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.

Fully percutaneous fetoscopic repair of myelomeningocele: 30-month follow-up data.

OBJECTIVE: This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. METHODS: Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. RESULTS: All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. CONCLUSION: Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Effect of plastic mulching on mycotoxin occurrence and mycobiome abundance in soil samples from asparagus crops.

Plastic mulching (PM) is widely used in modern agriculture because of its advantageous effects on soil temperature and water conservation, factors which strongly influence the microbiology of the soil. The aim of this study was to assess the effect of PM on mycotoxin occurrence in relation with mycobiome abundance/diversity and soil physicochemical properties. Soil samples were collected from green (GA) and white asparagus (WA) crops, the last under PM. Both crops were cultivated in a ridge-furrow-ridge system without irrigation. Samples were analyzed for mycotoxin occurrence via liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Total colony-forming unit was indicative of mycobiome abundance, and analysis of mycobiome diversity was performed by internal transcribed spacer (ITS) sequencing. PM avoided the drop of soil temperature in winter and allowed higher soil temperature in early spring compared to non-covered soil. Moreover, the use of PM provided controlled conditions for water content in soil. This was enough to generate a dissimilar mycotoxin occurrence and mycobiome diversity/abundance in covered and non-covered soil. Mycotoxin soil contamination was confirmed for deoxynivalenol (DON), range LOD to 32.1 ng/g (LOD = 1.1 ng/g). The DON values were higher under PM (average 16.9 ± 10.1 ng/g) than in non-covered soil (9.1 ± 7.9 ng/g); however, this difference was not statically significant (p = 0.09). Mycobiome analysis showed a fungal compartment up to fivefold higher in soil under PM compared to GA. The diversity of the mycobiome varied between crops and also along the soil column, with an important dominance of Fusarium species at the root zone in covered soils.

Pancreatic Abscess: An Unusual Presentation of Pancreatic Tail Cancer.

Pancreatic abscess usually occurs in the setting of pancreatitis especially if complicated by pseudocysts or pancreatic necrosis. On the other hand, pancreatic body and tail cancer is relatively uncommon cancer and rarely does it present as a pancreatic abscess. We describe a 50-year-old man with sepsis due to underlying pancreatic abscess, who was later diagnosed to have pancreatic tail adenocarcinoma with the help of endoscopic ultrasound guided fine needle aspiration cytology.

SAR simulations for high-field MRI: how much detail, effort, and accuracy is needed?

Accurate prediction of specific absorption rate (SAR) for high field MRI is necessary to best exploit its potential and guarantee safe operation. To reduce the effort (time, complexity) of SAR simulations while maintaining robust results, the minimum requirements for the creation (segmentation, labeling) of human models and methods to reduce the time for SAR calculations for 7 Tesla MR-imaging are evaluated. The geometric extent of the model required for realistic head-simulations and the number of tissue types sufficient to form a reliable but simplified model of the human body are studied. Two models (male and female) of the virtual family are analyzed. Additionally, their position within the head-coil is taken into account. Furthermore, the effects of retuning the coils to different load conditions and the influence of a large bore radiofrequency-shield have been examined. The calculation time for SAR simulations in the head can be reduced by 50% without significant error for smaller model extent and simplified tissue structure outside the coil. Likewise, the model generation can be accelerated by reducing the number of tissue types. Local SAR can vary up to 14% due to position alone. This must be considered and sets a limit for SAR prediction accuracy. All these results are comparable between the two body models tested.

The structure of focused, radially polarized fields.

We present a detailed analysis of the structure of strongly focused, radially polarized electromagnetic fields. The existence of phase singularities of the two components of the electric field is demonstrated. Two different mechanisms to obtain creation or annihilation of these phase singularities are discussed. These are changing the aperture angle of the lens and the width of the beam. Also, it is shown that in the focal plane the handedness of the electric polarization ellipse is an alternating function of the radial distance. Finally, the different contributions to the electric energy density are examined.

IGF-binding protein-4: biochemical characteristics and functional consequences.

IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.

Acupuncture for gastrointestinal and hepatobiliary disorders.

Acupuncture has been used for various gastrointestinal (GI) conditions. Voluminous data support the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have also shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture has also been used for a variety of other conditions including postoperative ileus, achalasia, peptic ulcer disease, functional bowel diseases (including irritable bowel syndrome and nonulcer dyspepsia), diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few prospective randomized clinical studies, the well-documented physiological basis of acupuncture effects on the GI tract, and the extensive history of successful clinical use of acupuncture, makes this a promising modality that warrants further investigation.

Regulation of the high-affinity H+/peptide cotransporter in renal LLC-PK1 cells.

Di- and tripeptides and peptide mimetics such as beta-lactam antibiotics are efficiently reabsorbed from the tubular lumen by a high-affinity peptide transporter. We have recently identified and characterized this H+-coupled high-affinity peptide transport system in the porcine proximal tubular cell line LLC-PK1. Here we describe for the first time the regulation of the renal high-affinity peptide cotransporter at the cellular level. Uptake of 5 microM 3H-D-Phe-L-Ala into LLC-PK1 cells was significantly increased by lowering [Ca2+]in and decreased by increasing [Ca2+] in. Moreover, it was shown that the [Ca2+]in effects on peptide transport activity were dependent on Ca2+ entry from the extracellular site (e.g., via a store-regulated capacitative Ca2+ influx). Protein kinase C (PKC) was found to transmit the effects of [Ca2+]in on peptide transport. Although we demonstrate by pHin measurements that the PKC inhibitor staurosporine did decrease the transmembrane H+ gradient and consequently should have reduced the driving force for peptide uptake, the only effect on transport kinetics of 3H-D-Phe-L-Ala observed was a significant decrease in Km from 22.7+/-2.5 microM to 10.2+/-1.9 microM with no change in maximal velocity.

Subtypes of constipation predominant irritable bowel syndrome based on rectal perception.

BACKGROUND: Patients who complain of constipation can be divided into those who have lost the natural call to stool, but develop abdominal discomfort after several days without a bowel movement (no urge); and those who experience a constant sensation of incomplete evacuation (urge). AIMS: To determine whether the two groups differ in symptoms, colonic transit, and perceptual responses to controlled rectal distension. METHODS: Forty four patients with constipation were evaluated with a bowel symptom questionnaire, colonic transit (radiopaque markers), and rectal balloon distension. Stool (S) and discomfort (D) thresholds to slow ramp (40 ml/min) and rapid phasic distension (870 ml/min) were determined with an electronic distension device. Fifteen healthy controls were also studied. RESULTS: All patients had Rome positive irritable bowel syndrome (IBS); 17 were no urge and 27 urge. Mean D threshold to phasic rectal distensions was 28 (3) mm Hg in no urge, 27 (3) mm Hg in urge (NS), but higher in the control group (46 (2) mm Hg; p < 0.01). Sixty seven per cent of no urge and 69% of urge were hypersensitive for D. Slow ramp distension thresholds were higher in no urge (S: 26 (3); D: 45 (4) mm Hg) compared with urge (S: 16 (2); D: 31 (3) mm Hg; p < 0.01), or with controls (S: 15 (1); D: 30 (3); p < 0.01). CONCLUSIONS: Hyposensitivity to slow rectal distension is found in patients with IBS who complain of constipation and have lost the call to stool even though their sensitivity to phasic distension is increased.

Endogenous expression of the renal high-affinity H+-peptide cotransporter in LLC-PK1 cells.

