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Traditional teacher professional development (PD) programs frequently lack sufficient face-to-face preparation time to adequately support the implementation of evidence-based pedagogical strategies in classrooms, with teachers citing insufficient preparedness and training time for new methods. To investigate potentials for online PD methods to effectively address these issues, while increasing sustainability, this study examined teachers in Title-I elementary schools spanning multiple school districts participating in a large-scale online PD certificate program preparing teachers over 10 instructional weeks to implement Next Generation Science Standards (NGSS) (S)cience, (T)echnology, (E)ngineering, (A)rts, (M)ath (STEAM) curricular instruction with goals of increasing teachers' science content knowledge, self-efficacy to implement STEAM instruction, and STEAM teaching perceptions. Paired sample t-tests indicate teachers' life science content knowledge, self-efficacy, and STEAM perceptions increased significantly after completing the online PD. Multiple regression analyses identified teachers' science content knowledge and STEAM perceptions as statistically significant predictors of teachers' self-efficacy to implement STEAM instructional strategies. Teachers' posttest course evaluations were gleaned, highlighting three emergent themes: learning experience design, modality, and online teacher collaboration. Utilizing a mixed method approach, these qualitative insights corroborated the quantitative trends, describing how specific aspects of the pedagogical learning experience design (LXD) framework operationalized in the online course fostered a practitioner development learning environment, focused on supporting teachers' learning needs. Results suggest practical design implications for sustainably increasing the efficacy of PD through online teacher training developed in conjunction with LXD models for iterative improvement and design of high-quality online instructional PD programs.

Background: Barbed sutures (BS) have been increasingly used in the last two decades across surgical disciplines but little is known about how widespread their adoption has been in ventral hernia repair (VHR). The aim of this study was to document the use of barbed sutures in VHR in a multicenter database with associated clinical and patient-reported outcomes., Method: Prospectively collected data from the Abdominal Core Health Quality Collaborative database was retrospectively reviewed, including all adult patients who underwent VHR with fascial closure from 2020 to 2022. A univariate analysis compared patients with BS against non-barbed sutures (NBS) across the preoperative, intraoperative, and postoperative timeframes including patient-reported outcomes concerning quality of life and pain scores., Results: A total of 4054 patients that underwent ventral hernia repair with BS were compared with 6473 patients with non-barbed sutures (NBS). Overall, BS were used in 86.2% of minimally invasive ventral hernia repairs and about 92.2% of robotic surgery compared to only 9.6% of open procedures. Notable differences existed in patient selection, including a higher BMI (32 vs 30.5; p < 0.001), more incisional hernias (63.3% vs 51.1%; p < 0.001), wider hernias (4 cm vs 3 cm; p < 0.001), and higher ASA score (p < 0.001) in patients with BS. Outcomes in patients with BS included a shorter length of stay (mean days; 1.4 vs 2.4; p < 0.001), less SSI (1.5% vs 3.6%; p < 0.001), while having similar SSO (7.6% vs 7.3%; p = 0.657), readmission (3.0 vs 3.2; p = 0.691), and reoperation (1.5% vs 1.45%; p = 0.855), at a longer operative time (p < 0.001). Hernia-specific questionnaires for quality of life (HerQLes) and pain in patients with BS had a worse preoperative score that was later matched and favorable compared to NBS (p = 0.048). PRO concerning hernia recurrence suggest around 10% at two years of follow-up (p = 0.532)., Conclusion: Use of barbed sutures in VHR is widespread and highly related to MIS. Outcomes from this multicenter database cannot be reported as superior but suggest that barbed sutures do not have a negative impact on outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite the paucity of evidence on robotic ventral hernia repair (RVHR) in patients with obesity, the robotic platform is being used more frequently in hernia surgery. The impact of obesity on RVHR outcomes has not been thoroughly studied. Obesity is considered a major risk factor for the development of recurrent ventral hernias and postoperative complications; however, we hypothesize that patients undergoing robotic repairs will have similar complication profiles despite their body mass index (BMI). We performed a retrospective analysis of patients aged 18-90 years who underwent RVHR between 2013 and 2023 using data from the Abdominal Core Health Quality Collaborative registry. Preoperative, intraoperative, and postoperative characteristics were compared in non-obese and obese groups, determined using a univariate and logistic regression analysis to compare short-term outcomes. The registry identified 9742 patients; 3666 were non-obese; 6076 were classified as obese (BMI > 30 kg/m 2 ). There was an increased odds of surgical site occurrence in patients with obesity, mostly seroma formation; however, obesity was