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Background: The expression of CD64 on neutrophils (nCD64), measured using flow cytometry, has been proposed as a biomarker for bloodstream infections (BSI). However, data regarding its use in the setting of liver cirrhosis are lacking. Methods: We compared nCD64 levels in 15 cirrhotic patients with BSI to those in 19 controls, including outpatients with stable decompensated cirrhosis without infection. Additionally, we compared nCD64 with C-reactive protein (CRP) and procalcitonin (PCT) in infected hospitalized cirrhotic patients. Results: Cirrhotic patients with infection had higher levels of nCD64 compared to controls (6.0 [5.4-7.1] vs. 2.0 [1.5-2.2]; p<0.001). Among infected patients, a correlation between nCD64 (AUC=0.934 [0.875-0.982 95% CI]), CRP (AUC=0.972 [0.942-0.993 95% CI]), and PCT (AUC=0.859 [0.739-0.953 95% CI]) was observed. However, in our sample of cirrhotic individuals, nCD64 values were not significantly different between patients with worse prognosis and those with positive outcomes (p=0.448), and its expression was not influenced by Gram stain. Conclusions: In our cohort, nCD64 appears to be a promising new biomarker for BSI. Additional prospective studies are needed to confirm its role and limitations in conjunction with other biomarkers and rapid microbiology in the diagnostic multidisciplinary pathway for septic cirrhotic patients.
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Classification criteria of autoimmune rheumatic diseases are an important means to define homogenous groups of patients that can be compared across studies for clinical trials and research purposes. The measurement of autoantibodies is a relevant aspect in the definition of classification criteria, with a significant weight in the scores necessary to classify patients with autoimmune rheumatic diseases. The impact of autoantibodies has gradually increased over the years, contributing to the evolution and improvement of the classification criteria. However, these criteria often do not take into consideration how autoantibodies are measured, i.e. differences in diagnostic accuracy of the methods. This is a critical point especially when obsolete analytical methods that are no longer used in many clinical laboratories are taken into consideration. In this review we have critically examined assays and methods for the determination of autoantibodies that are (or could be) included among the classification criteria of autoimmune rheumatic diseases in light of more recent evidence and technology evolution.
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Autoanticuerpos , Enfermedades Autoinmunes , Enfermedades Reumáticas , Humanos , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/inmunología , Enfermedades Reumáticas/clasificación , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/clasificación , Enfermedades Autoinmunes/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunologíaRESUMEN
BACKGROUND: Point-of-care tests (POCTs) may have a role in detecting undiagnosed cases of Celiac disease (CD). We assessed the diagnostic accuracy of a novel POCT, compared with the conventional serological methods, for simultaneous anti-transglutaminase (tTG) IgA and anti-deamidated gliadin (DGP) IgG antibody detection. Furthermore, we evaluated the effect of different biological matrices (whole blood and serum) on test performance. METHODS: Serum and whole blood from celiac or suspected celiac patients who underwent duodenal biopsy were assayed for the presence of anti-tTG IgA and anti-DGP IgG both with the reference standard methods (Thermo Fisher Scientific, Uppsala, Sweden) and with the POCT (PRIMA Lab SA, Balerna, Switzerland). RESULTS: 266 sera (101 negative and 165 positive) and 60 whole blood samples (34 positive and 26 negative) were included in the study. POCT for anti-DGP IgG showed a sensitivity of 84.3% and a specificity of 90.1%, with positive (PPV) and negative predictive values (NPV) of 91.07% and 82.73%. POCT for anti-tTG IgA showed a sensitivity of 98.31% and a specificity of 98.02%, with a PPV and NPV of 98.31% and 98.02%. Test accuracies were 86.94% and 98.17%, respectively. The agreement of the results between the two different matrices showed a strong correlation rate: 95% for anti-DGP IgG and 100% for anti-tTG IgA. CONCLUSION: The anti-tTG IgA/anti-DGP IgG-based POCT showed good diagnostic accuracy with comparable sensitivities and specificities to reference standard methods in detecting CD in symptomatic patients and could be considered as a mass screening test before referring to conventional serology.
