A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Iron-based nanoparticles prepared from yerba mate extract. Synthesis, characterization and use on chromium removal.

Iron-based nanoparticles were synthesized by a rapid method at room temperature using yerba mate (YM) extracts with FeCl3 in different proportions. Materials prepared from green tea (GT) extracts were also synthesized for comparison. These materials were thoroughly characterized by chemical analyses, XRD, magnetization, SEM-EDS, TEM-SAED, FTIR, UV-Vis, Raman, Mössbauer and XANES spectroscopies, and BET area analysis. It was concluded that the products are nonmagnetic iron complexes of the components of the extracts. The applicability of the materials for Cr(VI) (300 µM) removal from aqueous solutions at pH 3 using two Cr(VI):Fe molar ratios (MR), 1:3 and 1:0.5, has been tested. At Cr(VI):Fe MR = 1:3, the best YM materials gave complete Cr(VI) removal after two minutes of contact, similar to that obtained with commercial nanoscale zerovalent iron (N25), with dissolved Fe(II), and with a likewise prepared GT material. At a lower Cr(VI):Fe MR (1:0.5), although Cr(VI) removal was not complete after 20 min of reaction, the YM nanoparticles were more efficient than N25, GT nanoparticles and Fe(II) in solution. The results suggest that an optimal Cr(VI):Fe MR ratio could be reached when using the new YM nanoparticles, able to achieve a complete Cr(VI) reduction, and leaving very low Cr and Fe concentrations in the treated solutions. The rapid preparation of the nanoparticles would allow their use in removal of pollutants in soils and groundwater by direct injection of the mixture of precursors.

Temporary inhibition of the plasminogen activator inhibits periosteal chondrogenesis and promotes periosteal osteogenesis during appendicular bone fracture healing.

INTRODUCTION: Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration. METHODS: We employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid. Routine histological assays, biomechanical testing and micro-CT analyses were utilized to assess callus volume, and strength, progenitor cell proliferation, differentiation, and remodeling in vivo. Two disparate ectopic transplantation models were used to study the effect of the growth factor milieu within the early fracture hematoma on osteoprogenitor cell fate decisions. RESULTS: Aminocaproic acid treated femur fractures healed with a significantly smaller cartilaginous callus, and this effect was also observed in the ectopic transplantation assays. We hypothesized that aminocaproic acid treatment resulted in a stabilization of the early fracture hematoma, leading to a change in the growth factor milieu created by the early hematoma. Gene and protein expression analysis confirmed that aminocaproic acid treatment resulted in an increase in Wnt and BMP signaling and a decrease in TGF-ß-signaling, resulting in a shift from chondrogenic to osteogenic differentiation in this model of endochondral bone formation. CONCLUSION: These experiments demonstrate for the first time that inhibition of the plasminogen activator during fracture healing using aminocaproic acid leads to a change in cell fate decision of periosteal osteoprogenitor cells, with a predominance of osteogenic differentiation, resulting in a larger and stronger bony callus. These findings may offer a promising new use of aminocaproic acid, which is already FDA-approved and offers a very safe risk profile.

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats.

One would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity - 'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

Protein-Loosing Entropathy Induced by Unique Combination of CMV and HP in an Immunocompetent Patient.

Protein-losing gastroenteropathies are characterized by an excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoproteinemia (detected as hypoalbuminemia), edema, and, in some cases, pleural and pericardial effusions. Protein-losing gastroenteropathies can be caused by a diverse group of disorders and should be suspected in a patient with hypoproteinemia in whom other causes, such as malnutrition, proteinuria, and impaired liver protein synthesis, have been excluded. In this paper, we present a case of protein-losing enteropathy in a 22-year-old immunocompetent male with a coinfection of CMV and Hp.

Dapsone induced eosinophilic pneumonia.

