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Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton’s Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy.Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry.Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded.Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

Abstract Background A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation. Methods This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement. Results 373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%. Conclusion The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67 × 10−132, 2.23 × 10−107), the cytotoxic T-cell markers CD8a, LAGE3 and CD49a (p = 0.0006, p < 0.0001, and p = 0.0118) and proinflammatory caspase-1 (p = 0.0055) in CHD. Gene-set enrichment identified mitochondrial dysfunctional pathways, predominately changes within oxidative phosphorylation processes. The negative regulation of mitochondrial functions and metabolism was identified in the network analysis, with dysregulation of the mitochondrial complex formation. A histological analysis confirmed an increase in cellular bodies in the CHD RV tissue and positive staining for both CD45 and CD8, which was absent in the control. The deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). The network analysis identified positive regulation of the immune system and cytokine signalling clusters in the inflammation functional network, as there were lymphocyte activation and leukocyte differentiation. Utilising RV tissue from paediatric patients undergoing CHD cardiac surgery, this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T-cell presence prior to reparative surgery.

BackgroundOne mechanism that can explain the link between processed meat consumption and colorectal cancer (CRC) is the production of carcinogenic N-nitroso compounds (NOCs) in the gastrointestinal tract. Oral and gut microbes metabolize ingested proteins (a source of secondary and tertiary amines and amides) and can reduce nitrate to nitrite, generating potentially carcinogenic NOCs.ObjectiveWe evaluated whether nitrate/nitrite in processed meat or water influences the fecal or salivary microbiota.DesignIn this dietary intervention study, 63 volunteers consumed diets high in conventional processed meats for two weeks, switched to diets high in poultry for two weeks, and then consumed phytochemical-enriched conventional processed or low-nitrite processed meat diets for two weeks. During the intervention, they drank water with low nitrate concentrations and consumed a healthy diet with low antioxidants. Then the volunteers drank nitrate-enriched water for 1 week, in combination with one of the four different diets. We measured creatinine-adjusted urinary nitrate levels and characterized the oral and fecal microbiota using 16S rRNA amplicon sequencing.ResultsUsing linear mixed models, we found that, compared to baseline, urinary nitrate levels were reduced during the phytochemical-enriched low-nitrite meat diet (p-value = 0.009) and modestly during the poultry diet (p-value = 0.048). In contrast, urinary nitrate increased after 1-week of drinking nitrate-enriched water (p-value

Mitral valve prolapse (MVP) represents the most frequent cause of primary mitral regurgitation. For several years, biological mechanisms underlying this condition attracted the attention of investigators, trying to identify the pathways responsible for such a peculiar condition. In the last ten years, cardiovascular research has moved from general biological mechanisms to altered molecular pathways activation. Overexpression of TGF-β signaling, for instance, was shown to play a key role in MVP, while angiotensin-II receptor blockade was found to limit MVP progression by acting on the same signaling pathway. Concerning extracellular matrix organization, the increased valvular interstitial cells density and dysregulated production of catalytic enzymes (matrix metalloproteinases above all) altering the homeostasis between collagen, elastin and proteoglycan components, have been shown to possibly provide a mechanistic basis contributing to the myxomatous MVP phenotype. Moreover, it has been observed that high levels of osteoprotegerin may contribute to the pathogenesis of MVP by increasing collagen deposition in degenerated mitral leaflets. Although MVP is believed to represent the result of multiple genetic pathways alterations, it is important to distinguish between syndromic and non-syndromic conditions. In the first case, such as in Marfan syndrome, the role of specific genes has been clearly identified, while in the latter a progressively increasing number of genetic loci have been thoroughly investigated. Moreover, genomics is gaining more interest as potential disease-causing genes and loci possibly associated with MVP progression and severity have been identified. Animal models could be of help in better understanding the molecular basis of MVP, possibly providing sufficient information to tackle specific mechanisms aimed at slowing down MVP progression, therefore developing non-surgical therapies impacting on the natural history of this condition. Although continuous progress has been made in this field, further translational studies are advocated to improve our knowledge of biological mechanisms underlying MVP development and progression.

Infection of surgical wounds with acid-fast bacilli, including tubercle bacilli, is rare, and is poorly described in the literature. We present the case of a 74-year-old male who developed a sternal wound infection after cardiac surgery due to Mycobacterium tuberculosis complex, diagnosed post-mortem. SARS-CoV-2 infection contributed to worsened clinical conditions and surgical site infection. A high degree of suspicion to avoid unnecessary treatments and progression to severe disease with dismal prognosis is necessary in these types of infections.

