White paper peanut allergy—part 2: Diagnosis of peanut allergy with special emphasis on molecular component diagnostics

Summary Background Peanut allergy is an immunoglobulin E (IgE)-mediated immune response that usually manifests in childhood and can range from mild skin reactions to anaphylaxis. Since quality of life maybe greatly reduced by the diagnosis of peanut allergy, an accurate diagnosis should always be made. Methods A selective literature search was performed in PubMed and consensus diagnostic algorithms are presented. Results Important diagnostic elements include a detailed clinical history, detection of peanut-specific sensitization by skin prick testing and/or in vitro measurement of peanut (extract)-specific IgE and/or molecular components, and double-blind, placebo-controlled food challenge as the gold standard. Using these tools, including published cut-off values, diagnostic algorithms were established for the following constellations: 1) Suspicion of primary peanut allergy with a history of immediate systemic reaction, 2) Suspicion of primary peanut allergy with questionable symptoms, 3) Incidental findings on sensitization testing and peanut ingestion so far or 4) Suspicion of pollen-associated peanut allergy with solely oropharyngeal symptoms. Conclusion The most important diagnostic measures in determining the diagnosis of peanut allergy are clinical history and detection of sensitizations, also via component-based diagnostics. However, in case of unclear results, the gold standard—an oral food challenge—should always be used.

Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells

Sepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate mechanisms underlying inhibition of TNFα production. We identified quinolone antibiotics reduced TNFα production in lipopolysaccharide (LPS)-stimulated THP-1 cells. Sitafloxacin (STFX) is a broad-spectrum antibiotic of the quinolone class. STFX effectively suppressed TNFα production in LPS-stimulated THP-1 cells in a dose-dependent manner and increased extracellular signal-regulated kinase (ERK) phosphorylation. The percentage of intracellular TNFα increased in LPS-stimulated cells with STFX compared with that in LPS-stimulated cells. TNFα converting enzyme (TACE) released TNFα from the cells, and STFX suppressed TACE phosphorylation and activity. To conclude, one of the mechanisms underlying inhibition of TNFα production in LPS-stimulated THP-1 cells treated with STFX is the inhibition of TNFα release from cells via the suppression of TACE phosphorylation and activity. STFX may kill bacteria and suppress inflammation. Therefore, it can be effective for sepsis treatment.

Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1β, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.

The Employment Ecosystem of Bizkaia as an Emerging Common in the Face of the Impact of COVID-19

In the context of the impact of COVID-19 pandemic in Bizkaia (Basque Country, Spain), and from the renewed Commons paradigm, this research analyzes the initial response given by the region’s employment ecosystem. Based on extensive quantitative and qualitative methods, it empirically explores the catalytic role that local public and social entities could play in coordinating an organized and systemic response of the employment-related stakeholders to an external impact, such as the current pandemic. The study of databases specifically provided by the Public Administrations for this research, in combination with two survey processes conducted to the main agents of the ecosystem, led to a greater understanding of the benefits of an organized and systemic reaction. From the community identification of a priori unrecognized impacts by individual actors to the proposal of actions closely connected to their short and long-term needs, the article finally presents recommendations aimed at strengthening the resilience and collaboration of the collective action.

Evaluation of subcutaneous daratumumab injections in the ambulatory care setting

Introduction Subcutaneous daratumumab is non-inferior to intravenous daratumumab for the treatment of multiple myeloma and significantly reduced incidence of systemic reactions. However, manufacturer for subcutaneous daratumumab has not provided guidance regarding optimal methods for monitoring for hypersensitivity reactions following subcutaneous daratumumab administration. Methods A retrospective analysis was performed in two cohorts of patients who received at least two doses of subcutaneous daratumumab for the treatment of plasma cell disorders: patients with previous exposure to intravenous daratumumab (dara-exposed) and patients without history of intravenous daratumumab (dara-naïve). The primary outcome was incidence of systemic and injection-site reactions following first dose of subcutaneous daratumumab. Secondary analysis included time to systemic and injection-site reactions, grading of adverse reaction, and incidence of second systemic reaction. Results Thirty-one patients were dara-naïve and 49 patients were dara-exposed. Differences in incidence of systemic (dara-naïve: 9.7% vs dara-exposed: 6.1%, p = 0.67) and injection-site reactions (dara-naïve: 12.9% vs dara-exposed: 14.3%, p = 0.99) did not reach statistical significance. Difference in median time to systemic reaction (dara-naïve: 3 h vs dara-exposed: 12 h, p = 0.18) was clinically important but did not reach statistical significance. Median time to injection-site reactions (dara-naïve: 6 h vs dara-exposed: 24 h, p = 0.03) was shorter in the dara-naïve cohort. No clinically meaningful difference was observed for incidence of second systemic reaction. Conclusion Most reactions were mild and did not require medical intervention. Following first subcutaneous daratumumab dose, monitoring for 3 h for dara-naïve patients and no monitoring time for dara-exposed patients for hypersensitivity reactions may be a safe and reasonable practice.

