Evaluating the diagnostic and prognostic ability of ischemia modified albumin in COVID-19.

BACKGROUND: Patients with COVID-19 can rapidly deteriorate and develop acute hypoxic respiratory failure. Prominent features of the disease include severe inflammation, endotheliitis, and thrombosis. OBJECTIVES: The aim of the study was to evaluate the diagnostic and prognostic effectiveness of ischemia modified albumin (ΙΜΑ) in a cohort of COVID-19 patients. METHODS: This prospective observational study included adults with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test, who were hospitalized specifically for COVID-19. The outcomes of interest were progression to severe acute respiratory failure during the index hospitalization defined as partial pressure of oxygen/fraction of inspired oxygen lower or equal to 150, admission to the intensive care unit (ICU) and in-hospital mortality. Admission IMA levels were determined using the commercially available "IMA Assay Kit" method (Abbexa LTD, Cambridge, UK). Adults without SARS-CoV-2 infection were used as controls. RESULTS: 135 COVID-19 patients and 64 controls were included. Admission IMA levels were significantly higher in COVID-19 patients compared to controls [[24.38 (11.94) ng/ml vs. 14.69 (3.52) ng/ml, p < 0.01]. Receiver operating characteristic analysis of admission IMA showed an area under the curve (AUC) of 94% (p < 0.0001) for COVID-19 diagnosis (cut-off value: 17.5 ng/ml; sensitivity: 90.37%; specificity: 87.5%). Admission IMA was also associated with mortality (AUC: 68%, p = 0.01). However, it was not associated with severe acute respiratory failure (AUC: 47%, p = 0.53) or ICU admission (AUC: 58%, p = 0.41). CONCLUSION: Admission IMA was significantly increased in COVID-19 patients and was associated with in-hospital mortality.

Effects of a Diabetes Sports Summer Camp on the Levels of Physical Activity and Dimensions of Health-Related Quality of Life in Young Patients with Diabetes Mellitus Type 1: A Randomized Controlled Trial.

Physical activity (PA) is considered an important part of the treatment of children with diabetes mellitus type 1 (T1DM). Furthermore, health-related quality of life (HRQoL) affects both the physical and mental health of patients with T1DM. The purpose of the study was to evaluate through a randomized controlled trial the impact of participation in a summer diabetes sports camp on the PA and HRQoL of children and adolescents with T1DM. Eighty-four children and adolescents with T1DM were randomly assigned into an intervention (M = 12.64, SD = 1.82, 30 female) and a control group (M = 12.67, SD = 2.50, 30 female). Intervention group participants attended a ten-day summer diabetes sports camp which included an intensive program of PA (6 h of daily PA), educational and entertaining activities as well as education on the importance of PA in the management of the disease. At baseline and at the end of the study, participants completed measures of physical activity, self-esteem, depression, health status, intention to change behavior, and life satisfaction. Results of the two-way repeated measures analysis showed no statistically significant group differences in PA levels (p < 0.05) and HRQoL parameters (p < 0.05 for all parameters). In conclusion, the results did not support the effectiveness of a 10-day diabetes sports camp on PA levels and HRQoL for children with T1DM. Longer interventions may be more effective in exerting positive influence on trait parameters of children with T1DM's quality of life. Participation in such programs on multiple occasions should be evaluated in the future.

Allergen immunotherapy for respiratory allergy: to what extent can the risk of systemic reactions be reduced?

INTRODUCTION: Allergen immunotherapy is an effective treatment for respiratory allergy, but the administration to patients of extracts of the causative allergen may elicit systemic reactions, which include, particularly with subcutaneous immunotherapy (SCIT), anaphylaxis. In the past, the occurrence (tough rare) of fatal reactions has represented a serious problem that has limited the prescription of SCIT. AREAS COVERED: The authors analyzed in this review the safety data of SCIT, especially concerning the years following the identification of uncontrolled asthma at the moment of allergen injection as the major risk of life-threatening reactions and fatalities. The safety of SLIT, which is far better than SCIT, was analyzed and its specific risk factors for systemic reactions were highlighted. EXPERT OPINION: Presently, the safety profile of SCIT and SLIT is satisfactory, provided the treatment is administered by physicians experienced in this treatment, who are aware of the known risk factors for severe reactions and who implement all measures to avoid them. For SLIT, which is self-administered by the patient, receiving the first dose under medical control is recommended.

Mabs for treating asthma: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab.

