The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

BACKGROUND AND AIMS: The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. METHODS AND RESULTS: A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 109/L (95%CI: 9.8-29.3; p < 0.001) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. CONCLUSION: By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM.

Asthma management among allergists in Italy: results from a survey.

BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS AND OBJECTIVES: The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management. METHODS: An anonymous 16 item web questionnaire was available (April-October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy. RESULTS: One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence. CONCLUSIONS: Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

Polarity dependent strongly inhomogeneous In-incorporation in GaN nanocolumns.

In this work, GaN/InGaN/GaN nanocolumns (NCs) have been grown by molecular beam epitaxy. Selective area growth (SAG) and self-organized growth (SOG) were performed simultaneously in patterned and unpatterned regions of the same substrate, respectively. The resulting structures show different tip morphologies and structural properties due to the different polarity along the growth direction, namely Ga-polar with r-plane faceted tips for the SAG NCs and N-polar with c-plane top facet for the SOG ones. When growing Ga-polar GaN/InGaN NCs, no indium is incorporated at a substrate temperature of [Formula: see text]°C. Rather, indium incorporation takes place under the same growth conditions on the N-polar NCs. The In-incorporation is investigated by means of nano x-ray fluorescence and diffraction, high-angle annular dark-field scanning transmission electron microscopy and high-resolution transmission electron microscopy.

Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-Mediated Hypersensitivity to ß-Lactams.

BACKGROUND AND OBJECTIVE: Administration of carbapenems to ß-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated ß-lactam allergy. PATIENTS AND METHODS: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to ß-lactams. The inclusion criteria were a positive skin test result to at least 1 ß-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several ß-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. RESULTS: We examined 49 patients with a clinical history of immediate reactions to ß-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 ß-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. CONCLUSIONS: The practice of avoiding carbapenems in patients with ß-lactam allergy should be abandoned considering the very low rate of cross-reactivity. ß-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

Optical Emission of Individual GaN Nanocolumns Analyzed with High Spatial Resolution.

Selective area growth has been applied to fabricate a homogeneous array of GaN nanocolumns (NC) with high crystal quality. The structural and optical properties of single NCs have been investigated at the nanometer-scale by transmission electron microscopy (TEM) and highly spatially resolved cathodoluminescence (CL) spectroscopy performed in a scanning transmission electron microscope (STEM) at liquid helium temperatures. TEM cross-section analysis reveals excellent structural properties of the GaN NCs. Sporadically, isolated basal plane stacking faults (BSF) can be found resulting in a remarkably low BSF density in the almost entire NC ensemble. Both, defect-free NCs and NCs with few BSFs have been investigated. The low defect density within the NCs allows the characterization of individual BSFs, which is of high interest for studying their optical properties. Direct nanometer-scale correlation of the CL and STEM data clearly exhibits a spatial correlation of the emission at 360.6 nm (3.438 eV) with the location of basal plane stacking faults of type I1.

Blood or spores? A cautionary note on interpreting cellular debris on human skeletal remains.

The identification of red blood cells on both skeletal human remains and decomposed corpses is of remarkable importance in forensic sciences, irrespective of its diagnostic value; their presence is often perplexing and difficult to interpret especially when in the context of decomposition and taphonomical variables. Some clinical research has focused on the morphological changes of red blood cells over time by scanning electron microscopy (SEM), but no research has investigated whether botanical structures can be confused for red blood cells. Since some literature has recently presumed the detection of erythrocyte-like cells on skeletal remains (even ancient) as surely erythrocytes, and most have never taken into consideration the chance of an origin different from blood, such as botanical, the present study aims at verifying the possibility of confusion between erythrocytes and botanical cells by applying SEM analysis and at highlighting the pitfalls in this particular issue through a test submitted to pathologists and natural scientists asked to discriminate between red blood cells and different vegetal structures (60 images obtained by SEM analysis). The results showed that although there are diagnostic features useful in identifying red blood cells from botanical structures, some spores resulted very similar to decaying red blood cells, which calls for attention and great caution when studying decomposed human remains.

Phase separation in single In(x)Ga(1-x)N nanowires revealed through a hard X-ray synchrotron nanoprobe.

