Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Comprehensive analysis of the self-assembled formation of GaN nanowires on amorphous Al x O y : in situ quadrupole mass spectrometry studies.

A comprehensive description of the self-assembled formation of GaN nanowires (NWs) by plasma-assisted molecular beam epitaxy (PAMBE) on amorphous-Al x O y buffered Si is presented. The incubation time that precedes the formation of GaN NWs is analyzed as a function of the growth parameters using line-of-sight quadrupole mass spectrometry. We found that the incubation time follows an Arrhenius-type temperature dependence as well as an inverse power law with respect to the Ga flux. Our results reveal a weaker dependence of the incubation time on the Ga flux and faster nucleation on amorphous-Al x O y in comparison to conventional nitridated Si substrates. In addition, an unprecedented analysis of the dependence of the incubation time on the N flux demonstrates a stronger dependence of the incubation time on the N than on the Ga flux. Our results are summarized in growth diagrams to visualize the impact of the growth parameters on the incubation time. The diagrams can also be used to predict the incubation time for so far unexplored growth conditions. Finally, we measured the desorbing Ga flux upon the nucleation stage to determine the growth parameters that result in effective N-rich conditions as required for the self-assembled formation of GaN NWs. These original measurements were combined with the knowledge gained on the incubation time to create a growth map that illustrates the different growth regimes that can be obtained when GaN is grown on an amorphous-Al x O y buffer layer, regardless of the host substrate. Such a map provides a useful guide to induce the growth and control the morphology of GaN NW ensembles on amorphous-Al x O y . Results presented in this work allow to conclude that amorphous-Al x O y is preferred over nitridated Si as it enables shorter incubation times as well as a wider range of growth parameters to induce the self-assembled formation of GaN NWs in PAMBE.

Interfacial reactions during the molecular beam epitaxy of GaN nanowires on Ti/Al2O3.

We investigate the occurrence of interfacial reactions during the self-assembled formation of GaN nanowires on Ti/Al2O3(0001) substrates in plasma-assisted molecular beam epitaxy. The conditions typical for the synthesis of ensembles of long nanowires (>1 µm) are found to promote several chemical reactions. In particular, the high substrate temperature leads to the interdiffusion of Al and O at the Ti/Al2O3 interface resulting in the formation of Al x Ti y O1-x-y and Ti x O1-x compounds. Furthermore, O is found to incorporate into the nanowires degrading their luminescence by heavy n-type doping. At the same time, impinging Ga and N species react with the substrate giving rise to the simultaneous formation of single-crystalline TiN and Ga x Ti y O1-x-y compounds. The latter compounds tend to form hillocks at the substrate surface, on top of which nanowires elongate with large tilt angles with respect to the substrate normal. We develop here a specific process in order to mitigate the detrimental effects of these interfacial reactions, while maintaining the low areal density and absence of coalescence which is the strong asset of growing nanowires on Ti/Al2O3. We find that the combination of a thick Ti film with an intentional low temperature nitridation step preceding nanowire growth and a limited growth temperature results in ensembles of uncoalesced and well-oriented nanowires with luminescence properties comparable to those of standard GaN nanowires prepared on Si. All these properties, together with the inherent benefits of integrating semiconductors on metals, make the present materials combination a promising platform for the further development of group-III nitride nanowire-based devices.

Effect of surface roughness, chemical composition, and native oxide crystallinity on the orientation of self-assembled GaN nanowires on Ti foils.

We report on plasma-assisted molecular beam epitaxial growth of almost randomly oriented, uniformly tilted, and vertically aligned self-assembled GaN nanowires (NWs), respectively, on different types of polycrystalline Ti foils. The NW orientation with respect to the substrate normal, which is affected by an in situ treatment of the foil surface before NW growth, depends on the crystallinity of the native oxide. Direct growth on the as-received foils results in the formation of ensembles of nearly randomly oriented NWs due to the strong roughening of the surface induced by chemical reactions between the impinging elements and Ti. Surface nitridation preceding the NW growth is found to reduce this roughening by transformation of the uppermost layers into TiN and TiO x N y species. These compounds are more stable against chemical reactions and facilitate the growth of uniformly oriented GaN NW ensembles on the surface of the individual grains of the polycrystalline Ti foils. If an amorphous oxide layer is present at the foil surface, vertically oriented NWs are obtained all across the substrate because this layer blocks the transfering of the epitaxial information from the underlying grains. The control of NW orientation and the understanding behind the achievement of vertically oriented NWs obtained in this study represent an important step towards the realization of GaN NW-based bendable devices on polycrystalline metal foils.

Med Diet 4.0: the Mediterranean diet with four sustainable benefits.

OBJECTIVE: To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework - the Med Diet 4.0 - in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns. DESIGN: A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0. Setting/subjects We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined. RESULTS: The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet. CONCLUSIONS: By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.

Relationship between primary headache and nutrition: a questionnaire about dietary habits of patients with headache.

The role of food associated with the headache has been the subject of scientific research since 1900, especially for migraine patients. A substantial proportion of patients (ranging from 12 to 60 %) report that their migraine attacks may be precipitated by dietary elements, certain eating habits (fasting) and abuse (caffeine and alcoholic beverages abuse and withdrawal). The biological mechanism by means of triggers in general and food in particular precipitate migraine attacks remains obscure. Based on the data in the literature, we performed an osservational study searching for possible correlations between nutrition and primary headaches. We enrolled 50 consecutive patients from the Headache Center of the Neurology Department of Hospital "Cardinal Massaia" of Asti and submitted them a 14-item questionnaire for the assessment of relationship between primary headache and food. Our preliminary data, although the follow up is still in progress, show that there are strong associations between the onset of the headache and dietary habits. It will be necessary to analyze a larger sample in order to draw more precise conclusions on this topic.

