Administration of BNT162b2 mRNA COVID-19 vaccine to subjects with various allergic backgrounds

BackgroundThe mRNA-based COVID-19 vaccine was introduced to the general public in December 2020. Shortly thereafter, safety concerns were raised due to the reporting of allergic reactions. Allergy-related disorders were suspected to be significant risk factors and the excipient polyethylene glycol was suggested to be a robust allergen.MethodsThis is a retrospective study analysis. Subjects with putative risk factors for severe allergic reactions to the Pfizer-BioNTech BNT162b2 vaccine were referred for vaccination under observation at the Unit of Allergy and Clinical Immunology. Data was collected for each subject, including demographic details, medical history and previous reactions to any allergen. When appropriate, skin tests were done prior to vaccination.ResultsA total of 346 subjects received 623 vaccine doses under observation. The study included patients with various allergy-related disorders (n=290) and those with allergy to a previous COVID-19 vaccine dose (n=56). Both groups showed female predominance (78% and 88%, p=NS). Patients without reactions to previous doses reported more drug allergy (80% vs. 39%, p<0.001) and previous anaphylaxis (64% vs. 14%, p<0.001). There was no difference in sensitivity to other allergens, including polyethylene glycol. Under observation, mild allergic reactions were noted in 13 individuals characterized by female gender (100%), a history of anaphylaxis (69%) and drug allergy (62%). In 7 subjects, allergy was treated with antihistamines while others recovered spontaneously.ConclusionOur study demonstrates that vaccination under specialist-supervision is a powerful tool for reducing over-diagnosis of systemic reactions and for rapid and reliable collection of vaccine safety data

The career experiences of women with children who are working alternative arrangements in the big accounting firms

In recent years it has become common for women in the four large public accounting firms (hence forward to be called, Big Firms) to use alternative working arrangements during the first few years after the birth of their children. Though these arrangements provide women with flexibility for managing their life, they have not led to advancement in the status of women in the Big Firms. The main purpose of this study is to develop and improve our understanding of the experience of mothers who work alternative arrangements in the Big Firms. Using qualitative interviews, four women CA’s in management positions reflect on their own experiences and career progress. The study incorporates these women’s experiences in order to understand why, despite of the alternative arrangements offered by the Big Firms, women with children rarely progress in the Big Firms. Through social constructionism and feminist perspectives, the study attempts to understand the inner-workings of these arrangements and their effect on the careers of women with children in the Big Firms. Several important findings emerge from this study. First, women’s ambition to progress at work tends to decrease after their return from maternity leave. Second, though working arrangements allow some flexibility for moms in balancing work-family life, it is rarely sufficient. Women need to use several individual strategies to help them manage their responsibilities. Third, the study raises critical questions about the expectation that women should be responsible for accommodating the Big Firm’s structural and cultural norms, which somewhat defeats the purpose of providing alternative work arrangements. Forth, by allowing women to work alternative arrangements the Big Firms give impression that it is accommodating the needs of working mothers, but in reality it is still women who do most of the accommodating. Further, coming from a higher social class and higher position helps women succeed in their workplace as higher household income allow more flexibility in managing every day responsibilities. Recommendations for mother CAs and accounting practice are evaluated and suggested.Education, Faculty ofEducational Studies (EDST), Department ofGraduat

Research Progress on Neuroprotection of Insulin-like Growth Factor-1 towards Glutamate-Induced Neurotoxicity

Insulin-like growth factor-1 (IGF-1) and its binding proteins and receptors are widely expressed in the central nervous system (CNS), proposing IGF-1-induced neurotrophic actions in normal growth, development, and maintenance. However, while there is convincing evidence that the IGF-1 system has specific endocrine roles in the CNS, the concept is emerging that IGF-I might be also important in disorders such as ischemic stroke, brain trauma, Alzheimer’s disease, epilepsy, etc., by inducing neuroprotective effects towards glutamate-mediated excitotoxic signaling pathways. Research in rodent models has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 was administered by different routes, and several clinical studies have shown safety and promise of efficacy in neurological disorders of the CNS. Focusing on the relationship between IGF-1-induced neuroprotection and glutamate-induced excitatory neurotoxicity, this review addresses the research progress in the field, intending to provide a rationale for using IGF-I clinically to confer neuroprotective therapy towards neurological diseases with glutamate excitotoxicity as a common pathological pathway

Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro

The CNS is thought to develop from self-renewing stem cells that generate neurons, astrocytes, and oligodendrocytes. Other data, however, have suggested that astrocytes and oligodendrocytes are generated from separate progenitor populations. To reconcile these observations, we have prospectively isolated progenitors that do or do not express Olig2, an oligodendrocyte bHLH determination factor. Both Olig2− and Olig2+ progenitors can behave as tripotential CNS stem cells (CNS-SCs) in vitro. Growth in FGF-2 causes induction of Olig2 in the former population, permitting oligodendrocyte differentiation; extinction of Olig2 in the latter cells permits astrocyte differentiation. The induction of Olig2 by FGF-2 is mediated, in part, via endogenous Sonic Hedgehog. These data indicate that clonogenic competence to generate neurons, astrocytes, and oligodendrocytes reflects a deregulation of dorsoventral patterning during expansion in vitro, raising the question of whether such trifatent cells actually exist in vivo

