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OBJECTIVE: Dupilumab (Dupixent ®) is a monoclonal antibody that inhibits IL- 4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection. MATERIALS AND METHODS: We carried out a comprehensive data mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. RESULTS: Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the agegroup of 45-64 years (with an IC0.25 of 0.17). CONCLUSIONS: Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab. [ABSTRACT FROM AUTHOR]

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Objectives: Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD)., Methods: A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression., Results: An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P  < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33-1.54; P  < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31-1.51; P  < 0.0001)., Conclusion: Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The value of preventive medicine is superior to treatment with vaccinations occupying high priority. Nevertheless, heavy pressure has started to form in regard to strains not included in vaccines contributing to the changing epidemiology of pathogen subtypes leading to 'vaccine-induced strain replacement'. Among other mechanisms, increasing fitness of nonvaccine strains and metabolic shifts in the subtypes have been described. Classical examples include pneumococcal infections and viral diseases, such as the human papilloma virus. Recently, it has been described in SARS-CoV-2, leading to the emergence of new subtypes, such as Omicron and Delta variants. The phenomenon has also been reported in Mycobacterium tuberculosis , Neisseria meningitidis and rotavirus. This study addresses the concepts, examples and implications of this phenomenon.

If one had any doubts before the pandemic regarding the correlation between infections and autoimmunity, COVID-19 left us fascinated on the strong bond between the two entities. The immune and autoimmune reactions seen in patients infected with SARS-CoV-2 have served as a base for this assumption. Later on, the use of immunosuppressants such as systemic glucocorticoids, among other biological agents, turned this assumption to a fact. This was no different when it comes to the vaccines against COVID-19. Through several postulated mechanisms these vaccines, although generally considered safe, are thought to have the potential to result in autoimmune reactions making them not more innocent than the infection itself. When systemic lupus erythematous (SLE) is viewed as a classical autoimmune multisystemic disorder, the connection with SARS-CoV-2 infection and COVID-19 vaccination is of extreme importance. This is because early reports during the pandemic have shown increased rates of SARS-CoV-2 infection among patients known previously to have SLE and much more interestingly, cases of new-onset SLE after COVID-19 have been documented in the literature. Subsequently vaccines against COVID-19, those mRNA-based and adenovirus-vector based, were reported to induce new SLE cases, trigger immune thrombocytopenia or lupus nephritis, two common presentations of SLE, or exacerbate flares. In our paper, we concluded various aspects of available and recent data regarding SLE and COVID-19 as both an infection and vaccination., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The field of medical research has been always full of innovation and huge leaps revolutionizing the scientific world. In the recent years, we have witnessed this firsthand by the evolution of Artificial Intelligence (AI), with ChatGPT being the most recent example. ChatGPT is a language chat bot which generates human-like texts based on data from the internet. If viewed from a medical point view, ChatGPT has shown capabilities of composing medical texts similar to those depicted by experienced authors, to solve clinical cases, to provide medical solutions, among other fascinating performances. Nevertheless, the value of the results, limitations, and clinical implications still need to be carefully evaluated. In our current paper on the role of ChatGPT in clinical medicine, particularly in the field of autoimmunity, we aimed to illustrate the implication of this technology alongside the latest utilization and limitations. In addition, we included an expert opinion on the cyber-related aspects of the bot potentially contributing to the risks attributed to its use, alongside proposed defense mechanisms. All of that, while taking into consideration the rapidity of the continuous improvement AI experiences on a daily basis., Competing Interests: Declaration of Competing Interest The authors decalre no conflict of interests., (Copyright © 2023. Published by Elsevier B.V.)

Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are extraordinary in their ability to activate autoimmunity as well as to induce diverse autoimmune diseases. Here we reviewed the current knowledge on their relation. Further, we suggested that molecular mimicry could be a possible common mechanism of autoimmunity induction in the susceptible individuals infected with SARS-CoV-2. Molecular mimicry between SARS-CoV-2 and human proteins, and EBV and human proteins, are present. Besides, relation of the pathogenicity associated with both coronavirus diseases and EBV supports the notion. As a proof-of-the-concept, we investigated 8mer sequences with shared 5mers of SARS-CoV-2, EBV, and human proteins, which were predicted as epitopes binding to the same human leukocyte antigen (HLA) supertype representatives. We identified significant number of human peptide sequences with predicted-affinities to the HLA-A*02:01 allele. Rest of the peptide sequences had predicted-affinities to the HLA-A*02:01, HLA-B*40:01, HLA-B*27:05, HLA-A*01:01, and HLA-B*39:01 alleles. Carriers of these serotypes can be under a higher risk of autoimmune response induction upon getting infected, through molecular mimicry-based mechanisms common to SARS-CoV-2 and EBV infections. We additionally reviewed established associations of the identified proteins with the EBV-related pathogenicity and with the autoimmune diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier. In other words, ASIA came to define, arrange, and unite the variety of symptoms, related to autoimmunity, caused not by the vaccine itself, rather by the adjuvant part of the vaccine such as aluminum, among others. Accordingly, the introduction of ASIA enabled better understanding, proper diagnosis, and early treatment of the disorder. Furthermore, ASIA was shown to be associated with almost all body systems and various rheumatic and autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis. In addition, the correlation between COVID-19 and ASIA was noticed during the pandemic. In this review, we summarized the reported effects of adjuvants and medical literature before and after ASIA was defined, the several ways ASIA can manifest and impact different systems of the body, and the incidences of ASIA during the COVID-19 pandemic. It is important to clarify, that vaccines are among, if not the, most effective means of fighting infectious diseases however, we believe that vaccines manufacturing is not above criticism, particularly when it comes to added substances possessing a risk of side effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Rheumatoid arthritis is a chronic inflammatory disease marked by systemic symptoms and joint degeneration. Interestingly, the development and progression of rheumatoid arthritis have been linked to the microbiome, notably the gut microbiome. Dysbiosis, an alteration in the gut microbiome, has been connected to the etiology and pathogenesis of rheumatoid arthritis. For instance, dysbiosis increases intestinal permeability and promotes the movement of bacteria and their products, which in turn triggers and aggravates systemic inflammation., Areas Covered: The correlation between the gut microbiome and RA. Triggers of RA including dysbiosis. The therapeutic potential of the gut microbiome in RA due to its critical function in influencing the immune response. The fecal microbiota transplantation (FMT), a therapeutic strategy that involves the transfer of healthy fecal microbiota from a donor to a recipient, has produced encouraging results in the treatment of several autoimmune illnesses, including rheumatoid arthritis., Expert Opinion: The role of the gut microbiome in RA is critical and serves as a basis for etiology and pathogenesis, as well as having therapeutic implications. In our opinion, FMT is an excellent example of this correlation. Still, more investigations and well-designed studies are needed in order to make firm conclusions and recommendations.

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

The positive role of celebrities in spreading important medical information and contributing to increasing public awareness regarding the diagnosis, treatment, and prevention of various medical conditions cannot be overemphasized. Interestingly and importantly at the same time, this impact is not related to the rarity of the disease, as very rare diseases are looked up by the public due to the fact that a celebrity suffers from this disorder. Therefore, if taken seriously and used to address the public in regard to critical medical conditions, such as screening for cancer or the importance of vaccines in fighting infections, celebrities could have a huge impact in this field. As previously shown in the medical literature, the recent announcement of the famous Canadian singer Celine Dion concerning her newly diagnosed stiff-person syndrome has influenced the public interest regarding the syndrome which manifested as an increased search volume related to the disorder as seen in Google Trends. In brief, in this short communication we aimed to address the phenomenon of celebrities' impact on public apprehension, revise the syndrome for the medical community, and emphasize taking advantage of such involvement of celebrities for improving the spread of highly important medical information for the public.

