Mechanisms of Action of Topical Corticosteroids in Psoriasis

Psoriasis is a lifelong, chronic, and immune-mediated systemic disease, which affects approximately 1–3% of the Caucasian population. The different presentations of psoriasis require different approaches to treatment and appropriate prescriptions according to disease severity. The use of topical therapy remains a key component of the management of almost all psoriasis patients, and while mild disease is commonly treated only with topical agents, the use of topical therapy as adjuvant therapy in moderate-to-severe disease may also be helpful. This paper focuses on the cutaneous mechanisms of action of corticosteroids and on the currently available topical treatments, taking into account adverse effects, bioavailability, new combination treatments, and strategies to improve the safety of corticosteroids. It is established that the treatment choice should be tailored to match the individual patient’s needs and his/her expectations, prescribing to each patient the most suitable vehicle.

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Uveitis for the non-ophthalmologist

BMJ ◽

10.1136/bmj.m4979 ◽

2021 ◽

pp. m4979

Author(s):

Bryn M Burkholder ◽

Douglas A Jabs

Keyword(s):

Laboratory Testing ◽

Systemic Disease ◽

Severe Disease ◽

First Line ◽

Surgical Implants ◽

Immune Mediated ◽

Systemic Medication ◽

Ocular Imaging ◽

Infectious Organism ◽

First Line Treatment

Abstract The uveitides are a heterogeneous group of diseases characterized by inflammation inside the eye. The uveitides are classified as infectious or non-infectious. The non-infectious uveitides, which are presumed to be immune mediated, can be further divided into those that are associated with a known systemic disease and those that are eye limited,—ie, not associated with a systemic disease. The ophthalmologist identifies the specific uveitic entity by medical history, clinical examination, and ocular imaging, as well as supplemental laboratory testing, if indicated. Treatment of the infectious uveitides is tailored to the particular infectious organism and may include regional and/or systemic medication. First line treatment for non-infectious uveitides is corticosteroids that can be administered topically, as regional injections or surgical implants, or systemically. Systemic immunosuppressive therapy is used in patients with severe disease who cannot tolerate corticosteroids, require chronic corticosteroids at >7.5 mg/day prednisone, or in whom the disease is known to respond better to immunosuppression. Management of many of these diseases is optimized by coordination between the ophthalmologist and rheumatologist or internist.

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Soluble Urokinase Receptor as a Promising Marker for Early Prediction of Outcome in COVID-19 Hospitalized Patients

Journal of Clinical Medicine ◽

10.3390/jcm10214914 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4914

Author(s):

Filomena Napolitano ◽

Gaetano Di Spigna ◽

Maria Vargas ◽

Carmine Iacovazzo ◽

Biagio Pinchera ◽

...

Keyword(s):

Health Care Systems ◽

Severe Disease ◽

Multiple Organ ◽

Urokinase Receptor ◽

Clinical Severity ◽

Mild Disease ◽

Global Pandemic ◽

Care Systems ◽

The Individual ◽

Time Of Admission

The Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to become a global pandemic, putting a strain on health care systems. SARS-CoV-2 infection may be associated with mild symptoms or, in severe cases, lead patients to the intensive care unit (ICU) or death. The critically ill patients suffer from acute respiratory distress syndrome (ARDS), sepsis, thrombotic complications and multiple organ failure. For optimization of hospital resources, several molecular markers and algorithms have been evaluated in order to stratify COVID-19 patients, based on the risk of developing a mild, moderate, or severe disease. Here, we propose the soluble urokinase receptor (suPAR) as a serum biomarker of clinical severity and outcome in patients who are hospitalized with COVID-19. In patients with mild disease course, suPAR levels were increased as compared to healthy controls, but they were dramatically higher in severely ill patients. Since early identification of disease progression may facilitate the individual management of COVID-19 symptomatic patients and the time of admission to the ICU, we suggest paying more clinical attention on patients with high suPAR levels.

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Molecular Targets of Phytochemicals for Skin Inflammation

Current Pharmaceutical Design ◽

10.2174/1381612824666180426113247 ◽

2018 ◽

Vol 24 (14) ◽

pp. 1533-1550 ◽

Cited By ~ 3

Author(s):

Jong-Eun Kim ◽

Ki Won Lee

Keyword(s):

Skin Diseases ◽

Molecular Targets ◽

Skin Inflammation ◽

Mechanisms Of Action ◽

The Body ◽

Cellular Damage ◽

Aesthetic Appearance ◽

Immune Mediated ◽

Skin Conditions ◽

Effects Of Aging

Skin is a protective organ and the largest of the human body. Due to its pivotal role in aesthetic appearance, skin health has a significant impact on quality of life. Chronic inflammation of the skin often marks the beginning of various skin diseases. Immune-mediated responses serve to protect the body from external insults and require succinct control, and can lead to ongoing cellular damage and various skin conditions if left unchecked. Studies have shown that phytochemicals can alter processes involved in skin inflammation and alleviate the effects of aging, cancer, atopic dermatitis, psoriasis, and vitiligo. Direct molecular targets of some phytochemicals have been identified and their precise mechanisms of action investigated. In this review, we summarize recent findings on the effects of phytochemicals on skin inflammation and the mechanisms of action involved.

