principal Findings. Using SSR (simple sequence repeat) and AFLP (amplified fragment length polymorphism) markers, we found that interspecific genetic differentiation is significant and higher than the differentiation among populations within taxa. Bayesian clusters, principal coordinate analysis and population genetic distance trees all classified the oaks into two main groups consistent with the morphological differentiation of the two taxa rather than with geographic locations using both types of markers. Nevertheless, a few individuals in Northeast China and many individuals in North China have hybrid ancestry according to Bayesian assignment. One SSR locus and five AFLPs are significant outliers against neutral expectations in the interspecific FST simulation analysis, suggesting a role for divergent selection in differentiating species.[br/] Main Conclusions/Significance. All results based on SSRs and AFLPs reached the same conclusion: Q. liaotungensis and Q. mongolica maintain distinct gene pools in most areas of sympatry. They should therefore be considered as discrete taxonomic units. Yet, the degree of introgression varies between the two species in different contact zones, which might be caused by different population history or by local environmental factors

Bleeding and first-year mortality following hip fracture surgery and preoperative use of low-dose acetylsalicylic acid: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>Hip fracture is associated with high mortality. Cardiovascular disease and other comorbidities requiring long-term anticoagulant medication are common in these mostly elderly patients. The objective of our observational cohort study of patients undergoing surgery for hip fracture was to study the association between preoperative use of low-dose acetylsalicylic acid (LdAA) and intraoperative blood loss, blood transfusion and first-year all-cause mortality.</p> <p>Methods</p> <p>An observational cohort study was conducted on patients with hip fracture (cervical requiring hemiarthroplasty or pertrochanteric or subtrochanteric requiring internal fixation) participating in a randomized trial that found lack of efficacy of a compression bandage in reducing postoperative bleeding. The participants were 255 patients (≥50 years) of whom 118 (46%) were using LdAA (defined as ≤320 mg daily) preoperatively. Bleeding variables in patients with and without LdAA treatment at time of fracture were measured and blood transfusions given were compared using logistic regression. The association between first-year mortality and preoperative use of LdAA was analyzed with Cox regression adjusting for age, sex, type of fracture, baseline renal dysfunction and baseline cardiovascular and/or cerebrovascular disease.</p> <p>Results</p> <p>Blood transfusions were given postoperatively to 74 (62.7%) LdAA-treated and 76 (54%) non-treated patients; the adjusted odds ratio was 1.8 (95% CI 1.04 to 3.3). First-year mortality was significantly higher in LdAA-treated patients; the adjusted hazard ratio (HR) was 2.35 (95% CI 1.23 to 4.49). The mortality was also higher with baseline cardiovascular and/or cerebrovascular disease, adjusted HR 2.78 (95% CI 1.31 to 5.88). Patients treated with LdAA preoperatively were significantly more likely to suffer thromboembolic events (5.7% vs. 0.7%, P = 0.03).</p> <p>Conclusions</p> <p>In patients with hip fracture (cervical treated with hemiarthroplasty or pertrochanteric or subtrochanteric treated with internal fixation) preoperative use of low-dose acetylsalicylic acid was associated with significantly increased need for postoperative blood transfusions and significantly higher all-cause mortality during one year after surgery.</p