not a significant factor for a complication requiring a procedural intervention after RVHR. In contrast, the hernia-specific quality-of-life scores significantly improved following surgery for all patients, with those with obesity having more substantial improvement from baseline. Obesity does increase the risk of certain complications following RVHR in a BMI-dependent fashion; however, the odds of requiring a procedural intervention are not significantly increased by BMI. Patients with obesity have a significant improvement in their quality of life, and RVHR should be carefully considered in this population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Robotic hiatal hernia (HH) repair has been demonstrated to be feasible and safe. Recent conflicting reports have emerged on the higher incidence of perioperative complications with robotic HH repair when compared with laparoscopic repair. Materials and Methods: A retrospective review of a prospective database at an academic medical center for all robotic HH repairs performed by a high-volume foregut surgeon from 2018 to 2021 was performed. Outcome measures included operative time, estimated blood loss (EBL), length of stay (LOS), conversion rate, need for esophageal lengthening procedure, intra- and perioperative complications, and 30-day in-hospital mortality. Results: One hundred four patients were included in the analysis. Fifteen percent of patients had a type I HH, 2% had a type II, 73% had a type III, and 10% had a type IV HH. Eighty-four percent of cases were primary and 16% were revisional. Fifty-four percent of patients had mesh placed and 4.4% had an esophageal lengthening procedure. Mean EBL was 15 mL and mean operative time was 151 minutes. Median LOS was 2 days (interquartile range 1-2 days). There were zero conversions. Intraoperative complication rate was 1% and 30-day complication rate was 4%. The 30-day in-hospital mortality was zero. Conclusion: In this retrospective analysis of 114 consecutive robotic HH repairs performed, with 83% type III or IV HHs and 16% revisional hiatal cases, our results demonstrate favorable perioperative outcomes, with lower EBL, shorter LOS, lower complication rate, zero conversions, and comparable operative times compared with historical laparoscopic data.

Introduction: Reinforcement of crural closure with synthetic resorbable mesh has been proposed to decrease recurrence rates after hiatal hernia repair, but continues to be controversial. This systematic review aims to evaluate the safety, efficacy, and intermediate-term results of using biosynthetic mesh to augment the hiatus., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed throughout this systematic review. The Risk of Bias in Non-Randomized Studies of Interventions and Risk of Bias in Randomized Trials tools were used to perform qualitative assessment of all studies included in this review. Recommendations were then summarized for the following pre-defined key items: protocol, research question, search strategy, study eligibility, data extraction, study design, risk of bias, publication bias, and statistical analysis., Results: The systematic literature search found 520 articles, 101 of which were duplicates and 355 articles were determined to be unrelated to our study and excluded. The full text of the remaining 64 articles was thoroughly assessed. A total of 18 articles (1846 patients) were ultimately included for this review, describing hiatal hernia repair using three different biosynthetic meshes-BIO-A, Phasix ST, and polyglactin mesh. Mean operative time varied from 127 to 223 min. Mean follow up varied from 12 to 54 months. There were no mesh erosions or explants. One mesh-related complication of stenosis requiring reoperation was reported with BIO-A. Studies showed significant improvement in symptom and quality-of-life scores, as well as satisfaction with surgery. Recurrence was reported as radiologic or clinical recurrence. Overall, recurrence rate varied from 0.9 to 25%., Conclusion: The use of biosynthetic mesh is safe and effective for hiatal hernia repair with low complications rates and high symptom resolution. The reported recurrence rates are highly variable due to significant heterogeneity in defining and evaluating recurrences. Further randomized controlled trials with larger samples and long-term follow-up should be performed to better analyze outcomes and recurrence rates., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Introduction: After extensive mediastinal dissection fails to achieve adequate intra-abdominal esophageal length, a Collis gastroplasty(CG) is recommended to decrease axial tension and reduce hiatal hernia recurrence. However, concerns exist about staple line leak, and long-term symptoms of heartburn and dysphagia due to the acid-producing neoesophagus which lacks peristaltic activity. This study aimed to assess long-term satisfaction and GERD-related quality of life after robotic fundoplication with CG (wedge fundectomy technique) and to compare outcomes to patients who underwent fundoplication without CG. Outcomes studied included patient satisfaction, resumption of proton pump inhibitors (PPI), length of surgery (LOS), hospital stay, and reintervention., Methods: This was a single-center retrospective analysis of patients from January 2017 through December 2018 undergoing elective robotic hiatal hernia repair and fundoplication. 