Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses.

BACKGROUND: We aimed at investigating outcome of systemic treatments in advanced breast PT. METHODS: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. RESULTS: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. CONCLUSION: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Allergy in urban elderly population living in Campania region (Southern Italy). A multicenter study.

Given the increasing life expectancy observed in Western countries, there is a marked interest to know more about how aging could influence respiratory health. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic elders living in Campania region area (Southern Italy). Fourteen Allergy units or Centres examined a total of 462 patients. In this context 215 (46.53%) had positive skin prick tests (SPTs) to at least one allergen and were diagnosed with respiratory allergy. Parietaria represents the most common sensitizing agent in elders living in Campania region, followed by dust mites, grass pollen and Olea europaea. A relatively high percentage of atopic subjects suffered from respiratory symptoms at a fairly advanced age, namely 8.3% at 60-64 years, 10.2% at 65-70 and 5.7% at > 70 years. In conclusion, the prevalence and clinical significance of airway allergic sensitization in the elderly living in Campania region is more significant than expected in latter stages of life. Physicians should not neglect the role of atopy as a risk factor for the onset of allergic respiratory symptoms even in elderly patients.

Anharmonic damping of terahertz acoustic waves in a network glass and its effect on the density of vibrational states.

We report the observation, by means of high-resolution inelastic x-ray scattering, of an unusually large temperature dependence of the sound attenuation of a network glass at terahertz frequency, an unprecedentedly observed phenomenon. The anharmonicity can be ascribed to the interaction between the propagating acoustic wave and the bath of thermal vibrations. At low temperatures the sound attenuation follows a Rayleigh-Gans scattering law. As the temperature is increased the anharmonic process sets in, resulting in an almost quadratic frequency dependence of the damping in the entire frequency range. We show that the temperature variation of the sound damping accounts quantitatively for the temperature dependence of the density of vibrational states.

Structural evolution and medium range order in permanently densified vitreous SiO2.

Positron annihilation lifetime spectroscopy is employed to measure the size of the interstitial void spaces characterizing the structure of a set of permanently densified SiO2 glasses. The average volume of the voids is markedly affected by the densification process and linearly shrinks by almost an order of magnitude after a relative density variation of 22%. In addition, x-ray diffraction shows that this change of density does not modify appreciably the short range order, which remains organized in SiO4 tetrahedra. These results strongly suggest a porous medium description for v-SiO2 glasses where the compressibility and the medium range order are dominated by the density variation of the voids volume up to densities close to that of α-quartz.

Role of disorder in the thermodynamics and atomic dynamics of glasses.

We measured the density of vibrational states (DOS) and the specific heat of various glassy and crystalline polymorphs of SiO2. The typical (ambient) glass shows a well-known excess of specific heat relative to the typical crystal (α-quartz). This, however, holds when comparing a lower-density glass to a higher-density crystal. For glassy and crystalline polymorphs with matched densities, the DOS of the glass appears as the smoothed counterpart of the DOS of the corresponding crystal; it reveals the same number of the excess states relative to the Debye model, the same number of all states in the low-energy region, and it provides the same specific heat. This shows that glasses have higher specific heat than crystals not due to disorder, but because the typical glass has lower density than the typical crystal.

Comparison of the magnetic, radiolabeling, hyperthermic and biodistribution properties of hybrid nanoparticles bearing CoFe2O4 and Fe3O4 metal cores.

Metal oxide nanoparticles, hybridized with various polymeric chemicals, represent a novel and breakthrough application in drug delivery, hyperthermia treatment and imaging techniques. Radiolabeling of these nanoformulations can result in new and attractive dual-imaging agents as well as provide accurate in vivo information on their biodistribution profile. In this paper a comparison study has been made between two of the most promising hybrid core-shell nanosystems, bearing either magnetite (Fe3O4) or cobalt ferrite (CoFe2O4) cores, regarding their magnetic, radiolabeling, hyperthermic and biodistribution properties. While hyperthermic properties were found to be affected by the metal-core type, the radiolabeling ability and the in vivo fate of the nanoformulations seem to depend critically on the size and the shell composition.

Sensitization to cockroach allergens in the urban atopic populations living in Campania district (southern Italy). A multicenter study.

BACKGROUND: Although cockroach (CR) is an important cause of allergic sensitization worldwide, only a few data are available in Italy and in a previous study we have observed, in Naples area, a low prevalence of CR sensitization. OBJECTIVES: We sought to perform a prospective study for assessing the prevalence of allergic sensitization to CR in a sample of atopic population living in Campania district area (Southern Italy). METHODS: Ten Allergy Units or Centres of Campania district participated in this cross-sectional study. Each centre was required to collect the results of at least 100 allergy consultations in consecutive outpatients referred for actual or suspected respiratory allergy. We registered demographic data, type and duration of respiratory symptoms, pets ownership, possible exposure to CR allergens, results of the skin prick tests (SPTs). RESULTS: A total of 1477 patients were examined, 985 (66.68%) had a SPTs positivity to at least one allergen. In this context, ninety were sensitized to CR, thus the overall sensitization prevalence in subjects with respiratory allergy was 6.09% ranging between 0-11% and only five patients were mono-sensitized. Thirteen patients reported rhinitis (R) + bronchial asthma (A), twenty-one R + A + conjunctivitis (C), thirty-seven R + C, five only A and eleven individuals only R. Sixty-seven patients exhibited persistent and twenty-three intermittent symptoms. Dust mite constituted the first cause of associated sensitization to CR. CONCLUSIONS: The prevalence of allergic sensitization to CR is not negligible in population living in Campania district and shows a higher trend in comparison to that found recently and some years ago in Naples area. Finally, we suggest atopic individuals and especially those highly sensitized to mite allergens or those living in low-income areas to be tested by SPTs / evaluation of serum specific IgE to CR allergens to exclude the occurrence of CR allergic sensitization.

