A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and ...management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both ...classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.
Via a retrospective multicenter study, the authors investigate the impact of pretransplant donor‐specific HLA antibodies on long‐term graft survival in deceased and living donor kidney transplantations.
The pre-merging system of galaxy clusters Abell 3391-Abell 3395 located at a mean redshift of 0.053 has been observed at 1 GHz in an ASKAP/EMU Early Science observation as well as in X-rays with ...eROSITA. The projected separation of the X-ray peaks of the two clusters is ~50′ or ~3.1 Mpc. Here we present an inventory of interesting radio sources in this field around this cluster merger. While the eROSITA observations provide clear indications of a bridge of thermal gas between the clusters, neither ASKAP nor MWA observations show any diffuse radio emission coinciding with the X-ray bridge. We derive an upper limit on the radio emissivity in the bridge region of 〈
J
〉
1 GHz
< 1.2 × 10
−44
W Hz
−1
m
−3
. A non-detection of diffuse radio emission in the X-ray bridge between these two clusters has implications for particle-acceleration mechanisms in cosmological large-scale structure. We also report extended or otherwise noteworthy radio sources in the 30 deg
2
field around Abell 3391-Abell 3395. We identified 20 Giant Radio Galaxies, plus 7 candidates, with linear projected sizes greater than 1 Mpc. The sky density of field radio galaxies with largest linear sizes of >0.7 Mpc is ≈1.7 deg
−2
, three times higher than previously reported. We find no evidence for a cosmological evolution of the population of Giant Radio Galaxies. Moreover, we find seven candidates for cluster radio relics and radio halos.
In 2019, more than 30 % of all newly transplanted kidney transplant recipients in The Netherlands were above 65 years of age. Elderly patients are less prone to rejection, and death censored graft ...loss is less frequent compared to younger recipients. Elderly recipients do have increased rates of malignancy and infection-related mortality. Poor kidney transplant function in elderly recipients may be related to both pre-existing (i.e. donor-derived) kidney damage and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors. Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly. The OPTIMIZE study will test the hypothesis that reduced CNI exposure in combination with everolimus will lead to better kidney transplant function, a reduced incidence of complications and improved health-related quality of life for kidney transplant recipients aged 65 years and older, compared to standard immunosuppression.
This open label, randomized, multicenter clinical trial will include 374 elderly kidney transplant recipients (≥ 65 years) and consists of two strata. Stratum A includes elderly recipients of a kidney from an elderly deceased donor and stratum B includes elderly recipients of a kidney from a living donor or from a deceased donor < 65 years. In each stratum, subjects will be randomized to a standard, tacrolimus-based immunosuppressive regimen with mycophenolate mofetil and glucocorticoids or an adapted immunosuppressive regimen with reduced CNI exposure in combination with everolimus and glucocorticoids. The primary endpoint is 'successful transplantation', defined as survival with a functioning graft and an eGFR ≥ 30 ml/min per 1.73 m
in stratum A and ≥ 45 ml/min per 1.73 m
in stratum B, after 2 years, respectively.
The OPTIMIZE study will help to determine the optimal immunosuppressive regimen after kidney transplantation for elderly patients and the cost-effectiveness of this regimen. It will also provide deeper insight into immunosenescence and both subjective and objective outcomes after kidney transplantation in elderly recipients.
ClinicalTrials.gov: NCT03797196 , registered January 9th, 2019. EudraCT: 2018-003194-10, registered March 19th, 2019.
Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed ...size.
Women with PPH 1000–1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused.
Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3–1.7), P=0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th–75th centile) of 1 (0–4.5) unit of allogeneic blood products and had an additional 300 (100–350) ml blood loss whereas those who received placebo also received 3 (0–6) units of allogeneic blood products and had 700 (200–1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group.
Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre−1, but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis.
ISRCTN46295339 (http://www.isrctn.com/ISRCTN46295339, last accessed 5 July 2017), EudraCT 2012-005511-11 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11, last accessed 5 July 2017).
