9 research outputs found
Identification and characterization of Aspergillus-specific immune responses to diagnose invasive aspergillosis in high risk patients: a multicenter study
Background. The mortality of Invasive Aspergillosis (IA) still affects
from 27% to 55% of high risk hematologic patients. The reasons of
such a poor outcome also rely on several drawbacks limiting the di-
agnostic accuracy of non cultural based diagnostic methods
(NCBDM) and hampering the opportunities for an early intervention.
Studies in mice model of IA and in healthy subjects have shown that
Aspergillus-specific T-cells producing interferon-gamma (IFN-
gamma-T1) are protective, while Aspergillus-specific T-cells pro-
ducing interleukin-10 (IL-10-T2) are non-protective to IA. Aims. We
have investigated whether the identification of Aspergillus-specific
IFN-gamma-T1 and/or IL-10-T2 through an ex-vivo enzyme linked
immunospot (ELISPOT) assay may be effective in the diagnosis of IA
in high risk patients. Furthermore, in the proven IA patients, we have
functionally and phenotipically characterized such T cells through the
cytokine secretion assay (CSA). Methods. 180 patients (168 hemato-
logic and 12 solid organ transplant patients) have been enrolled. They
were classified, according the revised EORTC/MSG criteria, as fol-
lows: 18 proven, 35 probable, 17 possible IA cases and 110 controls.
The control patients were divided in two groups: group 1 included 86
(78.2%) patients with hystological and/or cultural verified infec-
tious/inflammatory/neoplastic diseases, but other than IA; group 2 in-
cluded 24 (21.8%) patients without clinical and/or microbiological
features of IA. ELISPOT has been performed, as described [Potenza et
al. Leukemia 2007; 21: 578-81], by using as antigens Aspergillus either
conidia or recombinant antigens, namely CRF1p, GEL1p, PEP1p,
SOD1p, α1-3 glucan, β1-3 glucan and galactomannan (GM). Results.
The patient and sample positivity rates were 94.4%/89.5% in proven,
45.7%/35.3% in probable, 35.3%/50% in possible IA cases and
1.8%/4.5% in the controls, respectively. The sensitivity and speci-
ficity of ELISPOT for the diagnosis of IA resulted 94.4% (95% CI,
73%-99%) and 98.2% (95% CI, 93%-99%), respectively. The PPV of
the test was 89.5% (95% CI, 67%-99%), the NPV was 99.1% (95%
CI, 94%-100%) and the efficiency was 97.6% (95% CI, 92.3%-
99.4%). The positive likelihood ratio (LR) resulted 51.89, the negative
LR was 0.06 (Table 1A,B). In proven IA patients, CSA demonstrated
that Aspergillus-specific IL-10-T2 were predominantly central
memory (CM) CD4+ T cells (median frequency 0.37%/0.22%), while
Aspergillus-specific IFN-gamma-T1 were either CD4+ or CD8+ cells
of either effector memory (EM) or CM phenotype (median frequen-
cies 0.24%/0.20%). Also lower frequencies of Aspergillus-specific ei-
ther CD4+ or CD8+ T cells producing IL-4 (0.11%/0.19%) of EM
phenotype, and EM CD8+ cells producing IL-17 (0.18%), were de-
tected. Moreover, although CRF1p, GEL1p, α1-3 glucan and SOD1p
resulted the antigens eliciting the highest number of Aspergillus-spe-
cific IFN-gamma-T1, only GEL1p and α1-3 glucan were those most
constantly targeted by protective immune responses along the entire
course of the IA. Conclusions. Our findings demonstrate the potential
of ELISPOT in the diagnosis of IA, suggesting that it may comple-
ment the other NCBDM, enabling a more consistent diagnosis of IA.
Furthermore, this study describes for the first time the Aspergillus-
specific immune responses in patients with proven IA, identifying
also the antigens predominantly targeted by protective IFN-gamma-
T1, with possible consequences in designing strategies of either
adoptive cell infusion or vaccine therapies
A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial
Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services
Surgeons’ practice and preferences for the anal fissure treatment: results from an international survey
The best nonoperative or operative anal fissure (AF) treatment is not yet established, and several options have been proposed. Aim is to report the surgeons' practice for the AF treatment. Thirty-four multiple-choice questions were developed. Seven questions were about to participants' demographics and, 27 questions about their clinical practice. Based on the specialty (general surgeon and colorectal surgeon), obtained data were divided and compared between two groups. Five-hundred surgeons were included (321 general and 179 colorectal surgeons). For both groups, duration of symptoms for at least 6 weeks is the most important factor for AF diagnosis (30.6%). Type of AF (acute vs chronic) is the most important factor which guide the therapeutic plan (44.4%). The first treatment of choice for acute AF is ointment application for both groups (59.6%). For the treatment of chronic AF, this data is confirmed by colorectal surgeons (57%), but not by the general surgeons who prefer the lateral internal sphincterotomy (LIS) (31.8%) (p = 0.0001). Botulin toxin injection is most performed by colorectal surgeons (58.7%) in comparison to general surgeons (20.9%) (p = 0.0001). Anal flap is mostly performed by colorectal surgeons (37.4%) in comparison to general surgeons (28.3%) (p = 0.0001). Fissurectomy alone is statistically significantly most performed by general surgeons in comparison to colorectal surgeons (57.9% and 43.6%, respectively) (p = 0.0020). This analysis provides useful information about the clinical practice for the management of a debated topic such as AF treatment. Shared guidelines and consensus especially focused on operative management are required to standardize the treatment and to improve postoperative results