The introduction of biologics for the treatment of patients with refractory asthma represented a marked therapeutic advance. For more than 10 y, the only biologic available has been the monoclonal anti-IgE antibody omalizumab, reserved for patients with asthma caused by perennial allergen. In recent years, other biologics have been licensed for the treatment of severe eosinophilic asthma. They include monoclonal antibodies that target the Th2-pathway cytokines, such as IL-5 (mepolizumab and reslizumab) or its receptor (benralizumab) and the IL-4 and IL-13 receptor (dupilumab). The effectiveness of these biologics was demonstrated in several placebo controlled trials, the main outcomes being the significant reduction of the rate of asthma exacerbation and the improvement of respiratory function in actively treated patients. Based on the further understanding of the pathogenesis of asthma, new cytokines network and new targets are emerging, such as thymic stromal lymphopoietin, which can activate Th2 cells, innate lymphoid cells, or both, or prostaglandin D2 (PGD2), to develop additional biologics.

Advances in allergen immunotherapy as a treatment of asthma.

Introduction: Specific immunotherapy is the only treatment acting on causes and not only on symptoms of respiratory allergy. It was first introduced as subcutaneous immunotherapy (SCIT) with the aim to induce immunological tolerance to the administered allergen(s). In the 1980s, sublingual immunotherapy (SLIT) was developed, mainly to improve the safety, which was a critical issue at that time.Areas covered: This article reviews the available literature, including a large number of randomized controlled trials, meta-analyses, and real-life studies as well, on the outcomes of SCIT and SLIT concerning the treatment critical issues of the two routes, that are efficacy, safety, cost-effectiveness, and compliance to treatment.Expert opinion: SCIT and SLIT are similarly effective in treating patients with respiratory allergy, providing, based on the induction of typical changes in the immunologic response, an early control of symptoms that steadily increases during the treatment and, once reached the recommended duration of 3 years, continues to work after stopping. This outcome is the major factor influencing the economic advantage of SCIT and SLIT over drug treatment.

The spectrum of therapeutic activity of mepolizumab.

Introduction: The basis of the development of the anti-interleukin-5 monoclonal antibody mepolizumab was the acknowledgment of the crucial importance of this cytokine in promoting eosinophils production, activation, and survival, which is associated with the eosinophilic asthma phenotype, as well as with other disorders characterized by high levels of eosinophils. Areas covered: All the available literature on the outcomes treatment with mepolizumab in eosinophilic disorders are reviewed, including asthma, chronic rhinosinusitis, esophagitis, granulomatosis with polyangiitis, eosinophilic chronic obstructive pulmonary disease, hypereosinophilic syndrome, and allergic bronchopulmonary aspergillosis. Expert opinion: The efficacy of mepolizumab in eosinophilic asthma is clearly demonstrated by a number of controlled trials and by meta-analyses. Among other eosinophilic disorders, controlled trials are available for chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic chronic obstructive pulmonary disease. Allergic bronchopulmonary aspergillosis, as well as other minor eosinophilic disorders, are backed only by case reports and are waiting controlled trials to verify the therapeutic role of mepolizumab.

Venom immunotherapy in patients with allergic reactions to insect stings.

INTRODUCTION: Allergy to Hymenoptera (Apis mellifera, Vespula species, Polistes species, Vespa crabro) venom can be safely and effectively treated by venom immunotherapy (VIT), which in the 40 years since its introduction has been able to prevent reactions to stings, and to treatment as well, though systemic reactions, occasionally severe, are possible. Areas covered: We reviewed the recent literature on VIT by searching in PubMed for the terms 'venom immunotherapy' and 'Hymenoptera venom immunotherapy' to highlight the current status of VIT and the likely development in the coming years. Expert commentary: VIT, provided the correct choice of the venom and adequate venom preparations and maintenance doses are used, is a treatment of great value in preventing systemic reactions to Hymenoptera stings. A 5-year duration ensures a prolonged tolerance to stings following VIT discontinuation, unless patients suffer from mastocytosis. In fact, due to reports of fatal reactions after stopping VIT, patients with mastocytosis, or with very severe reactions to stings, need an indefinite duration of treatment.