Background: Recent evidence has demonstrated the anti‐apoptotic of dexmedetomidine in different brain injury models. Herein, we investigated whether dexmedetomidine could directly protect against ...cortical injury in vitro and in vivo.
Methods: Apoptosis was induced by staurosporine or wortmannin treatment in cortical neuronal cultures in vitro or by 6 h of isoflurane (0.75%) administration to post‐natal day 7 rat pups in vivo. Dexmedetomidine was then applied in escalating doses to assess the neuroprotective potential of this agent. Cell survival was quantified using an MTT assay in vitro and in vivo apoptosis was assessed using cleaved caspase‐3 immunohistochemistry. Cortical Western blots were conducted for the cellular survival proteins Bcl‐2 and phosphorylated extracellular signal‐regulated protein kinase (pERK)1 and 2.
Results: In vitro dexmedetomidine dose‐dependently prevented both staurosporine‐ and wortmannin‐induced injury in cortical neuronal cultures, indicating that dexmedetomidine can prevent apoptosis when applied directly. In vivo isoflurane induced cortical neuroapoptosis compared with air (327±80 vs. 34±9 caspase‐3‐positive neurons; P<0.05). Dexmedetomidine inhibited isoflurane‐induced caspase‐3 expression (P<0.05), although the protection achieved did not completely attenuate the isoflurane injury (P<0.05 vs. air). Isoflurane treatment decreased Bcl‐2 and pERK protein expression relative to air, an effect reversed by dexmedetomidine treatment.
Conclusions: Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed.
The current internationally accepted gold standard for diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy. However, it has been suggested that the diagnosis might not be ...considered as confirmed if the villous atrophy is patchy. Our aim was to assess whether there is an optimal duodenal biopsy strategy for detecting villous atrophy in adult patients with suspected gluten-sensitive enteropathy.
Patients who had positive endomysial or tissue transglutaminase antibodies were prospectively recruited. Nine biopsies were taken from the duodenum: one from the duodenal bulb, four from the proximal duodenum, and four from the distal duodenum. Each biopsy was graded according to the Marsh criteria. All possible biopsy regimes were evaluated for their ability to detect the presence and severity of villous atrophy.
A total of 56 patients were recruited (23 men 41 %, 33 women 59 %; mean age 47, range 16 - 85): 53/56 patients had villous atrophy present in at least one biopsy; 10/53 patients had biopsy specimens that showed "patchy" villous atrophy. In all 53 patients with villous atrophy this was detected by taking a minimum of three biopsies (sensitivity 100 %, 95 % confidence interval CI 93.2 % - 100 %). However, this strategy always incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in all 56 patients was only detected by using a five-biopsy regime (sensitivity 100 %, 95 % CI 93.6 % - 100 %).
In this study we observed that villous atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody-positive) is patchy. For this reason we would suggest a minimum of three biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is detected. However, a five-biopsy regime is required for recognition of the most severe lesion.
This first comprehensive analysis of the global biogeography of marine protistan plankton with acquired phototrophy shows these mixotrophic organisms to be ubiquitous and abundant; however, their ...biogeography differs markedly between different functional groups. These mixotrophs, lacking a constitutive capacity for photosynthesis (i.e. non-constitutive mixotrophs, NCMs), acquire their phototrophic potential through either integration of prey-plastids or through endosymbiotic associations with photosynthetic microbes. Analysis of field data reveals that 40–60% of plankton traditionally labelled as (non-phototrophic) microzooplankton are actually NCMs, employing acquired phototrophy in addition to phagotrophy. Specialist NCMs acquire chloroplasts or endosymbionts from specific prey, while generalist NCMs obtain chloroplasts from a variety of prey. These contrasting functional types of NCMs exhibit distinct seasonal and spatial global distribution patterns. Mixotrophs reliant on ‘stolen’ chloroplasts, controlled by prey diversity and abundance, dominate in high-biomass areas. Mixotrophs harbouring intact symbionts are present in all waters and dominate particularly in oligotrophic open ocean systems. The contrasting temporal and spatial patterns of distribution of different mixotroph functional types across the oceanic provinces, as revealed in this study, challenges traditional interpretations of marine food web structures. Mixotrophs with acquired phototrophy (NCMs) warrant greater recognition in marine research.
