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Introduction There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Background and aims Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Eleonora Nucera,1 Sara Urbani,1 Alessandro Buonomo,1 Tiziana De Pasquale,2 Angela Rizzi,1 Arianna Aruanno,1 Stefano Pucci2 1Allergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 2Civitanova Marche Hospital, Civitanova Marche, ItalyCorrespondence: Eleonora NuceraAllergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito, 1, Rome, 00168, ItalyTel +39 3394475931Fax +06 30156999Email eleonora.nucera@policlinicogemelli.itAbstract: Gadolinium-based contrast agents (GBCAs) are considered to be safe, although sometimes patients report a hypersensitivity reaction when undergoing magnetic resonance imaging (MRI). The mechanisms of these reactions and of the sensitization to GBCAs are still largely unknown. We describe four cases of patients who experienced immediate adverse reactions to GBCAs with a demonstrated cutaneous hypersensitivity suggesting an IgE-mediated mechanism.Keywords: gadolinium-based contrast agents, hypersensitivity, IgE-mediated reactions

Allergy to natural rubber latex (NRLA) from Hevea brasiliensis is a relevant public health issue, in particular in healthcare workers and groups at risk. Clinical manifestations of NRLA can range from mild skin disorders to life-threatening systemic reactions. Prevention measures remain the gold-standard treatment for patients suffering from NRLA, but the only etiological therapy able to influence the natural history of NRLA is specific desensitization. This review aims to underline the epidemiological, clinical and diagnostic aspects of NRLA, and carries out a complete and wide-ranging review of the current literature on NRLA management and immunotherapy.

Background Ficus carica is an edible fruit, belonging to the Moraceae family, rarely described as cause of food allergy. We describe the first case of fig allergy that occurred as a cross-reactivity between fig and Derp 1. Case presentation We present a case of a 10-years-old-girl, with a history of no-seasonal mild intermittent rhinitis, who experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests (SPT) with commercial extracts of food, airborne allergens, latex and panallergens (profilin, PR-10 and lipid transfer protein) were performed. SPT revealed a sensitization only for dermatophagoides farina and dermatophagoides pteronyssinus which was then confirmed with by specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). We also carried out a positive SPT with a commercial fig allergen (Lofarma, Milan, Italy) and prick-by-prick (PBP) both with skin and pulp of green raw and cooked fig. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative. Conclusion The ficin, the major fig allergen, belongs to cysteine protease family like Der p 1. The symptoms presented by our patient could be related to a cross reactivity between these two proteins which present a structural homology.

The reduction in the number of visits to health care centers since the onset of the SARS-CoV-2 pandemic may affect mandatory vaccination.To assess the impact of the SARS-CoV-2 pandemic on the administration of the pentavalent and the measles, mumps, and rubella (MMR) vaccines to children younger than 2 years at the vaccination center of a children's hospital in the Autonomous City of Buenos Aires.Cross-sectional study using the vaccination center's digital records from January to May 2019 and 2020. Results. In the second fortnight of March 2020, vaccinations dropped by 64.2 %. When examining the first dose of the pentavalent and MMR vaccines, such reduction was 74.9 % and 55.1 %, respectively.As of the second fortnight of March 2020, vaccinations dropped by 64.2 % compared to the same period of the previous year.Introducción. El menor número de consultas a los centros de atención desde el comienzo de la pandemia por SARS-CoV-2 podría afectar la vacunación obligatoria. Objetivo. Evaluar el impacto de la pandemia por SARS-CoV-2 en la administración de vacunas pentavalente y triple viral a niños menores de 2 años en el vacunatorio de un hospital pediátrico de la Ciudad de Buenos Aires. Método. Estudio transversal, que utilizó registros informatizados del vacunatorio, de enero a mayo de 2019 y 2020. Resultados. Desde la segunda quincena de marzo de 2020, se observó un 64,2 % de disminución en la aplicación de vacunas. Al examinar la primera dosis de pentavalente y triple viral, la reducción fue del 74,9 % y del 55,1 %, respectivamente. Conclusión. A partir de la segunda quincena de marzo de 2020, se observó una disminución del 64,2 % en las vacunas aplicadas respecto del mismo período en el año anterior.

