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SummaryA novel and recently launched food for special medical purposes was discussed by a multidisciplinary expert panel as an option for allergic patients. The newly developed lozenge contains the whey protein beta-lactoglobulin (BLG) as well as the micronutrients iron, zinc and vitamin A. BLG loaded with ligands (holo-BLG) is discussed as one factor of the allergy-protective farm effect in numerous scientific studies. Further studies reveal that holo-BLG shuttles its ligands specifically to immune cells, where it balances the specific nutrient demand and can thus lead to immune resilience. Based on the scientific background, the experts see a broad range of possible applications for holo-BLG in the form of a lozenge, for example in patients suffering from multiple allergies, with sensitisation to rare allergens (including occupational allergens), tree pollen-associated food allergies or in general difficult treatment situations (e.g. allergies to animal dander or refusal of allergen immunotherapy). The expert panel describes the holo-BLG lozenge as an innovative and additional option for allergic patients.

Purpose To evaluate the impact of high-intensity interval training (HIIT) on health-related outcome parameters in the prehabilitation of patients diagnosed with cancer. Methods A systematic review and meta-analysis of comparative studies on HIIT in cancer prehabilitation conducted by screening standard databases from their inception to March 30, 2020. Outcomes of interest included cardiorespiratory fitness, feasibility, safety, clinical, and patient-reported outcomes. Results Of the 855 identified studies, 8 articles met the inclusion criteria (7 randomized, 1 non-randomized controlled trial) with a total of 896 patients. The study protocols were heterogeneous, but the methodological quality ranged from good to high according to PEDro scale. Meta-analysis revealed a significant improvement of peak oxygen consumption (VO2peak) achieved with HIIT compared to usual care. Furthermore, HIIT was feasible and safe, showing low risk of adverse events and positive effects on health-related outcomes in prehabilitative settings. Conclusion In the phase of prehabilitation, HIIT has potential health benefits in patients diagnosed with cancer and is feasible and safe to perform. Nonetheless, larger randomized controlled trials focusing on long-term effects (such as cancer recurrence or survival rates) are missing, to underline the potential relevance of HIIT for cancer patients.

SummaryBackgroundMatrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP‑2, MMP‑9 and their inhibitors TIMP‑1 and TIMP‑2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU).MethodsIn a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the ICU of a cardiology department. The most common underlying conditions were cardiac diseases (n = 42.5%), respiratory failure (n = 10.8%) and sepsis (n = 6.7%). Blood samples were taken within 12 h of ICU admission. The MMP‑2, MMP‑9, TIMP‑1 and TIMP‑2 levels in plasma were evaluated in terms of 30-day survival, underlying condition and clinical score.ResultsOn ICU admission 30-day survivors had significantly lower plasma MMP‑9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10−2.53;p = 0.016) and TIMP‑1 (OR 2.15 per 1 SD; 95% CI 1.27−3.64;p = 0.004) levels than non-survivors; furthermore, MMP‑9 and TIMP‑1 correlated well with SAPS II (bothp p = 0.002) and TIMP‑1 (p = 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP‑2 and TIMP‑2 levels, MMP/TIMP ratios and 30-day mortality.ConclusionThe MMP‑9 and TIMP‑1 levels are significantly elevated in acute critical care settings with increased short-term mortality risk, especially in patients with underlying heart disease. These findings support the value of MMPs and TIMPs as prognostic markers and potential therapeutic targets in conditions leading to systemic inflammation and acute organ failure.

Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy incidence at a population level remains uncharacterized. Here we aim to assess the use of anti-allergic medication following prescription of gastric acid inhibitors. We analyze data from health insurance records covering 97% of Austrian population between 2009 and 2013 on prescriptions of gastric acid inhibitors, anti-allergic drugs, or other commonly prescribed (lipid-modifying and antihypertensive) drugs as controls. Here we show that rate ratios for anti-allergic following gastric acid-inhibiting drug prescriptions are 1.96 (95%CI:1.95–1.97) and 3.07 (95%-CI:2.89–3.27) in an overall and regional Austrian dataset. These findings are more prominent in women and occur for all assessed gastric acid-inhibiting substances. Rate ratios increase from 1.47 (95%CI:1.45–1.49) in subjects 60 year olds. We report an epidemiologic relationship between gastric acid-suppression and development of allergic symptoms., Gastric acid inhibitors promote experimental allergy in animals, and have been linked to allergy risk in observational human studies. Here the authors show in a country-wide medical record analysis that allergy development risk is doubled in gastric acid inhibitor users, and is higher in women and in older age.