An emerging outbreak of monkeypox infection is quickly spreading worldwide, being currently reported in more than 30 countries, with slightly less than 1000 cases. In the present preliminary report, we collected and synthesized early data concerning epidemiological trends and clinical features of the ongoing outbreak and we compared them with those of previous outbreaks. Data were pooled from six clusters in Italy, Australia, the Czech Republic, Portugal, and the United Kingdom, totaling 124 cases (for 35 of which it was possible to retrieve detailed information). The ongoing epidemic differs from previous outbreaks in terms of age (54.29% of individuals in their thirties), sex/gender (most cases being males), risk factors, and transmission route, with sexual transmission being highly likely. Also, the clinical presentation is atypical and unusual, being characterized by anogenital lesions and rashes that relatively spare the face and extremities. The most prevalent sign/symptom reported was fever (in 54.29% of cases) followed by inguinal lymphadenopathy (45.71%) and exanthema (40.00%). Asthenia, fatigue, and headache were described in 22.86% and 25.71% of the subjects, respectively. Myalgia was present in 17.14% of the cases. Both genital and anal lesions (ulcers and vesicles) were reported in 31.43% of the cases. Finally, cervical lymphadenopathy was described in 11.43% of the sample, while the least commonly reported symptoms were diarrhea and axillary lymphadenopathy (5.71% of the case series for both symptoms). Some preliminary risk factors can be identified (being a young male, having sex with other men, engaging in risky behaviors and activities, including condomless sex, human immunodeficiency virus positivity (54.29% of the sample analyzed), and a story of previous sexually transmitted infections, including syphilis). On the other hand, being fully virally suppressed and undetectable may protect against a more severe infectious course. However, further research in the field is urgently needed., (© 2022 Wiley Periodicals LLC.)

Infectious diseases are known to act in both predictable and unpredictable ways, which leads to the notions of emerging and reemerging infectious diseases. Emerging diseases with their disastrous consequences might be surprising and unpredictable, but they could be foreseen. For instance, some emerging diseases and recently the coronavirus disease 2019 (COVID-19) were the reason for papers published by the World Health Organization (WHO) and other researchers addressing the likely pathogens causing future outbreaks, according to the reports of the WHO in 2016 and 2018. Although it might seem like a wisdom in retrospect, several studies had already indicated possible future outbreaks caused by coronaviruses. Announcements, which may be viewed as "warnings," appeared since the emergence of the first coronavirus-related outbreak caused by severe acute respiratory syndrome coronavirus (SARS-CoV) in the winter of 2002-2003 and a later outbreak caused by the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012-2013. Therefore, we were curious to review the medical literature prior to the COVID-19 pandemic with an aim to enumerate and evaluate studies addressing and warning against future outbreaks, and surprisingly pandemics, of members of coronaviruses. Interestingly, we found numerous studies that correctly predicted the current pandemic of COVID-19. While this part is highly interesting, how authorities reacted and prepared for warnings, if any, and how will they get prepared for the next warnings are our main messages. Taking these points into serious consideration will certainly aid in analyzing reports regarding possible future outbreaks as well as in developing various strategies for prevention and coping with such epidemics., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them. The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned. Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely "autoimmune autonomic dysfunction syndromes". Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Despite their proven efficacy and huge contribution to the health of humankind, vaccines continue to be a source of concern for some individuals around the world. Vaccinations against COVID-19 increased the number of distressed people and intensified their distrust, particularly as the pandemic was still emerging and the populations were encouraged to be vaccinated under various slogans like "back to normal life" and "stop coronavirus", goals which are still to be achieved. As fear of vaccination-related adverse events following immunization (AEFIs) is the main reason for vaccine hesitancy, we reviewed immune and autoimmune AEFIs in particular, though very rare, as the most worrisome aspect of the vaccines. Among others, autoimmune AEFIs of the most commonly administered COVID-19 vaccines include neurological ones such as Guillain-Barre syndrome, transverse myelitis, and Bell's palsy, as well as myocarditis. In addition, the newly introduced notion related to COVID-19 vaccines, "vaccine-induced immune thrombotic thrombocytopenia/vaccine-induced prothrombotic immune thrombotic thrombocytopenia" (VITT/VIPITT)", is of importance as well. Overviewing recent medical literature while focusing on the major immune and autoimmune AEFIs, demonstrating their rate of occurrence, presenting the cases reported, and their link to the specific type of COVID-19 vaccines represented the main aim of our work. In this narrative review, we illustrate the different vaccine types in current use, their associated immune and autoimmune AEFIs, with a focus on the 3 main COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx1). While the rate of AEFIs is extremely low, addressing the issue in this manner, in our opinion, is the best strategy for coping with vaccine hesitancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mahroum, Lavine, Ohayon, Seida, Alwani, Alrais, Zoubi and Bragazzi.)