Background Chlorhexidine is a synthetic biguanide with a broad antibacterial activity and has become an important cause of perioperative anaphylaxis. Objective Reactions due to chlorhexidine allergy are usually IgE-mediated. The aim of this report is to demonstrate utility of laboratory in-vitro testing for diagnosis. Methods We report the case of a 36-year old man who experienced severe anaphylaxis during general anesthesia. He underwent skin tests, specific detection of specific IgE to chlorhexidine and basophil activation test (BAT). Results Skin tests gave false positive results due to dermographism. So, on the basis of a clinical reaction to chlorhexidine and positive tests for IgE to chlorexidine and BAT, we assessed the diagnosis of chlorhexidine allergy. Conclusions Physicians should be aware of the role of chlorhexidine in the etiology of perioperative anaphylaxis. In vitro testing such specific IgE and BAT are useful in patient with suspected chlorexidine allergy and limitation to perform skin tests.

Background Thiocolchicoside is a muscle relaxant, anti-inflammatory, and analgesic. Administered orally, intramuscularly, or topically, this drug is used in the symptomatic treatment of muscular spasms and rheumatologic disorders. Despite its extensive use, thiocolchicoside is a very rare sensitizer. Objective To evaluate IgE-mediated reaction to thiocolchicoside by basophil activation test. Methods Allergological work-up with skin prick tests, intradermal tests and basophil activation test with thiocolchicoside. Results We report the first case of immediate reaction to thiocolchicoside confirmed by basophil activation test in addition to positive skin tests. Conclusions BAT can be considered a complementary diagnostic tool to demonstrate an IgE-mediated reaction also for muscle relaxant drugs.

Midazolam is a short-acting benzodiazepine with central nervous system depressing action, commonly used for conscious sedation for various procedures and for its pharmacologic properties. In literature, severe adverse reactions to this drug are described, but only in few cases positive allergological tests were demonstrated. The authors collected herein five clinical cases of different allergic reactions to midazolam demonstrated by positive skin tests. The 1° case is a suspected Kounis syndrome with cardiorespiratory arrest during an elective video laparoscopic cholecystectomy. The 2° and 5° cases are two systemic reactions with involvement of the skin and the gastrointestinal/respiratory system during elective surgeries in two patients with clinical history of atopia, while the 3° and 4° cases are local skin reactions in correspondence with the infusion site of midazolam during the execution of a colonoscopy. All the patients performed a complete allergological evaluation for the reaction involved drugs. In all cases, only the intradermal test (IDT) with midazolam at 0.5 mg/mL was positive.Allergological tests performed in 10 healthy controls with negative results supported the diagnosis. Therefore, midazolam is often considered a safe drug, because it does not have any active metabolites, in rare cases, it could cause different types of allergic adverse reactions: from severe anaphylaxis with cardiorespiratory arrest to simple local skin reactions. Skin tests remain the first line in the diagnosis of an immediate-type hypersensitivity to midazolam; even if they could lose in sensitivity with increasing latency from the event. However the concentrations recommended by current guidelines of European Network for Drug Allergy (ENDA) and the European Academy of Allergy and Clinical Immunology (EAACI) drug allergy interest groups might not rule out some false-positive reactions due to an irritant effect that should be considered. In doubt cases, other allergological or laboratory tests (i.e., basophil activation tests, serum tryptase, or provocation tests) remain useful to support the diagnosis of an IgE-mediated reaction. Midazolam associated anaphylaxis is relatively rare and the risk factors associated with this event are actually unknown; however, it remains important to obtain a detailed allergic history and each surgical/endoscopic examination unit should be prepared to handle any situation or emergency that may occur.