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Enfermedad Celíaca , Transglutaminasas , Humanos , Gliadina , Inmunoglobulina A , Inmunoglobulina G , Sensibilidad y Especificidad , Enfermedad Celíaca/diagnóstico , Pruebas en el Punto de Atención , AutoanticuerposRESUMEN
BACKGROUND: Pru p 7 was the first gibberellin-regulated protein (GRP) to be identified as a food allergen as the basis of a pollen food allergy syndrome. OBJECTIVE: To clinically and biologically characterize a group of patients with suspected allergy to Pru p 7 to optimize the diagnostic workup of GRP sensitization. METHODS: Allergy to Pru p 7 was suspected in the presence of a systemic allergic reaction to plant food, positive skin prick test results for cypress pollen and lipid-transfer protein-enriched peach extract, and absence of Pru p 3-specific immunoglobulin E. Controls were patients with food allergies, patients sensitized to Pru p 3, and patients with cypress allergy without food allergy. Diagnostic workup included skin tests, basophil activation test, Western blot, and single and multiplex assays. RESULTS: In total, 23 patients and 14 controls were enrolled. The most implicated food was peach (91.3%). Approximately 70% of patients reacted to multiple foods. Mueller 4 reactions were 8.7%. In 26.1% of cases, a cofactor triggered the reaction. The basophil activation test results were positive for rPru p 7 in 87% of the patients. Specific immunoglobulin E to Pru p 7 was detected in 95.7% by singleplex and in 73.9% by multiplex assays in patients with suspected allergies; 73.9% of them also reacted to cypress pollen GRP (Cup s 7) in Western blot analysis. CONCLUSION: Patients with Pru p 7-Cup s 7 allergy in our cohort confirm a mild-to-severe clinical syndrome characterized by pollen and food allergy. The diagnosis may benefit from the proposed selection criteria that can be used as preliminary steps to further characterize the cross-reactive GRP sensitization.
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Hipersensibilidad a los Alimentos , Prunus persica , Humanos , Proteínas de Plantas , Antígenos de Plantas , Giberelinas , Estudios de Cohortes , Alérgenos , Hipersensibilidad a los Alimentos/diagnóstico , Inmunoglobulina E , Prunus persica/efectos adversos , ItaliaRESUMEN
OBJECTIVE: Assessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential clinical manifestations. The purpose of this study was to evaluate the ability of multiparametric assay to correctly classify patients with multiple CTDs and healthy controls (HC), independent of clinical features, and to evaluate whether serological status could identify clusters of patients with similar clinical features. METHODS: Patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's syndrome (SjS), undifferentiated connective tissue disease (UCTD), idiopathic inflammatory myopathies (IIM) and HC were enrolled. Serum was tested for 29 autoantibodies. An XGBoost model, exclusively based on autoantibody titres was built and classification accuracy was evaluated. A hierarchical clustering model was subsequently developed and clinical/laboratory features compared among clusters. RESULTS: 908 subjects were enrolled. The classification model showed a mean accuracy of 60.84±4.05% and a mean area under the receiver operator characteristic curve of 88.99±2.50%, with significant discrepancies among groups. Cluster analysis identified four clusters (CL). CL1 included patients with typical features of SLE. CL2 included most patients with SjS, along with some SLE and UCTD patients with SjS-like features. CL4 included anti-Jo1 patients only. CL3 was the largest and most heterogeneous, including all the remaining subjects, overall characterised by low titre or lower-prevalence autoantibodies. CONCLUSION: Extended multiparametric autoantibody assay allowed an accurate classification of CTD patients, independently of clinical features. Clustering according to autoantibody titres is able to identify clusters of CTD subjects with similar clinical features, independently of their final diagnosis.
