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Introduction and Importance: Cardiac tamponade following hiatal hernia repair is a rare and potentially fatal complication most often associated with the use of mechanical fixation devices for hiatal mesh reinforcement. Only three cases have been reported with sutures alone, and none following robotic hiatal surgery., Case Presentation: A 54-year-old patient underwent elective robotic hiatal hernia repair with Toupet fundoplication during which a sling suture was placed to elevate the left lateral segment of liver. No mesh or mechanical fixation devices were used. Eight hours postoperatively, the patient developed hemodynamic instability. Cardiac tamponade was diagnosed on bedside echocardiogram and the patient underwent emergent pericardiocentesis with subsequent stabilization. The remainder of the postoperative course was notable for pericarditis which was treated with aspirin and colchicine., Clinical Discussion: While the use of suture-based liver retraction has the advantages of avoiding an additional port and potential collision between retractor holder and robot arms, it constitutes a novel risk factor for cardiac tamponade. Prompt diagnosis via bedside echocardiography is essential and may facilitate percutaneous rather than operative management., Conclusion: Suture-based liver retraction in minimally invasive foregut surgery should be used judiciously until further data is available. Surgeons should maintain a high index of suspicion for tamponade in the setting of postoperative hypotension after its use., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In Brief: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promise as off-the-shelf therapeutics; however, producing them in sufficient quantities can be challenging. In this study, MSCs were isolated from preimplantation equine embryos and used to produce EVs in two commercially available bioreactor designs., Abstract: Mesenchymal stromal cells (MSC) have recently been explored for their potential use as therapeutics in human and veterinary medicine applications, such as the treatment of endometrial inflammation and infertility. Allogeneic MSC-derived extracellular vesicles (EVs) may also provide therapeutic benefits with advantage of being an 'off-the-shelf' solution, provided they can be produced in large enough quantities, without contamination from bovine EVs contained in fetal bovine serum that is a common component of cell culture media. Toward this aim, we demonstrated the successful isolation and characterization of equine MSCs from preimplantation embryos. We also demonstrate that many of these lines can be propagated long-term in culture while retaining their differentiation potential and conducted a head-to-head comparison of two bioreactor systems for scalable EV production including in serum-free conditions. Based on our findings, the CELLine AD 1000 flasks enabled higher cell density cultures and significantly more EV production than the FiberCell system or conventional culture flasks. These findings will enable future isolation of equine MSCs and the scalable culture of their EVs for a wide range of applications in this rapidly growing field.

Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae. Four distinct mesenchymal subsets were identified; CD73 + CD90 + mesenchymal cells, CD146 + CD271 + perivascular cells, podoplanin + CD36 + stromal cells, and CD26 + CD90 + myofibroblasts. CD73 + CD90 + and podoplanin + CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73 + CD90 + cells and podoplanin + CD36 + cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73 + CD90 + CD31 - CD144 - CD45 - ). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplanin + CD36 + cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays., Competing Interests: AB, TD, TW, LC, JJ, AB No competing interests declared, (© 2022, Boss et al.)