BACKGROUND Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE To detect the risk factors for systemic reactions induced by labile food allergens. METHODS A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P

Background: 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. Patients: 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.

Summary The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abello, 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.

Supplemental material, SF-36v2TM for Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome by Angela Rizzi, Alessia Di Rienzo, Alessandro Buonomo, Arianna Aruanno, Valentina Carusi, Anna Giulia Ricci, Michele Centrone, Simona Mezzacappa, Lilli Romeo, Domenico Schiavino, Riccardo Inchingolo, Antonio Gasbarrini and Eleonora Nucera in International Journal of Immunopathology and Pharmacology

Supplemental material, Attached_file__CONSORT-2010-Checklist-MS-Word for Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome by Angela Rizzi, Alessia Di Rienzo, Alessandro Buonomo, Arianna Aruanno, Valentina Carusi, Anna Giulia Ricci, Michele Centrone, Simona Mezzacappa, Lilli Romeo, Domenico Schiavino, Riccardo Inchingolo, Antonio Gasbarrini and Eleonora Nucera in International Journal of Immunopathology and Pharmacology

Supplemental material, MMPI-2 for Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome by Angela Rizzi, Alessia Di Rienzo, Alessandro Buonomo, Arianna Aruanno, Valentina Carusi, Anna Giulia Ricci, Michele Centrone, Simona Mezzacappa, Lilli Romeo, Domenico Schiavino, Riccardo Inchingolo, Antonio Gasbarrini and Eleonora Nucera in International Journal of Immunopathology and Pharmacology

Virtual and Augmented Reality systems have been increasingly studied, becoming an important complement to traditional therapy as they can provide high-intensity, repetitive and interactive treatments. Several systems have been developed in research projects and some of these have become products mainly for being used at hospitals and care centers. After the initial cognitive rehabilitation performed at rehabilitation centers, patients are obliged to go to the centers, with many consequences, as costs, loss of time, discomfort and demotivation. However, it has been demonstrated that patients recovering at home heal faster because surrounded by the love of their relatives and with the community support.

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients. An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy.

Supplemental material, PGWBI for Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome by Angela Rizzi, Alessia Di Rienzo, Alessandro Buonomo, Arianna Aruanno, Valentina Carusi, Anna Giulia Ricci, Michele Centrone, Simona Mezzacappa, Lilli Romeo, Domenico Schiavino, Riccardo Inchingolo, Antonio Gasbarrini and Eleonora Nucera in International Journal of Immunopathology and Pharmacology

An 18-year-old man presented to our hospital with muscular pain, diffuse petechiae, spontaneous thigh ecchymosis, edema and pain of the right knee, bilateral pretibial subcutaneous nodules, and gingival hypertrophy and hemorrhage. His history was positive for a mixed anxiety-depressive disorder and a restrictive diet caused by self-diagnosed food allergies. Skin lesions appeared like hyperkeratotic papules with coiled hairs and perifollicular hemorrhages. A diagnosis of scurvy was made upon demonstration of low serum levels of ascorbic acid. An allergy evaluation found cross-reactivity between pollens and food, related to the presence of panallergens. Moreover, we found that our patient was also affected by celiac disease. In conclusion, scurvy should be considered in the differential diagnosis of patients with petechiae and ecchymosis, especially when food restriction, malabsorption, or psychiatric disorders are present.