Background Along with the newly approved vaccines against coronavirus disease 2019 (COVID-19), first reports of allergic or intolerance reactions were published. Subsequently, questions arose whether these vaccines pose an increased risk for intolerance reactions and whether allergic patients may be at higher risk for this. Results Allergic reactions following COVID-19 vaccinations have been reported, but mostly of mild severity and at normal (Moderna®) or only slightly increased frequency (BioNTech/Pfizer®) compared to established conventional vaccines. The risk of allergic reaction to the newly licensed vector vaccines (AstraZeneca®, Johnson&Johnson®) cannot be conclusively assessed yet, but also appears to be low. There is currently no evidence that patients with allergic diseases (atopic patients) react more frequently or more severely to these vaccines. It is currently assumed that intolerance reactions of the immediate-type are either type I allergic (IgE-mediated) reactions or occur via complement activation (CARPA, “complement activation-related pseudoallergy”). Polyethylene glycol (PEG) or polysorbate, which are present as stabilizers in the vaccines, are suspected as triggers for this. Conclusion The data available so far do not show a significantly increased risk of immediate-type allergic reactions in atopic persons. In almost all cases, atopic patients can be vaccinated without problems. Standardized follow-up tests after suspected allergic reactions or CARPA-mediated reactions are currently limited.

Since the discovery of IgE, almost all attention was given to conditions with elevated specific or total IgE levels such as atopy, type I hypersensitivity reactions, or parasitic infestations. Recent prospective and retrospective studies show that having very low IgE levels, such as those seen in IgE deficiency (IgE

Allergen immunotherapy (AIT) is the only setting in which a vaccine is applied in patients allergic exactly to the active principle in the vaccine. Therefore, AIT products need to be not only effective but also safe. In Europe, for subcutaneous AIT, this has been achieved by the allergoid strategy in which IgE epitopes are destroyed or masked. In addition, adjuvants physically precipitate the allergen at the injection site to prevent too rapid systemic distribution. The choice of adjuvant critically shapes the efficacy and type of immune response to the injected allergen. In contrast to TH2-promoting adjuvants, others clearly counteract allergy. Marketed products in Europe are formulated with aluminum hydroxide (alum) (66.7%), microcrystalline tyrosine (16.7%), calcium phosphate (11.1%), or the TH1 adjuvant monophosphoryl lipid A (5.6%). In contrast to the European practice, in the United States mostly nonadjuvanted extracts and no allergoids are used for subcutaneous AIT, highlighting not only a regulatory but maybe a “historic preference.” Sublingual AIT in the form of drops or tablets is currently applied worldwide without adjuvants, usually with higher safety but lower patient adherence than subcutaneous AIT. This article will discuss how AIT and adjuvants modulate the immune response in the treated patient toward immune activation, modulation, or—with new developments in the pipeline—immune resilience.

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 focusing on 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 cohort of 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.

Kidney transplantation (KTx) in end-stage renal disease is associated with a significant increase in quality of life (QoL) and self-perceived health, optimally leading to the maintenance of employment or return to work (RTW) in working-age patients. The aim of this study was to assess individual factors including the QoL and mental health of kidney transplant recipients (KTRs) associated with employment after transplantation. A cross-sectional study including working-age patients with a history of KTx after 2012 was conducted at two Austrian study centers (Vienna and Graz). Brief Symptom Inventory (BSI-18), World Health Organization Quality of Life (WHOQOL-Bref) and Workability Index (WAI) were assessed along with detailed questionnaires on employment status. Out of n = 139 KTRs (43.2 &plusmn, 9.07 years, 57.6% male), 72 (51.8%) were employed. Employed patients were more frequently in a partnership (p = 0.018) and had higher education levels (p = 0.01) and QoL scores (&lt, 0.001). Unemployed KTRs reported fatigue and mental health issues more often (p &lt, 0.001), and had significantly higher anxiety, depression and somatization scores (BSI-18). In unadjusted logistical regression, workability score (WAS, odds ratio (OR) = 3.39, 95% confidence interval (CI) = 1.97&ndash, 5.82, p &lt, 0.001), partnership (OR = 5.47, 95% CI 1.43&ndash, 20.91, p = 0.013) and no psychological counseling after KTx (OR = 0.06, 95% CI = 0.003&ndash, 0.969, p = 0.048) were independently associated with employment. Self-assessed mental health, workability and QoL were significantly associated with employment status after KTx. Thus, in order to facilitate RTW after KTx in Austria, vocational rehabilitation and RTW programs addressing KTRs should focus on increasing social support and care for their mental health.