Outcome improvement with chemotherapy and radiotherapy in primary, localized, radiation-associated angiosarcoma of the breast region: a retrospective case series analysis.

BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.

Emergence of crystal-like atomic dynamics in glasses at the nanometer scale.

The vibrational dynamics of a permanently densified silica glass is compared to the one of an α-quartz polycrystal, the silica polymorph of the same density and local structure. The combined use of inelastic x-ray scattering experiments and ab initio numerical calculations provides compelling evidence of a transition, in the glass, from the isotropic elastic response at long wavelengths to a microscopic regime as the wavelength decreases below a characteristic length ξ of a few nanometers, corresponding to about 20 interatomic distances. In the microscopic regime the glass vibrations closely resemble those of the polycrystal, with excitations related to the acoustic and optic modes of the crystal. A coherent description of the experimental results is obtained assuming that the elastic modulus of the glass presents spatial heterogeneities of an average size a ~ ξ/2 π.

Compressed correlation functions and fast aging dynamics in metallic glasses.

We present x-ray photon correlation spectroscopy measurements of the atomic dynamics in a Zr(67)Ni(33) metallic glass, well below its glass transition temperature. We find that the decay of the density fluctuations can be well described by compressed, thus faster than exponential, correlation functions which can be modeled by the well-known Kohlrausch-Williams-Watts function with a shape exponent ß larger than one. This parameter is furthermore found to be independent of both waiting time and wave-vector, leading to the possibility to rescale all the correlation functions to a single master curve. The dynamics in the glassy state is additionally characterized by different aging regimes which persist in the deep glassy state. These features seem to be universal in metallic glasses and suggest a nondiffusive nature of the dynamics. This universality is supported by the possibility of describing the fast increase of the structural relaxation time with waiting time using a unique model function, independently of the microscopic details of the system.

[Survey on the prevalence, duration and exclusivity of breastfeeding in the province of Rieti, Italy]. / Indagine su prevalenza, esclusività e durata dell'allattamento al seno nel territorio reatino.

BACKGROUND: The aim of the survey was to estimate the prevalence, duration and exclusivity of breastfeeding (AS) in the province of Rieti, using standardized indicators, for further assessment. METHODS: this is an observational prospective study, through questionnaires self-administered to parents of children receiving the first two vaccinations mandatores. The survey was conducted in the outpatient paediatric vaccine clinics and attended by parents of 198 children born in 2010, who carried out the vaccinations required by law in the first six months of life. The main outcome measures were the prevalence of exclusive breastfeeding (AE), predominant breastfeeding (AP), partial breastfeeding (AC) and with formula feeding only (not AS) after three and six months in postpartum. Have been also studied a number of factors that may affect the ability of the mothers to breastfeed and its continuation. RESULTS: At 3 months of age, the proportion of infants who were being breastfed was 65.5%, (AE 39.7%, AP 11.7%, 14.1% AC), while, after 5 months in postpartum the proportion of any AS was 51.7% ( AE 18.5%, AP 15.6% and 17.9% AC). Based on the regression model, significant associations were observed between AS complete at the 3rd and 5th month, and natural delivery (OR 2.6, respectively, and OR 1.9); having breastfed her son during the first 48 hours of birth was associated with increased prevalence of AS at 3rd month (OR 3.5), but it was not significant associated at the 5th month. Pre-term birth reduces significantly the probability of BF (OR 0.3) at the first vaccination. The use of pacifiers has been associated with reduced prevalence and early discontinuation of BF (respectively, OR 0.2 at 3rd month and OR 0.3 at 5th month). CONCLUSION: The survey confirms the need to assist the new mothers in the postpartum to promote the practice of exclusive breastfeeding and its continuation. The identification of specific risk groups, such as women who have caesarean delivery or who started late lactation, allows health professionals to act with greater awareness and achieve greater efficiency in interventions.

Extreme ultraviolet transient gratings: A tool for nanoscale photoacoustics.

Collective lattice dynamics determine essential aspects of condensed matter, such as elastic and thermal properties. These exhibit strong dependence on the length-scale, reflecting the marked wavevector dependence of lattice excitations. The extreme ultraviolet transient grating (EUV TG) approach has demonstrated the potential of accessing a wavevector range corresponding to the 10s of nm length-scale, representing a spatial scale of the highest relevance for fundamental physics and forefront technology, previously inaccessible by optical TG and other inelastic scattering methods. In this manuscript we report on the capabilities of this technique in the context of probing thermoelastic properties of matter, both in the bulk and at the surface, as well as discussing future developments and practical considerations.