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Enfermedades del Tejido Conjuntivo , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Humanos , Autoanticuerpos , Punto Alto de Contagio de Enfermedades , Enfermedades del Tejido Conjuntivo/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Síndrome de Sjögren/diagnósticoRESUMEN
OBJECTIVES: The advent of new technologies and the discovery of new antigenic targets of autoantibodies has led to significant changes in autoimmune diagnostics worldwide. To address the extent to which autoimmunology laboratories adhere to such innovation in testing and reporting practices, the Italian Society of Clinical Pathology and Laboratory Medicine launched a national survey to assess the current status of autoimmune diagnostics and to provide direction for further harmonisation. METHODS: A questionnaire covering topics related to the diagnosis of autoimmune systemic rheumatic diseases was distributed to 152 Italian autoimmunology laboratories. The 59 closed-answer questions were subdivided into four main sections: 1. the setting (university, hospital or private laboratory) and the number of tests carried out; 2. the technologies used and their level of automation; 3. the analytical phase (antibody tests and methods), including awareness of the International Consensus on ANA Patterns (ICAP) initiative; 4. reporting of results and clinician relations. RESULTS: A total of 121 laboratories (79.6%) responded to the survey (15% universities, 70 hospitals, and 15% private laboratories). Indirect immunofluorescence is used by 94.8% of respondents, chemiluminescence by 78.4%, fluoro-immuno-enzymatic assays by 67.5%, immunodot by 52.6%, line-immunoassay by 47.4%, addressable laser bead immunoassay by 10.3% and radioimmunological methods by 10.2%. The great majority of respondents implemented complete automation of the listed methodologies. 65% of participants state that they add an interpretative comment in the report. 45% of participants enjoy a collaborative relationship with clinicians; counselling activities are provided by almost half of participants. CONCLUSIONS: Survey results indicated that almost all respondent laboratories have broadened their antibody panel and that high-throughput technologies have been widely introduced. Gaps identified by the survey include a still incomplete compliance with guidelines in antibody profiles (e.g. in antiphospholipid syndrome and rheumatoid arthritis and reporting of test results. Awareness of these differences provides insights that may further contribute to achieving harmonisation in autoimmune diagnostics.
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Enfermedades Autoinmunes , Enfermedades Reumáticas , Humanos , Autoanticuerpos , Enfermedades Autoinmunes/diagnóstico , Italia , Encuestas y Cuestionarios , Enfermedades Reumáticas/diagnósticoRESUMEN
Background: In a pre-vaccination era serologic tests may be used to evaluate the seroprevalence and efficacy of containment strategies applied to the community. Subsequently, SARS-CoV-2 vaccination has successfully reduced hospitalization and admission to intensive care. The role of antiviral treatment for COVID-19 remains debated. Objective: We investigated the effect of SARS-CoV-2 IgG Spike (S) antibody responses in hospitalized patients on 30-day mortality. Finally, we assessed whether other predictive factors affected mortality after 30 days. Methods: Observational study on COVID-19 patients admitted from October 1, 2021, to January 30, 2022. Results: 520 patients were studied; 108 died at the 30-day follow-up (21%). A borderline significance for mortality was observed in favour of the high antibody titer group (24% vs 17%, p=0.05). From the univariate Cox regression analysis, a high IgG-S titer was significantly correlated to lower 30-day mortality (p=0.04, HR: 0.7; 95%CI: 0.44-0.98). The administration of remdesivir (p=0.01) and the age <65 years (p=2.3e-05) were found to be protective for the considered outcome (respectively, HR: 0.5, 95%CI: 0.34-0.86, and HR: 0.1, 95%CI: 0.04-0.30). Conclusions: S-antibodies and remdesivir could play a protecting role in increasing the survival of hospitalized COVID-19 patients who are not suffering from a critical disease. Advanced age is a risk factor for poor outcomes among infected people.
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BACKGROUND: In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls. METHODS: Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies. RESULTS: Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies. CONCLUSIONS: This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.
