EFFICACY AND SAFETY OF DAZODALIBEP (VIB4920/HZN4920) IN SUBJECTS WITH SJÖGREN'S SYNDROME: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

BackgroundSjögren's syndrome (SS) is a chronic, systemic autoimmune disease affecting exocrine glands, primarily the salivary and tear glands, with potentially severe manifestations in multiple organs. No approved disease-modifying therapies exist. Dazodalibep (DAZ) is a biologic antagonist of CD40L.ObjectivesThe objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity (NCT04129164).MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Eligible subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses. Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks. The primary endpoint was the change from Baseline in ESSDAI at Day 169. Safety assessments included the incidence of adverse (AEs), serious AEs (SAEs), and AEs of special interest (AESIs).ResultsThe 74 randomized subjects all received ≥1 dose of study medication (DAZ, N=36;PBO, N=38). The baseline demographics and disease characteristics were balanced between the two groups. The change from Baseline to Day 169 in ESSDAI score (LS mean ± SE), was -6.3 ± 0.6 in DAZ-treated subjects compared to -4.1 ± 0.6 in the PBO group, a difference of -2.2 (p = 0.0167). Compared to the PBO group, the DAZ group showed positive trends in the EULAR Sjögren's Syndrome Patient Reported Index score, and Functional Assessment of Chronic Illness Therapy-Fatigue score at Day 169. A post-hoc responder analysis of subjects achieving high levels (5 and 6 points) of improvement on ESSDAI favored DAZ (61.1% and 60.0%) over PBO (35.1% and 34.3%).The reported AEs were generally mild through Day 169 and similar in frequency between treatment groups. The most frequently reported AEs occurring in ≥5% of DAZ-treated subjects and >PBO were COVID-19, diarrhea, dizziness, ligament sprain, upper respiratory tract infection, contusion, device allergy, fatigue, hypertension, and oropharyngeal pain. Two SAEs were reported in a single DAZ-treated subject: this subject was a 59-year-old female who experienced a grade 3 SAE of COVID-19 infection and later died of unknown cause 46 days after last administration of DAZ (12 days after COVID-19 diagnosis). There was a single AESI of herpes zoster in a DAZ-treated subject.ConclusionDAZ is a potential new therapy for the treatment of systemic disease activity in patients with SS. SS subjects with moderate-to-high systemic disease receiving DAZ experienced a statistically significant reduction in disease activity relative to PBO as measured by the improvement in ESSDAI score. Except for a case of severe COVID-19 infection, DAZ therapy in SS subjects appeared to be well tolerated. Larger controlled trials of DAZ therapy for SS are warranted to further explore its safety profile and confirm its clinical efficacy.Table 1.Efficacy and Safety DataPBO N=38DAZ 1500 mg N=36EfficacyΔESSDAI, LS mean (SE) †-4.1 (0.6)-6.3 (0.6)*ΔESSPRI, LS mean (SE) †-1.12 (0.29)-1.80 (0.31)ΔFACIT-Fatigue, LS mean (SE) †5.8 (1.6)8.1 (1.6)AE Summary, n (%)≥1 AE23 (60.5)28 (77.8)≥1 related AE8 (21)10 (27.8)≥1 SAE01 (2.8)≥1 related SAE00≥1 AE leading to discontinuation00≥1 AESI01 (2.8)≥1 Death01 (2.8)Efficacy endpoints as of Day 169;† Analyzed using MMRM;Comparisons vs PBO;*p<0.05;AE summaries based on AEs that occurred through Day 169;AE, adverse event;AESI, adverse event of special interest;ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index;ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index;FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue;PBO, placebo;SAE, serious adverse eventFigure 1.AcknowledgementsFunded by Horizon herapeutics. Medical writing support provided by B Lujan, PhD, an employee of Horizon Therapeutics.Disclosure of InterestsE. William St. Clair Consultant of: Horizon Therapeutics, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics. Royalties: UpToDate, Liangwei Wang Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ilias Alevizos Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, William Rees Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Alan Baer Consultant of: Bristol Myers Squibb, Wan Fai Ng Consultant of: Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen and UCB, Ghaith Noaiseh Consultant of: Novartis, Chiara Baldini Consultant of: GSK, and Sanofi.

Feature tracking cardiac magnetic resonance imaging to assess cardiac manifestations of systemic diseases.