HIV/AIDS still imposes a high epidemiological and societal burden. Together with antiretroviral therapy, pre-exposure prophylaxis (PrEP) represents a fundamental tool in the fight against HIV/AIDS. PrEP is considered effective and safe, even though it may affect organs like the kidney, bone, and liver, as shown by randomized clinical trials (RCTs). These side effects may be mediated by alterations of the gut microbiome. Whilst the impact of the human rectal and vaginal microbiome on HIV prevention has been highly investigated among women, less is known about its effect among men having sex with men (MSM), a vulnerable population at high risk for HIV and disproportionately affected by HIV/AIDS. In the present paper, we will overview the effects of PrEP on the gut microbiota in MSM. Mining PubMed/MEDLINE, we identified three studies that have found significant changes affecting the gut microbiota. However, these shifts in the gut microbiome composition are variable, probably due to methodological differences, even though all studies reviewed in the present overview consistently report aberrations at the level of the gut microbiota. More data are needed, especially concerning the long-term side effects of PrEP: despite the studies included being a high-quality RCT, and two well-designed cross-sectional studies, evidence related to the impact of HIV PrEP on the gut microbiome in MSM is scarce and based on small populations. A better understanding of the interactions between the gut microbiota, sexual orientation/identity, and HIV prevention is expected to improve PrEP adherence and devise strategies to counteract PrEP-related side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bragazzi, Khamisy-Farah, Tsigalou and Mahroum.)

Autoimmunity is a process by which the loss of self-tolerance results in an immune attack against the body own tissues and organs. For autoimmunity to occur, various elements serving as triggers were described by which infections are considered one of the leading factors. In turn, renal involvement in autoimmune diseases, whether by an organ-specific attack, or as part of a systemic disease process, is well known. As bacterial and viral infections are considered to be common triggers for autoimmunity in general, we aimed to study their association with renal autoimmunity in particular. We performed an extensive search of the recent and relevant medical literature regarding renal autoimmunity syndromes such as infection-associated glomerulonephritis and vasculitis, associated with bacterial and viral infections. By utilizing PubMed and Google Scholar search engines, over 200 articles and case reports were reviewed. Among other mechanisms, direct infection of the renal parenchyma, molecular mimicry, induction of B-cells or secretion of superantigens, bacterial and viral pathogens were found to correlate with the development of renal autoimmunity. Nevertheless, this was not true for all pathogens, as some mimic autoimmune diseases and others show a surprisingly protective effect. The exact immunopathogenesis is yet to be determined, however. For conclusion, bacterial and viral infections are linked to renal autoimmunity by both direct damage and as mediators of systemic diseases. Further research particularly on the immunopathogenetic mechanisms of renal autoimmunity associated with infections is required., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To date, around 60% of the world population has been protected by vaccines against SARS-CoV-2, significantly reducing the devastating effect of the pandemic and restoring social economic activity through mass vaccination. Multiple studies have demonstrated the effectiveness and safety of vaccines against COVID-19 in healthy populations, in people with risk factors, in people with or without SARS-CoV-2 infection, and in immunocompromised people. According to the criteria for post-vaccine adverse events established by the World Health Organization, a minority of individuals may develop adverse events, including autoimmune syndromes. The exact mechanisms for the development of these autoimmune syndromes are under study, and to date, a cause-effect relationship has not been established. Many of these autoimmune syndromes meet sufficient criteria for the diagnosis of Adjuvant-Induced Autoimmune Syndrome (ASIA syndrome). The descriptions of these autoimmune syndromes open new perspectives to the knowledge of the complex relationship between the host, its immune system, with the new vaccines and the development of new-onset autoimmune syndromes. Fortunately, most of these autoimmune syndromes are easily controlled with steroids and other immunomodulatory medications and are short-lived. Rheumatologists must be alert to the development of these autoimmune syndromes, and investigate the relationship between autoimmune/inflammatory symptoms and vaccination time, and assess their therapeutic response., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Heart rate disorders and in particular sinus arrhythmias are known to accompany viral infections. Sinus tachycardia is prevalent in the presence of increased body temperature and respiratory rate. However, bradycardia has also been described for centuries to complicate viral illnesses.

