An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay.

Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5'UTR/Npro, Npro and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10-3 substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development.

Ag5-induced stabilization of multiple surface polarons on perfect and reduced TiO2 rutile (110).

The recent advent of cutting-edge experimental techniques allows for a precise synthesis of subnanometer metal clusters composed of just a few atoms, opening new possibilities for subnanometer science. In this work, via first-principles modeling, we show how the decoration of perfect and reduced TiO2 surfaces with Ag5 atomic clusters enables the stabilization of multiple surface polarons. Moreover, we predict that Ag5 clusters are capable of promoting defect-induced polarons transfer from the subsurface to the surface sites of reduced TiO2 samples. For both planar and pyramidal Ag5 clusters, and considering four different positions of bridging oxygen vacancies, we model up to 14 polaronic structures, leading to 134 polaronic states. About 71% of these configurations encompass coexisting surface polarons. The most stable states are associated with large inter-polaron distances (>7.5 Å on average), not only due to the repulsive interaction between trapped Ti3+ 3d1 electrons, but also due to the interference between their corresponding electronic polarization clouds [P. López-Caballero et al., J. Mater. Chem. A 8, 6842-6853 (2020)]. As a result, the most stable ferromagnetic and anti-ferromagnetic arrangements are energetically quasi-degenerate. However, as the average inter-polarons distance decreases, most (≥70%) of the polaronic configurations become ferromagnetic. The optical excitation of the midgap polaronic states with photon energy at the end of the visible region causes the enlargement of the polaronic wave function over the surface layer. The ability of Ag5 atomic clusters to stabilize multiple surface polarons and extend the optical response of TiO2 surfaces toward the visible region bears importance in improving their (photo-)catalytic properties and illustrates the potential of this new generation of subnanometer-sized materials.

Health-related quality of life in men with prostate cancer undergoing active surveillance versus radical prostatectomy, external-beam radiotherapy, prostate brachytherapy and reference population: a cross-sectional study.

BACKGROUND: The purpose of this study is to describe Health-Related Quality of Life (HRQoL) of localized prostate cancer patients in an Active Surveillance (AS) program, and to compare them with those undergoing radical prostatectomy (RP), external-beam radiotherapy (XRT) and brachytherapy (BT). METHODS: Multi-institutional pooled cross-sectional analysis on patients in an AS protocol: < 75 years old; pathologically confirmed LPC (maximum of three positive cylinders); Gleason score < 3 + 4; clinical stage T1a-T2b; and PSA < 15 ng/ml. Exclusion criteria for this study were: less than 6 months in AS, termination of AS protocol, or incomplete data. Patients in AS were matched with those treated with RP, XRT or BT from the 'Spanish Multicentric Study of Clinically Localized Prostate Cancer' cohort according to risk group, time from treatment selection to HRQoL survey, and age. Prostate-specific (EPIC) and generic (SF-36) HRQoL instruments were completed. Analysis was stratified by HRQoL survey moment (>or < 2.5 years from treatment selection), and age (>or < 70 years old). RESULTS: Median of time from treatment selection to HRQoL survey in the total 396 patients (99 per treatment group) was 2.4 years (range 0.5-8.3). Patients in AS presented higher (better) urinary incontinence scores than RP ones in both stratus of time from treatment selection to HRQoL survey (92.6 vs 67.0 and 81.4 vs 64.4, p <  0.01). Patients in AS for < 2.5 years presented greater sexual scores than any active treatment (p <  0.01), but only statistically higher than RP for those in AS for longer than 2.5 years. The magnitude of the differences between AS and RP groups in both EPIC domains ranged from moderate (0.7 SD) to large (1.0 SD). Regardless of treatment applied, patients presented similar and slightly increased SF-36 scores than US general population reference norms. Nonetheless, patients in AS for < 2.5 years reported worse outcomes than other treatment groups on physical health domains, especially in bodily pain (0.5-0.6 SD), and vitality (0.6-0.8 SD). CONCLUSIONS: Considering patients' well-being, AS can be a good therapeutic option due to the low impact caused on urinary continence and sexual function. However, longitudinal studies are required to take into account HRQoL evolution over time.

What can we learn in drug allergy management from World Health Organization's international classifications?

Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population, and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization, and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions. To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD-11 revision agenda, we report the advances and use of the pioneering "Drug hypersensitivity" subsection of ICD-11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies and better facilitate healthcare planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs.

Prevalence and viability of group A rotavirus in dairy farm water sources.