Feature-tracking cardiac magnetic resonance (FT-CMR), with the ability to quantify myocardial deformation, has a unique role in the evaluation of subclinical myocardial abnormalities. This review aimed to evaluate the clinical use of cardiac FT-CMR-based myocardial strain in patients with various systemic diseases with cardiac involvement, such as hypertension, diabetes, cancer-therapy-related toxicities, amyloidosis, systemic scleroderma, myopathies, rheumatoid arthritis, thalassemia major, and coronavirus disease 2019 (COVID-19). We concluded that FT-CMR-derived strain can improve the accuracy of risk stratification and predict cardiac outcomes in patients with systemic diseases prior to symptomatic cardiac dysfunction. Furthermore, FT-CMR is particularly useful for patients with diseases or conditions which are associated with subtle myocardial dysfunction that may not be accurately detected with traditional methods. Compared to patients with cardiovascular diseases, patients with systemic diseases are less likely to undergo regular cardiovascular imaging to detect cardiac defects, whereas cardiac involvement in these patients can lead to major adverse outcomes; hence, the importance of cardiac imaging modalities might be underestimated in this group of patients. In this review, we gathered currently available data on the newly introduced role of FT-CMR in the diagnosis and prognosis of various systemic conditions. Further research is needed to define reference values and establish the role of this sensitive imaging modality, as a robust marker in predicting outcomes across a wide spectrum of patients.

The Relationship Between Ferroptosis and Diseases.

Ferroptosis is an iron-dependent mode of cell death. It can occur through two major pathways, exogenous (or transporter-dependent) and endogenous (or enzyme-regulated) pathways are activated by biological or chemical inducers, and glutathione peroxidase activity is inhibited, which causes intracellular iron accumulation and lipid Peroxidation. Ferroptosis is closely related to the pathological process of many diseases. How to intervene in the occurrence and development of related diseases by regulating ferroptosis has become a hot research topic. At present, studies have shown that ferroptosis is found in common diseases such as tumors, inflammatory diseases, bacterial infections, pulmonary fibrosis, hepatitis, inflammatory bowel disease, neurodegenerative diseases, kidney injury, ischemia-reperfusion injury and skeletal muscle injury. This article reviews the characteristics and mechanism of ferroptosis, and summarizes how ferroptosis participates in the pathophysiological process in various systemic diseases of the body, which may provide new references for the treatment of clinical diseases in the future.

A case of fatal acute necrotising encephalopathy associated with probable SARS-CoV-2

Introduction. Clinical studies during the epidemic of a new coronavirus infection caused by the SARS-CoV-2 virus confirm not only neurotropic damage to the central nervous system, but also complex immune-mediated neurological complications of COVID 19, one of which is acute necrotizing encephalopathy. Purpose of the study. Presentation of a clinical case of acute fatal necrotizing encephalopathy resulting from a severe respiratory infection probably caused by the SARS-CoV-2 virus. Research methods. Retrospective analysis of the medical history, interpretation of clinical and laboratory data, neuroimaging studies and autopsy results in a 22-year-old patient with a fatal neurological complication of a respiratory infection that occurs with bilateral polysegmental interstitial pneumonia. Conclusions. Characteristic ground-glass lung changes suggested a new coronavirus infection caused by the SARS-CoV-2 virus, despite a negative PCR result for virus RNA in a nasopharyngeal and cerebrospinal fluid swab. The rapid increase in focal and cerebral neurological symptoms, diffuse changes and edema of the brain substance according to CT scan and subsequently according to the results of autopsy, signs of systemic inflammation and changes in the coagulating blood system confirmed the changes characteristic of the "cytokine storm" and DIC syndrome developing against the background of systemic endothelitis in COVID 19.

[Acceptance of video consultation among patients with inflammatory rheumatic diseases depends on gender and location-Results of an online survey among patients and physicians]. / Akzeptanz der Videosprechstunde unter Patienten/innen mit entzündlich rheumatischen Erkrankungen ist geschlechts- und ortsabhängig ­ Ergebnisse einer Online-Umfrage unter Patienten/innen und Ärzten/innen.

INTRODUCTION: In order to successfully integrate telemedicine into the daily routine of rheumatology, both the patient's and the physician's perspective are important. For this purpose, a detailed study by means of a web-based survey was conducted by the Working Group Young Rheumatology (AGJR) of the German Society for Rheumatology (DGRh) and the German Rheumatism League National Association. By means of subgroup analysis of the data regarding video consultation, the aim was now to find out which requirements and wishes patients and physicians have for video consultations. METHODS: The prospective survey was distributed via social media, QR code and email. Descriptive statistics and regression analysis related to video consultation were performed and correlations were shown. RESULTS: The data indicated positive attitudes toward video consultation on the part of both patients (n = 299) and rheumatologists (n = 129). A correlation between age and positive opinion of the video consultation was found among the patients (r = 0.161, p = 0.006), especially among female patients a positive approval of the video consultation was found with increasing age (r = 0.244, p < 0.001 to male patients: r = -0.190, p = 0.145). Regarding the travelling time to the treating rheumatologist, male patients found the video consultation more attractive with increasing travelling time (r = 0.229, p = 0.078). With respect to the wishes of patients and physicians, video consultation should be used primarily for follow-up or emergency appointments. Video consultation for initial appointments, on the other hand, was very rarely mentioned. CONCLUSION: During the COVID 19 pandemic, video consultation was increasingly popular among rheumatology patients as well as among rheumatologists.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