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Enfermedades del Tejido Conjuntivo , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Síndrome de Sjögren , Humanos , Autoanticuerpos , Enfermedades del Tejido Conjuntivo/diagnóstico , Síndrome de Sjögren/diagnóstico , Enfermedades Reumáticas/diagnósticoRESUMEN
Anti-double-stranded DNA antibodies (anti-dsDNA) are considered a specific marker for systemic lupus erythematosus (SLE). Though the Farr technique was once the reference method for their detection, it has been almost entirely replaced by more recently developed assays. However, there is still no solid evidence of the commutability of these methods in terms of diagnostic accuracy and their correlation with the Crithidia luciliae immunofluorescence test (CLIFT). Anti-dsDNA antibody levels were measured in 80 subjects: 24 patients with SLE, 36 disease controls drawn from different autoimmune rheumatic diseases (14 systemic sclerosis, 10 Sjögren's syndrome, nine autoimmune myositis, three mixed connective tissue disease), 10 inflammatory arthritis and 10 apparently healthy blood donors by eight different methods: fluorescence enzyme immunoassay, microdot array, chemiluminescent immunoassay (two assays), multiplex flow immunoassay, particle multi-analyte technology immunoassay and two CLIFT. At the recommended manufacturer cut-off, the sensitivity varied from 67% to 92%, while the specificity ranged from 84% to 98%. Positive agreement among CLIFT and the other assays was higher than negative agreement. Mean agreement among methods assessed by the Cohen's kappa was 0.715, ranging from moderate (0.588) to almost perfect (0.888). Evaluation of the concordance among quantitative values by regression analysis showed a poor correlation index (mean r2, 0.66). The present study shows that current technologies for anti-dsDNA antibody detection are not fully comparable. In particular, their different correlation with CLIFT influences their positioning in the diagnostic algorithm for SLE (either in association or sequentially). Considering the high intermethod variability, harmonization and commutability of anti-dsDNA antibody testing remains an unachieved goal.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Humanos , Anticuerpos Antinucleares , Lupus Eritematoso Sistémico/diagnósticoRESUMEN
The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.
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COVID-19 , Trasplante de Riñón , Humanos , Vacuna nCoV-2019 mRNA-1273 , Interferón gamma/análisis , Linfocitos T/química , Vacunas contra la COVID-19 , Formación de Anticuerpos , SARS-CoV-2 , COVID-19/prevención & control , Receptores de Trasplantes , Anticuerpos AntiviralesRESUMEN
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.
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BACKGROUND: Autoantibodies against extractable nuclear antigens (ENA) play a pivotal role in the diagnosis and classification of systemic autoimmune rheumatic diseases (SARD). In recent years, newly developed methods have enabled the simultaneous and quantitative detection of multiple anti-ENA reactivities. However, data regarding the comparability of results obtained using different technologies across different platforms are scarce. In this study we compared eight different immunoassays, commonly used in current laboratory practice for detection of anti-ENA antibodies. METHODS: Sixty patients suffering from different SARD, 10 inflammatory arthritis patients (disease controls) and 10 healthy blood donors were included in this comparative study. Sera were collected in 15 centers belonging to the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine. We evaluated the analytical sensitivity, specificity and diagnostic accuracy of each method for antibodies to Sm, RNP, Ro60, Ro52, Scl70, CENP-B and Jo1. Cohen's kappa was used to analyze the agreement among methods. RESULTS: Average agreement among methods was 0.82, ranging from substantial (k = 0.72) to almost perfect (k = 0.92). However, while the specificity was very good for all methods, some differences emerged regarding the analytical sensitivity. CONCLUSIONS: Diagnostic performance of current technologies for anti-ENA antibody detection showed good comparability. However, as some differences exist among methods, laboratory scientists and clinicians must be aware of the diagnostic accuracy of the testing method in use.
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Anticuerpos Antinucleares , Enfermedades Autoinmunes , Antígenos Nucleares , Autoanticuerpos , Humanos , InmunoensayoRESUMEN
BACKGROUND AND AIMS: Diagnosis of fish may represent an important challenge for the allergists. This study aimed to evaluate the diagnostic sensitivity of an in vitro multiplex assay using a comprehensive panel of fish allergens and the cross-reactivity patterns between different molecular components. METHODS: 56 subjects with fish allergy were enrolled. All patients underwent specific IgE measurement using the Allergy Explorer-Alex 2™ multiplex assay (Macroarray Diagnostics, Vienna, Austria) RESULTS: The single ß-parvalbumins Clu h 1, Cyp c 1, Gad m 1, Sal s 1, Sco s 1, Thu a 1 and Xyp g 1 scored positive in 75.0%, 67.8%, 62.5%, 80.3%,80.3%, 78.8% and 73,2% patients, respectively. 14.3% scored positive for the α-parvalbumin (Raj c-parvalbumin), and 16.1% for the aldolase + enolase (Gad m 2 + 3) components. 92.8% reacted to at least one ß-parvalbumin and 96.4% to at least one of the allergens tested. Overall sensitivity was higher than that obtained using commercial extracts of cod, salmon and tuna for skin prick test (75.8%) and IgE detection (92.3%). CONCLUSIONS: The Alex 2 showed high diagnostic sensitivity and it might be used as an additional assay to investigate the cross-reactivity patterns between different molecular components, looking for potentially safe fish species.