AIM: To analyse group A rotavirus (RVA) environmental contamination in waters used for calves' consumption and to assess viral viability in dairy farm water sources. METHODS AND RESULTS: We analysed 202 samples of water used for calves' consumption and RVA was detected by RT-qPCR in 35·1% (95% CI: 28·9-42·0%). A marked pattern of seasonality was observed with higher frequency of detection in colder than warmer months (P = 0·002). There was no association between viral load and season or between the number of milking cows in the herd and the detection of RVA in the farm. The viability of the RVA particles detected was confirmed by isolation of RVA in cell culture from 5 of 10 water samples. Furthermore, an RVA waterborne outbreak of neonatal calf diarrhoea was described. CONCLUSIONS: We demonstrate that RVA is frequent in dairy farm waters, and that the virus is infectious and capable of generating a diarrhoea outbreak. SIGNIFICANCE AND IMPACT OF THE STUDY: Neonatal diarrhoea syndrome leads to economic losses to the livestock industry worldwide. To determine transmission routes is essential to take action in this regard and reduce the impact that this syndrome has for the livestock production. The results obtained in this work alert the dairy industry and highlight that mitigation strategies are crucial to improve the microbiological quality of this water.

Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology.

This consensus document summarizes the current knowledge on the potential for precision medicine in food allergy, drug allergy, and anaphylaxis under the auspices of the PRACTALL collaboration platform. PRACTALL is a joint effort of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology, which aims to synchronize the European and American approaches to allergy care. Precision medicine is an emerging approach for disease treatment based on disease endotypes, which are phenotypic subclasses associated with specific mechanisms underlying the disease. Although significant progress has been made in defining endotypes for asthma, definitions of endotypes for food and drug allergy or for anaphylaxis lag behind. Progress has been made in discovery of biomarkers to guide a precision medicine approach to treatment of food and drug allergy, but further validation and quantification of these biomarkers are needed to allow their translation into practice in the clinical management of allergic disease.

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

Norovirus molecular detection in Uruguayan sewage samples reveals a high genetic diversity and GII.4 variant replacement along time.

AIMS: To determine the prevalence and molecular epidemiology of norovirus (NoV) genogroup I (GI) and GII in Uruguay. METHODS AND RESULTS: One hundred and sixteen sewage samples were collected in six cities (Bella Unión, Salto, Paysandú, Fray Bentos, Melo and Treinta y Tres) from March 2011 to April 2013, viruses were concentrated by ultracentrifugation and NoV studies were performed by semi-nested RT-PCR (partial capsid region). NoV were detected in samples from all the cities and detected in 72% (84/116) of the samples with nine of them belonging to GI, 48 to GII and 27 to both genogroups. Remarkably, a high genetic diversity was identified: GII.2 (n = 13), GII.4 (n = 13), GI.1 (n = 5), GI.4 (n = 5), GI.8 (n = 4), GII.13 (n = 4), GII.1 (n = 3), GII.6 (n = 3), GI.3 (n = 1), GI.5 (n = 1), GI.6 (n = 1), GII.3 (n = 1), GII.17 (n = 1). Interestingly, a complete replacement of GII.4 New Orleans 2009 by GII.4 Sydney 2012 variants during 2012 was evidenced. CONCLUSION: This study reveals a high circulation of different NoV GI and GII genotypes in sewage evidencing a replacement of GII.4 variants. SIGNIFICANCE AND IMPACT OF STUDY: This approach can be used as an indicator of the presence of a new GII.4 variant which can originate an increase in acute gastroenteritis outbreaks worldwide.

International Consensus on drug allergy.

When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term 'allergy') are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis.

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.

Sex and gender perspectives in colorectal cancer.

Historically women were frequently excluded from clinical trials and drug usage to protect unborn babies from potential harm. As a consequence, the impact of sex and gender on both tumour biology and clinical outcomes has been largely underestimated. Although interrelated and often used interchangeably, sex and gender are not equivalent concepts. Sex is a biological attribute that defines species according to their chromosomal makeup and reproductive organ, while gender refers to a chosen sexual identity. Sex dimorphisms are rarely taken into account, in either preclinical or clinical research, with inadequate analysis of differences in outcomes according to sex or gender still widespread, reflecting a gap in our knowledge for a large proportion of the target population. Underestimation of sex-based differences in study design and analyses has invariably led to 'one-drug' treatment regimens for both males and females. For patients with colorectal cancer (CRC), sex also has an impact on the disease incidence, clinicopathological features, therapeutic outcomes, and tolerability to anticancer treatments. Although the global incidence of CRC is higher in male subjects, the proportion of patients presenting right-sided tumours and BRAF mutations is higher among females. Concerning sex-related differences in treatment efficacy and toxicity, drug dosage does not take into account sex-specific differences in pharmacokinetics. Toxicity associated with fluoropyrimidines, targeted therapies, and immunotherapies has been reported to be more extensive for females with CRC than for males, although evidence about differences in efficacy is more controversial. This article aims to provide an overview of the research achieved so far into sex and gender differences in cancer and summarize the growing body of literature illustrating the sex and gender perspective in CRC and their impact in relation to tumour biology and treatment efficacy and toxicity. We propose endorsing research on how biological sex and gender influence CRC as an added value for precision oncology.

