Allergen immunotherapy for respiratory allergy: to what extent can the risk of systemic reactions be reduced?

Introduction: Allergen immunotherapy is an effective treatment for respiratory allergy, but the administration to patients of extracts of the causative allergen may elicit systemic reactions, which include, particularly with subcutaneous immunotherapy (SCIT), anaphylaxis. In the past, the occurrence (tough rare) of fatal reactions has represented a serious problem that has limited the prescription of SCIT. Areas covered: The authors analyzed in this review the safety data of SCIT, especially concerning the years following the identification of uncontrolled asthma at the moment of allergen injection as the major risk of life-threatening reactions and fatalities. The safety of SLIT, which is far better than SCIT, was analyzed and its specific risk factors for systemic reactions were highlighted. Expert opinion: Presently, the safety profile of SCIT and SLIT is satisfactory, provided the treatment is administered by physicians experienced in this treatment, who are aware of the known risk factors for severe reactions and who implement all measures to avoid them. For SLIT, which is self-administered by the patient, receiving the first dose under medical control is recommended

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the exon

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and investigated the predictive role of type and gene location of the KIT exon 11 mutations in metastatic patients treated with first-line imatinib. Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p < 0.001). These results reached an independent value in the multivariate model, which showed that the absence of exon 11 deletions or delins 557/558, the female gender, primitive tumor diameter (≤5 cm) and polymorphonuclear leucocytosis (>7.5 109/L) were significant prognostic factors for longer PFS. Analysis of the predictive role of PDGFRA PVs showed no significant results. Our results also confirm the aggressive biology of 557/558 deletions/delins in the metastatic setting and allow for prediction at the baseline which GIST patients would develop resistance to first-line imatinib treatment earlier

Recent advances in desmoid tumor therapy

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents

Characterizing HR3549B using SPHERE

Aims. In this work, we characterize the low mass companion of the A0 field star HR3549. Methods. We observed HR3549AB in imaging mode with the the NIR branch (IFS and IRDIS) of SPHERE@VLT, with IFS in YJ mode and IRDIS in the H band. We also acquired a medium resolution spectrum with the IRDIS long slit spectroscopy mode. The data were reduced using the dedicated SPHERE GTO pipeline, purposely designed for this instrument. We employed algorithms such as PCA and TLOCI to reduce the speckle noise. Results. The companion was clearly visible both with IRDIS and IFS.We obtained photometry in four different bands as well as the astrometric position for the companion. Based on our astrometry, we confirm that it is a bound object and put constraints on its orbit. Although several uncertainties are still present, we estimate an age of ~100-150 Myr for this system, yielding a most probable mass for the companion of 40-50MJup and T_eff ~300-2400 K. Comparing with template spectra points to a spectral type between M9 and L0 for the companion, commensurate with its position on the color-magnitude diagram.Comment: Accepted by A&A, 13 pages, 10 Figures (Figures 9 and 10 degraded to reduce the dimension

Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study

Background: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). Patients and methods: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan–Meier method was used to estimate survival and the log-rank test to make comparisons. Results: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). Conclusions: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy

Expected performance of the ASTRI-SST-2M telescope prototype

ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is an Italian flagship project pursued by INAF (Istituto Nazionale di Astrofisica) strictly linked to the development of the Cherenkov Telescope Array, CTA. Primary goal of the ASTRI program is the design and production of an end-to-end prototype of a Small Size Telescope for the CTA sub-array devoted to the highest gamma-ray energy region. The prototype, named ASTRI SST-2M, will be tested on field in Italy during 2014. This telescope will be the first Cherenkov telescope adopting the double reflection layout in a Schwarzschild-Couder configuration with a tessellated primary mirror and a monolithic secondary mirror. The collected light will be focused on a compact and light-weight camera based on silicon photo-multipliers covering a 9.6 deg full field of view. Detailed Monte Carlo simulations have been performed to estimate the performance of the planned telescope. The results regarding its energy threshold, sensitivity and angular resolution are shown and discussed.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223