While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Notwithstanding the fact that the 12th international congress of autoimmunity (AUTO12) was held virtual this year, the number of the abstracts submitted and those presented crossed the thousand marks. Leading investigators and researchers from all over the world presented the latest developments of their research in the domain of autoimmunity and its correlation with various diseases. In terms of mechanisms of autoimmunity, an update on the mechanisms behind the association of autoimmunity with systemic diseases focusing on hyperstimulation was presented during AUTO12. In addition, a new mechanism of ASIA syndrome caused by an intrauterine contraceptive device was revealed demonstrating a complete resolution of symptoms following device removal. In regard to the correlation between autoimmunity and neurogenerative diseases, the loss of structural protein integrity as the trigger of immunological response was shown. Schizophrenia as well, and its correlation to pro-inflammatory cytokines was also addressed. Furthermore, and as it was said AUTO12 virtual due to COVID-19 pandemic, various works were dedicated to SARS-CoV-2 infection and COVID-19 in terms of autoimmune mechanisms involved in the pathogenesis, treatment and complications of COVID-19. For instance, the correlation between autoimmunity and the severity of COVID-19 was viewed. Moreover, the presence and association of autoantibodies in COVID-19 was also demonstrated, as well as the clinical outcomes of COVID-19 in patients with rheumatic diseases. Finally, immune-mediated reactions and processes secondary to SARS-CoV-2 vaccination was displayed. Due to the immense importance of all of the topics addressed and while several hundreds of works were presented which cannot be summed up in one paper, we aimed hereby to highlight some of the outstanding abstracts and presentations during AUTO12., (Copyright © 2021. Published by Elsevier B.V.)

Background: Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called "cytokine storm" related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic., Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed., Results: Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates ( n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55-1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53-9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38-37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38-0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06-0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36-0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34-1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001-5.54], p = 0.050; based on unadjusted estimates)., Conclusion: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.

