Impaired control of the contact system in hereditary angioedema with normal C1-inhibitor.

BACKGROUND: Hereditary angioedema (HAE) comprises HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nl-C1-INH-HAE), due to mutations in factor XII (FXII-HAE), plasminogen (PLG-HAE), angiopoietin 1 (ANGPT1-HAE), kininogen 1 genes (KNG1-HAE), or angioedema of unknown origin (U-HAE). The Italian network for C1-INH-HAE (ITACA) created a registry including different forms of angioedema without wheals. OBJECTIVE: We analyzed clinical and laboratory features of a cohort of Italian subjects with nl-C1-INH-HAE followed by ITACA to identify specific biomarkers. METHODS: A total of 105 nl-C1-INH-HAE patients were studied. Plasma concentrations of cleaved high-molecular-weight kininogen (cHK), vascular endothelial growth factors (VEGFs), angiopoietins (Angs), and secreted phospholipase A2 enzymes (sPLA2 ) were evaluated. RESULTS: We identified 43 FXII-HAE patients, 58 U-HAE, and 4 ANGPT1-HAE. We assessed a prevalence of 1:1.4 × 106 for FXII-HAE and 1:1.0 × 106 for U-HAE. cHK levels in U-HAE patients were similar to controls in plasma collected using protease inhibitors cocktail (PIC), but they significantly increased in the absence of PIC. In FXII-HAE patients, cHK levels, in the absence of PIC, were significantly higher than in controls. We found a significant increase of VEGF-A, VEGF-C, and Ang1 levels in U-HAE patients compared to controls. In FXII-HAE, only VEGF-C levels were increased. Ang2 concentrations and sPLA2 activity were not modified. The levels of these mediators in ANGPT1-HAE patients were not altered. CONCLUSIONS: Our results suggest that pathogenesis of FXII-, ANGPT1-, and U-HAE moves through an unbalanced control of kallikrein activity, with bradykinin as most likely mediator. VEGFs and Ang1 participate in the pathophysiology of U-HAE increasing the basal vascular permeability.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

BACKGROUND: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year. METHODS: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. CONCLUSIONS: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations.

Clinically amyopathic dermatomyositis (CADM), described almost 50 years ago, is defined on the basis of still not validated criteria and characterized by skin findings almost without muscle weakness. Autoantibodies directed against the cytosolic pathogen sensor MDA5 (CADM 140) can mark this subtype of dermatomyositis which has been reported to associate, in particular ethnic groups, with severe progressive interstitial lung disease, poor prognosis and an hyperferritinemic status resembling hemophagocytic-like syndromes. MDA5 may be relevant in that Interferon-signature claimed to characterize inflammatory myopathies and dermatomyosits itself, but its role is not clear. However, the titre of anti-MDA5 autoantibodies seems to correlate with the outcome. In Caucasian populations the association between anti-MDA5 positive CADM and rapidly progressive interstitial lung disease seems to be weaker, but the limited numbers of patients described so far could explain the lack of statistical significance. As a fact, European patients with circulating anti-MDA5 autoantibodies may be clinically inhomogeneous and exhibit different rates of severity. The two patients affected by anti-MDA5 positive dermatomyositis described hereafter provide a clear example of the extreme variability of the disease in terms of laboratory findings and clinical features.

Dosimetric evaluation of a 256-slice computed tomography scanner.

PURPOSE: This study evaluated the effectiveness of patient dose reduction tools on a 256-slice computed tomography scanner (Brilliance iCT, Philips). MATERIALS AND METHODS: The performance of the Brilliance iCT scanner was described in terms of cumulative dose and dose-normalised contrast-to-noise ratio (CNRD). The efficiency of automatic tube current modulation (Z-Dom and D-Dom), shaping filters (SmartShape and IntelliBeam) and asymmetric collimator (Eclipse) was evaluated using appropriate phantoms. RESULTS: The scattered radiation contribution from the peripheral regions to the cumulative dose is not negligible. The CNRD is 20 % better compared to a traditional 16-slice scanner, with a dose reduction of 40 %. The application of shaping filters decreases the dose in the peripheral regions. The application of D-Dom and Z-Dom modulations reduces the current-time product (mAs) values by 23 and 18 %, respectively, but they are not yet integrated. The over-ranging effect is not negligible, despite the use of an Eclipse asymmetric collimator. CONCLUSIONS: Brilliance iCT dose reduction tools are efficient, but should be analysed carefully and used correctly.

Socio-demographic and clinical characteristics of SARS-CoV-2-positive psychiatric in-patients: A case-control study in the psychiatric wards of a Great Metropolitan Hospital in Milan.

During the first Covid-19 outbreak, the Niguarda Hospital of Milan featured two Psychiatry wards, one for SARS-CoV-2 positive patient and one for patients requiring hospitalization and negative for SARS-CoV-2. The two groups of patients were compared and were similar in distribution of psychiatric diagnosis, duration of illness and previous hospitalizations. SARS-CoV-2 positive participants had a lower severity of symptoms both at admission and discharge, a lower frequency of psychotic symptoms and substance intoxication at admission. These findings suggest that patients admitted to the COVID ward were hospitalized not only for their mental health condition but also because of the infection.

