Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

Objectives

The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).

Methods

This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).

Results

The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.

Conclusions

EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034929","term_id":"NCT02034929"}}NCT02034929.     

Small Dense Low Density Lipoprotein Particles Are Associated with Poor Outcome after Angioplasty in Peripheral Artery Disease

Purpose

In patients suffering from symptomatic peripheral artery disease (PAD), percutaneous revascularization is the treatment of choice. However, restenosis may occur in 10 to 60% in the first year depending on a variety of factors. Small dense low density lipoprotein (sdLDL) particles are associated with an increased risk for cardiovascular events, but their role in the process of restenosis is not known. We conducted a prospective study to analyze the association of sdLDL particles with the outcome of balloon angioplasty in PAD. The composite primary endpoint was defined as improved walking distance and absence of restenosis.

Methods

Patients with angiographically documented PAD of the lower extremities who were scheduled for lower limb revascularization were consecutively recruited for the study. At baseline and at three month follow-up triglyceride, total cholesterol, LDL size and subclasses and HDL cholesterol and ankle-brachial index (ABI) were measured. Three months after the intervention duplex sonography was performed to detect restenosis.

Results

Sixty-four patients (53% male) with a mean age of 68.6±9.9 years were included. The proportion of small- dense LDL particles (class III and IV) was significantly lower (33.1±11.0% vs. 39.4±12.1%, p = 0.038) in patients who reached the primary end-point compared with those who did not. Patients with improved walking distance and without restenosis had a significantly higher LDL size at baseline (26.6±1.1 nm vs. 26.1±1.1 nm, p = 0.046) and at follow-up (26.7±1.1 nm vs. 26.2±0.9 nm, p = 0.044) than patients without improvement.

Conclusions

Small-dense LDL particles are associated with worse early outcome in patients undergoing percutaneous revascularization for symptomatic PAD.     

MiRNA-1/133a Clusters Regulate Adrenergic Control of Cardiac Repolarization

The electrical properties of the heart are primarily determined by the activity of ion channels and the activity of these molecules is permanently modulated and adjusted to the physiological needs by adrenergic signaling. miRNAs are known to control the expression of many proteins and to fulfill distinct functions in the mammalian heart, though the in vivo effects of miRNAs on the electrical activity of the heart are poorly characterized. The miRNAs miR-1 and miR-133a are the most abundant miRNAs of the heart and are expressed from two miR-1/133a genomic clusters. Genetic modulation of miR-1/133a cluster expression without concomitant severe disturbance of general cardiomyocyte physiology revealed that these miRNA clusters govern cardiac muscle repolarization. Reduction of miR-1/133a dosage induced a longQT phenotype in mice especially at low heart rates. Longer action potentials in cardiomyocytes are caused by modulation of the impact of β-adrenergic signaling on the activity of the depolarizing L-type calcium channel. Pharmacological intervention to attenuate β-adrenergic signaling or L-type calcium channel activity in vivo abrogated the longQT phenotype that is caused by modulation of miR-1/133a activity. Thus, we identify the miR-1/133a miRNA clusters to be important to prevent a longQT-phenotype in the mammalian heart.     

Stable Composition of the Nano- and Picoplankton Community during the Ocean Iron Fertilization Experiment LOHAFEX

The iron fertilization experiment LOHAFEX was conducted in a cold-core eddy in the Southern Atlantic Ocean during austral summer. Within a few days after fertilization, a phytoplankton bloom developed dominated by nano- and picoplankton groups. Unlike previously reported for other iron fertilization experiments, a diatom bloom was prevented by iron and silicate co-limitation. We used 18S rRNA gene tag pyrosequencing to investigate the diversity of these morphologically similar cell types within the nano- and picoplankton and microscopically enumerated dominant clades after catalyzed reported deposition fluorescence in situ hybridization (CARD-FISH) with specific oligonucleotide probes. In addition to Phaeocystis, members of Syndiniales group II, clade 10–11, and the Micromonas clades ABC and E made up a major fraction of the tag sequences of the nano- and picoplankton community within the fertilized patch. However, the same clades were also dominant before the bloom and outside the fertilized patch. Furthermore, only little changes in diversity could be observed over the course of the experiment. These results were corroborated by CARD-FISH analysis which confirmed the presence of a stable nano- and picoplankton community dominated by Phaeocystis and Micromonas during the entire course of the experiment. Interestingly, although Syndiniales dominated the tag sequences, they could hardly be detected by CARD-FISH, possibly due to the intracellular parasitic life style of this clade. The remarkable stability of the nano- and picoplankton community points to a tight coupling of the different trophic levels within the microbial food web during LOHAFEX.     

Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing.     

CT-Angiography–Based Evaluation of the Aortic Annulus for Prosthesis Sizing in Transcatheter Aortic Valve Implantation (TAVI)–Predictive Value and Optimal Thresholds for Major Anatomic Parameters

Background/Objectives

To evaluate the predictive value of CT-derived measurements of the aortic annulus for prosthesis sizing in transcatheter aortic valve implantation (TAVI) and to calculate optimal cutoff values for the selection of various prosthesis sizes.

Methods

The local IRB waived approval for this single-center retrospective analysis. Of 441 consecutive TAVI-patients, 90 were excluded (death within 30 days: 13; more than mild aortic regurgitation: 10; other reasons: 67). In the remaining 351 patients, the CoreValve (Medtronic) and the Edwards Sapien XT valve (Edwards Lifesciences) were implanted in 235 and 116 patients. Optimal prosthesis size was determined during TAVI by inflation of a balloon catheter at the aortic annulus. All patients had undergone CT-angiography of the heart or body trunk prior to TAVI. Using these datasets, the diameter of the long and short axis as well as the circumference and the area of the aortic annulus were measured. Multi-Class Receiver-Operator-Curve analyses were used to determine the predictive value of all variables and to define optimal cutoff-values.

Results

Differences between patients who underwent implantation of the small, medium or large prosthesis were significant for all except the large vs. medium CoreValve (all p’s<0.05). Furthermore, mean diameter, annulus area and circumference had equally high predictive value for prosthesis size for both manufacturers (multi-class AUC’s: 0.80, 0.88, 0.91, 0.88, 0.88, 0.89). Using the calculated optimal cutoff-values, prosthesis size is predicted correctly in 85% of cases.

Conclusion

CT-based aortic root measurements permit excellent prediction of the prosthesis size considered optimal during TAVI.     

Rapid Rebound of the Treg Compartment in DEREG Mice Limits the Impact of Treg Depletion on Mycobacterial Burden,but Prevents Autoimmunity

The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3⁺ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3^GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity.     

Murine Endoscopy for In Vivo Multimodal Imaging of Carcinogenesis and Assessment of Intestinal Wound Healing and Inflammation

Mouse models are widely used to study pathogenesis of human diseases and to evaluate diagnostic procedures as well as therapeutic interventions preclinically. However, valid assessment of pathological alterations often requires histological analysis, and when performed ex vivo, necessitates death of the animal. Therefore in conventional experimental settings, intra-individual follow-up examinations are rarely possible. Thus, development of murine endoscopy in live mice enables investigators for the first time to both directly visualize the gastrointestinal mucosa and also repeat the procedure to monitor for alterations. Numerous applications for in vivo murine endoscopy exist, including studying intestinal inflammation or wound healing, obtaining mucosal biopsies repeatedly, and to locally administer diagnostic or therapeutic agents using miniature injection catheters. Most recently, molecular imaging has extended diagnostic imaging modalities allowing specific detection of distinct target molecules using specific photoprobes. In conclusion, murine endoscopy has emerged as a novel cutting-edge technology for diagnostic experimental in vivo imaging and may significantly impact on preclinical research in various fields.     

K-antigen-specific,but not O-antigen-specific natural human serum antibodies promote phagocytosis of Klebsiella pneumoniae

Infections due to Klebsiella pneumoniae and other Klebsiella spp. are a leading cause of hospital-associated morbidity, especially in the intensive care setting. In this study, the hypothesis that normal human sera contain sufficient concentrations of K-antigen-specific antibodies to promote phagocytic killing of encapsulated, highly virulent Klebsiella organisms was tested. K2-antigen-specific IgG and IgM antibodies were detected in each of 10 normal sera, and such antibodies were functionally active in a phagocytic killing assay. Phagocytosis depended critically on sufficient numbers of neutrophils and was impaired by the presence of soluble Klebsiella capsular polysaccharide (CPS). Thus, insufficient numbers of neutrophils and circulation of soluble CPS but not lack of K-specific antibodies may be detrimental in Klebsiella sepsis. The efficacy of hyperimmune sera might be based not on enhancement of phagocytosis but on the neutralization of these detrimental effects of circulating CPS and LPS.