Aims. Long gamma-ray bursts (LGRB) have been proposed as promising tracers of star formation owing to their association with the core-collapse of massive stars. Nonetheless, previous studies we ...carried out at z < 1 support the hypothesis that the conditions necessary for the progenitor star to produce an LGRB (e.g. low metallicity), were challenging the use of LGRBs as star-formation tracers, at least at low redshift. The goal of this work is to characterise the population of host galaxies of LGRBs at 1 < z < 2, investigate the conditions in which LGRBs form at these redshifts and assess their use as tracers of star formation. Methods. We performed a spectro-photometric analysis to determine the stellar mass, star formation rate, specific star formation rate and metallicity of the complete, unbiased host galaxy sample of the Swift/BAT6 LGRB sample at 1 < z < 2. We compared the distribution of these properties to the ones of typical star-forming galaxies from the MOSDEF and COSMOS2015 Ultra Deep surveys, within the same redshift range. Results. We find that, similarly to z < 1, LGRBs do not directly trace star formation at 1 < z < 2, and they tend to avoid high-mass, high-metallicity host galaxies. We also find evidence for an enhanced fraction of starbursts among the LGRB host sample with respect to the star-forming population of galaxies. Nonetheless we demonstrate that the driving factor ruling the LGRB efficiency is metallicity. The LGRB host distributions can be reconciled with the ones expected from galaxy surveys by imposing a metallicity upper limit of logOH ∼ 8.55. We can determine upper limits on the fraction of super-solar metallicity LGRB host galaxies of ∼20%, 10% at z < 1, 1 < z < 2, respectively. Conclusions. Metallicity rules the LGRB production efficiency, which is stifled at Z ≳ 0.7 Z⊙. Under this hypothesis we can expect LGRBs to trace star formation at z > 3, once the bulk of the star forming galaxy population are characterised by metallicities below this limit. The role played by metallicity can be explained by the conditions necessary for the progenitor star to produce an LGRB. The moderately high metallicity threshold found is in agreement with the conditions necessary to rapidly produce a fast-rotating Wolf-Rayet stars in close binary systems, and could be accommodated by single star models under chemically homogeneous mixing with very rapid rotation and weak magnetic coupling.
Aliment Pharmacol Ther 2010; 32: 1392–1397
Summary
Background Lymphocytic duodenosis is defined by normal villous architecture and intraepithelial lymphocytes (IELs) >25 per 100 enterocytes. Such ...patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with lymphocytic duodenosis.
Aim To study prospectively the aetiology of lymphocytic duodenosis.
Methods One hundred patients with lymphocytic duodenosis were investigated rigorously for coeliac disease and other known associations for lymphocytic duodenosis by initial investigations of coeliac serology, and exclusion of infection. Of 34 with no explanation for lymphocytic duodenosis, 29 underwent repeat duodenal biopsies following a gluten challenge.
Results Coeliac disease was present in 16% of patients with lymphocytic duodenosis. In the absence of a positive coeliac diagnosis, lymphocytic duodenosis was most commonly associated with drugs (21%), infection (19%), immune dysregulation (4%), inflammatory bowel disease (2%), microscopic colitis (2%), sarcoidosis (1%) and IgA deficiency (1%). Of 34 with no known associations, 18 had symptoms of irritable bowel syndrome (IBS), and in 29 patients investigated with repeat duodenal biopsies, the IEL count returned to normal in 22.
Conclusions In 66% of cases of lymphocytic duodenosis, a known association can be found by further investigations; importantly, 16% will have coeliac disease. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 76%.
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