The reabsorption of filtered di- and tripeptides as well as certain peptide mimetics from the tubular lumen into renal epithelial cells is mediated by an H+-coupled high-affinity transport process. Here we demonstrate for the first time H+-coupled uptake of dipeptides into the renal proximal tubule cell line LLC-PK1. Transport was assessed 1) by uptake studies using the radiolabeled dipeptide D-[3H]Phe-L-Ala, 2) by cellular accumulation of the fluorescent dipeptide D-Ala-Lys-AMCA, and 3) by measurement of intracellular pH (pHi) changes as a consequence of H+-coupled dipeptide transport. Uptake of D-Phe-L-Ala increased linearly over 11 days postconfluency and showed all the characteristics of the kidney cortex high-affinity peptide transporter, e.g., a pH optimum for transport of D-Phe-L-Ala of 6.0, an apparent Km value for influx of 25.8 +/- 3. 6 microM, and affinities of differently charged dipeptides or the beta-lactam antibiotic cefadroxil to the binding site in the range of 20-80 microM. pHi measurements established the peptide transporter to induce pronounced intracellular acidification in LLC-PK1 cells and confirm its postulated role as a cellular acid loader.

Efficacy of an oral vaccinia-rabies glycoprotein recombinant vaccine in controlling epidemic raccoon rabies in New Jersey.

A field trial to evaluate the efficacy of an oral vaccinia-rabies glycoprotein recombinant virus vaccine in controlling epidemic raccoon (Procyon lotor) rabies was conducted by distributing 180,816 doses (10(8.2)TCID50/ml) of vaccine in wax ampules within fish-meal polymer baits at a rate of 64 doses/km2/treatment throughout a 552 km2 area, forming an 18 km wide band across the northern Cape May Peninsula of New Jersey (USA). Vaccination treatments were conducted in the spring and fall between May 1992 and October 1994 from a helicopter along ecotones and from motor vehicles along roads. Vaccine-laden baits were removed by animals from tracking stations within 3 wk and 61% of the identifiable tracks were those of raccoons. Tetracycline incorporated in the baits as a biomarker was detected in 155 (73%) of the vaccination area raccoons following the fall 1993 and spring 1994 vaccinations. Eleven (61%) of the raccoons sampled in the same time period seroconverted (> or = 0.5 IU) in response to rabies virus glycoprotein. A raccoon diagnosed with rabies from the northern border of the vaccination area on 30 April 1993 provided the first evidence that the barrier was being challenged by the rabies epidemic. The prevalence of rabies in raccoons from the vaccination area for the first year (10%, n = 96) and second year (8%, n = 61) of challenge was reduced more than six-fold by vaccination compared to unvaccinated raccoons from northern adjacent surveillance areas during the corresponding first (65%, n = 189) and second years (53%, n = 43). Vaccination also effectively reduced by three-fold the rate at which the epidemic moved through the raccoon population (15 km/yr). The breach of the vaccination area resulted in a resumption of the high rate (43 km/yr) of epidemic movement and a significant nine-fold increase in rabies prevalence (77%, n = 47). The maximum linear movement (12.9 km) among five ear-tagged rabid raccoons in the study area was significantly greater than that of 19 normal radio-collared raccoons (2.58 km) in the area. These large movements of rabid raccoons, together with relocation of nuisance raccoons, spillover of raccoon rabies in skunks (Mephitis mephitis) and other species, insufficient funding and a decision to discontinue the program in 1994 (which could have resulted in insufficient population immunity among raccoons in the vaccination area) may have contributed to the eventual breach of the barrier.

Use of acupuncture by American physicians.

OBJECTIVES: Little is known about the characteristics of American physicians who currently practice acupuncture. We asked: (1) Do the demographics of physicians practicing acupuncture differ from the general physician population? (2) Do these physicians use or endorse other alternative therapies? (3) For which conditions is acupuncture most commonly used? (4) For which conditions is acupuncture perceived to be most efficacious? DESIGN: Mailed survey of physicians who incorporate acupuncture into their practice. PARTICIPANTS: Membership of the American Academy of Medical Acupuncture (AAMA). OUTCOME MEASURES: Demographic information regarding physicians and practice characteristics; specific illnesses treated, and perceived efficacy; use of other complementary modalities; personal reasons for practicing acupuncture. RESULTS: Compared with national data, respondents were more likely to be nonspecialists, in private practice, and age 35 to 54. There was an equal proportion of men and women. Most had been doing acupuncture for < 5 years; most use it on < 25% of their patients. Endorsement or use of other complementary methods (spinal manipulation, herbal medicine, supplements, homeopathy) was common. Acupuncture was more commonly used for pain conditions than general medical problems or addiction management. Reasons for use included: efficacy of the technique, an alternative in cases of inadequacy of standard medical approach, and a multidimensional approach to health care. CONCLUSIONS: Physicians surveyed in this study who incorporate acupuncture into their practice do so mainly to treat pain problems. They are more likely to be in the 35 to 54 age group, nonspecialists, and in private practice when compared with national averages. These physicians are also more likely to use or endorse other complementary modalities.