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SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.801 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1227.3-1228

Author(s):

M. E. Tezcan ◽

N. Şen ◽

M. Yilmaz ◽

Ö. Volkan ◽

E. Tükel ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Scoring System ◽

Disease Duration ◽

Severe Disease ◽

Smoking History ◽

Disease Group ◽

Severity Scoring ◽

Mild Disease ◽

Co Morbidity ◽

Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

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A Case Series of SARS-CoV-2 RT-PCR-Positive Hospitalized Infants 60 Days of Age or Younger From 2 New York City Pediatric Emergency Departments

Clinical Pediatrics ◽

10.1177/00099228211006688 ◽

2021 ◽

Vol 60 (4-5) ◽

pp. 247-251

Author(s):

Ameer Hassoun ◽

Nessy Dahan ◽

Christopher Kelly

Keyword(s):

New York ◽

Case Reports ◽

Severe Disease ◽

Case Series ◽

Pediatric Emergency ◽

Rt Pcr ◽

Vulnerable Group ◽

Mild Disease ◽

Young Infants ◽

Novel Coronavirus

The emergence of novel coronavirus disease-2019 poses an unprecedented challenge to pediatricians. While the majority of children experience mild disease, initial case reports on young infants are conflicting. We present a case series of 8 hospitalized infants 60 days of age or younger with coronavirus disease-2019. A quarter of these patients had coinfections (viral or bacterial). None of these infants had severe disease. Continued vigilance in testing this vulnerable group of infants is warranted.

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SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

Journal of Personalized Medicine ◽

10.3390/jpm11050431 ◽

2021 ◽

Vol 11 (5) ◽

pp. 431

Author(s):

Sabine Hofer ◽

Norbert Hofstätter ◽

Albert Duschl ◽

Martin Himly

Keyword(s):

Risk Factor ◽

Particle Deposition ◽

Early Stage ◽

Severe Disease ◽

Ambient Air ◽

Aerosol Deposition ◽

Pulmonary Involvement ◽

Mild Disease ◽

Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

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POS1232 COVID-19 IN PATIENTS WITH SYSTEMIC SCLEROSIS: ONE RHEUMATOLOGY CENTER EXPERIENCE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3086 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 899.2-899

Author(s):

M. Starovoytova ◽

O. Desinova ◽

L. P. Ananyeva ◽

O. Koneva ◽

L. Garzanova ◽

...

Keyword(s):

Systemic Sclerosis ◽

Severe Disease ◽

High Risk Group ◽

Nasopharyngeal Swab ◽

Frequent Use ◽

Diffuse Form ◽

Novel Coronavirus ◽

Almost All ◽

Dose Prednisone ◽

Frequent Presence

Background:Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) virus infection or COVID-19 is a serious problem for patients with systemic autoimmune diseases Given the serious complications, including acute lung injury, patients with systemic sclerosis (SSc), especially SSs associated with interstitial lung disease (ILD), may represent a high risk group for infection and the development of severe COVID-19.Objectives:We present an analysis of the COVID-19 course and outcomes in 110 SSc pts.Methods:The study included 147 patients with SSc. The information was clarified by means of telephone survey after 10 months of the pandemic (December 2020). Covid-19 was diagnosed when confirmed by positive oral /nasopharyngeal swab, in the presence of positive antibodies and/or characteristic symptoms, and data from chest computed tomography (CT). 110 pts (77%) out of 147 patients in the SSc registry, gave the necessary information. COVID-19 was diagnosed in 59 pts (53 %). 42 pts (71%) had SSc-ILD. Pts mean age was 54.96 (s.d.11, min 31, max 79), 83% women (49 women and 10 men). 38 pts (65%) had a limited form of SSc, 15 (26%) pts had diffuse form SSc, 6% had overlap (SSc-polymyositis (PM) and SSc had rheumatoid arthritis (RA) and 3% had visceral form of SSc). All patients received low-dose prednisone, and more than half of the pts received immunosuppressive therapy. Rituximab therapy was performed in 24 pts (41%).Results:Almost all patients had positive swab from the oral cavity/nasopharynx. And only in 4 (7%) pts nasopharyngeal swabs were negative, in these patients specific antibodies and characteristic CT changes were detected. Chest CT was performed in 51 (86%) pts. Novel coronavirus pneumonia developed in the vast majority of pts - in 46 (78 %) pts. CT1 (up to 25% of lung lesions) had 10 (17%) pts, CT2 (25-50%) – 21(36%) pts, CT 3 (50-75%) – 15(25%) pts. In 5 (8.5%) pts no changes were detected on CT. The course of COVID-19 was mild and moderate (20 (34%) pts and 18 (31%) pts respectively), severe course was observed in 21 (35%) pts, including fatal in 12 (20%) pts. Among the deceased pts, only 1 patient with SSc-PM had not had ILD, but 7 patients had been treated with rituximab.Conclusion:SSc SARS-CoV-2-infected patients may be at risk of severe disease and mortality due to the frequent presence of ILD and the frequent use of immunosuppressive, including biological, therapy.Disclosure of Interests:None declared