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Hipersensibilidad a los Alimentos , Parvalbúminas , Alérgenos , Animales , Reacciones Cruzadas , Peces , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Inmunoglobulina ERESUMEN
BACKGROUND: Mobile health technologies enable allergists to monitor disease trends by collecting daily patient-reported outcomes of allergic rhinitis. To this end, patients with allergies are usually required to enter their symptoms and medication repetitively over long time periods, which may present a risk to data completeness and quality in the case of insufficient effort reporting. Completeness of patient's recording is easily measured. In contrast, the intrinsic quality and accuracy of the data entered by the patients are more elusive. OBJECTIVE: The aim of this study was to explore the association of adherence to digital symptom recording with a predefined set of parameters of the patient-generated symptom and medication scores and to identify parameters that may serve as proxy measure of the quality and reliability of the information recorded by the patient. METHODS: The @IT.2020 project investigates the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In its pilot phase, 101 children with seasonal allergic rhinitis were recruited in Rome and instructed to record their symptoms, medication intake, and general conditions daily via a mobile app (AllergyMonitor) during the relevant pollen season. We measured adherence to daily recording as the percentage of days with data recording in the observation period. We examined the patient's trajectories of 3 disease indices (Rhinoconjunctivitis Total Symptom Score [RTSS], Combined Symptom and Medication Score [CSMS], and Visual Analogue Scale [VAS]) as putative proxies of data quality with the following 4 parameters: (1) intravariation index, (2) percentage of zero values, (3) coefficient of variation, and (4) percentage of changes in trend. Lastly, we examined the relationship between adherence to recording and each of the 4 proxy measures. RESULTS: Adherence to recording ranged from 20% (11/56) to 100% (56/56), with 64.4% (65/101) and 35.6% (36/101) of the patients' values above (highly adherent patients) or below (low adherent patients) the threshold of 80%, respectively. The percentage of zero values, the coefficient of variation, and the intravariation index did not significantly change with the adherence to recording. By contrast, the proportion of changes in trend was significantly higher among highly adherent patients, independently from the analyzed score (RTSS, CSMS, and VAS). CONCLUSIONS: The percentage of changes in the trend of RTSS, CSMS, and VAS is a valuable candidate to validate the quality and accuracy of the data recorded by patients with allergic rhinitis during the pollen season. The performance of this parameter must be further investigated in real-life conditions before it can be recommended for routine use in apps and electronic diaries devoted to the management of patients with allergic rhinitis.
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Aplicaciones Móviles , Rinitis Alérgica Estacional , Rinitis Alérgica , Niño , Humanos , Polen , Reproducibilidad de los Resultados , Rinitis Alérgica/diagnóstico , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/tratamiento farmacológicoRESUMEN
BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.
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BACKGROUND AND AIMS: Long-term kinetics of anti-RBD IgG and neutralizing antibodies were analyzed in a cohort of COVID-19 naïve health care workers (HCW) undergoing SARS-CoV-2 vaccination. METHODS: An anti-RBD IgG immunoassay and a surrogate virus neutralization test (sVNT) were performed at different time points up to 6 months after vaccination in 57 HCWs. Values of anti-RBD IgG predicting an high neutralizing bioactivity (>60%) were also calculated. RESULTS: Mean (range) values of anti-RBD IgG were 294.7 (11.6-1554), 2583 (398-8391), 320.4 (42.3-1134) BAU/mL at T1 (21 days after the 1st dose [T0]), T2 (30 days after the 2nd dose) and T3 (+180 days after T0), respectively. Mean (range) percentages of neutralization (NS%) were 24 (0-76), 86 (59-96) and 82 (52-99) at T1, T2 and T3, respectively. Anti-RBD IgG values and NS% were positively correlated at T2 and T3 while anti-RBD IgG value predicting a NS% > 60 markedly differed at T2 and T3 (594 vs. 108 BAU/mL, respectively). CONCLUSION: While a high neutralizing bioactivity was maintained at least 6 months after vaccination in almost all individuals, the mean values of anti-RBD-IgG showed a marked decline at 6 months. The absolute value of anti-RBD IgG is a poor marker of neutralizing bioactivity.