Biliary interleukin-6 and tumor necrosis factor-alpha in patients undergoing endoscopic retrograde cholangiopancreatography.

Cytokines are low-molecular-weight protein mediators that possess a wide spectrum of inflammatory, metabolic, and immunomodulatory properties. Cytokines have been shown to be produced by monocytes/macrophages, lymphocytes, fibroblasts, endothelial cells, and more recently, hepatocytes and biliary epithelium. The aim of this study was to define biliary levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) in various disease states. Fifty-four patients undergoing ERCP comprised the study group. IL-6 and TNF-alpha were measured in aspirated bile using an ELISA technique. Levels of both TNF-alpha and IL-6 were significantly higher in patients with cholangitis (P < 0.00001). Moreover, IL-6 was 100% specific for cholangitis since none of the patients without bacterial cholangitis-including patients with biliary obstruction secondary to cholangiocarcinoma or pancreatic carcinoma-had measurable IL-6 in their bile. Low levels of biliary TNF-alpha were detectable in five patients without cholangitis; the sensitivity and specificity of TNF-alpha for cholangitis were 100% and 82%, respectively. There was a strong statistical correlation between biliary IL-6 and TNF-alpha levels (r = 0.819, P < 0.0001). In contrast, the correlations between biliary cytokines and serum biochemical parameters were weak. These results suggest that IL-6 and TNF-alpha are sensitive markers for cholangitis and may differentiate it from other types of biliary tract disease.

Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography.

Recent positron emission tomography (PET) studies have demonstrated areas of pain processing in the human brain. Given the inhibitory effects of opioids on neuronal activity, we predicted that fentanyl's analgesic effects would be associated with suppression of pain-evoked responses in these distinct brain areas. To test this, PET was used to measure cerebral blood flow responses, as reflections of regional neuronal activity, to painful and nonpainful thermal stimuli both in the absence and presence of fentanyl in humans. During each PET scan in nine healthy volunteers a tonic heat source was placed against the subject's left forearm, delivering a preset temperature of either 40 degrees C (nonpainful) or 47-48 degrees C (painful). Subjects underwent eight blood flow studies, each consisting of 50 mCi [15O]water injection and a PET scan. The first four studies were performed during placebo administration in the stimulus sequence: nonpainful, painful, painful, nonpainful. This sequence was then repeated during intravenous (i.v.) administration of fentanyl 1.5 micrograms/kg [corrected]. Significant differences in regional cerebral blood flow (rCBF) between the placebo and the fentanyl conditions during nonpainful and painful stimuli were identified using statistical parametric mapping. It was found that pain increased rCBF in the anterior cingulate, ipsilateral thalamus, prefrontal cortex, and contralateral supplementary motor area. Fentanyl increased rCBF in the anterior cingulate and contralateral motor cortices, and decreased rCBF in the thalamus (bilaterally) and posterior cingulate during both stimuli. During combined pain stimulation and fentanyl administration, fentanyl significantly augmented pain-related rCBF increases in the supplementary motor area and prefrontal cortex. This activation pattern was associated with decreased pain perception, as measured on a visual analog scale. In contrast to our hypothesis, these data indicate that fentanyl analgesia involves augmentation of pain-evoked cerebral responses in certain areas, as well as both activation and inhibition in other brain regions unresponsive to pain stimulation alone.