Evaluating outcomes of endoscopic full-thickness plication for gastroesophageal reflux disease (GERD) with impedance monitoring

Background  

Endoscopic full-thickness plication allows transmural suturing at the gastroesophageal junction to recreate the antireflux barrier. Multichannel intraluminal impedance monitoring (MII) can be used to detect nonacid or weakly acidic reflux, acidic swallows, and esophageal clearance time. This study used MII to evaluate the outcome of endoscopic full-thickness plication.     

IRF6 gene variants in Central European patients with non‐syndromic cleft lip with or without cleft palate

Variants in the interferon regulatory factor 6 (IRF6) gene have repeatedly been associated with non‐syndromic cleft lip with or without cleft palate (NSCL/P). A recent study has suggested that the functionally relevant variant rs642961 is the underlying cause of the observed associations. We genotyped rs642961 in our Central European case–control sample of 460 NSCL/P patients and 952 controls. In order to investigate whether other IRF6 variants contribute independently to the etiology of NSCL/P, we also genotyped the non‐synonymous coding variant V274I (rs2235371) and five IRF6‐haplotype tagging single nucleotide polymorphisms (SNPs). A highly significant result was observed for rs642961 (P = 1.44 × 10^?6) in our sample. The odds ratio was 1.75 [95% confidence interval (CI): 1.38–2.22] for the heterozygous genotype and 1.94 (95% CI: 1.21–3.10) for the homozygous genotype, values that are similar to those reported in a previously published family‐based study. Our results thus confirm the involvement of the IRF6 variant, rs642961, in the etiology of NSCL/P in the Central European population. We also found evidence suggestive of an independent protective effect of the coding variant V274I. In order to understand fully the genetic architecture of the IRF6 locus, it will be necessary to conduct additional SNP‐based and resequencing studies using large samples of patients.     

GATE based Monte Carlo simulation of planar scintigraphy to estimate the nodular dose in radioiodine therapy for autonomous thyroid adenoma

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400 Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE.The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms “Adult Female” (AF, 16 ml thyroid) and “Adult Male” (AM, 19 ml thyroid) were used as source regions.Nodules of 1 ml and 3 ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias.The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1 ml nodule) to 15.3 (AM, 3 ml nodule).Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1 ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM).For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r² > 0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM.The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy.     

C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons

Neuronal circuits are shaped during development by the coordinated action of guidance factors and signals that regulate axonal branching. Unlike guidance cues, the molecules and signaling cascades that underlie axonal branching remain to be resolved. Here we show that the secreted molecule C-type natriuretic peptide (CNP) induces a cGMP signaling cascade via its receptor particulate guanylyl cyclase Npr2 which is essential for sensory axon bifurcation at the dorsal root entry zone (DREZ) of the spinal cord. In contrast, another form of sensory axon branching—collateral formation—is not affected by this pathway. We also demonstrate that cGMP signaling via the nitric oxide-stimulated soluble guanylyl cyclase system (NO-GC) is dispensable for sensory axon branching. Functionally, the bifurcation error in CNP mutant mice is maintained at mature stages and results in a reduced input on secondary neurons as detected by patch-clamp recordings.     

Immunogenicity of rituximab in patients with severe pemphigus

Pemphigus is a life-threatening autoimmune bullous disease associated with autoantibodies to desmoglein 1 and/or 3. The anti-CD20 chimeric mouse monoclonal antibody rituximab has previously been successfully applied in more than 130 reported pemphigus patients with severe and/or refractory disease. Since antibodies against other therapeutics such as IFNα and β, erythropoietin, and TNFα antagonists had led to decreased efficacy of these drugs, we determined anti-rituximab antibodies in 11 patients with pemphigus before rituximab administration as well as 3, 9, and 15 months thereafter. For this purpose, a novel, affinity capture elution assay was established using rabbit IgG against the F(ab)₂ fragment of rituximab. In addition, serum levels of rituximab were determined by a competition ELISA. In 2 of 11 pemphigus patients, antibodies to rituximab were detected. In both patients, only a partial remission was observed under treatment. In addition, when followed over a longer period of time, the occurrence of anti-rituximab antibodies paralleled an increase in disease activity. Of the 9 patients without development of antiantibodies to rituximab, in 5, all lesions healed and in 4, partial remissions were seen. These observations show that antibodies to rituximab are generated in some patients during rituximab treatment and may be associated with a less favourable response to treatment.     

Electronic health records: new opportunities for clinical research

Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.     

Antiviral Treatment of Patients with Recurrent Hepatitis C After Liver Transplantation with Pegylated Interferon

Background  

The recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) leads to recurrent cirrhosis in up to 40% of patients.     

Anatomical and surgical study of volume determination of the anterolateral epidural space nerve root L5/S1 under the aspect of epidural perineural injection in minimal invasive treatment of lumbar nerve root compression

Herniated intervertebral disc causes in a great number of cases of lumbar nerve root compression, especially in the segment L5/S1. Other reasons responsible for stress to the lumbar spinal root are the spinal canal stenosis and the postdiscotomy syndrome. For patients without neurological deficiencies, the conservative treatment includes different epidural injection techniques. Steroids are often applied. A specific injection technique needing only a small drug amount is the epidural perineural approach using a special two-needle technique. The anatomical spaces of the nerve roots have received little attention in therapy. We have determined the anterolateral epidural space nerve volume of the nerve root L5/S1, and compared the data collected in an anatomical study with operative measurements during discectomy. The volume determination in the human cadavers was performed with liquid silicone filling the anterolateral space after dissection. The in vivo measurements were performed during surgery at the site of the anterolateral space after discectomy. The anatomical studies showed us a mean value volume of 1.1 ml. The surgical volume determinations result in a mean volume of 0.9 ml. A better understanding of the anterolateral epidural space may allow a reduction of the injection volume in the conservative nerve root compression treatment, especially using the epidural perineural technique, avoiding the risk of side effects of high doses of steroids.