Trocar vs. Seldinger small bore pleural drains: does the technique influence the outcomes? A prospective single-centre study.

OBJECTIVE: The aim of this study is to compare two positioning techniques of 12-French (Fr) thoracic drains in terms of efficacy, safety, and patient comfort. PATIENTS AND METHODS: This is a prospective, non-randomized, competitive, non-inferiority study comparing the Seldinger vs. Trocar technique. The primary endpoint was an analysis of the factors that led to unsuccessful drainage positioning. Between the two groups, clinical variables, procedure times, pain, and complications were compared. RESULTS: Seventy-two patients were enrolled in group 1 (Seldinger) and 45 in group 2 (Trocar). The mean procedural time was 7.93±3.02 min vs. 7.09±3.67 min, respectively (p: 0.33). The mean VAS for procedural pain was 2.22±1.47 vs. 2.80±1.88, p: 0.07, and the mean at day 2 was 3.6±1.2 in the SBWGD group vs. 2.7±1.1 in the Unico Group (p: 0.04). There was no difference in terms of complications, residual effusion, and pneumothorax at the first post-procedural chest X-ray. Four days after the procedure, the drain removal rate was 11.6% in group 1 vs. 25% in group 2 p: 0.063). The chest tube was removed after a mean period of 8.87±7.20 days after resolution of pleural effusion or tube dislodgement (7 cases in group 1 vs. 11 in group 2, p: 0.053). CONCLUSIONS: The two techniques resulted in comparable pain and complication rates. Both drains are well-tolerated and efficient at draining pleural effusion, with very low rates of complications and failure. We recommend inserting a longer tube for patients who require chest drainage for an extended period of time.

Experimental characterization of gaseous ion beams produced with the advanced ion source for hadrontherapy (AISHa) at 18 GHz.

The Advanced Ion Source for Hadrontherapy (AISHa) is an electron cyclotron resonance ion source operating at 18 GHz, developed at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud, with the aim of producing high intensity and low emittance highly charged ion beams for hadrontherapy purposes. Moreover, thanks to its unique peculiarities, AISHa is a suitable choice for industrial and scientific applications. In the framework of the INSpIRIT and IRPT projects, in collaboration with the Centro Nazionale di Adroterapia Oncologica, new candidates for cancer treatment are being developed. In particular, the paper presents the results of the commissioning of four ion beams of interest for hadrontherapy: H+, C4+, He2+, and O6+. Their charge state distribution in the best experimental conditions, their emittance, and brightness will be critically discussed, along with the role of ion source tuning and space charge effects in beam transport. Perspectives for further developments will also be presented.

A new case of pure partial 7q duplication.

We report on an 18-month-old boy conceived by assisted reproduction technology with developmental delay, hypotonia, microcephaly, frontal bossing, a mild convergent squint, malformed ears, and a short neck. Karyotype analysis revealed a de novo 7q21.1q22.3 duplication characterized by array comparative genomic hybridization (array-CGH) as a segment of 18.69 Mb. Duplications of the long arm of chromosome 7 are uncommon. There are 18 reported cases of different 7q segments with a pure duplication with no additional deletion of other chromosomes. As a consequence, duplications of chromosome 7q have been classified in 4 groups on the basis of the involved region. The present case is included in group 3 which involves interstitial duplications of different sizes. In the literature, only one case with an apparently smaller duplication of the same region has been described. Despite this, the phenotype is different. Moreover, the 2 patients share some phenotypic features, such as psychomotor delay, hypotonia, frontal bossing, short neck, and strabismus. However, the absence of physical characterization in most of the reported cases could justify the lacking phenotype-genotype correlation in patients with partial 7q duplication. Further studies using recent molecular approaches such as array-CGH might permit a more clinically useful grouping of 7q duplications.

Detection of chromosomal aneuploidies in fetal cells isolated from maternal blood using single-chromosome dual-probe FISH analysis.

Detection of chromosomal aneuploidies using fetal cells isolated from maternal blood, for prenatal non-invasive genetic investigation, has been a long-sought goal of clinical genetics to replace amniocentesis and chorionic villous sampling to avoid any risk to the fetus. The purpose of this study was to develop a sensitive and specific new assay for diagnosing aneuploidy with circulating fetal cells isolated from maternal blood as previously reported using two novel approaches: (i) simultaneous immunocytochemistry (ICC) evaluation using a monoclonal antibody for i-antigen, followed by fluorescence in situ hybridization (FISH); (ii) dual-probe FISH analysis of interphase nuclei using two differently labeled probes, specific for different loci of chromosomes 21 and 18; in addition, short tandem repeats (STR) analysis on single cells isolated by micromanipulation was applied to confirm the presence of fetal cells in the cell sample enriched from maternal blood. Blood samples were obtained from women carrying trisomic fetuses, and from non-pregnant women and men as controls. Using ICC-FISH approach, a large heterogeneity in immunostaining pattern was observed, which is a source of very subjective signal interpretation. Differently, dual-probe FISH analysis provided for a correct diagnosis of all pregnancies: the mean percentage of trisomic cells was 0.5% (range, 0.36-0.76%), while the mean percentage of trisomic cells in the control group (normal pregnancies or non-pregnant women) was ≤0.20%. The application of the dual-probe FISH protocol on fetal cells isolated from maternal blood enables accurate molecular detection of fetal aneuploidy, thus providing a foundation for development of non-invasive prenatal diagnostic testing.