61 patients were contacted for follow-up, of which 20 responded. Of those 20 patients, 7 had a CG performed during surgery while 13 did not. There was no significant difference in size and type of hiatal hernias in the 2 groups. These patients agreed to give their feedback via a GERD health-related quality of life (GERD HRQL) questionnaire. Their medical records were reviewed for LOS, length of hospital stay (LOH), and reintervention needed. Statistical analysis was performed using SPSS v 25. Satisfaction and need for PPIs were compared between the treatment and control groups using the chi-square test of independence., Results: Statistical analysis showed that satisfaction with outcome and PPI resumption was not significantly different between both groups ( P > .05). There was a significant difference in the average ranks between the 2 groups for the question on postoperative dysphagia on the follow-up GERD HRQL questionnaire, with the group with CG reporting no dysphagia. There were no significant differences in the average ranks between the 2 groups for the remaining 15 questions ( P > .05). The median LOS was longer in patients who had a CG compared to patients who did not (250 vs. 148 min) ( P = .01). The LOH stay was not significantly different ( P > .05) with a median length of stay of 2 days observed in both groups. There were no leaks in the Collis group and no reoperations, conversions, or blood transfusions needed in either group., Conclusion: Collis gastroplasty is a safe option to utilize for short esophagus noted despite extensive mediastinal mobilization and does not adversely affect the LOH stay, need for reoperation, or patient long-term satisfaction.

Background: Elective paraesophageal hernia (PEH) repair in asymptomatic or minimally symptomatic patients ≥ 65 years of age remains controversial. The widely cited Markov Monte Carlo decision analytic model recommends watchful waiting in this group, unless the mortality rate for elective repair was to reach ≤ 0.5%; at which point, surgery would become the optimal treatment. We hypothesized that with advances in minimally invasive surgery, perioperative care, and practice specialization, that mortality threshold has been reached in the contemporary era. However, the safety net would decrease as age increases, particularly in octogenarians., Methods: We identified 12,422 patients from the 2015-2017 ACS-NSQIP database, who underwent elective minimally invasive PEH repair, of whom 5476 (44.1%) were with age ≥ 65. Primary outcome was 30-day mortality. Secondary outcomes were length of stay (LOS), operative time, pneumonia, pulmonary embolism, unplanned intubation, sepsis, bleeding requiring transfusion, readmission, and return to OR., Results: Patients age ≥ 65 had a higher 30-day mortality (0.5% vs 0.2%; p < 0.001). Subset analysis of patients age 65-80 and > 80 showed a 30-day mortality of 0.4% vs. 1.8%, respectively (p < 0.001). Independent predictors of mortality in patients ≥ 65 years were age > 80 (OR 5.23, p < 0.001) and COPD (OR 2.59, p = 0.04). Patients ≥ 65 had a slightly higher incidence of pneumonia (2% vs 1.2%; p < 0.001), unplanned intubation (0.8% vs 0.5%; p < 0.05), pulmonary embolism (0.7% vs 0.3%; p = 0.001), bleeding requiring transfusion (1% vs 0.5%; p < 0.05), and LOS (2.38 vs 1.86 days, p < 0.001) with no difference in sepsis, return to OR or readmission., Conclusion: This is the largest series evaluating elective PEH repair in the recent era. While morbidity and mortality do increase with age, the mortality remains below 0.5% until age 80. Our results support consideration for a paradigm shift in the management of patients < 80 years toward elective repair of PEH., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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

Fascial closure at 8-mm robotic port sites continues to be controversial. As the use of the robotic platform increases across multiple abdominal specialties, there are more case reports describing reoperation and small bowel resection for acute port-site hernias. A retrospective review of all robotic abdominal surgeries performed from 2012 to 2019 at NYU Langone Medical Center was conducted. Patients who had a reoperation in our facility within 30 days were identified, and medical records reviewed for indications for reoperation and findings. The study included 11,566 patients, of which 82 patients (0.71%) underwent a reoperation related to the index robotic surgery within 30 days. Fifteen of 11,566 patients (0.13%) had acute port-site hernias, and 3 of these 15 patients required small bowel resection. Eleven of 15 acute port-site hernias (73%) were at 8-mm robotic port site, 2 of which required a small bowel resection. More than a third of the patients had a hernia at an 8-mm port site where a surgical drain had been placed. Considering that each robotic case, regardless of specialty, has three ports at a minimum, the true incidence of acute postoperative robotic port-site hernia is 0.032% (11/34,698), with the incidence of concomitant small bowel resection being 0.006% (2/34,698). The incidence of acute port-site hernias from 8-mm robotic ports is exceedingly low across specialties. Our results do not support routine fascial closure at 8-mm robotic port sites due to an extremely low incidence. However, drain sites require special consideration.

