100 research outputs found
Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6
Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV
Randomised Italian Sonography for Occiput POSition Trial Ante Vacuum (R.I.S.POS.T.A.)
Objective: To assess whether sonographic diagnosis of fetal head position before instrumental vaginal delivery can reduce the risk of failed vacuum extraction and improve delivery outcome. Methods: Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.) is a randomized controlled trial of term (37 + 0 to 41 + 6 weeks' gestation) singleton pregnancies with cephalic presentation requiring instrumental delivery by vacuum extraction, which was conducted between April 2014 and June 2017 and involved 13 Italian maternity hospitals. Patients were randomized to assessment of fetal head position before attempted instrumental delivery by either vaginal examination (VE) alone or VE plus transabdominal sonography (TAS). Primary outcome was incidence of emergency Cesarean section due to failed vacuum extraction. A sample size of 653 women per group was planned to compare the primary outcome between the two groups. The sample size estimation was based on the hypothesis that the risk of failed vacuum delivery in the VE group would be 5% and that ultrasound assessment of fetal position prior to vacuum extraction would decrease this risk to 2%. Results: On interim analysis, the trial was stopped for futility. During this period, 222 women were randomized and 221 were included in the final data analysis, of whom 132 (59.7%) were randomized to evaluation of fetal head position by VE only and 89 (40.3%) to assessment by VE plus TAS prior to vacuum extraction. No significant differences were observed between the two groups with respect to incidence of emergency Cesarean section due to failed instrumental delivery and other maternal and fetal outcomes. Women randomized to assessment by VE plus TAS showed higher incidence of non-occiput anterior position of the fetal head at randomization and lower incidence of incorrect diagnosis of occiput position compared with women undergoing assessment by VE alone. A higher rate of episiotomy was noted in the women undergoing both VE and TAS compared with those in the VE-only group. Conclusions: Our prematurely discontinued randomized controlled trial did not demonstrate any benefit in terms of reduced risk of failed instrumental delivery or maternal and fetal morbidity in women undergoing sonographic assessment of fetal head position prior to vacuum extraction. Copyright \ua9 2018 ISUOG. Published by John Wiley & Sons Ltd
Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia
Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9-14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ-producing and IL2-producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients
Vancomycin resistant enterococcus risk factors for hospital colonization in hematological patients: a matched case-control study
BackgroundVancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group.MethodsA retrospective, single center, case-control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (>= 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization.ResultsA total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively).ConclusionsAntimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches
All-trans retinoic acid (ATRA) in non-promyelocytic acute myeloid leukemia (AML): results of combination of ATRA with low-dose Ara-C in three elderly patients with NPM1-mutated AML unfit for intensive chemotherapy and review of the literature
Based upon the clinical behavior of three patients, we suggest that the combination of low-dose Ara-C and all-trans retinoic acid may potentially be effective in some elderly patients, unfit for intensive chemotherapy, affected with NPM1-mutated acute myeloid leukemia without FLT3 mutations, warranting perspective clinical studies in these selected patients
Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies
: Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies
A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope
Globular clusters with their large populations of millisecond pulsars (MSPs)
are believed to be potential emitters of high-energy gamma-ray emission. Our
goal is to constrain the millisecond pulsar populations in globular clusters
from analysis of gamma-ray observations. We use 546 days of continuous
sky-survey observations obtained with the Large Area Telescope aboard the Fermi
Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular
clusters. Steady point-like high-energy gamma-ray emission has been
significantly detected towards 8 globular clusters. Five of them (47 Tucanae,
Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices and clear evidence for an exponential cut-off in the range
1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission
from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral
indices , however the presence of an exponential cut-off
can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC
6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral
properties. From the observed gamma-ray luminosities, we estimate the total
number of MSPs that is expected to be present in these globular clusters. We
show that our estimates of the MSP population correlate with the stellar
encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters,
commensurate with previous estimates. The observation of high-energy gamma-ray
emission from a globular cluster thus provides a reliable independent method to
assess their millisecond pulsar populations that can be used to make
constraints on the original neutron star X-ray binary population, essential for
understanding the importance of binary systems in slowing the inevitable core
collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J.
Kn\"odlseder, N. Webb, B. Pancraz
Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe
The Extragalactic Background Light (EBL) includes photons with wavelengths
from ultraviolet to infrared, which are effective at attenuating gamma rays
with energy above ~10 GeV during propagation from sources at cosmological
distances. This results in a redshift- and energy-dependent attenuation of the
gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts
(GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray
blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using
photons above 10 GeV collected by Fermi over more than one year of observations
for these sources, we investigate the effect of gamma-ray flux attenuation by
the EBL. We place upper limits on the gamma-ray opacity of the Universe at
various energies and redshifts, and compare this with predictions from
well-known EBL models. We find that an EBL intensity in the optical-ultraviolet
wavelengths as great as predicted by the "baseline" model of Stecker et al.
(2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication
in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A.
Reimer, L.C. Reye
The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars
We present 294 pulsars found in GeV data from the Large Area Telescope (LAT)
on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs)
discovered in deep radio searches of LAT sources will likely reveal pulsations
once phase-connected rotation ephemerides are achieved. A further dozen optical
and/or X-ray binary systems co-located with LAT sources also likely harbor
gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and
candidates, 10% of all known pulsars, compared to known before Fermi.
Half of the gamma-ray pulsars are young. Of these, the half that are undetected
in radio have a broader Galactic latitude distribution than the young
radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall,
>235 are bright enough above 50 MeV to fit the pulse profile, the energy
spectrum, or both. For the common two-peaked profiles, the gamma-ray peak
closest to the magnetic pole crossing generally has a softer spectrum. The
spectral energy distributions tend to narrow as the spindown power
decreases to its observed minimum near erg s, approaching the
shape for synchrotron radiation from monoenergetic electrons. We calculate
gamma-ray luminosities when distances are available. Our all-sky gamma-ray
sensitivity map is useful for population syntheses. The electronic catalog
version provides gamma-ray pulsar ephemerides, properties and fit results to
guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen
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