[Holistic semi-presential evaluation of oropharygeal dysphagia with the framework of International Classification of Functioning, Disability and Health: Optimizing evaluation to improve rehabilitation treatment]. / Evaluación holística semipresencial de la disfagia orofaríngea en el marco de la Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud: optimizar la valoración para mejorar el tratamiento rehabilitador.

INTRODUCTION: Oropharyngeal dysphagia can lead to medical complications and decreased quality of life. Although there is a wide diversity of instrumental and clinical procedures to assess it, consensus for its holistic evaluation is scarce and poorly defined. The objective of this article is to present the design of a model for the holistic examination of oropharyngeal dysphagia that takes into account the components of the International Classification of Functioning, Disability and Health (ICF) and that can be carried out both face to face and semi-presentially using Information and Communication Technology (ICT) tools. MATERIAL AND METHODS: A non-systematic review of the literature is carried out in order to select validated oropharyngeal dysphagia assessment tools with the highest degree of recommendation. These tools are analyzed by a group of experts in oropharyngeal dysphagia from the Hospital de la Santa Creu i Sant Pau in Barcelona to design a holistic exploration model. RESULTS: This evaluation model includes an assessment at the beginning and at the end of the treatment, as well as continuous monitoring during the rehabilitation process. It is implemented in a semi-presential and multidisciplinary way, and its purpose is to understand oropharyngeal dysphagia holistically to design and monitor an individualized therapeutic plan. CONCLUSIONS: The evaluation of oropharyngeal dysphagia should be within the biopsychosocial framework proposed by the ICF. The application of ICT in blended interventions facilitates this.

Desensitization regimens for drug allergy: state of the art in the 21st century.

Adverse reactions to drugs are increasingly being recognized as important contributions to disease in their own right as well as impediments to the best treatment of various conditions, including infectious, autoimmune, and neoplastic maladies. Rapid drug desensitization (RDD) is an effective mechanism for safely administering important medications while minimizing or entirely circumventing such adverse reactions in sensitized patients. We reviewed the literature on RDD in the last 10 years, including our experience from the Brigham and Women's Hospital Desensitization Program with hundreds of patients desensitized to a broad variety of drugs. RDD in our programme has been uniformly successful in patients with hypersensitivity reactions to antibiotics, chemotherapeutics, and monoclonal antibodies. Any reactions that occur during desensitization are generally much less severe than the initial hypersensitivity reaction to the drug, and patients have received the full dose of the desired medication 99.9% of the time out of (796) desensitizations. To date, there have been no fatalities. RDD is a safe and highly effective method for treating sensitized patients with the optimal pharmacologic agents. Its use should be expanded, but because patient safety is paramount, protocols must be created, reviewed, and overseen by allergist-immunologists with special training and experience in modern techniques of desensitization.

[Anaphylaxis and COVID-19 vaccines]. / L'anaphylaxie et les vaccins COVID-19.

Vaccines against COVID-19 are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1,000,000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. It is important to restore confidence about vaccination with COVID-19 mRNA and other vaccines and current data confirm their safety with no greater mortality than previous vaccines. Anaphylaxis is a complication that should be recognized immediately, be treated with epinephrine and which is not limiting and allows re-vaccination of some patients with pre-medication. It is important to recognize populations at risk such as women, patients with a history of allergies and anaphylaxis and to recognize the rare patients who have mast cell activating diseases. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

General considerations on rapid desensitization for drug hypersensitivity - a consensus statement.

Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.

Effect of the administration of Lactobacillus spp. strains on neonatal diarrhoea, immune parameters and pathogen abundance in pre-weaned calves.

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.

Modeling the Transport of Human Rotavirus and Norovirus in Standardized and in Natural Soil Matrix-Water Systems.

We modeled Group A Rotavirus (RVA) and Norovirus genogroup II (GII NoV) transport experiments in standardized (crystal quartz sand and deionized water with adjusted pH and ionic strength) and natural soil matrix-water systems (MWS). On the one hand, in the standardized MWS, Rotavirus and Norovirus showed very similar breakthrough curves (BTCs), showing a removal rate of 2 and 1.7 log10, respectively. From the numerical modeling of the experiment, transport parameters of the same order of magnitude were obtained for both viruses. On the other hand, in the natural MWS, the two viruses show very different BTCs. The Norovirus transport model showed significant changes; BTC showed a removal rate of 4 log10, while Rotavirus showed a removal rate of 2.6 log10 similar to the 2 log10 observed on the standardized MWS. One possible explanation for this differential behavior is the difference in the isoelectric point value of these two viruses and the increase of the ionic strength on the natural MWS.

AllergoOncology: ultra-low IgE, a potential novel biomarker in cancer-a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI).

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.