Outcomes of a hybrid technique using EMR and endoscopic full-thickness resection for polyps not amenable to standard techniques (with video).

BACKGROUND AND AIMS: The full-thickness resection device (FTRD) offers a safe and effective approach for resection of complex colorectal lesions but is limited to lesions <2 cm in size. A hybrid approach-combining EMR with the FTRD-significantly expands the pool of lesions amenable to this technique; however, its safety and efficacy has not been well established. METHODS: We report a single-center retrospective study of consecutive patients who underwent full-thickness resection (FTR) of colorectal lesions, either with a standalone FTRD or a hybrid (EMR + FTRD) approach. Outcomes of technical success, clinical success (macroscopically complete resection), R0 resection, and adverse events (AEs) were evaluated. RESULTS: Sixty-nine FTR procedures (38 standalone FTR and 31 hybrid EMR + FTR) were performed on 65 patients. The most common indications were nonlifting polyp (43%) or suspected high-grade dysplasia or carcinoma (38%). Hybrid EMR + FTR permitted resection of significantly larger lesions (mean, 39 mm; range, 15-70 mm) compared with standalone FTR (mean, 17 mm; range, 7-25 mm; P < .01). Clinical success (91%), technical success (83%), and R0 resection (81%) rates did not differ between standalone and hybrid groups. Most patients (96%) were discharged home on the day of the procedure. Three AEs occurred, including 2 patients who developed acute appendicitis. CONCLUSIONS: A hybrid approach combining EMR and FTRD maintains safety and efficacy while permitting resection of significantly larger lesions than FTRD alone.

Rare diagnosis of intestinal lipomatosis complicated by intussusception in an adult: A case report.

INTRODUCTION: Intestinal Lipomatosis consists of diffuse lipomas in various regions from the small to large bowel. They can remain asymptomatic or present with complications such as Intussusception. DISCUSSION: Intestinal lipomatosis complicated by Intussusception is a rare occurrence that has not been well documented. Rare condition management is difficult to approach because of the customizability each scenario requires. We hope through sharing our approach this can serve as a rough template to physicians who find themselves in a similar scenario. Overtime, as more case reports and surgical approaches are recorded we can establish future advancements in surgery. PRESENTATION OF CASE: We present the case of a 47 year-old male who arrived at the Emergency Department with a chief complaint of abdominal pain. A CT scan revealed ileocolic intussusception. An intramural lipoma of the terminal ileum served as the lead point. Exploratory laparotomy confirmed the Intussusception and a right hemicolectomy was performed to repair the affected area. Examination of the resected large bowel showed diffuse thickening of the mucosa in the area of the cecum confirmed to be submucosal lipomatosis on histological examination. Patient was discharged on the fifth post-operative day. CONCLUSION: This case confirmed previous treatment modalities in the management of intussusception. It also corroborates the complication of intussusception with Intestinal lipomatosis. It teaches us the importance of keeping a wide differential when considering a diagnosis of bowel obstruction. Through imaging, surgical exploration, and pathological interpretation, this case, which began as a complaint of abdominal pain, concluded as a rare clinical entity.

Brain Function Is Linked to LDL Cholesterol in Older Adults with Cardiovascular Risk.

OBJECTIVES: To determine how cardiovascular risk is associated with working memory task performance and task-related suppression of default-mode network (DMN) activity in cognitively intact older adults. DESIGN: A cross-sectional functional magnetic resonance imaging study of older adults with cardiovascular risk factors. SETTING: Rotman Research Institute, Baycrest Health Sciences. PARTICIPANTS: Thirty older adults with cardiovascular risk factors. MEASUREMENTS: Participants provided health information and a blood sample, and underwent functional magnetic resonance imaging during a working memory task and during a breath-hold task to assess cerebrovascular reactivity. RESULTS: Higher plasma low-density lipoprotein cholesterol (LDL-C) was associated with poorer working memory task performance (P = 0.008) and reduced task-related DMN suppression (P = 0.005). A composite index of cardiovascular risk, the Framingham General Cardiovascular Risk Profile, showed no associations with task performance or task-related DMN suppression. These findings were independent of white matter burden and cerebrovascular reactivity and thus cannot be accounted for by individual differences in neurovascular health. CONCLUSION: These findings suggest a deleterious effect of elevated LDL-C on working memory task performance and task-related DMN suppression in older adults with cardiovascular risk. The relations between the Framingham General Cardiovascular Risk Profile, cognitive task performance, and DMN function require further study.

A systematic review of type 2 diabetes mellitus and hypertension in imaging studies of cognitive aging: time to establish new norms.

The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults, and the deleterious effect of these conditions on cerebrovascular and brain health, is creating a growing discrepancy between the "typical" cognitive aging trajectory and a "healthy" cognitive aging trajectory. These changing health demographics make T2DM and hypertension important topics of study in their own right, and warrant attention from the perspective of cognitive aging neuroimaging research. Specifically, interpretation of individual or group differences in blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or positron emission tomography (PET H2O(15)) signals as reflective of differences in neural activation underlying a cognitive operation of interest requires assumptions of intact vascular health amongst the study participants. Without adequate screening, inclusion of individuals with T2DM or hypertension in "healthy" samples may introduce unwanted variability and bias to brain and/or cognitive measures, and increase potential for error. We conducted a systematic review of the cognitive aging neuroimaging literature to document the extent to which researchers account for these conditions. Of the 232 studies selected for review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%). A large portion had exclusion criteria that made it difficult to determine whether T2DM or hypertension were excluded (44 and 37%), and many did not mention any selection criteria related to T2DM or hypertension (34 and 22%). Of all the surveyed studies, only 29% acknowledged or addressed the potential influence of intersubject vascular variability on the measured BOLD or PET signals. To reinforce the notion that individuals with T2DM and hypertension should not be overlooked as a potential source of bias, we also provide an overview of metabolic and vascular changes associated with T2DM and hypertension, as they relate to cerebrovascular and brain health.

