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.

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.

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.

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.

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.

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.

Positron emission tomographic imaging of serotonin activation effects on prefrontal cortex in healthy volunteers.

Serotonergic system abnormalities have been implicated in major depression, suicide, violence, alcoholism, and other psychopathologies. The prolactin response to fenfluramine has been widely used as a neuroendocrine probe to study brain serotonin responsivity. We have extended this methodology by using the positron emission tomography (PET) 18F-fluorodeoxyglucose (18FDG) method to examine the fenfluramine-induced changes in regional cerebral glucose metabolism (rCMRglu), an indicator of changes in regional neuronal activity. We report results on 16 healthy controls, each of whom underwent two PET studies. One group of six subjects had a placebo on day 1 and a single 60 mg oral dose of fenfluramine on day 2. The second group, of 10 subjects, was tested on two consecutive occasions without drug or placebo. Data were analyzed for significant rCMRglu changes on day 2 vs day 1 using the statistical parametric mapping method (p < 0.01). Subjects who did not receive drugs showed no statistically significant areas of rCMRglu increase or decrease on day 2 versus day 1. In contrast, the group that received fenfluramine showed significant fenfluramine-induced responses. Areas of rCMRglu increases involved mainly the left prefrontal and left temperoparietal cortex. Within the prefrontal cortex, two major areas of rCMRglu increase included, first, an area centered on the anterior cingulate and, second, an area in the lateral prefrontal cortex involving principally the inferior, middle, and superior frontal gyri. Some decreases in rCMRglu were observed, principally in the right hemisphere. This PET-fenfluramine paradigm is a potentially useful method for studying abnormalities of serotonin function in the prefrontal cortex.

Demonstration in vivo of reduced serotonin responsivity in the brain of untreated depressed patients.

OBJECTIVE: For over 25 years, it has been hypothesized that major depression is due to a deficiency of available serotonin or subsensitivity of key serotonin receptors in relevant brain regions. Direct evidence supporting this hypothesis has been lacking because of the difficulty in studying regional brain serotonergic function. The authors have developed a method for visualizing in vivo regional brain responses to serotonin release by comparing regional brain glucose metabolism after administration of the serotonin-releasing drug dl-fenfluramine, relative to placebo. METHOD: Results with healthy subjects (N = 6) were compared to those obtained with drug-free inpatients with moderately severe major depression (N = 6). RESULTS: Healthy subjects had several areas of statistically significant increases in metabolism, mostly in the left prefrontal and temporoparietal cortex, and areas of decreased metabolism, such as in the right prefrontal cortex. In contrast, the depressed patients had no areas of increase or decrease in metabolism, differing significantly from healthy subjects. Results with patients resembled those with healthy subjects (N = 10) who were scanned twice without active drug on either occasion. CONCLUSIONS: This study provides the first direct visualization of blunted regional brain responses to serotonin release in the brain of patients with major depression, a finding that supports the hypothesis of impaired serotonergic transmission in depression.

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.

Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma.

We determined the prevalence of hemorrhage within 1 disc diameter of the optic nerve head by masked examination of stereoscopic color and red-free fundus photographs in a multilayer study of 1123 patients. At the first (baseline) examination, disc hemorrhages were present in none of the normal subjects (0 of 661), 0.44% (6/1377) of "glaucoma suspect" subjects, and 2.44% (3/123) of glaucomatous eyes. Disc hemorrhage prevalence in glaucomatous eyes was significantly higher than in normal or glaucoma suspect eyes. Glaucoma suspect eyes with disc hemorrhage, compared with matched suspect eyes without disc hemorrhage, had a larger mean vertical cup-disc ratio, an increased rate of nerve fiber layer atrophy 1 year following disc hemorrhage, and a higher rate of conversion to initial visual field loss (numerically higher conversion though not statistically significant). While the number of eyes with disc hemorrhages in this study is small, in a patient with glaucoma or ocular hypertension, disc hemorrhage appears to be associated with a greater likelihood of ongoing damage. The low disc hemorrhage prevalence in an unselected population limits its usefulness as a screening tool for glaucoma.