Background: Surgical interventions in patients with systemic sclerosis (SSc), in particular plastic procedures, might cause undesired consequences. Notably, liposuction seems to possess greater risk as adipose tissue has been shown to play an important role in treating wounds and ulcers in patients with SSc. While anticentromere antibodies were found to be correlated with vasculopathy in SSc, patients with SSc and anticentromere antibodies might be more vulnerable to surgical wound complications following liposuction. A 46-year-old female patient, who had been diagnosed with SSc at the age of 31 years, had antinuclear as well as anticentromere antibodies. She underwent abdominoplasty with liposuction and developed severe skin necrosis of the abdomen following the procedure and at the site of liposuction. The correlation with anticentromere and the role of liposuction in skin necrosis in SSc are presented.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Tuberculosis is a very serious respiratory infectious disease, caused by the bacillus Mycobacterium tuberculosis, which generates a relevant societal and clinical burden. It has always represented a permanent concern and a public health challenge over the course of human history, because of its severe epidemiological, and economic-financial implications. The present review aims at over-viewing the impact of tuberculosis on the Israeli healthcare system, its temporal trend and evolution, stratified according to ethnicities and minorities, the need of establishing new facilities and implementing screening techniques, public health strategies and diagnostic tests, following massive immigration waves from countries characterized by a high incidence rate of tuberculosis during the fifties-sixties until the nineties, and the policies implemented by the Israeli government in the control, management and treatment of tuberculosis, as well as the role played by Israeli prominent scientists in discovering new druggable targets and finding bioactive compounds and bio-molecules in the fight against tuberculosis. Israel represents a unique, living laboratory in which features of developed and developing countries mix together. This country as a case-study of immigrant, pluralistic society underlines the importance of adopting a culturally-sensitive community intervention approach. The understanding of the subtle interplay between race/ethnic host and pathogen factors, including the role of gene variations and polymorphisms can pave the way for a personalized treatment and management of tuberculosis patients, contributing to the development of new tools for targeted tuberculosis therapeutics, immunodiagnostics and vaccination products., (©2020 Pacini Editore SRL, Pisa, Italy.)

Human immunodeficiency virus vaccination and pre-exposure prophylaxis represent two different emerging preventive tools. Google Trends was used to assess the public interest toward these tools in terms of digital activities. Worldwide web searches concerning the human immunodeficiency virus vaccine represented 0.34 percent, 0.03 percent, and 46.97 percent of human immunodeficiency virus, acquired immune deficiency syndrome, and human immunodeficiency virus/acquired immune deficiency syndrome treatment-related Google Trends queries, respectively. Concerning temporal trends, digital activities were shown to increase from 0 percent as of 1 January 2004 percent to 46 percent as of 8 October 2017 with two spikes observed in May and July 2012, coinciding with the US Food and Drug Administration approval. Bursts in search number and volume were recorded as human immunodeficiency virus vaccine trials emerged. This search topic has decreased in the past decade in parallel to the increase in Truvada-related topics. Concentrated searches were noticed among African countries with high human immunodeficiency virus/acquired immune deficiency syndrome prevalence. Stakeholders should take advantage of public interest especially in preventive medicine in high disease burden countries.

Purpose of the Study: Takayasu arteritis (TA) is an idiopathic large vessel vasculitis, which involves the aorta and its major branches. Our aim was to examine the association between TA and the development of ischemic heart disease (IHD) and its impact on survival., Study Design: Using data from Clalit Health Services (CHS), the largest Health Maintenance Organization (HMO) in Israel, the proportion of IHD was compared between patients diagnosed with TA and age- and gender-matched controls. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was employed for multivariate analysis. Survival analysis was performed using Kaplan-Meier plots and cox regression., Results: The study included 155 TA patients and 755 age- and gender-frequency matched controls. The proportion of IHD in TA patients was increased in comparison with controls (32.3% and 8.9%, p<0.001). In multivariate analysis, IHD was associated with TA (OR=6.576, 95% CI: 4.09-10.64) and male gender (OR=2.29, 95% CI: 1.43-4.26). Survival analysis over 15 years of follow-up showed a higher proportion of all-causes mortality in the TA group. In a multivariate analysis, TA (HR=2.58, 95%CI: 1.64-4.06) and IHD (HR=1.64, 95%CI: 1.05-2.55) were found to be associated with reduced survival., Conclusions: TA patients present an increased proportion of IHD, and a reduced 15-years survival rate compared to controls., (© 2019 The Mediterranean Journal of Rheumatology (MJR).)