Introduction The first therapeutic choice for food allergy is avoidance of the responsible food, but when this approach is not possible, specific oral desensitization could be considered as a good alternative. It is not clear yet whether the acquired tolerance is transient or persistent. Aim We report on a subset of 13 patients of a larger study, treated successfully with specific oral tolerance induction who experienced secondary loss of tolerance after a period of allergen avoidance. Material and methods Thirteen patients affected by IgE-mediated food allergy: to cow milk (3 patients), to hen egg (3 patients), to cod fish (2 patients), to peanuts (1 patient) and to corn (1 patient) confirmed by a complete allergological workup and a double-blind placebo-controlled food challenge (DBPCFC), were treated with sublingual-oral desensitization. After the interruption of the maintenance phase, the laboratory tests were performed and 12 of 13 patients underwent DBPCFC. Results Oral specific desensitization was completed successfully in all the 13 reported patients. At different times after the end of treatment, they decided, on their own initiative, to stop the ingestion of incriminated food. A new food allergen re-exposure caused adverse reactions in 12 of 13 patients. The detection of specific IgE and IgG4 during the period of allergen avoidance showed an increase in or a stable level of specific IgE and a decrease in specific IgG4 in 8 patients. Conclusions According to our experience, the tolerance obtained through the desensitizing treatment is transient and so the regular allergen intake is necessary for its maintenance.

Introduction The only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization. Aim To verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years. Material and methods We enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization. Results We observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked. Conclusions Although the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients.

It has been debated whether the Hippocratic Oath’s commitment referring to not administering poisonous/ deadly drugs prohibits: euthanasia, assisted suicide or murder. The first goal was to analyze if the prohibition of administering poisonous/deadly drugs was kept and how it changed in medical oaths of Hippocratic stemma of different time periods and religious orientations. The second aim was discern what is forbidden: euthanasia, assisted suicide or murder. Seventeen medical oaths: 4 Medieval, 2 Modern and 11 Contemporary oaths were studied and divided into those expressing the commitment like the original, those that may include it depending on the interpretation and those that do not mention it. Medieval and Modern oaths express it similarly to the Hippocratic Oath, possibly due to religious and Hippocratic/Galenic influences. What they forbid cannot be inferred. Contemporary oaths maintaining the commitment tend to include phrases regarding active euthanasia and assisted suicide. Other contemporary oaths may generalize it. . It would be advisable that medical oaths would contain clear and specific premises regarding this commitment depending on the country, school and the student body’s idiosyncrasies.

Echinocandins (caspofungin, micafungin, anidulafungin), targeting β-1,3-glucan synthesis of the cell wall, represent one of the three currently available antifungal drug classes for the treatment of invasive fungal infections. Despite their limited antifungal activity against Aspergillus spp., echinocandins are considered an alternative option for the treatment of invasive aspergillosis (IA). This drug class exhibits several advantages, such as excellent tolerability and its potential for synergistic interactions with some other antifungals. The objective of this review is to discuss the in vitro and clinical efficacy of echinocandins against Aspergillus spp., considering the complex interactions between the drug, the mold, and the host. The antifungal effect of echinocandins is not limited to direct inhibition of hyphal growth but also induces an immunomodulatory effect on the host’s response. Moreover, Aspergillus spp. have developed important adaptive mechanisms of tolerance to survive and overcome the action of echinocandins, such as paradoxical growth at increased concentrations. This stress response can be abolished by several compounds that potentiate the activity of echinocandins, such as drugs targeting the heat shock protein 90 (Hsp90)-calcineurin axis, opening perspectives for adjuvant therapies. Finally, the present and future places of echinocandins as prophylaxis, monotherapy, or combination therapy of IA are discussed in view of the emergence of pan-azole resistance among Aspergillus fumigatus isolates, the occurrence of breakthrough IA, and the advent of new long-lasting echinocandins (rezafungin) or other β-1,3-glucan synthase inhibitors (ibrexafungerp).