Topical timolol decreases plasma high-density lipoprotein cholesterol level.

beta-Adrenergic antagonists taken orally adversely alter plasma lipid profiles. This study was designed to determine whether 0.5% topical timolol maleate has a similar effect. Forty volunteers who were not using medications known to alter plasma lipid levels were recruited for an unmasked study in which each subject served as his or her own control. Twelve subjects did not complete the study because of ocular and systemic side effects or extraneous factors. Twenty-eight subjects used topical timolol for an average of 76 days, with two 12-hour fasting plasma specimens obtained at the beginning and end of the period. Mean total cholesterol and low-density lipoprotein cholesterol levels did not change significantly with treatment. Triglyceride values increased 12%; high-density lipoprotein cholesterol levels decreased 9%; and the total cholesterol-high-density lipoprotein cholesterol ratio increased 8%. Higher baseline high-density lipoprotein cholesterol levels were associated with larger reductions in high-density lipoprotein cholesterol levels. Changes in high-density lipoprotein cholesterol levels of this magnitude have been estimated to increase the risk of coronary artery disease by 21%.

Molecular cytogenetic analysis of RB-1 deletions in chronic B-cell leukemias.

Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis. By G-banding, 5/45 (11%) patients with B-CLL had deletions or translocations affecting band 13q14; in contrast, ISH to interphase cells showed RB-1 deletion in 19/90 (21%) patients with B-CLL. No 13q14 abnormalities or RB-1 deletion were detected in patients with B-PLL and HCL. Our data confirm the high frequency of RB-1 deletions in B-CLL and further emphasize the possible pathogenetic role of this genomic region.

The influence of iris pigmentation on the miotic effect of thymoxamine.

We performed a randomly assigned, double-masked, placebo-controlled study in 78 patients with varied iris pigmentation to evaluate the influence of iris pigmentation on the ability of 0.1% thymoxamine to reverse mydriasis produced by 2.5% phenylephrine. Patients were chosen so that a 1.6:1 ratio of dark to light irides was obtained. Within one-half hour after medication, thymoxamine-treated nonbrown irides constricted significantly compared to their fellow placebo-treated irides (P less than .001). Thymoxamine-treated pupils of nonbrown irides were 1.0 to 3.1 mm smaller than placebo-treated fellow eyes. Thymoxamine-treated light brown irides constricted less (0.6 to 2.0 mm) and more slowly compared to fellow placebo-treated irides. Thymoxamine did not reverse the mydriasis in eyes of patients with dark brown irides. Thymoxamine appears similar to other adrenergic agents that bind to melanin, delaying onset and strength of action. Its efficacy as presently formulated may be limited, in part, by iris color.

Post-ECT increases in MRI regional T2 relaxation times and their relationship to cognitive side effects: a pilot study.

This pilot study examined the hypothesis that magnetic resonance imaging T2 relaxation times of specific brain regions increase after electroconvulsive therapy (ECT) and that these increases are related to the cognitive side effects of ECT. Six depressed patients undergoing unilateral ECT were studied. The results demonstrate significant post-ECT T2 increases in the right and left thalamus, and suggest a correlation between regional T2 increase and anterograde memory impairment following ECT. These findings are consistent with a post-ECT increase in brain water content (perhaps secondary to a breakdown of the blood-brain barrier) and suggest that this process may be related to the memory impairment following ECT.

Reproductive impairment in a fish inhabiting a contaminated coastal environment off Southern California.

White croaker (Genyonemus lineatus), collected from a highly contaminated site in San Pedro Bay and from a reference site 80 km away (Dana Point), were induced to spawn in the laboratory. Forty-one per cent of San Pedro Bay females and 54% of Dana Point females spawned. Examination of the ovaries of non-spwaning females revealed that spawning was imminent in the remainder of Dana Point fish but only in 16% of the San Pedro Bay fish. The remainder of the San Pedro Bay fish (43%) contained only immature, yolky oocytes. No croakers containing more than 3.8 ppm ovarian total DDT could be induced to spawn whereas 36% of a contemporaneous San Pedro Bay sample had ovarian total DDT residues in excess of 4 ppm. This suggests that the inability to induce spawning in white croaker may be associated with an ovarian total DDT threshold of about 4 ppm. These data, coupled with observed decreases in fecundity (32%), fertility (14%), and early oocyte loss (30%) relative to reference fish, could partially explain the population declines observed for many southern California fishes since the 1940s.

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.

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.

A vaccinia-vectored rabies vaccine field trial: ante- and post-mortem biomarkers.

During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive.

Nanophthalmos in sisters, one with exfoliation syndrome.

In a consanguineous family of two siblings, both with nanophthalmos, one was found to also have bilateral exfoliation syndrome. This combination of conditions has not, to our knowledge, previously been reported and has not had any apparent negative consequences. Her sister has manifested typical complications of nanophthalmos, including angle-closure glaucoma initially and, eventually, severe uveal effusion after cataract surgery.