Eosinophilic lung diseases (ELD) are a variety of several clinical entities, which may result from different etiologies, including drug treatment. Dapsone, a sulfone antibiotic widely used in leprosy (among other indications), has been described as a possible cause of ELD. We report a patient with leprosy who presented with respiratory symptoms and pulmonary infiltrates and was diagnosed as suffering from eosinophilic pneumonia. To the best of our knowledge, this is the first report in which the diagnosis of dapsone-induced eosinophilic pneumonia was supported by bronchoalveolar lavage, lung biopsy and typical response to therapy.

Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells.

Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH.

Perinatal outcome and peripartum complications in preterm singleton and twins deliveries: a comparative study.

OBJECTIVE: Multiple pregnancy is one of the major risk factors for preterm births. The aim of the present study was to compare perinatal outcome and peripartum complications between twins and singletons, born preterm. STUDY DESIGN: The study population consisted of preterm deliveries of 435 pairs of twins (870 neonates) and the comparison group included 4754 preterm deliveries of singletons, born in the same period (January 1, 1989-December 31, 1996). Exclusion criteria were lack of prenatal care and births following infertility treatments. The three steps in statistical analysis consisted of (1) degree of concordance between the twins; (2) comparison between each twin (I and II) to their singleton comparison groups using SPSS computer program; (3) stratified analysis to examine perinatal mortality rates at different gestational age groups. RESULTS: The prevalence of preterm deliveries was 7.9% (6192/77610). Perinatal mortality was lower in twins of both birth orders, however, it was statistically significant only when APD is considered. Mortality rates in all gestational age groups and for both twin groups were lower than that of singleton [OR=0.45 (0.26-0.75; 95% CI) for twin-I; OR=0.36 (0.21-0.59; 95% CI) for twin-II]. Compared to singletons, twin gestations had less congenital malformations. Twin gestation had statistically lower rates of preterm premature rupture of membranes, severe pregnancy induced hypertension, oligohydramnios, placenta previa, placental abruption and clinical chorioamnionitis [12.2 vs.17.3%, 2.5 vs. 6.3%, 2.3 vs. 4.7%, 0.9 vs. 2.9%, 1.8 vs. 5%, 1.8 vs. 5.2%, respectively (P<0.01)]. Mothers of twins had less diabetes mellitus class B-R, hydramnios and chronic hypertension than that of singleton (1.8 vs. 2.6%, 5.5 vs. 7.4%, 3.7 vs. 4.8%, respectively). Cesarean section rates were significantly higher in twin's gestation. Mothers of twins tended to be older and of higher birth and gravidity order. CONCLUSIONS: Perinatal mortality rates and peripartum complications were lower in twin compared to singleton gestations.

Relation between postprandial gastric emptying and cutaneous electrogastrogram in primates.

The relation between the cutaneous electrogastrogram (EGG) and gastric emptying was investigated in six rhesus monkeys. Gastric emptying was measured using scintigraphy after administration of two 80-ml mixed solid liquid meals (1.5 and 5.0 kcal/kg) tagged with 99mTc-sulfur colloid and 111In-diethylenetriamine pentaacetic acid. Six epigastric bipolar recordings of the EGG were concurrently obtained, digitized, and band-pass filtered. Portions of the signal with motion artifacts were automatically detected and excluded using two microwave motion sensors. During the early postprandial period, gastric emptying was greater after the 1.5-kcal/kg meal than after the 5-kcal/kg meal, and EGG amplitude increased significantly compared with fasting only after the 1.5-kcal/kg meal. Both emptying and EGG amplitude subsequently decreased after the 1.5-kcal/kg meal, whereas these two parameters increased after the 5-kcal/kg meal. As a result, EGG amplitude was significantly correlated with gastric emptying of solids in all six animals. In contrast, EGG frequency was not significantly different between the two meals and was not correlated with emptying. These results indicate that both the EGG and gastric emptying are modified differently by meals with different caloric contents and that the EGG may represent a useful, although indirect, index of gastric emptying.

[The hemodynamic profile of the response to amrinone treatment in severe heart failure]. / Perfil hemodinámico de la respuesta al tratamiento con amrinona en la insuficiencia cardíaca severa.

