Autoimmune/inflammatory syndrome induced by adjuvants (ASIA): past, present, and future implications.

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.

Epidemiological trends and clinical features of the ongoing monkeypox epidemic: A preliminary pooled data analysis and literature review.

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.

COVID-19 and SLE: Infection and autoimmunity at its best.

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.

Vaccines and Autoimmunity-From Side Effects to ASIA Syndrome.

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.

Ferritin - from iron, through inflammation and autoimmunity, to COVID-19.

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.

Bradycardia in a Patient with Severe COVID-19.

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.

Conceptual Paper: Abdominoplasty and Liposuction in Systemic Sclerosis.

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.

Leveraging Google Trends, Twitter, and Wikipedia to Investigate the Impact of a Celebrity's Death From Rheumatoid Arthritis.

BACKGROUND: Technological advancements, such as patient-centered smartphone applications, have enabled to support self-management of the disease. Further, the accessibility to health information through the Internet has grown tremendously. This article aimed to investigate how big data can be useful to assess the impact of a celebrity's rheumatic disease on the public opinion. METHODS: Variable tools and statistical/computational approaches have been used, including massive data mining of Google Trends, Wikipedia, Twitter, and big data analytics. These tools were mined using an in-house script, which facilitated the process of data collection, parsing, handling, processing, and normalization. RESULTS: From Google Trends, the temporal correlation between "Anna Marchesini" and rheumatoid arthritis (RA) queries resulted 0.66 before Anna Marchesini's death and 0.90 after Anna Marchesini's death. The geospatial correlation between "Anna Marchesini" and RA queries resulted 0.45 before Anna Marchesini's death and 0.52 after Anna Marchesini's death. From Wikitrends, after Anna Marchesini's death, the number of accesses to Wikipedia page for RA has increased 5770%. From Twitter, 1979 tweets have been retrieved. Numbers of likes, retweets, and hashtags have increased throughout time. CONCLUSIONS: Novel data streams and big data analytics are effective to assess the impact of a disease in a famous person on the laypeople.

On status epilepticus and pins: A systematic content analysis.

Status epilepticus (SE) can be defined as abnormally prolonged, persistent, or recurrent clinical and/or electrographic epileptic activity and, as such, is a challenging medical emergency requiring an aggressive treatment aimed at promptly terminating the seizures. It imposes a relevant clinical burden, both in terms of comorbidity and mortality. In the era of the Web 2.0, most people search the Web to obtain SE-related information. The current investigation aimed at qualitatively characterizing the pins related to SE: Pinterest, "the world's catalog of ideas", is a visual social networking site that enables users to freely upload visual material, to bookmark, and to share it (repin). Using SE as a keyword, 192 pins were extracted and analyzed on the basis of their content. Fifty-five were found to meet the inclusion criteria. Fifty-six point four percent of the pins reported at least one cause of SE, the most quoted of which being remote brain injuries (47.3% of the pins); 54.5% and 45.5% of the included pins reported SE symptoms and diagnosis, respectively; 72.7% and 40.0% of pins focused on SE treatment and on prognosis, respectively; and 50.9%, 30.9%, and 40.0% of the pins were intended for physicians, medical/nursing students, and lay people, respectively. Only 12.7% of pins were patient-centered and devoted to fund-raising and advocacy. In the field of neurological diseases, Pinterest, despite being a "pinstructive" tool, is too much overlooked and underused for advocacy purposes. Healthcare workers and stakeholders should be aware of the opportunities offered by Pinterest and exploit this visual social networking site for raising awareness of the life-threatening condition of SE, promoting fund-raising campaigns.

The Association Between Giant Cell Arteritis and Ischemic Heart Disease: A Population Based Cross-Sectional Study.

BACKGROUND: Patients with giant cell arteritis (GCA) suffer from inflammatory diseases often treated by large amounts of corticosteroids. Whether this inflammatory burden also carries an increased risk for cardiovascular morbidity, and especially ischemic heart disease, is not clearly established. OBJECTIVES: To clarify the linkage between GCA and ischemic heart disease. METHODS: In a cross-sectional study, we assessed the association between GCA and ischemic heart disease, adjusting for cardiovascular risk factors, among GCA patients and matched controls using the database of the largest healthcare provider in Israel. RESULTS: The study group was comprised of 5659 GCA patients and 28,261 age and gender matched controls. The proportion of ischemic heart disease was higher in the GCA group (27.5% vs. 12.5% among controls, odds ratio 2.65). Diabetes mellitus, hypertension, hyperlipidemia and smoking were also found to have higher concurrency in GCA. After stratifying for those cardiovascular co-morbidities using logistic regression, GCA remained independently associated with ischemic heart disease with an odds ratio of 1.247 (1.146-1.357 P < 0.001). CONCLUSIONS: GCA is associated with both cardiovascular risk factors and ischemic heart disease. Healthcare professionals should not overlook this aspect of the disease when managing GCA patients.

[Syphilis snarls].

Syphilis is an infectious disease. It is unique and interesting, and even to this day it continues to be a major challenge to the medical community in the prevention of the spread, the diagnosis and treatment of the disease. In recent years in Israel, 200 new cases have been revealed annually. During this period, several reports were published on the outbreaks of the disease. We believe that due to the increase in the rate of patients with the disease there is a strong need to educate the medical staff about the disease and to raise awareness regarding the symptoms of the disease, methods of diagnosis, increased risk populations, and methods of treatment. In this article we present four cases of syphilis that we encountered in our institution, which presented relatively in different ways. Furthermore, in these cases the diagnosis was not simple. So it is important to be aware that this disease still exists and must be recognized in order to know how to diagnose it.

Diagnosis and classification of adult Still's disease.

The cornerstone of adult onset Still's disease is the triad of daily fever, arthritis and rash. This syndrome remains enigmatic and most often a disease of exclusion. There are both musculoskeletal as well as systemic features. More importantly, reactive hemophagocytic syndrome may occur in patients. In this review we attempt to place this syndrome in perspective, including data on geoepidemiology, clinical and laboratory features.