The eosinophilic oesophagitis (EoE) is a chronic immune/antigen disorder of the oesophagus clinically characterized by dysphagia and pathologically by mucosa eosinophilic infiltration. Th2-type allergic reactions are considered having important roles in the aetiopathogenesis of EoE. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the oesophagus are the most important treatments. ‘Systemic nickel allergy syndrome’ (SNAS) interests about 20% of patients with nickel contact allergy which could present systemic cutaneous manifestations (urticaria, oedema, etc.) and also respiratory and digestive symptoms (meteorism, abdominal pain, diarrhoea, etc.). In the literature, it is demonstrated that nickel oral immunotherapy is effective in reducing symptoms of SNAS and in modulating inflammatory parameters. We describe the case of a 48-year-old woman suffering from EoE not responsive to the topical steroid administration and diagnosis of SNAS. The patient started nickel oral desensitization according to the literature protocol continuing nickel-free diet. After 1 year from the beginning of the treatment, during the maintenance dose (500 ng three times a week), she decreased gradually the dosage of immunotherapy and reintroduced all the culprit foods. After the immunotherapy interruption, during the free diet, she repeated the oesophagogastroscopy with a complete macroscopic and histological resolution. We showed the first case of an EoE in a patient affected by SNAS responsive to the nickel-free diet and the oral immunotherapy.

Aspergillus fumigatus is an opportunistic mold responsible for invasive aspergillosis. Triazoles (e.g., voriconazole) represent the first-line treatment, but emerging resistance is of concern. The echinocandin drug caspofungin is used as second-line treatment but has limited efficacy. The heat shock protein 90 (Hsp90) orchestrates the caspofungin stress response and is the trigger of an adaptive phenomenon called the paradoxical effect (growth recovery at increasing caspofungin concentrations). The aim of this study was to elucidate the Hsp90-dependent mechanisms of the caspofungin stress response. Transcriptomic profiles of the wild-type A. fumigatus strain (KU80) were compared to those of a mutant strain with substitution of the native hsp90 promoter by the thiA promoter (pthiA-hsp90), which lacks the caspofungin paradoxical effect. Caspofungin induced expression of the genes of the mitochondrial respiratory chain (MRC), in particular, NADH-ubiquinone oxidoreductases (complex I), in KU80 but not in the pthiA-hsp90 mutant. The caspofungin paradoxical effect could be abolished by rotenone (MRC complex I inhibitor) in KU80, supporting the role of MRC in the caspofungin stress response. Fluorescent staining of active mitochondria and measurement of oxygen consumption and ATP production confirmed the activation of the MRC in KU80 in response to caspofungin, but this activity was impaired in the pthiA-hsp90 mutant. Using a bioluminescent reporter for the measurement of intracellular calcium, we demonstrated that inhibition of Hsp90 by geldanamycin or MRC complex I by rotenone prevented the increase in intracellular calcium shown to be essential for the caspofungin paradoxical effect. In conclusion, our data support a role of the MRC in the caspofungin stress response which is dependent on Hsp90.

The development of systems for supporting neuro-rehabilitation is of primary importance, due to the high number of people in need of rehabilitation and the limited effectiveness of most of the current developed systems. Our research work aims at developing more engaging interaction modalities for neuro rehabilitation systems, through virtual reality, music based on harp therapy and fragrance feedback modalities and which are also fun and motivational for the patients. The proposed interaction modalities consist of a set of virtual immersive environments which includes an olfactory feedback, where odours are used to increase the sense of presence and the attention of the patients during the execution of the exercises. While the patient performs the rehabilitation exercise, the harp therapist plays the harp accordingly to the patient emotional condition. The system shows a virtual scenario, including virtual objects and/or 360\(^{\circ }\) videos used to increase his sense of presence in the scenario. Odours are associated with virtual scenarios.