Women with antiphospholipid antibodies (aPL) have increased risks of pregnancy complications, including a ten-fold increased risk of preeclampsia, which is potentially triggered by the release of placental toxins. Previously, aPL were shown to enter the outer layer of the placenta, the syncytiotrophoblast, associate with mitochondria, and alter mitochondrial function. We hypothesised that aPL may also increase mitochondrial reactive oxygen species (ROS) production, leading to cellular dysfunction and release of toxins. First trimester placental explants were incubated with monoclonal aPL, ID2 and IIC5 (25, 50, and 100 μg/mL), for 3 h at 37 °C and ROS production followed using CellROX Deep Red. In addition, the candidate treatment compounds chloroquine, melatonin, and Mito-Q were tested at therapeutic concentrations for their ability to prevent ROS production. Mitochondria isolated from term placentae were incubated with fluorescently-labelled ID2, IIC5, or control IgG antibodies (2.5, 5, 10, or 20 μg/mL) for 30 min, and mitochondria with bound antibodies were quantified using flow cytometry. In addition, respirometry coupled with fluorimetry was used to interrogate explant mitochondrial respiration and ROS production following incubation with 25, 50, or 100 μg/mL ID2, IIC5, or control IgG for 3 h at 37 °C. ID2 increased explant ROS production in a manner that was completely prevented by the endocytosis inhibitor chloroquine, and partially prevented by the antioxidants melatonin and Mito-Q. Both ID2 and IIC5 displayed a greater ability to bind isolated mitochondria than control antibodies, and increased ROS production attributable to the mitochondrial enzyme glycerol 3-phosphate dehydrogenase (mGPDH). Our evidence supports the hypothesis that aPL interact with syncytiotrophoblast mitochondria, likely via the binding of cardiolipin and β 2 glycoprotein I in mitochondrial membranes, and induce ROS production which contributes to overall oxidative stress and placental dysfunction., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Robotic-assisted surgery for benign esophageal disease is described for treatment of achalasia, gastroesophageal reflux, paraesophageal hernias, epiphrenic diverticula, and benign esophageal masses. Robotic Heller myotomy has operative times, relief of dysphagia, and conversion rates comparable to laparoscopic approach, with lower incidence of intraoperative esophageal perforation. The use of robotic platform for primary antireflux surgery is under evaluation, due to prolonged operative time and increased operative costs, with no differences in postoperative outcomes or hospital stay. Studies have shown benefits of robotic surgery in complex reoperative foregut surgery with respect to decreased conversion rates, lower readmission rates, and improved functional outcomes., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Several dyes are currently available for use in detecting differentiation of mesenchymal cells into adipocytes. Dyes, such as Oil Red O, are cheap, easy to use and widely utilized by laboratories analyzing the adipogenic potential of mesenchymal cells. However, they are not specific to changes in gene transcription. We have developed a gene-specific differentiation assay to analyze when a mesenchymal cell has switched its fate to an adipogenic lineage. Immuno-labelling against fatty acid binding protein-4 (FABP4), a lineage-specific marker of adipogenic differentiation, enabled visualization and quantification of differentiated cells. The ability to quantify adipogenic differentiation potential of mesenchymal cells in a 96 well microplate format has promising implications for a number of applications. Hundreds of clinical trials involve the use of adult mesenchymal stromal cells and it is currently difficult to correlate therapeutic outcomes within and especially between such clinical trials. This simple high-throughput FABP4 assay provides a quantitative assay for assessing the differentiation potential of patient-derived cells and is a robust tool for comparing different isolation and expansion methods. This is particularly important given the increasing recognition of the heterogeneity of the cells being administered to patients in mesenchymal cell products. The assay also has potential utility in high throughput drug screening, particularly in obesity and pre-diabetes research.