Objective: The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. Materials and methods: For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. Results: The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1ß, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p < 0.05). Loss of taste was observed in patients with elevated serum IL-8 (p < 0.05). Conclusions: Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part III: Implementations for the Diagnosis of Non-Cancerous Disorders, Both Oral and Systemic.

This communication represents Part III of our series of reports based on the applications of human saliva as a useful and conveniently collectable medium for the discovery, identification and monitoring of biomarkers, which are of some merit for the diagnosis of human diseases. Such biomarkers, or others reflecting the dysfunction of specific disease-associated metabolic pathways, may also be employed for the prognostic pathological tracking of these diseases. Part I of this series set the experimental and logistical groundwork for this report, and the preceding paper, Part II, featured the applications of newly developed metabolomics technologies to the diagnosis and severity grading of human cancer conditions, both oral and systemic. Clearly, there are many benefits, both scientific and economic, associated with the donation of human saliva samples (usually as whole mouth saliva) from humans consenting to and participating in investigations focused on the discovery of biomolecular markers of diseases. These include usually non-invasive collection protocols, relatively low cost when compared against blood sample collection, and no requirement for clinical supervision during collection episodes. This paper is centred on the employment and value of 'state-of-the-art' metabolomics technologies to the diagnosis and prognosis of a wide range of non-cancerous human diseases. Firstly, these include common oral diseases such as periodontal diseases (from type 1 (gingivitis) to type 4 (advanced periodontitis)), and dental caries. Secondly, a wide range of extra-oral (systemic) conditions are covered, most notably diabetes types 1 and 2, cardiovascular and neurological diseases, and Sjögren's syndrome, along with a series of viral infections, e.g., pharyngitis, influenza, HIV and COVID-19. Since the authors' major research interests lie in the area of the principles and applications of NMR-linked metabolomics techniques, many, but not all, of the studies reviewed were conducted using these technologies, with special attention being given to recommended protocols for their operation and management, for example, satisfactory experimental model designs; sample collection and laboratory processing techniques; the selection of sample-specific NMR pulse sequences for saliva analysis; and strategies available for the confirmation of resonance assignments for both endogenous and exogenous molecules in this biofluid. This article also features an original case study, which is focussed on the use of NMR-based salivary metabolomics techniques to provide some key biomarkers for the diagnosis of pharyngitis, and an example of how to 'police' such studies and to recognise participants who perceive that they actually have this disorder but do not from their metabolic profiles and multivariate analysis pattern-based clusterings. The biochemical and clinical significance of these multidimensional metabolomics investigations are discussed in detail.

COVID-19 vaccine immunogenicity in 16 patients with autoimmune systemic diseases. Lack of both humoral and cellular response to booster dose and ongoing disease modifying therapies.

Background: Patients with autoimmune systemic diseases (ASDs) represent a frail population during the ongoing COVID-19 pandemic. The vaccination is the major preventive measure; however, a significant number of ASD patients show an impaired production of anti-COVID-19 neutralizing antibodies (NAb), possibly counterbalanced by adequate T-cell response. The present study aimed at evaluating both humoral and cellular response to COVID-19 vaccine booster dose in this particular setting. Patients and methods: Serum NAb titer and T-cell response (measuring interferon gamma -IFN-γ- release) were evaluated 3 weeks after the COVID-19 vaccine booster dose, in 17 patients (12 F, mean age 68.8 ± 15.3 SD yrs) with different ASDs, compared to 17 healthy controls (HCs). Results: The analysis excluded one patient reporting symptoms of COVID-19 only after the immunogenicity tests had been performed.The NAb levels were significantly lower in ASD compared to HCs (p < 0.0001); moreover, patients showed a higher percentage of negative/sub-optimal humoral response (31% vs 0% of HCs; p = 0.0184).The study of cellular response showed lower levels of IFN-γ for both Ag1 (p = 0.0032) and Ag2 (p = 0.0136) in ASD patients compared to HCs, as well lower rate of adequate T-cell response compared to HCs (50% vs 94%; p = 0.0066).Disease modifying therapies (DMT) were administered in all patients with deficient NAb production (5/5, 100%), but in only 3/11 (27%) of responders (p = 0.025).Worthy to note, 3/16 (19%) ASD patients developed neither humoral nor cellular responses, all treated with DMT. Conclusions: The impaired immunogenicity to COVID-19 vaccine booster and even more the concomitant lack of both humoral and cellular response might represent a high risk for severe COVID-19, particularly in ASD patients undergoing DMT.These frail subjects should be tightly monitored for their immune protection and prioritized for the fourth dose of COVID-19 vaccine. Moreover, in the occurrence of SARS-CoV2 infection, treatments with specific monoclonal antibodies and/or antivirals may be highly recommendable.

Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases.

Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p < 0.0001) were constantly lower compared to controls (p < 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p < 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p < 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p < 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable.

Chronic Obstructive Pulmonary Disease and Apical Periodontitis and Other Oral Health Variables: A Case-Control Study

Background: The relationship between chronic inflammatory diseases and their comorbidities and correlation with periodontal diseases has become an increasing focus of research. Objectives: The aim of this case-control study was to conclude if patients suffering from COPD (Chronic Obstructive Pulmonary Disease) tend to have more AP (Apical Periodontitis) than non-COPD patients. Materials and Methods: The study was conducted on 30 patients assigned as cases, associated with 30 control patients linked by age (+/−5 years) and sex. Results: A total of 60 patients were recorded, and a total of 12 radiographic variables were analyzed. A total of 43 (71.7%) patients were registered with PAI (Periapical Index) ≥ 3, and there was a slightly tendency in the patients from the control group 22 (73.3%) compared to those from the cases 21 (70%), respectively (p > 0.05). Conclusions: It was concluded that there was not a significant association between the levels of PAI (Periapical Index) ≥ 3 per patient in those suffering from COPD. In fact, it could be concluded that patients diagnosed with COPD tend to have more teeth with PAI ≥ 3, more endodontic treatments and their periodontitis tended to accumulate more caries. Clinical Significance: This study establishes, in a case-control study, some specific aspects of oral health in patients with COPD, as well as analyzing the importance of oral health in this disease.

Evaluation of oral hygiene habits and periodontal disease according to the COVID-19 history by teledentistry: a cross-sectional study

Objective: To evaluate oral hygiene habits and periodontal disease status with teledentistry and to compare oral hygiene and periodontal disease status according to the COVID-19 history. Materials and Methods: Patients who had applied to our faculty before the pandemic and were reached via teledentistry were included. A questionnaire consisting of 4 sections and 25 questions was administered through telephone conversation. Demographic information, medical history, smoking habits, and COVID-19 history (with [COVID(+)] or without COVID-19 [COVID(-)]) were questioned in the first section, while dental hygiene (DH), environmental dental hygiene (EH), history of periodontal disease (PH) were evaluated in the next three sections. The answers were scored in a way that increased values symbolize negative attitude. Taking into account the minimum and maximum values that can be obtained from the sum of the scores;DH, EH and PH scales with low, medium and high value ranges were created. The groups were compared in terms of the mean value from the scales and the distribution in the scale ranges.

aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases.

The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75-85% and specificity in the range of 80-90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.

Prevalence and Death Rate of COVID-19 in Autoimmune Systemic Diseases in the First Three Pandemic Waves. Relationship with Disease Subgroups and Ongoing Therapies.

OBJECTIVE: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients. METHODS: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59±12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire. RESULTS: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p<0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000). CONCLUSION: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19- related mortality was recorded in only SSc patients' subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients' population.

Translating Science into Improved Health for All.

Our world is at a turning point with biological and social pathogens wreaking havoc at the same time that science and technology are exploding with new discoveries. It is a pivotal time for the new report Oral Health in America: Advances and Challenges to be released and a pivotal time for our profession to take action and lead. The art, science, and practice of dentistry is very different from 20 y ago when the original Surgeon General's report was released. We are on the precipice of individualized health care where providers will collaborate to deliver diagnostics and therapeutics that are data driven and inclusive of the social determinants of health. To move forward with alacrity requires a strong scientific foundation, effective educational approaches, an understanding of the upstream determinants of health, and partnerships across the health professions and beyond. Oral health has never been more important, and now is the time for our profession to further develop, elevate, and translate the science into practice and policy to improve the nation's health.