Summary Background and Objective. Sensitization and allergy to shrimp among Italian house dust mite allergic patients are not well defined and were investigated in a large multicenter study. Methods. Shrimp sensitization and allergy were assessed in 526 house dust mite (HDM)-allergic patients submitted to the detection of IgE to Der p 10 and 100 atopic control not sensitized to HDM. Results. Shrimp allergy occurred in 9% of patients (vs 0% of 100 atopic controls not sensitized to HDM; p minor 0.001). Shrimp-allergic patients were less frequently hypersensitive to airborne allergens other than HDM than crustacean-tolerant subjects (35% vs 58.8%; p minor 0.005). Only 51% of tropomyosin-sensitized patients had shrimp allergy, and these showed significantly higher Der p 10 IgE levels than shrimp-tolerant ones (mean 22.2 KU/l vs 6.2 KU/l; p minor 0.05). Altogether 53% of shrimp-allergic patients did not react against tropomyosin. Conclusions. Shrimp allergy seems to occur uniquely in association with hypersensitivity to HDM allergens and tropomyosin is the main shrimp allergen but not a major one, at least in Italy. Along with tropomyosin-specific IgE levels, monosensitization to HDM seems to represent a risk factor for the development of shrimp allergy among HDM allergic patients.

Clinical relevance of Der p23 in a multicenter Italian study

The role of profilin as an allergen has long been questioned. The capacity of profilin to induce respiratory symptoms has recently been demonstrated; moreover, over 50% of patients sensitized to profilin experienced symptoms after the ingestion of plant-derived foods, suggesting that profilin should be considered as a clinically relevant food allergen. We describe the cases of seven allergic patients with oral allergy syndrome and other adverse reactions after eating plant-derived food, that have been undergone to profilin desensitization treatment. The protocol started with a drop of profilin solution (50 µg/mL) diluted 1:1018 in water until the highest dose of 10 drops of undiluted solution three times a week. At the end of the treatment we observed a decreased mean diameter of profilin wheal in skin prick test (SPT) in five of the seven participants and in profilin specific IgE values in six patients that repeated the test. Regarding basophil activation test (BAT) and the detection of IgG4, we do not have significant results because the tests have to be repeated in some patients. Regarding the double-blind placebo-controlled challenges, after about 10 months of induction phase all the patients showed tolerance to several foods that they previously did not tolerate. Moreover, the immunotherapy with profilin has proved to be safe because no serious adverse events have been reported in our patients. In summary, the results of this exploratory study of sublingual immunotherapy (SLIT) for profilin allergy show that it can be a promising therapeutic option that could modify the clinical reactivity of the patients to the intake of plant-derived food.

Nickel (Ni) oral hyposensitization treatment (NiOHT) is an effective management approach for Ni allergy. No health-related quality of life (HRQoL) data exist for the pre- and post-treatment with NiOHT in systemic nickel allergy syndrome (SNAS). The aims of this study were (a) to explore HRQoL in SNAS patients, (b) to assess changes of HRQoL after 1 year of NiOHT; (c) to evaluate psychological status of patients. SNAS patients completed the Short-Form 36-Item Health Survey and Psychological General Well-Being Index before and 1 week after the end of NiOHT. Moreover, psychological state was assessed with the Minnesota Multiphasic Personality Inventory (MMPI-2). A total of 52 patients self-reported pre- and post-treatment questionnaires. HRQoL was poor at baseline. After 1 year of NiOHT, all outcome measure scores improved by about 20% with respect to baseline data ( P

Invasive fungal infections due to Aspergillus calidoustus with decreased azole susceptibility are emerging in the setting of azole prophylaxis and are associated with poor outcomes. We assessed the in vitro activity of antifungal drugs used alone or in combinations against A. calidoustus and found a synergistic effect between voriconazole and terbinafine at concentrations within the therapeutic range.

The impairment of finger movements after a stroke results in a significant deficit in hands everyday performances. To face this kind of problems different rehabilitation techniques have been developed, nevertheless, they require the presence of a therapist to be executed. To overcome this issue have been designed several apparatuses that allow the patient to perform the training by itself. Thus, an easy to use and effective device is needed to provide the right training and complete the rehabilitation techniques in the best way. In this paper, a review of state of the art in this field is provided, along with an introduction to the problems caused by a stroke and the consequences for the mobility of the hand. Then follows a complete review of the low cost home based exoskeleton project design. The objective is to design a device that can be used at home, with a lightweight and affordable structure and a fast mounting system. For implementing all these features, many aspects have been analysed, starting from the rehabilitation requirements and the ergonomic issues. This device should be able to reproduce the training movements on an injured hand without the need for assistance by an external tutor.

