Serum midkine level might be a diagnostic tool for COVID19 disease in pregnancy: From the disease severity, hospitalization and disease progression respects.

BACKGROUND: New biomarkers for diagnosis and monitoring the COVID-19 disease are the most important topics to be studied recently. We aimed to investigate the association between midkine levels and disease severity in pregnant women with COVID-19. METHODS: Totally 186 pregnant women were participated in this study. 96 of them were healthy pregnant women, 90 of them were pregnant women with COVID19. Pregnant women were evaluated according to their trimesters. Serum midkine level, biochemical profile clinical and disease severity outcomes of pregnant women were obtained. RESULTS: Our results showed that pregnant women with COVID19 have significantly increased serum midkine level compared to healthy pregnant women (1.801 ± 0.977 vs 0.815 ± 0.294 ng/dL). According to the data among each trimester, it was shown that there were significant increase in serum midkine level during all pregnancy trimesters (1st trimester Control Group: 0.714 ± 0.148, COVID-19 group 1.623 ± 0.824, p < 0.0001; 2nd trimester Control Group: 0.731 ± 0.261, COVID-19 group 2.059 ± 1.146, p < 0.0001; 3rd trimester Control Group: 1.0 ± 0.35, COVID-19 group 1.723 ± 0.907, p = 0.001). Serum midkine levels were significantly different between disease severity subgroups of pregnant women with COVID19; moderate and severe/critic groups had significantly higher serum midkine level than mild group. There was also significant correlation between serum midkine level and severity status (p:0.0001, r: 0.468). The most striking results of serum midkine levels were corelation between length of hospitalization (p: 0.01, r: 0.430) and O2 saturation (p < 0.0001, r: -0.521). ROC curve analysis showed that serum midkine level might be a tool for predicting COVID-19 in pregnant women with COVID-19 (AUC: 0.912, 95% CI: [0.871, 0.952], p < 0.0001) CONCLUSION: Our data showed that there is an obvious relation between COVID19 progression and serum midkine level for the first time which might be used for monitoring the disease process.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease.

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs). PURPOSE: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used. RESULTS: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin. CONCLUSION: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics.

BACKGROUND: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab. METHODS: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used. RESULTS: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions. CONCLUSION: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.

Potentially inappropriate prescribing according to the STOPP/START criteria for older adults.

BACKGROUND: The aim of this study was to demonstrate the prevalence and possible predictors of potentially inappropriate medications (PIMs) and potentially prescription omissions (PPOs) according to the Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) criteria in geriatric patients. METHODS: A total of 374 patients (140 male, 234 female) aged ≥65 years were included. Comprehensive demographic and clinical data including age, gender, current diagnoses/medications, comorbid diseases and medical problems were noted. RESULTS: There were 154 (41.2 %) patients with at least one PIM. Most common PIMs were proton pump inhibitors for peptic ulcer disease (9.6 %), calcium-channel blockers (6.4 %) and anticholinergic/antispasmodic drugs (5.9 %) in chronic constipation. There were 274 (73.3 %) patients with at least one PPO. Most common PPOs were calcium-vitamin D supplement in osteoporosis (OP) (39.6 %), statin (22.5 %) and antiplatelet therapies (16.0 %) in diabetes mellitus (DM) with cardiovascular risk factors. PIM was independently associated with female gender (OR = 2.21, p = 0.003), number of medications (OR = 1.35, p < 0.001), Katz scores of daily life activities (OR = 0.87, p = 0.013) and OP (OR = 0.29, p < 0.001). PPO was independently associated with age (OR = 1.06, p = 0.009), Geriatric Depression Scale score (OR = 1.20, p = 0.007), DM (OR = 6.50, p < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 5.29, p = 0.010), number of medications (OR = 0.88, p = 0.019), and incontinence (OR = 0.39, p = 0.043). CONCLUSION: High prevalence of PIMs and PPOs were found in geriatric patients. Number of medications, female gender, and dependency were associated with PIM. Age, higher scores of Geriatric Depression Scale, DM, and COPD were related with PPOs.

Adult-Onset Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome on the Basis of Selective IgA Deficiency.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) is an autoinflammatory disease that is thought to occur with the contribution of genetic and environmental factors, but its etiology has not been clearly elucidated. It is characterized by recurrent attacks with fever, pharyngitis, oral aphthous lesions, and cervical lymphadenopathy, and an increase in the level of serum acute phase reactants is observed during the attacks. Although PFAPA usually begins in childhood, adult-onset cases are also reported in the literature. In the pathogenesis of PFAPA, an increase in the expression of various inflammatory cytokines, especially interleukin-1ß (IL-1ß), is observed as a result of the increase in inflammasome activity. Selective IgA deficiency (SIgAD) is the most prevalent primary immunodeficiency. Although most SIgAD cases remain asymptomatic and remain undiagnosed, it is known that the risk of mucosal infection is generally increased in SIgAD cases. In addition, the frequency of autoinflammatory diseases is increased in SIgAD cases compared with the general population. We aim to present a case of adult-onset PFAPA and SIgAD coexistence.

