Shaping a universally broad antibody response to influenza amidst a variable immunoglobulin landscape

Sarah F Andrews | Adrian B McDermott

https://ift.tt/2Ik6EPV

Influenza vaccines: ‘tailor-made’ or ‘one fits all’

Giulietta Saletti | Thomas Gerlach | Guus F Rimmelzwaan

https://ift.tt/2HYSL6l

Immune evasion of the CD1d/NKT cell axis

Randy R Brutkiewicz | Laura Yunes-Medina | Jianyun Liu

https://ift.tt/2HXvphm

Elective endoscopic clipping for the treatment of symptomatic diverticular disease: a potential for 'cure

Message

Symptomatic diverticular disease (DD) is a major worldwide healthcare burden, and diverticular bleeding is one of its most common manifestations. Endoscopic clipping of selected diverticula in the acute or early posthaemorrhage period has been reported as a haemostatic intervention, but the effect of elective clipping is not known.

We present the prospective series of elective endoscopic clipping with the aim of treating all visible diverticula in patients with previous bleeding, resulting in near-complete disappearance of DD.

This may have significant implications for the management of DD worldwide and warrants further prospective research.

In more detail

This was a prospective, single-centre study enrolling consecutive patients attending a specialist DD clinic at our institution, who had been previously hospitalised for lower GI bleeding due to DD (table 1). The procedures and follow-up colonoscopies were carried out from April 2015 to April 2017 at King's College Hospital, London, UK. Patients with other GI pathologies...

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Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease

Objective

Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.

Design

Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy.

Results

Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4β7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation.

Conclusion

Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD.

Trial registration number

NCT02694588

https://ift.tt/2FLW9PO

Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study

Objective

We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images.

Design

A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2).

Results

AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied.

Conclusion

DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients.

Trial registration number

NCT02313649; Post-results.

https://ift.tt/2KDQY8r

Early application of haemostatic powder added to standard management for oesophagogastric variceal bleeding: a randomised trial

Background

Acute variceal bleeding (AVB) requires early therapeutic management by experienced endoscopists that often poses logistical challenges for hospitals. We assessed a different management concept with early application of haemostatic powder—which does not require high endoscopic expertise—added to conventional management in a randomised trial.

Methods

Cirrhotic patients with AVB received standard medical therapy and were randomised to either immediate endoscopy with haemostatic powder application within 2 hours of admission, followed by early elective endoscopy on the next day, that is, within 12–24 hours of admission for definitive treatment (study group) or to early elective endoscopy only (control group). In both groups, failures to achieve clinical haemostasis until the time of early elective endoscopy underwent rescue endoscopy with attempted conventional haemostasis. Primary outcome was endoscopic haemostasis at the elective endoscopy.

Results

Of 86 randomised patients with AVB, 5/43 in the study group required rescue endoscopy for failure of controlling spurting bleeding (n=4) after powder application or for early bleeding recurrence in one patient who died before repeating rescue endoscopy. In the control group, 13/43 patients required rescue endoscopic haemostasis for failure of clinical haemostasis (12%vs30%, p=0.034). In the remaining patients, early elective endoscopic haemostasis was achieved in all 38 patients in the study group, while all remaining 30 patients in the control group had fresh gastric blood or (10%) spurting bleeding at early elective endoscopy with successful haemostasis in all of them. Six-week survival was significantly improved in the study group (7%vs30%, p=0.006).

Conclusion

The new concept of immediate powder application improves early clinical and endoscopic haemostasis. This simplified endoscopic approach may have an impact on early and 6-week survival.

Trial registration number

NCT03061604 .

https://ift.tt/2FNGoI9