Background: Regional heart attack services have improved clinical outcomes following ST-segment elevation myocardial infarction (STEMI) by facilitating early reperfusion by primary percutaneous coronary intervention (PCI). Early discharge after primary PCI is welcomed by patients and increases efficiency of health care., Objectives: This study aimed to assess the safety and feasibility of a novel early hospital discharge pathway for low-risk STEMI patients., Methods: Between March 2020 and June 2021, 600 patients who were deemed at low risk for early major adverse cardiovascular events (MACE) were selected for inclusion in the pathway and were successfully discharged in <48 hours. Patients were reviewed by a structured telephone follow-up at 48 hours after discharge by a cardiac rehabilitation nurse and underwent a virtual follow-up at 2, 6, and 8 weeks and at 3 months., Results: The median length of hospital stay was 24.6 hours (interquartile range [IQR]: 22.7-30.0 hours) (prepathway median: 65.9 hours [IQR: 48.1-120.2 hours]). After discharge, all patients were contacted, with none lost to follow-up. During median follow-up of 271 days (IQR: 88-318 days), there were 2 deaths (0.33%), both caused by coronavirus disease 2019 (>30 days after discharge), with 0% cardiovascular mortality and MACE rates of 1.2%. This finding compared favorably with a historical group of 700 patients meeting pathway criteria who remained in the hospital for >48 hours (>48-hour control group) (mortality, 0.7%; MACE, 1.9%) both in unadjusted and propensity-matched analyses., Conclusions: Selected low-risk patients can be discharged safely following successful primary PCI by using a pathway that is supported by a structured, multidisciplinary virtual follow-up schedule., Competing Interests: Funding Support and Author Disclosures Dr Rathod has received funding from the National Institute for Health and Research (NIHR) in the form of an Academic Clinical Lectureship. Dr Jones has received funding from the Barts Charity; and has received financial support for blood pressure machines from the Barts Guild. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the use of smartphone-based direct ophthalmoscope photography for screening of diabetic retinopathy (DR) in known diabetic patients walking into a general practitioner's clinic and referring them to a vitreoretinal specialist for further evaluation and management if required., Methodos: The study included 94 eyes of 47 walk-in patients in a general practitioner's OPD who were known to have type 2 diabetes mellitus and were already on treatment for the same., Results: The study included 47 patients with diabetes with a mean age of 56.2 ± 9.4 years. The Cohen's kappa values revealed that the diagnosis related to the DR status made using a camera was in substantial agreement with the clinical diagnosis (Kappa value: 0.770). The Cohen's kappa values revealed that the diagnosis related to the DME made using a camera was in moderate agreement with the clinical diagnosis (Kappa value: 0.410). The agreement between the findings of the camera and clinical diagnosis was statistically significant (P < 0.05)., Conclusion: Direct ophthalmoscope-based smartphone imaging can be a useful tool in the OPD of a general practitioner. These images can be assessed for retinopathy, and patients can be referred to a vitreoretinal specialist for further evaluation and management if needed. Hence, the burden of vision loss due to complications of DR in the rural sector can be abridged., Competing Interests: None

There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.

Human adipose-derived mesenchymal stromal cells (ASC) are showing clinical promise for the treatment of a range of inflammatory and degenerative conditions. These lipoaspirate-derived cells are part of the abundant and accessible source of heterogeneous stromal vascular fraction (SVF). They are typically isolated and expanded from the SVF via adherent cell culture for at least 2 weeks and as such represent a relatively undefined population of cells. We isolated ex vivo ASC directly from lipoaspirate using a cocktail of antibodies combined with immunomagnetic bead sorting. This method allowed for the rapid enrichment of a defined and untouched ex vivo ASC population (referred to as MACS-derived ASC) that were then compared to culture-derived ASC. This comparison found that MACS-derived ASC contain a greater proportion of cells with activity in in vitro differentiation assays. There were also significant differences in the secretion levels of some key paracrine molecules. Moreover, when the MACS-derived ASC were subjected to adherent tissue culture, rapid changes in gene expression were observed. This indicates that culturing cells may alter the clinical utility of these cells. Although MACS-derived ASC are more defined compared to culture-derived ASC, further investigations using a comprehensive multicolor flow cytometry panel revealed that this cell population is more heterogeneous than previously appreciated. Additional studies are therefore required to more precisely delineate phenotypically distinct ASC subsets with the most therapeutic potential. This research highlights the disparity between ex vivo MACS-derived and culture-derived ASC and the need for further characterization., (Copyright © 2020 Brooks, Iminitoff, Williams, Damani, Jackson-Patel, Fan, James, Dunbar, Feisst and Sheppard.)

Gastrointestinal stromal tumors are uncommon when compared to all gastrointestinal neoplasms but are the most common mesenchymal tumors of the gastrointestinal tract. The largest gastrointestinal stromal tumor ever recorded in literature weighed approximately 6.1 kg and measured 39 cm × 27 cm × 14 cm. About two-thirds of GISTs are malignant. The tumor size, mitotic rate, cellularity, and nuclear pleomorphism are the most important parameters when considering prognosis and recurrence. The definitive treatment for these tumors is resection. In the year 2000, the first patient was treated with the tyrosine kinase inhibitor imatinib and since then, gastrointestinal stromal tumors with high-risk features have been treated successfully with tyrosine kinase inhibitors. We present the largest gastrointestinal stromal tumor recorded in medical literature measuring 42.0 cm × 31.0 cm × 23.0 cm in maximum dimensions and weighing in at approximately 18.5 kg in a 65-year-old African-American male who presented with increased abdominal distention. The mass was successfully excised, and the patient was treated with imatinib without local or distant recurrence 1.5 years postoperatively.