In this work, we report on the composition, short- and long-range structural order of single molecular beam epitaxy grown In(x)Ga(1-x)N nanowires using a hard X-ray synchrotron nanoprobe. Nano-X-ray fluorescence mapping reveals an axial and radial heterogeneous elemental distribution in the single wires with Ga accumulation at their bottom and outer regions. Polarization-dependent nano-X-ray absorption near edge structure demonstrates that despite the elemental modulation, the tetrahedral order around the Ga atoms remains along the nanowires. Nano-X-ray diffraction mapping on single nanowires shows the existence of at least three different phases at their bottom: an In-poor shell and two In-rich phases. The alloy homogenizes toward the top of the wires, where a single In-rich phase is observed. No signatures of In-metallic precipitates are observed in the diffraction spectra. The In-content along the single nanowires estimated from X-ray fluorescence and diffraction data are in good agreement. A rough picture of these phenomena is briefly presented. We anticipate that this methodology will contribute to a greater understanding of the underlying growth concepts not only of nanowires but also of many nanostructures in materials science.

Spontaneous core­shell elemental distribution in In-rich In(x)Ga1-xN nanowires grown by molecular beam epitaxy.

The elemental distribution of self-organized In-rich In(x)Ga1-xN nanowires grown by plasma-assisted molecular beam epitaxy has been investigated using three different techniques with spatial resolution on the nanoscale. Two-dimensional images and elemental profiles of single nanowires obtained by x-ray fluorescence and energy-dispersive x-ray spectroscopy, respectively, have revealed a radial gradient in the alloy composition of each individual nanowire. The spectral selectivity of resonant Raman scattering has been used to enhance the signal from very small volumes with different elemental composition within single nanowires. The combination of the three techniques has provided sufficient sensitivity and spatial resolution to prove the spontaneous formation of a core­shell nanowire and to quantify the thicknesses and alloy compositions of the core and shell regions. A theoretical model based on continuum elastic theory has been used to estimate the strain fields present in such inhomogeneous nanowires. These results suggest new strategies for achieving high quality nonpolar heterostructures.

Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study.

BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach. AIM: To compare the H. pylori eradication rate of a nickel free-diet associated with standard triple therapy and standard triple therapy alone as the first-line regimen. METHODS: Fifty-two sex- and age-matched patients at the first diagnosis of H. pylori infection were randomized 1:1 into two different therapeutic schemes: (1) standard LCA (26 patients): lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid for 7 days with a common diet; (2) standard LCA plus a nickel free-diet (NFD-LCA) (26 patients). Patients followed 30 days of a nickel-free diet plus a week of lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid starting from day 15 of the diet. RESULTS: All patients completed the study. A significantly higher eradication rate was observed in the NFD-LCA group (22/26) versus LCA group (12/26) (p < 0.01). Only a few patients (9 of 52) reported the occurrence of mild therapy-related side effects, without any significant differences between the two groups. CONCLUSIONS: The addition of a nickel-free diet to standard triple therapy significantly increases the H. pylori eradication rate. The reduction of H. pylori urease activity due to the nickel-free diet could expose the bacterium to gastric acid and increase H. pylori's susceptibility to amoxicillin. Further studies are necessary to confirm this preliminary result.

Cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins.

BACKGROUND AND OBJECTIVE: 13-Lactams are the most commonly used antibiotics but they can cause hypersensitivity reactions. We sought to estimate cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins. METHODS: We studied 97 patients with a clinical history of nonimmediate reactions to a penicillin and a positive patch test result to at least 1 of the penicillins tested. All patients also underwent patch testing with several cephalosporins. Patients with a negative patch test to a cephalosporin underwent test dosing in order to assess tolerability. RESULTS: We recorded 129 reactions. The most commonly involved drugs were aminopenicillins, and the most widely reported symptoms were delayed urticaria and maculopapular exanthema. Seventeen patients had positive patch test results for cephalosporins, mostly for cephalexin (n=10), cefaclor (n=9), and cefuroxime axetil (n=5). All the patients-except 4 who experienced an exanthema after the challenge test with cephalexin-tolerated a therapeutic dose of the cephalosporin tested without any adverse effects. CONCLUSIONS: Our data show that cross-reactivity between penicillins and cephalosporins may be as high as 10.9% for first-generation cephalosporins and 1.1% for third-generation cephalosporins, possibly due to the involvement of similar side chains. Patch tests are a useful diagnostic tool to assess cross-reactivity, but a graded challenge is mandatory because a negative patch test does not always mean tolerability.