INTRODUCTION: Lipid transfer proteins (LTP), profilin and PR-10 are the most important panallergens in central and southern Italy. Lipid transfer proteins are stable molecules, predominantly present in the fruit peel, which can induce systemic symptoms after ingestion of vegetables. Profilin and PR-10 are randomly distributed in the pulp and peel. Both are labile proteins and usually determine reactions restricted to the oral cavity. Panallergens-specific IgE may cross-react with homologues from different plant sources, due to their conserved structure. AIM: To assess the pattern of sensitization to panallergens and the correlation with the clinical history and the allergological evaluation of food and aeroallergens. MATERIAL AND METHODS: One hundred and twenty patients with adverse reactions after vegetables ingestion underwent skin prick tests (SPT) with commercial extracts of plant-derived foods and inhalant allergens and commercial extracts of LTP, profilin and PR-10. RESULTS: Many patients presented positive SPT with different plant-food allergens. We found that 76 patients were sensitized to LTP, 14 to profilin and 5 to PR-10. In the LTP-sensitized group, 64 (84%) patients suffered from systemic symptoms while the patients sensitized only to profilin referred the oral allergy syndrome. CONCLUSIONS: This study shows a high rate of sensitization to LTP in our population according to the literature about food allergy in our geographical area and confirms the literature data about the symptoms referred by patients with sensitization to panallergens. Panallergens should be considered as clinically relevant food allergens.

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden.Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18-45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment.Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p

Background and objective Administration of carbapenems to β-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 β-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 β-lactams. The inclusion criteria were a positive skin test result to at least 1 β-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several β-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 β-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 β-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 β-lactam allergy should be abandoned considering the very low rate of cross-reactivity. β-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

The allergic risk in sport is an emerging issue of relevance for public health. Several natural and synthetic allergens are present in indoor and outdoor sport environments. Epidemiological data show the widespread high incidence of allergies in the population. Elite athletes have been observed to have a high prevalence of allergic reactions and exposure to allergens during training and competitions is a concern for environmental occupational medicine. The connection between exercise-induced bronchoconstriction, genetics and environment is still debated. In recent decades, interest in this field has been growing as shown by the increasing number of ISI/PubMed publications. The main allergens present in the sport and physical activity environments are classified and reported here.

The multiple drug intolerance syndrome is a clinical entity characterized by adverse drug reactions to at least three drugs, chemically, pharmacologically and immunogenically unrelated, manifested upon three different occasions, and with negative allergy testing. Symptoms referred by the patients are often subjective, of neurovegetative origin. The aim of the study is to characterize patients suffering from the multiple drug intolerance syndrome from a psychological point of view, and to compare them to healthy subjects. We studied 30 women suffering from the multiple drug intolerance syndrome. All subjects underwent the following psychodiagnostic tests: (1) the State Trait Anxiety Inventory-Form Y, (2) the Zung Self-rating Anxiety Scale, (3) the Zung Self-rating Depression Scale, (4) the Quality of life enjoyment and satisfaction questionnaire, (5) the Minnesota Multiphasic Inventory-2, (6) the Toronto Alexithymia Scale. The study group was compared to 30 healthy women. When compared with the control group, our patients showed: a higher anxiety, a higher grade of depression, this difference was statistically significant (p < 0.01); a high difference (p < 0.01) between the two groups as regards somatic symptoms; a higher grade of alexithymia (p < 0.01); and a worse quality of life, in all the analyzed ambits. These findings clearly demonstrate the importance of psychological symptoms in patients with the multiple drug intolerance syndrome, and show that a complex allergy and psychological work-up is mandatory in the management of these patients.