Heterogeneous and anisotropic dynamics of a 2D gel.

We report x-ray photon correlation spectroscopy (XPCS) results on bidimensional (2D) gels formed by a Langmuir monolayer of gold nanoparticles. The system allows an experimental determination of the fourth order time correlation function, which is compared to the usual second order correlation function and to the mechanical response measured on macroscopic scale. The observed dynamics is anisotropic, heterogeneous and superdiffusive on the nanoscale. Different time scales, associated with fast heterogeneous dynamics inside 2D cages and slower motion of larger parts of the film, can be identified from the correlation functions. The XPCS results are discussed in view of other experimental results and models of three-dimensional gel dynamics.

Acoustic excitations in glassy sorbitol and their relation with the fragility and the boson peak.

We report a detailed analysis of the dynamic structure factor of glassy sorbitol by using inelastic X-ray scattering and previously measured light scattering data [B. Ruta, G. Monaco, F. Scarponi, and D. Fioretto, Philos. Mag. 88, 3939 (2008)]. The thus obtained knowledge on the density-density fluctuations at both the mesoscopic and macroscopic length scale has been used to address two debated topics concerning the vibrational properties of glasses. The relation between the acoustic modes and the universal boson peak (BP) appearing in the vibrational density of states of glasses has been investigated, also in relation with some recent theoretical models. Moreover, the connection between the elastic properties of glasses and the slowing down of the structural relaxation process in supercooled liquids has been scrutinized. For what concerns the first issue, it is here shown that the wave vector dependence of the acoustic excitations can be used, in sorbitol, to quantitatively reproduce the shape of the boson peak, supporting the relation between BP and acoustic modes. For what concerns the second issue, a proper study of elasticity over a wide spatial range is shown to be fundamental in order to investigate the relation between elastic properties and the slowing down of the dynamics in the corresponding supercooled liquid phase.

Occupational risk of nano-biomaterials: Assessment of nano-enabled magnetite contrast agent using the BIORIMA Decision Support System.

The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (Fe3O4) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.

Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network.

BACKGROUND: Clear cell sarcoma (CCS) is a translocated aggressive malignancy with a high incidence of metastases and poor prognosis. There are few studies describing the activity of systemic therapy in CCS. We report a multi-institutional retrospective study of the outcomes of patients with advanced CCS treated with systemic therapy within the World Sarcoma Network (WSN). MATERIALS AND METHODS: Patients with molecularly confirmed locally advanced or metastatic CCS treated with systemic therapy from June 1985 to May 2021 were included. Baseline demographic and treatment information, including response by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, was retrospectively collected by local investigators. Descriptive statistics were carried out. RESULTS: Fifty-five patients from 10 institutions were included. At diagnosis, the median age was 30 (15-73) years and 24% (n = 13/55) had metastatic disease. The median age at diagnosis was 30 (15-73) years. Most primary tumours were at aponeurosis (n = 9/55, 16%) or non-aponeurosis limb sites (n = 17/55, 31%). The most common fusion was EWSR1-ATF1 (n = 24/55, 44%). The median number of systemic therapies was 1 (range 1-7). The best response rate was seen for patients treated with sunitinib (30%, n = 3/10), with a median progression-free survival of 4 [95% confidence interval (CI) 1-7] months. The median overall survival for patients with advanced/metastatic disease was 15 months (95% CI 3-27 months). CONCLUSIONS: Soft tissue sarcoma-type systemic therapies have limited benefit in advanced CCS and response rate was poor. International, multicentre prospective translational studies are required to identify new treatments for this ultra-rare subtype, and access to early clinical trial enrolment remains key for patients with CCS.

Debye to non-Debye scaling of the Boson peak dynamics: critical behavior and local disorder in vitreous germania.

We report on the observation of a significant softening of the Boson peak (BP) frequency of vitreous GeO(2) above the glass transition temperature. The softening reminds a critical trend, with a transition temperature intermediate between the glass transition temperature, T(g), and the melting point. The softening of the BP frequency corresponds to a transition from a region dominated by Debye scaling to a non-Debye one. Below T(g) the density of vibrational states varies according to the modification of the elastic continuum medium. Above T(g) the relevant softening of the BP modes can be explained by a broadening of the distribution of elastic constants between neighboring atoms, induced by the structural rearrangement. These findings are discussed together with recent experimental and theoretical results on the low frequency vibrations in glasses.

Communication: are metallic glasses different from other glasses? A closer look at their high frequency dynamics.

Using high resolution inelastic x-ray scattering we studied the collective dynamics of the Pd(77)Si(16.5)Cu(6.5) metallic glass, focusing on the energy-momentum region where the boson peak appears. The dispersion relation and the width of the acoustic excitations are determined showing how the longitudinal acoustic modes maintain their dispersive character for frequencies well above the boson peak frequencies. Moreover, we prove that close to these frequencies there is a softening of the apparent sound speed indicating a failure of the Debye continuum approximation at the boson peak frequencies and challenging previous results on other metallic glasses.