Mollusk allergy in shrimp-allergic patients: Still a complex diagnosis. An Italian real-life cross-sectional multicenter study.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly. Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p < 0.001), also using fresh cooked or raw food (p < 0.001). The reactivity profile of mollusk reactors was dominated by Pen m 1, over Pen m 2 and Pen m 4 compared to tolerant subjects, but 33% of patients were not detected by any of the available molecules. Overall, a higher frequency of IgE rectivity to shrimp was recorded in northern Italy, while mollusk reactivity was more frequent in the center-south. Conclusion: The current diagnostic methods are inadequate to predict the cross-reactivity between crustaceans and mollusks. The detection of mollusks hypersensitivity should still rely on skin tests with fresh material. The exclusion of mollusks from shrimp allergic patients' diets should occur when clinical history, available diagnostic instruments, and/or tolerance tests support such a decision.

Peanut allergy in Italy: A unique Italian perspective.

Background: Peanut allergy has not been well characterized in Italy. Objective: Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions. Methods: A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by in vivo and/or in vitro diagnostic means in all cases. Potential risk factors for peanut allergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured. Results: A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2- and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients (P < .01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset. Conclusions: In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries.

Omalizumab for prevention of anaphylactic episodes in a patient with severe mosquito allergy.

Anaphylaxis after mosquito bite is rare, but life threatening. No approved preventive therapy is available to date, but omalizumab could be a promising therapeutic option for reducing risk and improving quality of life in these patients.

A single phantom, a single statistical method for low-contrast detectability assessment.

PURPOSE: The assessment of low-contrast-details is a part of the quality control (QC) program in digital radiology. It generally consists of evaluating the threshold contrast (Cth) detectability details for different-sized inserts, appropriately located in dedicated QC test tools. This work aims to propose a simplified method, based on a statistical model approach for threshold contrast estimation, suitable for different modalities in digital radiology. METHODS: A home-madelow-contrast phantom, made of a central aluminium insert with a step-wedge, was assembled and tested. The reliability and robustness of the method were investigated for Mammography, Digital Radiography, Fluoroscopy and Angiography. Imageswere analysed using our dedicated software developed on Matlab®. TheCth is expressed in the same unit (mmAl) for all studied modalities. RESULTS: This method allows the collection of Cthinformation from different modalities and equipment by different vendors, and it could be used to define typical values. Results are summarized in detail. For 0.5 diameter detail, Cthresults are in the range of: 0.018-0.023 mmAl for 2D mammography and 0.26-0.34 mmAl DR images. For angiographic images, for 2.5 mm diameter detail, the Cths median values are 0.55, 0.4, 0.06, 0.12 mmAl for low dose fluoroscopy, coronary fluorography, cerebral and abdominal DSA, respectively. CONCLUSIONS: The statistical method proposed in this study gives a simple approach for Low-Contrast-Details assessment, and the typical values proposed can be implemented in a QA program for digital radiology modalities.

Antibiotic usage and risk of colonization and infection with antibiotic-resistant bacteria: a hospital population-based study.

Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa (CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.

Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study.

This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up and to detect disease activity. We retrospectively evaluated 12 patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the mean glucocorticoid (GC) dose were used to assess disease activity. Tocilizumab achieved complete disease remission in all patients. Mean FDG-PET-detected standard uptake value decreased from 2.05 ± 0.64 to 1.78 ± 0.45 ( P = .005). In 2 patients in whom temporal arteries color Doppler sonography examination was consistent with temporal arteritis, the hypoechoic halo disappeared after TCZ treatment. Mean GC dose was tapered from 26.6 ± 13.4 mg/d to 3.3 ± 3.1 mg/d ( P < .0001). One-half of the patients discontinued GC therapy. Three patients experienced severe adverse reactions and had to stop TCZ therapy. In accordance with previous reports, TCZ is an effective steroid-sparing agent for GCA, although careful monitoring of adverse drug reactions is needed. 18F-fluorodeoxyglucose positron emission tomography could be used to monitor disease activity in TCZ-treated patients, but prospective studies are needed to confirm these data.

Chronic Urticaria Patient Perspective (CUPP): The First Validated Tool for Assessing Quality of Life in Clinical Practice.

BACKGROUND: There is a need for validated tools to assess health-related quality of life (HRQoL) in routine clinical practice. OBJECTIVE: The aim of this study was to validate the Chronic Urticaria Patient Perspective (CUPP) for assessment of patients with chronic urticaria (CU) in clinical practice. METHODS: A provisional CUPP was developed from candidate items identified by following an iterative process in a retrospective analysis of 249 Chronic Urticaria Quality of Life Questionnaire questionnaires. The psychometric properties of the CUPP were then tested on a sample of patients enrolled in 13 Italian centers. RESULTS: The study population in the validation phase comprised 152 patients. The 10-item version of the CUPP showed satisfactory internal consistency (Cronbach's alpha values of 0.76 at visit 1 and 0.90 at visit 2), good criteria, and discriminative and convergent validity. Reliability was assessed in 34 patients with no changes in health (Global Rating Scale = 0 at visit 2) and was satisfactory (CCC [concordance correlation coefficient] = 0.9). Changes in CUPP scores were significantly associated with changes in Urticaria Activity Score (UAS)-Hive count (r = 0.36, P < .001), UAS-Itch severity (r = 0.48, P < .001), and UAS-Total score (r = 0.342, P < .001), all of which indicated good responsiveness. The minimal important difference was 1.5. CONCLUSIONS: CUPP is a simple 10-question tool with good psychometric properties that provides a valid, reliable, and standardized measurement of HRQoL in patients with CU.