Autoimmune Diseases Induced or Exacerbated by COVID-19: A Single Center Experience

The association between infectious diseases and autoimmunity has long been reported. Specifically, during the coronavirus disease 2019 (COVID-19) pandemic, this relation was further emphasized. The interplay between the two disease processes remains interesting, yet incompletely defined. Herein, we report a case series of six patients presenting with autoimmune phenomena first developed or exacerbated following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe the disease course and discuss the possible mechanisms underlying the association between autoimmunity and COVID-19

Pharmacological therapies and drug development targeting SARS-CoV-2 infection

The development of therapies for SARS-CoV-2 infection, based on virus biology and pathology, and of large- and small-scale randomized controlled trials, have brought forward several antiviral and immunomodulatory drugs targeting the disease severity. Casirivimab/Imdevimab monoclonal antibodies and convalescent plasma to prevent virus entry, Remdesivir, Molnupiravir, and Paxlovid nucleotide analogs to prevent viral replication, a variety of repurposed JAK-STAT signaling pathway inhibitors, corticosteroids, and recombinant agonists/antagonists of cytokine and interferons have been found to provide clinical benefits in terms of mortality and hospitalization. However, current treatment options face multiple clinical needs, and therefore, in this review, we provide an update on the challenges of the existing therapeutics and highlight drug development strategies for COVID-19 therapy, based on ongoing clinical trials, meta-analyses, and clinical case reports

Dupilumab for cancer-associated refractory pruritus

Background: Pruritus can be an intolerable symptom in patients with cancer. Type 2 inflammation, and specifically, the cytokines IL-4, IL-13, and IL-31, play major roles in the itching process. Dupilumab is an antibody against IL-4Rα, which is a common IL-4 and IL-13 receptor subunit. Blocking IL-4 and IL-13 activity reduces the synthesis of IL-31, the “itch cytokine,” and receptors for these 3 cytokines are expressed on itch nerves. Dupilumab is approved for treating moderate-to-severe atopic dermatitis, of which itching is a significant symptom. Objective: The objective of this case study was to present the initial evidence of the safety and efficacy of dupilumab as a treatment for intractable malignancy-associated pruritus in 3 patients, thereby providing a basis for further investigation in a larger cohort. Methods: As a proof of concept, we used dupilumab in our center to treat 3 patients with intractable malignancy-associated pruritus. The first patient was a 73-year-old male with a history of prostate cancer, the second patient was a 75-year-old female with cutaneous T-cell lymphoma, and the third patient was a 32-year-old male with metastatic melanoma. All 3 patients experienced debilitating itching, which started at some stage after the malignancy had been diagnosed. Moreover, none of the 3 patients showed clinical evidence of atopic dermatitis or other causes of itching (eg, uremia or liver failure), and none of the 3 patients responded to conventional treatments for pruritus. Results: Biweekly treatment with dupilumab led to an immediate improvement in itching, which subsided entirely after a few doses without any significant adverse effects. Conclusion: We propose that dupilumab is a safe and effective treatment for intractable malignancy-associated pruritus, and we are currently testing it in a large cohort

Predictors of Hypoxemia and Related Adverse Outcomes in Patients Hospitalized with COVID-19: A Double-Center Retrospective Study

Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine predictors of hypoxemia and related adverse outcomes among patients hospitalized with COVID-19 in the two largest hospitals in Jerusalem, Israel, from 9 March through 16 July 2020. Patients were categorized as those who developed reduced (<94%) vs. preserved (≥94%) arterial oxygen saturation (SpO2) within the first 48 h after arrival to the emergency department. Overall, 492 hospitalized patients with COVID-19 were retrospectively analyzed. Patients with reduced SpO2 were significantly older, had more comorbidities, higher body surface area (BSA) and body mass index (BMI), lower lymphocyte counts, impaired renal function, and elevated liver enzymes, c-reactive protein (CRP), and D-dimer levels as compared to those with preserved SpO2. In the multivariable regression analysis, older age (odds ratio (OR) 1.02 per year, p < 0.001), higher BSA (OR 1.16 per 0.10 m2, p = 0.003) or BMI (OR 1.05 per 1 kg/m2, p = 0.011), lower lymphocyte counts (OR 1.72 per 1 × 103/μL decrease, p = 0.002), and elevated CRP (1.11 per 1 mg/dL increase, p < 0.001) were found to be independent predictors of low SpO2. Severe hypoxemia requiring ventilatory support, older age, and pre-existing comorbidities, including underlying renal dysfunction and heart failure, were found to be significantly associated with in-hospital mortality. These findings suggest that assessment of predictors of hypoxemia early at the time of hospitalization with COVID-19 may be helpful in risk stratification and management