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

BACKGROUND: Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

Statistical platform to discern spatial and temporal coordination of endothelial sprouting.

Many biological processes, including angiogenesis, involve intercellular feedback and temporal coordination, but inference of these relations is often drowned in low sample sizes or noisy population data. To address this issue, a methodology was developed to statistically study spatial lateral inhibition and temporal synchronization in one specific biological process, endothelial sprouting mediated by Notch signaling. Notch plays an essential role in the development of organized vasculature, but the effects of Notch on the temporal characteristics of angiogenesis are not well understood. Results from this study showed that Notch lateral inhibition operates at distances less than 31 µm. Furthermore, combining time lapse microscopy with an intraclass correlation model typically used to analyze family data showed intrinsic temporal synchronization among endothelial sprouts originating from the same microcarrier. Such synchronization was reduced with Notch inhibitors, but was enhanced with the addition of Notch ligands. These results indicate that Notch plays a critical role in the temporal regulation of angiogenesis, as well as spatial control, and this method of analysis will be of significant utility in studies of a variety of other biological processes.

Transient mitochondrial permeability transition pore opening after neonatal cardioplegic arrest.

BACKGROUND: Neonatal cardioplegic arrest is associated with apoptosis-related mitochondrial dysfunction, including Bax translocation to the mitochondria, mitochondrial permeabilization, cytochrome c release, and electron transport chain dysfunction. We sought to characterize the time course and mode of postcardioplegic mitochondrial membrane permeabilization and hypothesize that permeabilization is transient and mediated by the mitochondrial permeability transition pore. METHODS: Isolated, perfused neonatal rabbit hearts underwent 60 minutes of warm crystalloid cardioplegic arrest followed by 120 minutes of reperfusion. Mitochondrial permeabilization was evaluated by means of infusion of 2-deoxy [(3)H] glucose and subsequent detection of entrapment in isolated mitochondrial fractions. Groups included preloading with 2-deoxy [(3)H] glucose followed by cardioplegia and reperfusion (CCP), cardioplegia and cyclosporin A (specific inhibitor of mitochondrial permeability transition pore opening; CCP + CsA) or HA14-1 (Bcl-2 inhibitor; CCP + HA), and noncardioplegia control hearts (non-CCP). Reconstitution of mitochondrial integrity was tested by means of delayed infusion of 2-deoxy [(3)H] glucose 30 minutes after reperfusion (P-CCP). RESULTS: Cardioplegic arrest was associated with mitochondrial permeability transition pore opening, Bax translocation, cytochrome c release, radical oxygen species production, and electron transport chain dysfunction. Inhibition of mitochondrial permeability transition pore opening by cyclosporin A ameliorated this response, whereas inhibition of Bcl-2 exacerbated these changes. Postreperfusion entrapment of 2-deoxy [(3)H] glucose was significantly reduced in comparison with that seen in CCP hearts, suggesting that closure of the mitochondrial permeability transition pore ensues within 30 minutes after reperfusion. CONCLUSIONS: Apoptosis-related mitochondrial dysfunction in postcardioplegic neonatal hearts is mediated by mitochondrial permeability transition pore opening, which is transient and associated with deficits in electron transport. Clinical strategies directed to minimize mitochondrial permeability transition pore opening are likely to improve postoperative myocardial dysfunction after neonatal cardiac surgery.

Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones.

Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Further, the contradictory action of the two agents leads to a stable level of proangiogenic stimulation in this region, in spite of significant variations in the individual release rates over time. The resulting spatially restrictive and temporally sustained profiles of active signaling allow the creation of a spatially heterogeneous and functional vasculature.

Integrated approach to designing growth factor delivery systems.

Growth factors have been widely used in strategies to regenerate and repair diseased tissues, but current therapies that go directly from bench to bedside have had limited clinical success. We hypothesize that engineering successful therapies with recombinant proteins will often require specific quantitative information of the spatiotemporal role of the factors and the development of sophisticated delivery approaches that provide appropriate tissue exposures. This hypothesis was tested in the context of therapeutic angiogenesis. An in vitro model of angiogenesis was adapted to quantify the role of the concentration/gradient of vascular endothelial growth factor [VEGF(165)] on microvascular endothelial cells, and a delivery system was then designed, based on a mathematical model, to provide the desired profile in ischemic mice hindlimbs. This system significantly enhanced blood vessel formation, and perfusion and recovery from severe ischemia. This general approach may be broadly applicable to growth factor therapies.

Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation.

PURPOSE: Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation. MATERIALS AND METHODS: A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds. RESULTS: In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation. CONCLUSIONS: Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.