Background: The transfemoral (TF) approach is the most common route in TAVI, but it is still associated with a risk of bleeding and vascular complications. The aim of this study was to compare the clinical outcomes between surgical cut-down (SC) and percutaneous (PC) approach. (2) Methods: Between January 2018 and June 2022, 774 patients underwent a transfemoral TAVI procedure. After propensity matching, 323 patients underwent TAVI in each group. (3) Results: In the matched population, 15 patients (4.6%) in the SC group vs. 34 patients in the PC group (11%) experienced minor vascular complications (p = 0.02), while no difference for major vascular complication (1.5% vs. 1.9%) were reported. The rate of minor bleeding events was higher in the percutaneous group (11% vs. 3.1%, p <.001). The SC group experienced a higher rate of non-vascular-related access complications (minor 8% vs. 1.2%; major 2.2% vs. 1.2%; p < 0.001). (4) Conclusions: SC for TF-TAVI did not alter the mortality rate at 30 days and was associated with reduced minor vascular complication and bleeding. PC showed a lower rate of non-vascular-related access complications and a lower length of stay. The specific approach should be tailored to the patient's clinical characteristics. [ABSTRACT FROM AUTHOR]

Myocardial revascularization in coronary artery disease via percutaneous coronary intervention or coronary artery bypass graft (CABG) surgery effectively relieves symptoms, significantly improves prognosis and quality of life when combined with guideline-directed medical therapy. Hybrid coronary revascularization is a promising alternative to percutaneous coronary intervention or CABG in selected patients and is defined as a planned and/or intended combination of consecutive CABG surgery using at least 1 internal mammary artery to the left anterior descending (LAD), and catheter-based coronary intervention to the non-LAD vessels for the treatment of multivessel disease. The main indications for hybrid coronary revascularization are (i) to achieve complete revascularization in patients who cannot undergo conventional CABG, (ii) to treat patients with acute coronary syndromes and multivessel disease with a non-LAD vessel as the culprit lesion that needs revascularization and (iii) in highly select patients with multivessel disease with complex LAD lesions and simple percutaneous coronary intervention targets for all other vessels. Hybrid coronary revascularization patients receive a left internal mammary artery graft to the LAD artery through a minimal incision along with percutaneous coronary intervention to the remaining diseased coronary vessels using latest generation drug-eluting stents. A collaborative environment with a dedicated heart team is the optimal platform to perform such interventions, which aim to improve the quality and outcome of myocardial revascularization. This position paper analyses the rationale of hybrid coronary revascularization and the currently available evidence on the various techniques and delves into the sequence of the interventions and pharmacological management during and after the procedure. [ABSTRACT FROM AUTHOR]

Abstract Monitoring water quality at high frequency is challenging and costly. Compressed sensing (CS) offers an approach to reconstruct high‐frequency water quality data from limited measurements, given that water quality signals are commonly “sparse” in the frequency domain. In this study, we investigated the sparsity of stream flow and concentration time‐series and tested reconstruction with CS. All stream signals were sparse using 15‐min discrete time‐series transformed to the Fourier domain. Stream temperature, conductance, dissolved oxygen, and nitrate plus nitrite (NOx‐N) concentration were sparser than discharge, turbidity, and total phosphorus (TP) concentration. CS effectively reconstructed these signals with only 5%–10% of measurements needed. Stream NOx‐N and TP loads were well estimated with errors of −6.6% ± 3.8% and −9.0% ± 2.9% with effective sampling frequencies of 10 and 0.4 days, respectively. For broader applications in environmental geosciences and engineering domains, CS can be integrated with dimensionality reduction and optimization techniques for more efficient sampling schemes.

Heart failure symptoms, in particular dyspnea, may be difficult to frame in a patient with cancer. We report the case of an oncological patient whose dyspnea could have been attributable to various causes and whose management was challenging in the context of the coronavirus disease-2019 pandemic. (Level of Difficulty: Beginner.)

Esta breve reflexión introduce la discusión sobre el artículo de Ghidoni y Morondo titulado El papel de los estereotipos en las formas de la desigualdad compleja: algunos apuntes desde la teoría feminista del derecho antidiscriminatorio. En particular, después de señalar las aportaciones más interesantes e innovadoras de la propuesta de las autoras, se indicarán algunas cuestiones abiertas, a partir de las observaciones de las comentaristas Peroni y Ronconi, aunque sin limitarse a ellas. Sin embargo, preliminarmente, se ofrecerán unas breves consideraciones, por un lado, sobre la compleja relación entre derecho y estereotipos y, por otro lado, sobre las posibles aportaciones específicas de la perspectiva de género en el análisis de esta relación.