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Abbreviations GERD Gastroesophageal reflux disease GI Gastroenterology H2RA H2 antagonist PCP Primary care physician PPI Proton pump inhibitor Many infants with fussiness or spitting-up are prescribed acid suppression therapy with proton pump inhibitors (PPIs) and H2 antagonists (H2RAs) despite data suggesting these therapies do not improve symptoms over placebo.1,2 Furthermore, there are risks with acid suppression treatment, including increasing rates of gastroenteritis, pneumonia and necrotising enterocolitis.3 In 2018, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) released updated clinical practice guidelines for the management of gastroesophageal reflux disease (GERD) for infants.4 The guidelines recommend thickening and trial of hypoallergenic formula as first-line therapies for the treatment of GERD in infants, as well as referral to gastroenterology (GI) clinician prior to starting acid suppression. Also, the patients in this study had severe enough symptoms to require referral to GI clinic; thus, our data does not capture changes made by primary care providers for patients who had symptom resolution. [Extracted from the article]

The primary graft-related complication during the first clinical trial evaluating the use of tissue-engineered vascular grafts (TEVGs) was stenosis. We investigated the role of macrophages in the formation of TEVG stenosis in a murine model. We analyzed the natural history of TEVG macrophage infiltration at critical time points and evaluated the role of cell seeding on neovessel formation. To assess the function of infiltrating macrophages, we implanted TEVGs into mice that had been macrophage depleted using clodronate liposomes. To confirm this, we used a CD11b-diphtheria toxin-receptor (DTR) transgenic mouse model. Monocytes infiltrated the scaffold within the first few days and initially transformed into M1 macrophages. As the scaffold degraded, the macrophage infiltrate disappeared. Cell seeding decreased the incidence of stenosis (32% seeded, 64% unseeded, P=0.024) and the degree of macrophage infiltration at 2 wk. Unseeded TEVGs demonstrated conversion from MI to M2 phenotype, whereas seeded grafts did not. Clodronate and DTR inhibited macrophage infiltration and decreased stenosis but blocked formation of vascular neotissue, evidenced by the absence of endothelial and smooth muscle cells and collagen. These findings suggest that macrophage infiltration is critical for neovessel formation and provides a strategy for predicting, detecting, and inhibiting stenosis in TEVGs. [ABSTRACT FROM AUTHOR]

A major limitation of tissue engineering research is the lack of noninvasive monitoring techniques for observations of dynamic changes in single tissue-engineered constructs. We use cellular magnetic resonance imaging (MRI) to track the fate of cells seeded onto functional tissue-engineered vascular grafts (TEVGs) through serial imaging. After in vitro optimization, murine macrophages were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanopartides and seeded onto scaffolds that were surgically implanted as inferior vena cava interposition grafts in SCID/bg mice. Serial MRI showed the transverse relaxation times (T2) were significantly lower immediately following implantation of USPIO-labeled scaffolds (T2=44±6.8 vs. 71±10.2 ms) but increased rapidly at 2 h to values identical to control implants seeded with unlabeled macrophages (T2=63±12 vs. 63±14 ms). This strongly indicates the rapid loss of seeded cells from the scaffolds, a finding verified using Prussian blue staining for iron containing macrophages on explanted TEVGs. Our results support a novel paradigm where seeded cells are rapidly lost from implanted scaffolds instead of developing into cells of the neovessel, as traditionally thought. Our findings confirm and validate this paradigm shift while demonstrafing the first successful application of noninvasive MRI for serial study of cellular-level processes in tissue engineering. [ABSTRACT FROM AUTHOR]

We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to "regenerate" neotissue from preexisting committed tissue cells. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 8-year-old child who have obstruction of the suprahepatic inferior vena cava (IVC) secondary after liver transplantation for stage three hepatoblastoma, for that doctors constructed a hybrid cardiopulmonary support system that offered an extracorporeal therapy in safe, and cost-effective package.