The COVID-19 pandemic: manifestations and complications of neurological disorders

In late December 2019, an outbreak of a novel coronavirus causing severe acute respiratory syndrome (SARS) was reported in Wuhan, Hubei Province, China. The disease has been referred to as COVID-19, and the causative agent has been labelled SARS-CoV-2 due to its genetic resemblance to the virus SARS-CoV-1 responsible for SARS epidemic almost 20 years before. The epidemic has since spread to much of the world, having been considered as a pandemic with over 12 million confirmed cases and 5,52,143 deaths worldwide till July 10, 2020. COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. Initially thought to be restricted to the respiratory system, it is now understood that (COVID-19) also affects other multiple organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly increasing. The pathobiology of the COVID-19 in CNS is still not known. Of the neurological disorders, some appear to be the consequence of direct viral invasion of the tissues of nervous systems, others arise as a postviral autoimmune process, and still, others are the result of metabolic and systemic complications due to the associated critical illness. This review deals with the preliminary observations regarding the neurological disorders reported with COVID-19 to date and illustrates some of the disorders that are anticipated from prior experience with similar coronaviruses.

Evaluation of Demographic and Clinical Data of Herpes Zoster Patients Admitted To Tertiary Referral Dermatology Clinic During COVID-19 Pandemic

Objectives: The aim of this study is to evaluate the demographic and clinical data collected from patients admitted to our tertiary referral medical center and diagnosed with herpes zoster during the COVID-19 pandemic. The aim of this study is to evaluate the demographic and clinical data collected from patients admitted to our tertiary referral medical center and diagnosed with herpes zoster during the COVID-19 pandemic period. The aim of our study was to evaluate the course of herpes infection triggered by immune deficiency during the COVID-19 pandemic period and to evaluate demographic and clinical data in order to compare this course with other immunodeficiency conditions. The age of the patients, the localization of the shingles lesions, the season and month at the time of shingles, comorbidities, hospitalization status, accompanying complications, association with COVID-19 vaccine/infection, predisposing factors, and prescribed systemic antiviral treatments were recorded.

Oral Microbiome: Getting to Know and Befriend Neighbors, a Biological Approach.

The oral microbiome, forming a biofilm that covers the oral structures, contains a high number of microorganisms. Biofilm formation starts from the salivary pellicle that allows bacterial adhesion-colonization-proliferation, co-aggregation and biofilm maturation in a complex microbial community. There is a constant bidirectional crosstalk between human host and its oral microbiome. The paper presents the fundamentals regarding the oral microbiome and its relationship to modulator factors, oral and systemic health. The modern studies of oral microorganisms and relationships with the host benefits are based on genomics, transcriptomics, proteomics and metabolomics. Pharmaceuticals such as antimicrobials, prebiotics, probiotics, surface active or abrasive agents and plant-derived ingredients may influence the oral microbiome. Many studies found associations between oral dysbiosis and systemic disorders, including autoimmune diseases, cardiovascular, diabetes, cancers and neurodegenerative disorders. We outline the general and individual factors influencing the host-microbial balance and the possibility to use the analysis of the oral microbiome in prevention, diagnosis and treatment in personalized medicine. Future therapies should take in account the restoration of the normal symbiotic relation with the oral microbiome.

Frequency, characteristics and outcome of corona virus disease 2019 (COVID-19) infection in Iranian patients with rheumatic diseases

Aim of the work to investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndromecoronavirus 2(SARS-CoV-2) infection in rheumatic diseases patients. Patients and methods One thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren’s syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared. Results The 1000 patients mean age was 43.4±13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%;p=0.048). Conclusion Most rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20mg/d are at higher risk of developing COVID-19 infection.

Practical Issues in Managing Systemic Inflammatory Disorders During the COVID-19 Pandemic.

The global coronavirus disease 2019 (COVID-19) situation threatens not only the health of populations, but also the coherence and function of health care systems. Patients with systemic inflammatory disorders feel the overwhelming strain of COVID-19, since their disease, administered treatments, and associated comorbidities may all contribute to increased vulnerability to infection. At the same time, monitoring the activity status of rheumatic diseases and adjusting the treatments where appropriate, are important for preventing flares and other complications, which could pose additional health risks. Considering the urgent need to maintain physical distancing and self-quarantine as much as possible, we herein discuss the challenges and possible solutions pertaining to the assessment and monitoring of patients with systemic inflammatory diseases. We also discuss issues related to the prescription and supply of anti-rheumatic drugs, as well as opportunities provided by the use of technological and wireless tools. From an optimistic viewpoint, the end of this pandemic may leave us with an important legacy in utilising and implementing e-health solutions that may both improve the clinical care standards for patients with systemic inflammatory diseases and also reduce the burden placed on healthcare systems.