Evaluation of a particle enhanced turbidimetric assay for the measurement of neutrophil gelatinase-associated lipocalin in plasma and urine on Architect-8000: Analytical performance and establishment of reference values.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury. NGAL can be measured in both blood and urine. Apart from kidney injury, NGAL levels in both plasma and urine can be influenced by various pathological situations. Accurate evaluation and comparison of results deriving from clinical studies require robust assays, appropriate specimen handling and reference intervals that will reflect its levels in a healthy population for both biological matrices. METHODS: We report the analytical validation of a latex particle-enhanced turbidimetric immunoassay (PETIA) aimed to measure NGAL in plasma and urine on an automated biochemistry analyzer (ABBOTT-Architect-8000). Assay performance characteristics were evaluated using standard protocols. Urine and plasma specimen storage requirements were determined and reference ranges for blood and urine were determined using healthy controls. RESULTS: The assay is precise (total CV%<4.8%), and sensitive (limit of quantification: 8.4 ng/mL for plasma and 9.0 ng/mL for urine), showing no hook effect. Calibration is stable for at least 30 days. The assay showed excellent linearity over the studied interval (20-4450 ng/mL). The analyte is stable at 4 °C for at least 5 days, and at 20 °C for 4h. Gender specific reference ranges for plasma (male: 38.7-157.6 ng/mL, female: 24.4-142.5 ng/mL) and unisex for urine (<9.0-49.41 ng/mL) are proposed. CONCLUSION: Our data indicate that NGAL can be measured with adequate precision and sensitivity on automated biochemistry analyzers and its measurement could easily be added to a standard panel to screen kidney diseases.

A Pitfall to Avoid When Using an Allergen Microarray: The Incidental Detection of IgE to Unexpected Allergens.

The introduction of new laboratory techniques to detect specific IgE antibodies against single allergen molecules rather than whole extracts represents a significant advance in allergy diagnostics. The advantages of such component-resolved diagnosis can be summarized as follows: (1) the ability to identify the truly responsible allergens in polysensitized patients, whether they be genuine (causing specific sensitization to their corresponding allergen source) or primary (the original sensitizing molecule); (2) distinguishing these allergens from simply cross-reactive components; (3) improving the appropriateness of the prescribed specific immunotherapy; and (4) identifying a risk profile for food allergens. Component-resolved diagnosis is performed using either a singleplex (1 assay per sample) platform or a multiplex (multiple assays per sample) platform. Using an immuno solid-phase allergen chip microarray that falls into the latter category--it currently tests sensitivity to 112 allergens--may lead to a pitfall: detecting IgE to unexpected allergens, such as Hymenoptera venom. In fact, testing insect venom sensitivity in individuals with no history of reactions to stings is contrary to current guidelines and presents the physician with the dilemma of how to manage this information; moreover, this may become a legal issue. Based on what is currently known about venom allergy, it remains likely that a positive sensitization test result will have no clinical significance, but the possibility of reacting to a future sting cannot be completely ruled out. Because this problem has not been previously encountered using the more common allergy tests, no indications are currently available on how to effectively manage these cases.

New product development with the innovative biomolecular sublingual immunotherapy formulations for the management of allergic rhinitis.

The molecular allergy technique, currently defined as component-resolved diagnosis, significantly improved the diagnosis of allergy, allowing for differentiation between molecules actually responsible for clinical symptoms (genuine sensitizers) and those simply cross-reacting or shared by several sources (panallergens), thus influencing the appropriate management of a patient's allergy. This also concerns allergen immunotherapy (AIT), which may be prescribed more precisely based on the component-resolved diagnosis results. However, the advance in diagnosis needs to be mirrored in AIT. According to consensus documents and to expectations of specialists, therapy should be based on standardized extracts containing measured amounts of the clinically relevant molecules, ie, the major allergens. The new generation of extracts for sublingual immunotherapy fulfills these requirements and are thus defined as biomolecular (BM). BM refers to natural extracts with a defined content of major allergens in micrograms. All Staloral BM products are indicated for the treatment of allergic rhinitis with or without asthma. The effectiveness of AIT is related to its ability to modify the immunological response of allergic subjects. The 5-grass and house dust mite extracts were evaluated addressing the T helper 1, T helper 2, and T helper 3 cells by polymerase chain reaction array on mRNA extracted from Waldeyer's ring tissue (adenoids). Sublingual immunotherapy with a defined content of major allergens in micrograms induced a strong downregulation of genes involved in T helper 2 and T helper 1 activation and function, allowing the definition of the immunologic effect as "bio-homeostatic". This clinical and immunological model must be implemented with respect to other allergens, thus expanding the application of a treatment with a unique disease-modifying capacity.

Food allergy as defined by component resolved diagnosis.