The hemodynamic response to amrinone was analyzed in 19 patients with severe heart failure (NYHA III or IV). In 17 patients, 2 bolus of amrinone (0.75 mg/kg) were administered with an interval of 30 minutes, while a single bolus only was administered in 2 patients. In all patients the initial bolus was followed by continuous perfusion of Amrinone (10 micrograms/kg/min in 17 patients; 7 and 5 micrograms/kg/min in the remaining two). Cardiac index increased from 1.8 +/- 0.2 to 2.5 +/- 0.4 l/min/m2 (p less than 0.01), and pulmonary capillary wedge pressure and mean right atrial pressure decreased significantly (from 24 +/- 5.2 to 14 +/- 6 mmHg, p less than 0.01; and from 8.7 +/- 6.5 to 3.2 +/- 3.4, p less than 0.05 respectively). There were no significant changes in mean blood pressure (93 +/- 17 versus 88 +/- 13), heart rate (81 +/- 15 versus 84 +/- 14 beats per minute) and systolic work index (26.4 +/- 10.7 versus 37.7 +/- 12.3 g-m/m2). The maximum effect was obtained at 60 minutes and maintained throughout the period of monitoring (8 hours). In the 2 patients who received a single bolus of amrinone the maximum effect was reached at 30 minutes (cardiac index 1.3 +/- 0.1 versus 2.5 +/- 0.1 l/min/m2; pulmonary capillary pressure 24 +/- 5 versus 16.8 +/- 6.5 mmHg; mean right atrial pressure 11 +/- 1 versus 3.5 +/- 3.5 mmHg), and was followed by a progressive loss of efficiency, until effect had totally disappeared and situation basal returned, between the third and fourth hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission of Plasmodium vivax malaria in San Diego County, California, 1986.

Between 18 June and 20 September 1986, 28 cases of Plasmodium vivax malaria were documented in Carlsbad, California, a coastal town north of San Diego. Malaria occurred in 1 local resident who had no risk factors, a second local resident who had traveled to a malarious area 9 months earlier, and 26 Mexican migrant workers (MWs). Among the 28 cases, 27 lived in a square mile marshy area where Anopheles hermsi, a newly described American species of the Anopheles maculipennis group, was known to be breeding. An investigation of MWs residing in the affected area was done to determine the extent of the outbreak and to identify risk factors for acquiring malaria. We interviewed and drew blood from 304 healthy MWs and 17 (65%) of the MWs with malaria. Fluorescent antibody titers to P. vivax greater than or equal to 1:256 occurred in 14 (82%) of the 17 MWs with malaria tested and 9 (3%) of the healthy MWs. The principal risk factor identified for contracting malaria was sleeping outside on a hillside adjacent to the marshy area. Malaria in a local resident with no malaria risk factors and the clustering in time and place of 26 cases suggest that P. vivax malaria was introduced and local transmission was sustained through several generations, producing the largest outbreak of introduced malaria in the United States since 1952.

The influence of acute hyperinsulinemia on the insulin-related material in brain, testis, liver, and kidney.

Insulin-related material was measured in acid ethanol extracts of brain, testis, liver, and kidney from adult rats acutely injected with insulin or saline. Insulin injection resulted in a twofold to threefold increase in plasma insulin during a two-hour period after injection. Plasma glucose was greatly depressed. Insulin injection had no effect on the insulin-related material in most areas of brain (cerebral cortex, olfactory bulbs, and medial hypothalamus) and the cerebrospinal fluid; lateral hypothalamus was an exception and paradoxically exhibited a decrease of this material. The testis insulin-related material was unaffected; purification of the testis extracts using the C18 Sep pak method revealed no further difference between the animals. In liver, the insulin-related material was not significantly different in the control and the insulin-injected group; however, we found a significant correlation between this material and plasma insulin within the insulin-injected group. In contrast, insulin injection resulted in an important increase in kidney insulin-related material that paralleled the change in plasma insulin. Thus, like chronic experiments, acute hyperinsulinemia revealed that the insulin-related material was largely independent from blood insulin in tissues that exhibit very different insulin uptake from the blood; kidney appeared to be an exception.