Background: Symptoms secondary to dumping have been suggested to help patients refrain from simple carbohydrate ingestion after Roux-en-Y gastric bypass (RYGB). During follow-up examinations, we noted many patients with weight regain complaining of fatigue shortly after eating. Thus, we decided to study the glucose tolerance test (GTT) results in a cohort of post-RYGB patients., Methods: A total of 63 RYGB patients, >6 months postoperatively, were studied with a GTT and measurement of insulin levels. The mean age was 48.5 ± 10.8 years, mean preoperative body mass index was 49.0 ± 6.5 kg/m(2), mean percentage of excess body mass index lost was 64.5% ± 29.0%, mean weight regain at follow-up was 11.6 ± 12.4 lb, and mean follow-up period was 47.9 months., Results: Of the 63 patients, 49 had abnormal GTT results. Of the 63 patients, 6 were diabetic; however, only 1 of these patients had an elevated fasting glucose level. All 6 patients were diabetic preoperatively. Of the 63 patients, 43 had evidence of reactive hypoglycemia at 1-2 hours after the glucose load. Of these patients, 22 had a maximum/minimum glucose ratio >3:1, including 7 with a ratio >4:1., Conclusion: The results of the present study have demonstrated that an abnormal GTT result is a common finding after RYGB. Reactive hypoglycemia was found in 43 of 63 patients, with insulin values that do not support nesidioblastosis. It is our hypothesis, that rather than preventing simple carbohydrate ingestion, the induced hypoglycemia that occurs might contribute to weight regain and maladaptive eating in certain post-RYGB patients., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Our group has reported a high incidence of reactive hypoglycemia following Roux-en-Y gastric bypass (RYGB) with specific interest in postprandial insulin and the ratio of 1- to 2-h serum glucose levels. The purpose of this study is to compare the 6-month response to oral glucose challenge in patients undergoing RYGB, duodenal switch (DS), and vertical sleeve gastrectomy (VSG)., Methods: Thirty-eight patients meeting the NIH criteria for bariatric surgery who have reached the 6-month postoperative mark are the basis of this report. Preoperatively and at 6 months follow-up, patients underwent blood draw to determine levels of fasting glucose, fasting insulin, HbA1c, C peptide, and 2 h oral liquid glucose challenge test (OGTT). HOMA-IR and 1 to 2 h ratios of glucose and fasting to 1 h ratio of insulin were calculated., Results: All patients underwent a successful laparoscopic bariatric procedure (VSG =13, DS =13, and RYGB = 12). All operations reduced BMI, HgbA1c, fasting glucose, and fasting insulin. HOMA IR and glucose tolerance improved with all procedures. In response to OGTT at 6 months, there was a 20-fold increase in insulin at 1 h in RYGB, which was not seen in DS. At 6 months, 1-h insulin was markedly lower in DS (p < .05), yet HbA1C was also lower in DS (p < .05). This resulted in 1- to 2-h glucose ratio of 1.9 for RYGB, 1.8 for VSG, and 1.3 for DS (p < .05)., Conclusions: All operations improve insulin sensitivity and decrease HgbA1c. Six-month weight loss was substantial in all groups between 22-29% excess body weight. RYGB results in marked rise in glucose following challenge with corresponding rise in 1-h insulin. VSG has a similar response to RYGB. In comparison, at 6 months following surgery, DS causes a much lower rise in 1-h insulin, with this difference being statistically significant at p < .05. As a result, DS results in a less abrupt reduction in blood glucose. Although 1-h insulin is lower, DS patients had the lowest HbA1C at 6 months (p < .05). We believe that these findings have important implications for the choice of bariatric procedure for both diabetic and non-diabetic patients.

Background: Symptoms of reactive hypoglycemia have been reported by patients after Roux-en-Y gastric bypass (RYGB) surgery who experience maladaptive eating behavior and weight regain. A 4-h glucose tolerance test (GTT) was used to assess the incidence and extent of hypoglycemia., Methods: Thirty-six patients who were at least 6 months postoperative from RYGB were administered a 4-h GTT with measurement of insulin levels. Mean age was 49.4±11.4 years, mean preoperative body mass index (BMI) was 48.8±6.6 kg/m2, percent excess BMI lost (%EBL) was 62.6 ± 21.6%, mean weight change from nadir weight was 8.2±8.6 kg, and mean follow-up time was 40.5±26.7 months. Twelve patients had diabetes preoperatively., Results: Thirty-two of 36 patients (89%) had abnormal GTT. Six patients (17%) were identified as diabetic based on GTT. All six of these patients were diabetic preoperatively. Twenty-six patients (72%) had evidence of reactive hypoglycemia at 2 h post glucose load. Within this cohort of 26 patients, 14 had maximum to minimum glucose ratio (MMGR)>3:1, 5 with a ratio>4:1. Eleven patients had weight regain greater than 10% of initial weight loss (range 4.9-25.6 kg). Ten of these 11 patients (91%) with weight recidivism showed reactive hypoglycemia., Conclusions: Abnormal GTT is a common finding post RYGB. Persistence of diabetes was noted in 50% of patients with diabetes preoperatively. Amongst the nondiabetic patients, reactive hypoglycemia was found to be more common and pronounced than expected. Absence of abnormally high insulin levels does not support nesidioblastosis as an etiology of this hypoglycemia. More than 50% of patients with reactive hypoglycemia had significantly exaggerated MMGR. We believe this may be due to the nonphysiologic transit of food to the small intestine due to lack of a pyloric valve after RYGB. This reactive hypoglycemia may contribute to maladaptive eating behaviors leading to weight regain long term. Our data suggest that GTT is an important part of post-RYGB follow-up and should be incorporated into the routine postoperative screening protocol. Further studies on the impact of pylorus preservation are necessary.