The diagnosis of food allergy, as assessed by skin tests or in vitro tests with allergen extracts, has insufficient diagnostic performance and needs to be confirmed by food challenges. However, the availability of molecular allergens (recombinant or highly purified) for laboratory methods has profoundly changed the diagnostic approach to food allergy. In fact, the allergy diagnosis conducted at the molecular level, which is defined internationally as component resolved diagnosis (CRD), allows to characterize more precisely the sensitization profile of the individual patient, distinguishing the sensitizations to allergens that are strongly associated with a given source (genuine sensitizers) from those to molecules that are common to many sources (panallergens) or cross-react with other components from the same family or from other families. This review provides an update on the allergen molecules from foods, including plant foods and animal foods, and on the techniques to detect them, by means of a single reagent (singleplex) or an array of molecules tested at the same time (multiplex). Such testing offers detailed information on the sensitization profile of patients and enables the physician to suitably manage their allergy. Moreover, identifying the real causative allergens will be crucial when allergen immunotherapy for food allergy will be introduced in the near future. We also address patents concerning food allergens in this review.

A case of apparent contact dermatitis caused by Toxocara infection.

Infection from Toxocara species may give rise to a large array of clinical symptoms, including apparent manifestations of allergy such as asthma, urticaria/angioedema, and dermatitis. We report a case, thus far not described, of contact dermatitis attributed to nickel allergy but caused by Toxocara infection. The patient was a 53-year-old woman presenting from 10 years a dermatitis affecting head, neck, and thorax. Patch tests initially performed gave a positive result to nickel, but avoidance of contact with nickel did not result in recovery. The patient referred to our Allergy Service in 2010 because of dermatitis to feet. Patch testing confirmed the positive result for nickel, but expanding the investigation a positive result for IgG antibodies to Toxocara was detected by Western blotting and ELISA. Treatment with mebendazole achieved immediate efficacy on feet dermatitis. Then, two courses of treatment with albendazole resulted in complete regression of dermatitis accompanied by development of negative ELISA and Western blotting for Toxocara antibodies. This report adds another misleading presentation of Toxocara infection as apparent contact dermatitis caused by nickel and suggests bearing in mind, in cases of contact dermatitis not responding to avoidance of the responsible hapten and to medical treatment, the possible causative role of Toxocara.

[Allergic rhinitis: pathology of general interest]. / Rinite allergica: una patologia di interesse medico generale.

Allergic rhinitis may appear of little value but at present its high and still increasing prevalence, its socio-economic burden, the frequent association with asthma and the significant impairment of quality of life in affected patients make it a disease of general importance. The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines allow to properly recognize the mild forms and the moderate/severe forms, and, based on the duration of symptoms, the intermittent and persistent forms. Etiologic diagnosis can be suspected by history data but the certainty can be achieved only by allergy testing. The treatment is mainly based on oral or nasal topical antihistamines and topical corticosteroids, that ensure in most cases a satisfactory control of symptoms. However, there are patients who have an insufficient response to drugs, event at high doses. Recent studies showed that patients not controlled by drug treatment achieve a significant benefit from allergen specific immunotherapy, currently available by the subcutaneous and sublingual route. This should be considered as a criterion to choose patients for specific immunotherapy, who must be referred to the allergy specialist.

Treating allergic rhinitis by sublingual immunotherapy: a review.

OBJECTIVE: Allergic rhinitis (AR) is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT), but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT) was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

Seroprevalence of IgG anti-Toxocara species antibodies in a population of patients with suspected allergy.

BACKGROUND: Toxocara canis is an intestinal nematode affecting dogs and cats, which causes human infection when embryonated eggs excreted in dog feces are ingested. Humans are paratenic hosts. Although the larvae do not develop into adult worms in the human body, they may migrate to various tissues and organs where they can survive for several years, giving rise to several clinical symptoms, which can present in allergy-like form. METHODS: Over 5 years, we examined 9985 patients referred for suspected allergies, based on symptoms such as dermatitis, urticaria, rhinitis, asthma, and conjunctivitis; 753 patients who had allergy tests negative or unrelated to clinical history were tested for seropositivity to T. canis by enzyme-linked immunosorbent assay (ELISA) or Western blotting (WB). RESULTS: In 240 patients (31.8%), ELISA or WB or both tests were positive for T. canis immunoglobulin G (IgG) antibodies: in particular, 64 of them (26.7%) were positive to ELISA, 110 (45.8%) to WB, and 66 (27.5%) to both tests. Asthma was the most common clinical presentation. Two thirds of patients underwent subsequent anthelmintic therapy and showed a complete remission of symptoms and, in 43% of patients retested by ELISA and WB, became negative to Toxocara. CONCLUSION: These findings strongly suggest that T. canis plays a significant role in inducing chronic symptoms presenting as suspected allergies.