Clinical, histopathological, and molecular characterization of Mycoplasma species in sheep and goats in Egypt

Background and Aim: Mycoplasma infection in small ruminants is a serious problem in sheep and goat herds around the world. It is responsible for high economic losses and decreased animal productivity. This study aimed to highlight the clinical, histopathological, minimum inhibitory concentration (MIC), and molecular characterization of Mycoplasma species in sheep and goats in Menoufiya Governorate, Egypt. Materials and Methods: A total of 234 samples were collected; 104 samples were collected from pneumonic lung tissues from the abattoir, in addition, 10 and 20 samples collected from apparently and diseased sheep, respectively, and 40 and 60 samples were collected from apparently and diseased goats, respectively, which were subjected to isolation onto pleuropneumonia-like organism medium. Polymerase chain reaction (PCR), histopathological examination, and determination of the MIC were also performed. Results: Of 104 samples of lung tissues showing pneumonic lesions, 56 (53.84%) were positive for Mycoplasma isolation. The positive isolation of Mycoplasma from 10 and 20 samples from apparently and diseased sheep was 30% and 40%, respectively as well as the positive isolation of Mycoplasma was 17% and 56.66% out of 40 and 60 apparently healthy and diseased field goat's cases, respectively. All the diseased sheep and goats showed respiratory manifestations, including cough, bilateral nasal discharge, conjunctivitis, and systemic reaction. Evaluation of the MIC for Mycoplasma ovipneumoniae revealed that lincospectin and tylosin were the most effective antibiotics at 2.5 μg/mL. Histopathological examination of affected lung tissue showed extensive hemorrhagic pneumonia with extensive alveolar hemorrhage. The PCR technique proved to be a rapid, specific, and sensitive method for the detection of M. ovipneumoniae and Mycoplasma arginini at 390 and 326 bp, respectively. Conclusion: M. ovipneumoniae and M. arginini were the most prevalent species associated with respiratory infections in sheep and goats in the study area. Further studies are needed to investigate the role of these species in dissemination of the disease within herds of small ruminants.

COVID-19-related headache and sinonasal inflammation: A longitudinal study analysing the role of acute rhinosinusitis and ICHD-3 classification difficulties in SARS-CoV-2 infection

Background The genesis of headache in coronavirus disease 2019 (COVID-19) is currently unclear and the multitude of disease symptoms often further hinders locating the source of pain. Interestingly, many subjects with COVID-19 have symptoms of acute rhinosinusitis. The relation between nasal symptoms and headache in SARS-CoV-2 infection remains unknown. Methods This bi-center longitudinal study evaluated symptoms in consecutive COVID-19 patients in the participating practices. The first assessment was performed during the initial consultation after infection confirmation. That was followed up by a second consultation after a median 9 days. Results 130 patients were included in the study (80 women, 50 men; mean age 46.9 years). Headache was highly prevalent at the first visit (72%) and significantly associated with acute rhinosinusitis symptoms. The odds ratio for headache in subjects with rhinosinusitis was 3.5. Headache could be attributed to systemic viral infection in 96% and to acute rhinosinusitis in 51% of cases according to 3rd edition of the International Classification of Headache Disorders. Criterium C.3 (exacerbation of headache by pressure applied over paranasal sinuses) and C.4 (ipsilaterality of headache and sinusitis) had low sensitivity in headache attributed to acute rhinosinusitis. Conclusions Nasal inflammation is associated with headache in COVID-19, although the pain mechanism lies probably in a systemic reaction to the virus. 3rd edition of the International Classification of Headache Disorders criteria for headache attributed to acute rhinosinusitis need adjusting to the current understanding of acute sinonasal infection.

The Crohn’s Disease and Proinflammatory Cytokines

The aim of the study was to examine the profile of the main proinflammatory cytokines in the serum of patients with Crohn's disease and establish their association with the severity and activity of the disease. A total of 61 patients (29 women (47.5%), 32 men (52.5%) aged from 18 to 40 years (mean age (30.42 ± 2.51) years) with the verified diagnosis of Crohn's disease in the active phase were examined. The control group consisted of 30 virtually healthy people (VHP) of corresponding age. Crohn's disease is characterized by reliable (p<0.05) increase of pro-inflammatory cytokines in blood compared to virtually healthy people: TNF-α – by 4.45 times (p<0.05), IL-1α – by 5.08 times (p<0.05), IL-6 – by 2.16 times (p<0.05), IL-8 – by 2.04 times (p<0.05), and IFN-γ – by 5.30 times (p<0.05), which can be due to the development of the active inflammatory process in the intestine and the systemic reaction of the body. The degree of increase in TNF-α and IFN-γ content, as well as the presence of direct correlations between the Best activity index and the content of these cytokines in the blood of the examined patients, confirm their leading role in the cascade of immune-inflammatory reactions during Crohn's disease.

Sitafloxacin Inhibits TNFα Release from Monocytic THP-1 Cells Stimulated by LPS

Sepsis is a systemic reaction to infection and excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study was designated to find out which quinolone antibiotic reduces TNFα production the most and to elucidate its mechanisms. We examined which quinolone antibiotic reduced TNFα production from THP-1 cells stimulated by lipopolysaccharide (LPS). Then, we examined the mechanism of inhibition of TNFα production by the antibiotic. STFX most effectively reduced TNFα concentrations within LPS-stimulated THP-1 cells supernatant. STFX suppressed TNFα production in a dose-dependent manner. We found that STFX did not inhibit the NF-kB, ERK, or p38 pathways, nor did it inhibit the production of TNFα mRNA. The percentage of intracellular TNFα was increased in cells stimulated by LPS and with STFX compared to that of cells stimulated by LPS alone. In conclusion, one of the mechanisms reducing TNFα production from LPS-stimulated THP-1 cells treated with STFX involves inhibition of TNFα release from these cells. STFX has a broad antimicrobial spectrum for gram-positive, gram-negative, and anaerobic bacteria, and may be effective for treating sepsis by both killing bacteria and suppressing inflammation.