Patients undergoing endovascular abdominal aortic aneurysm (AAA) repair have lower perioperative morbidity and leave the hospital earlier than patients undergoing open repair. However, potential complications require continuous surveillance of endografts and there are few data regarding their long-term fate. If an open operation were well tolerated, this might be a preferable alternative. The purpose of this study was to identify patients with lower morbidity and shorter hospital stay following open AAA repair and to analyze factors that might point to open repair as the preferred approach. We performed a retrospective review of all patients who underwent AAA repair between 1995 and 2000 at our institution. All patients with ruptured aneurysms and those that required renal, celiac, or superior mesenteric reconstructions during the AAA repair were excluded. Patient demographics, preoperative comorbid conditions, intraoperative data, and postoperative complications were analyzed in detail. A total of 115 patients fulfilled the inclusion criteria. There was only one perioperative death (0.9%). The mean hospital stay was 8.1 days. A history of chronic obstructive pulmonary disease (COPD) and longer operative time were independent factors associated with prolonged hospital stay. Forty-one patients (35.6%) left the hospital in 5 or less days. Compared to the group with hospital stay >5 days, these patients had a lower incidence of COPD (7.3% vs. 25.7%, p < 0.05) and smaller-size AAAs (5.6 vs. 6.4 cm, p < 0.0001), and were more often operated on via a retroperitoneal approach (61% vs. 40.5%, p < 0.05). Their time in the operating room was less (3.5 vs. 4.5 hr, p < 0.0001), and they had less estimated blood loss (750 vs. 1500 cc, p < 0.001) and fewer transfusions (0.95 vs. 2.45 units, p < 0.0001). Patients without COPD and smaller AAAs that can be repaired via a retroperitoneal approach have a lower incidence of perioperative complications and a shorter hospital stay following open AAA repair. Until long-term results for endografts are available, our data suggest that these patients are well served with an open repair.

Perlecan is a specific proteoglycan that binds to amyloid precursor protein and beta-amyloid peptide, is present within amyloid deposits, and has been implicated in plaque formation. Because plaque formation is associated with local inflammation, we hypothesized that the mechanisms involved in brain inflammatory responses could influence perlecan biosynthesis. To test this hypothesis, we first studied perlecan regulation in mice after inflammation induced by a brain stab wound. Perlecan mRNA and immunoreactivity were both increased 3 days after injury. Interleukin-1alpha (IL-1alpha) is a cytokine induced after injury and plays an important role in inflammation. As such, IL-1alpha may be one of the factors participating in regulating perlecan synthesis. We thus studied perlecan regulation by IL-1alpha, in vivo. Regulation of perlecan mRNA by this cytokine was area-specific, showing up-regulation in hippocampus, whereas in striatum, perlecan mRNA was unchanged. To support this differential regulation of perlecan mRNA by IL-1alpha, basic fibroblast growth factor (bFGF), a growth factor also present in plaques, was studied in parallel. bFGF mRNA did not show any regional difference, being up-regulated in both hippocampus and striatum in vivo. In vitro, both astrocyte and microglia were immunoreactive for perlecan. Moreover, perlecan mRNA was increased in hippocampal glial cultures after IL-1alpha but not in striatal glia. These results show an increase in perlecan biosynthesis after injury and suggest a specific regulation of perlecan mRNA by IL-1alpha, which depends on brain area. Such regulation may have important implications in the understanding of regional brain variations in amyloid plaque formation.