Background Human Papillomavirus (HPV) is associated with development of oropharyngeal cancer. Aim of this review was to assess airborne transmission risk of infectious particles from HPV lesions to airway mucosa of medical staff during established ablation procedures. Methods A systematic review of human and animal studies, published before 09/2020, relevant to airborne HPV transmission. Controlled studies reporting prevalence of HPV-associated upper airway (nasal/oral/pharyngeal) disease in staff performing ablation procedures (laser, loop electrosurgical excision [LEEP], cryosurgery) on HPV lesions were included in meta-analysis. Additionally, we aimed for a comprehensive systematic overview of studies regarding occupational risk of airborne HPV transmission and safety measures during ablation procedures. Results A total of n = 30 original studies report outcomes related to HPV transmission risk in medical staff conducting ablation procedures. HPV DNA detection in ablation smoke (n = 7), matching HPV genotypes on ablated HPV lesions and face/airways of medical staff after ablation (n = 2), and evidence for infectivity of papillomavirus in ablation smoke (n = 3, animal models only) were reported. Three case reports describe occupational HPV disease of upper airway mucosa. Three controlled studies assessed warts (in CO2 laser-users only); when pooling all controls (general population, non-laser users), nasal/oral/pharyngeal lesion sites were more common amongst laser-users (OR = 5.75; 95%CI[1.55, 21.38]; p Discussion Airborne HPV dispersal with matching “high-risk” HPV-genotypes in airways of medical staff after ablations (LEEP and CO2-laser) and cases of HPV-associated upper airways neoplasms based on exposure to laser and LEEP smoke are documented. Upper airway mucosa is a more common anatomical site for warts in CO2 laser users compared to controls. Simple safety measures greatly reduce HPV contamination and transmission risk.

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.

The neurotoxicity of lead is well-known and even low exposure levels potentially impact neurocognitive abilities. This metaanalysis aimed to investigate associations between neurocognitive performance and lead exposure in adults and further assess potential effect thresholds.Articles indexed in Medline published until January 2017 reporting associations between lead exposure, blood lead, cognitive abilities and sensomotoric performance were included. The unbiased, standardized mean differences g between lead exposure and control groups extracted from the primary studies were pooled using a three-level, random-effects meta-analytic model with a restricted maximum likelihood estimator. Moderator analyses were conducted using weighted, mixedeffects regression analyses.We identified 22 articles (n=3,849 participants, mean age 39.94±7.87years) published between 1976 and 2014 reporting lead exposure effects on cognitive and sensomotoric parameters (verbal abilities, visuospatial abilities, memory, attention, psychomotor function). On average, blood lead concentrations were 21.09±6.44 μg/dl higher in exposed than in control subjects. After exclusion of outliers, the random-effects three-level meta-analysis identified a significant (p.001) pooled mean difference between exposure and control groups. Except for a smaller effect in the digit symbol test (p.05), lead exposure did not result in different outcomes across the examined cognitive measures. Based on a marginally significant (p=.06) effect of difference in exposure levels, a blood lead increase of 10 μg/dl translated into a decline in cognitive abilities of Hedges g=.09.Neurocognitive performance in adults with occupational or environmental lead exposure was significant impaired with regard to the examined parameters. However, further studies are needed for the determination of effect thresholds and reversibility.

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, “real-world” cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment. At baseline, significantly higher levels of salivary cortisol were observed in the burnout group compared to the control group. This was even more pronounced in midday- (p