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Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience

Journal of Personalized Medicine ◽

10.3390/jpm11080709 ◽

2021 ◽

Vol 11 (8) ◽

pp. 709

Author(s):

Adamantia Liapikou ◽

Eleni Tzortzaki ◽

Georgios Hillas ◽

Miltiadis Markatos ◽

Ilias C. Papanikolaou ◽

...

Keyword(s):

Preventive Measures ◽

Severe Disease ◽

Hospital Setting ◽

Guidance Document ◽

Outpatient Management ◽

Patient Centered ◽

Mild Disease ◽

Novel Coronavirus ◽

Second Wave ◽

Close Contacts

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients’ isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

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Natural variants in SARS-CoV-2 Spike protein pinpoint structural and functional hotspots with implications for prophylaxis and therapeutic strategies

Scientific Reports ◽

10.1038/s41598-021-92641-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Suman Pokhrel ◽

Benjamin R. Kraemer ◽

Scott Burkholz ◽

Daria Mochly-Rosen

Keyword(s):

Amino Acid ◽

Severe Disease ◽

Single Amino Acid ◽

Amino Acid Substitutions ◽

Severe Respiratory Distress ◽

S Protein ◽

Individual Sequences ◽

Natural Variants ◽

Novel Coronavirus ◽

The Individual

AbstractIn December 2019, a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of pneumonia with severe respiratory distress and outbreaks in Wuhan, China. The rapid and global spread of SARS-CoV-2 resulted in the coronavirus 2019 (COVID-19) pandemic. Earlier during the pandemic, there were limited genetic viral variations. As millions of people became infected, multiple single amino acid substitutions emerged. Many of these substitutions have no consequences. However, some of the new variants show a greater infection rate, more severe disease, and reduced sensitivity to current prophylaxes and treatments. Of particular importance in SARS-CoV-2 transmission are mutations that occur in the Spike (S) protein, the protein on the viral outer envelope that binds to the human angiotensin-converting enzyme receptor (hACE2). Here, we conducted a comprehensive analysis of 441,168 individual virus sequences isolated from humans throughout the world. From the individual sequences, we identified 3540 unique amino acid substitutions in the S protein. Analysis of these different variants in the S protein pinpointed important functional and structural sites in the protein. This information may guide the development of effective vaccines and therapeutics to help arrest the spread of the COVID-19 pandemic.

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Adolescent Musicians' Perceptions of Conductors Within Musical Context

Journal of Research in Music Education ◽

10.1177/0022429409333352 ◽

2009 ◽

Vol 57 (1) ◽

pp. 16-25 ◽

Cited By ~ 2

Author(s):

Clifford K. Madsen ◽

John M. Geringer ◽

Katia Madsen

Keyword(s):

College Students ◽

Summer Camp ◽

The Individual ◽

Almost All ◽

Audio Video ◽

Musical Context

Attention to subtle changes in music, whether inadvertent or purposeful, occupies a great deal of practice and rehearsal time for the performer. Regardless of the extremely subtle acoustic changes that have been found to be perceptible within almost all studies, it is the total overall effect that most occupies the individual listener. This study investigated perception of digitally edited performances of Johann Strauss's Blue Danube Waltz, all performed by the Vienna Philharmonic Orchestra with various conductors across an 18-year period. Two groups of string musicians in grades 7 through 12 participated ( N = 104). One group was an intact class; the second was a group of summer camp students. All participants listened to two conditions: (a) audio only and (b) audio-video combination. Results indicated that there were no significant differences between groups and that no one was able to identify correctly that there were five different conductors in the audio-only condition. Results were much the same as earlier research with college students. In addition, many students indicated that there were differences in the audio portions of the two conditions when in fact there were not.

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