Asthma management among different specialists: results from a national Italian survey.

In Europe more than 50% of asthmatic treated patients have a not well-controlled asthma. The present survey aims at investigating how different specialists approach asthmatic patients. A web anonymous questionnaire was randomly administered to 604 General Practitioners (GPs), 241 Pneumologists and 131 Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk factors, treatment and future risk. A general agreement emerges about asthma diagnostic work-up. All categories are aware of the impact of comorbidities on asthma. LABA/inhaled steroids combination is considered the first choice treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA) alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely on inflammation biomarkers, whereas reduction of rescue medication is more relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more than 50% of all physicians and is not known by most of GPs. Adherence is considered a crucial problem in asthma management. All categories seem to have a good knowledge about asthma. The cultural background may account for mild differences in asthma control tools and treatment options. GPs have a pivotal role in discriminating patients who need specific assessment by specialists. It is thus important that GPs and specialists share common tools for recognizing and managing those patients.

Persistence of spermatozoa on decomposing human skin: a scanning electron microscopy study.

Finding spermatozoa is of the utmost importance in judicial cases involving both the living and the dead; however, most of literature actually deals with inner genitalia and does not take into consideration the chance of external deposition of semen on skin, which is not rare. In addition, the most advanced microscopic technologies such as scanning electron microscopy (SEM) have not been thoroughly investigated within this specific field of research. This study aims at applying SEM analysis to samples of decomposed skin in order to test its potential in detecting spermatozoa particularly in decomposed cadavers. A sample of skin was obtained at autopsy and divided into two thin strips; one of the samples was used as a negative control. Semen was then taken from a "donor" (with a normal spermiogram) and was spread onto the other skin sample. Every 3 days for the first 15 days (for a total of six samples), a standard slide was prepared from swabs on the treated and control skin and analyzed by standard light microscopy. In addition, every 7 days up to 91 days (3 months circa), a skin sample was taken from the positive and negative control and examined by SEM for a total of 14 samples. Results show that after 12 days, light microscopy failed in detecting spermatozoa, whereas they were still visible up to 84 days by SEM analysis. This study therefore suggests the persistence of sperm structures in time and in decomposing material as well as the possible application of SEM technology to decomposed skin in order to detect semen.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

Profilin desensitization in two patients with plant-derived food allergy.

Profilins are "panallergens", responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.

The clinical meaning of positive latex sIgE in patients with food/pollen adverse reactions.

Natural rubber latex allergy (NRL-A) is an international problem of public health. About 50-60% of NRL-A patients may present adverse reactions after ingestion of cross-reacting vegetable foods. This condition, called "Latex-fruit Syndrome", is a matter of research. The aim of our study is to distinguish between clinical/subclinical latex-fruit syndrome and cross-sensitization to latex and food/pollen allergens on the basis of latex recombinant allergens. We studied 51 patients with food hypersensitivity and serological evidence of NRL sensitization. The subjects underwent an accurate allergological evaluation (skin prick test with latex, food and pollen extracts, specific IgE to latex and recombinant allergens, challenge provocation tests). The patients were divided in two groups: group A) 34 patients with clinical and serological latex and fruit/vegetable allergies; group B) 17 patients allergic to fruits/vegetables and/or pollens, with serological, but not clinical NRL-A. All the latex challenge tests resulted positive in group A patients and only two patients of group B presented positive cutaneous challenge tests. Moreover, specific IgE-antibodies were detected to rHev b 5, to rHev b 6.01, to rHev b 6.02 and to rHev b 8 (and other profilins) of group A patients, while in group B we observed a monosensitization to Hev b8, probably linked to a cross-sensitization to pollens and foods. At the present state of knowledge, we need a multi-parametric approach based on a combination of clinical history, diagnostic tests (CRD) and latex challenge tests to make diagnosis of latex-fruit syndrome.