Vaccination against respiratory tract pathogens in primary immune deficiency patients receiving immunoglobulin replacement therapy.

Introduction: Inborn errors of immunity (IEI) increase morbidity and mortality risks, particularly from respiratory tract infections. Hence, vaccination becomes pivotal for IEI patients. This study aims to examine the vaccination and respiratory tract infection rates in a diverse IEI patient cohort undergoing immunoglobulin replacement therapy (IGRT). Materials and Methods: We retrospectively evaluated IEI patients on IGRT at a tertiary care center. Data on vaccinations and respiratory infections were extracted from medical records. Result: : The study included 33 patients (mean age= 37.7 ± 11.4 years; 17 male). The most common clinical phenotype in our cohort was primary antibody deficiencies (90.9%). Only two patients had a genetic diagnosis, both of whom were brothers diagnosed with Wiskott-Aldrich syndrome (WAS). Almost half (48.5%) of our patients had bronchiectasis and 81.8% were on prophylactic antibiotics. All patients with IEI included in the study were regularly receiving IGRT. The vaccination rate of patients against respiratory tract infections was 42.4%, 57.6%, and 78.8% for influenza, pneumococcus, and COVID-19, respectively. Only one patient (7.1%) who received the influenza vaccine developed an upper respiratory tract infection. However, viral panel analysis could not be performed for this patient as they did not present to the hospital. The COVID-19 vaccination rate was notably higher than that of other vaccines, likely due to increased awareness during the pandemic, aided by public advisories and media influence. Conclusions: We observed higher vaccination rates for the COVID-19 vaccine compared to other vaccines (influenza and pneumococcal vaccines). Although we observed the potential impact of social and governmental influence in increasing vaccination rates, it is crucial to acknowledge that vaccination decisions in IEI patients must be individualized.

Evaluation of the safety and efficacy of AdvaxTM as an adjuvant: A systematic review and meta-analysis.

PURPOSE: Developing a vaccine with improved immunogenicity is still a growing priority for many diseases. Different types of adjuvants may be beneficial to initiate and maintain the long-lasting immunogenicity of vaccines. Evidence has shown that polysaccharide adjuvants are efficient in improving immunological mechanisms with their biocompatibility and biodegradability characteristics. In this study, we aimed to investigate the safety and efficacy of AdvaxTM an adjuvant derived from delta inulin. METHODS: A systematic research was performed in Pubmed, Web of Science, and Scopus databases for the following keywords; "AdvaxTM" OR "delta inulin" until December 14th, 2020. RevMan 5.4.1 software was used for cumulative meta-analysis and bias analysis. We also used GraphPad Prism 6 software for the figures. RESULTS: In the cumulative meta-analysis, it was found that seroconversion and geometric mean titers (GMT) levels significantly increased in AdvaxTM-adjuvanted group (mean difference: 12.31, 95% Cl [4.14, 20.47], p â€‹= â€‹0.003; 17.10, 95% Cl [4.35, 29.85], p â€‹= â€‹0.009, respectively). We also observed that AdvaxTM could be effective in improving immunogenicity by inducing T-cell responses and plasmablast generation in viral vaccines. CONCLUSIONS: In this study, it was shown that AdvaxTM is a safe and well-tolerated adjuvant. AdvaxTM could be a potent adjuvant in increasing the protection and immunogenicity of different vaccines without safety issues. However, further studies are needed to verify these effects of AdvaxTM adjuvant.

The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis.

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem. Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis. Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results. Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues. Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Investigating the role of IL-33 in the pathogenesis of Behçet's Disease.

OBJECTIVES: Behçet's disease (BD) is an inflammatory disease, characterized by oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations. Increased release of several cytokines may play a role in the inflammatory stages of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role in inflammation. We analyzed serum IL-33 concentration in BD patients to assess its possible role in the pathophysiology of this disease. METHODS: The study included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18 matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 ± 2.81 pg/ml in the BD patients (6.16 ± 2.94 pg/ml in the active stage and 2.86 ± 0.54 pg/ml in the inactive stage) and 2.88 ± 0.42 pg/ml in the healthy controls. Serum IL-33 levels were significantly higher in patients with BD compared with the healthy controls (p < 0.01). In active Behçet patients with arthritis the mean serum IL-33 level was higher but this finding was not statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant role of in the pathogenesis of BD.