Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and ...synonyms was performed on November 28.sup.th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the correlation of HRCT findings with pulmonary metabolic activity in the corresponding regions using 18F-FDG PET/CT and inflammatory markers in patients with systemic sclerosis ...(SSc)-associated interstitial lung disease (ILD).
This was a cross-sectional study involving 23 adult patients with SSc-associated ILD without other connective tissue diseases. The study also involved 18F-FDG PET/CT, HRCT, determination of serum chemokine levels, clinical data, and pulmonary function testing.
In this cohort of patients with long-term disease (disease duration, 11.8 ± 8.7 years), a nonspecific interstitial pneumonia pattern was found in 19 (82.6%). Honeycombing areas had higher median standardized uptake values (1.95; p = 0.85). Serum levels of soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 10 were higher in SSc patients than in controls. Serum levels of CCL2-a marker of fibroblast activity-were correlated with pure ground-glass opacity (GGO) areas on HRCT scans (p = 0.007). 18F-FDG PET/CT showed significant metabolic activity for all HRCT patterns. The correlation between serum CCL2 levels and GGO on HRCT scans suggests a central role of fibroblasts in these areas, adding new information towards the understanding of the mechanisms surrounding cellular and molecular elements and their expression on HRCT scans in patients with SSc-associated ILD.
18F-FDG PET/CT appears to be unable to differentiate the intensity of metabolic activity across HRCT patterns in chronic SSc patients. The association between CCL2 and GGO might be related to fibroblast activity in these areas; however, upregulated CCL2 expression in the lung tissue of SSc patients should be investigated in order to gain a better understanding of this association.
A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The ...molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piperidine subunit of donepezil, the substituted hydroxy-piperidine fragment of the AChE inhibitor LASSBio-767, and an acylhydrazone linker, a privileged structure present in a number of synthetic aryl- and aryl-acylhydrazone derivatives with significant AChE and anti-inflammatory activities. Among them, compounds 4c, 4d, 4g and 4j presented the best AChE inhibitory activities, but only compounds 4c and 4g exhibited concurrent anti-inflammatory activity in vitro and in vivo, against amyloid beta oligomer (AβO) induced neuroinflammation. Compound 4c also showed the best in vitro and in vivo neuroprotective effects against AβO-induced neurodegeneration. In addition, compound 4c showed a similar binding mode to donepezil in both acetylated and free forms of AChE enzyme in molecular docking studies and did not show relevant toxic effects on in vitro and in vivo assays, with good predicted ADME parameters in silico. Overall, all these results highlighted compound 4c as a promising and innovative multi-target drug prototype candidate for AD treatment.
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•Novel aryl-acylhydrazone-donepezil hybrids 4c and 4g were synthesized as MTDLs.•Compounds 4c and 4g showed IC50 = 25.4 and 8.65 μM, respectively for AChE inhibition.•4c and 4g showed anti-inflammatory activity against AβO-induced neuroinflammation.•4c and 4g inhibited COX-1/2 and the release of TNF-α in activated microglial cells.•Compound 4c seems to be a promising MTDL drug prototype candidate for AD.
The effect of periodontal treatment on clinical, microbiological and serological parameters of patients with rheumatoid arthritis (RA) are scarce and controversial. The aim of this study was to ...investigate the influence of non-surgical periodontal treatment on clinical periodontal status, subgingival bacterial levels of
Aggregatibacter actinomycetemcomitans
,
Porphyromonas gingivalis
,
Tannerella forsythia, Treponema denticola
and RA activity through a controlled clinical trial on individuals with RA and periodontitis (PE). From a convenience sample, 107 individuals were considered eligible and consecutively allocated in four groups: (1) individuals without PE and RA (− PE-RA,
n
= 30); (2) individuals without PE and with RA (− PE + RA,
n
= 23); (3) individuals with PE and RA (+ PE + RA,
n
= 24); and (4) individuals with PE and without RA (+ PE-RA,
n
= 30). Full-mouth periodontal clinical examinations, microbiological analysis and Disease Activity Score (DAS-28) evaluations were performed at baseline (T1) and 45 days after non-surgical periodontal treatment (T2). At T1, individuals + PE + RA showed greater severity of PE than + PE-RA individuals. At T2, significant reductions were observed in all periodontal clinical parameters in both groups (
p
< 0.001) with a significant reduction in DAS-28 in + PE + RA (
p
= 0.011). Individuals + PE-RA and + PE-RA showed significant reductions for all bacteria (
p
< 0.001). Additionally,
P. gingivalis
demonstrated an expressively significant reduction in + PE + RA (
p
< 0.001). Non-surgical periodontal treatment was effective on improving the clinical periodontal condition, improving the RA clinical status and reducing the presence of periodontal pathogens. Brazilian Registry of Clinical Trials (ReBEC) protocol #RBR-8g2bc8 (
https://www.ensaiosclinicos.gov.br/rg/RBR-8g2bc8/
).
Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterized by vascular abnormalities and connective tissue disorders. In 2021, the multidisciplinary team of the university hospital ...recognized a demand for oral health information among SSc patients. This study aims to describe the development of an SSc oral health booklet and its validation by people with SSc.
For the development of the booklet, the project creators employed the action research methodology involving ten stages. SSc patients evaluated the material by filling out a digital form.
One hundred and thirty-one people with SSc evaluated the booklet. It received an average score of 9.73 (SD: 0.80) in relevance, 9.82 (SD: 0.47) in explicitness, and 9.49 (SD: 0.93) in aesthetics. The final version was emailed to the participants and posted on social media.
This is the first booklet that deeply addresses these issues in Portuguese and constitutes a soft technology to instruct and assist patients with SSc.
The production of high-quality educational materials on oral health for patients with SSc is necessary. The online distribution increased its reach and had great importance in the context of the COVID-19 pandemic.
•Systemic sclerosis orofacial abnormalities impose challenges to health professionals.•Health education enables patients to self-manage systemic sclerosis.•Educational booklets must use simple language and illustrations to improve patients' understanding.•Patients' suggestions are essential to improve educational booklets.•The online distribution of educational materials improves their reach.
The immune system has an important role in the development of systemic lupus erythematosus (SLE) and chronic periodontitis (CP). Altered cytokines levels characterise both diseases and contributes to ...periodontal tissue damage in CP and to macrocomplexes deposition with connective tissue destruction in SLE. This study aimed to evaluate the production of salivary cytokines in patients with SLE and its association with periodontal status.
The sample comprised 70 SLE patients and 70 paired controls. SLE activity and damage were scored using Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Subjects were classified as without or with CP. Salivary concentrations of IL-33, MMP2/TIMP2, RANK and OPG were measured by ELISA, while IL-2, IFNγ, TNFα, IL-4, IL-6, IL-10 and IL-17A were determined by Cytometric Bead Array. Linear regression models analysed association among SLE, CP and salivary cytokines.
IL-6 and IL-17A concentrations were significantly higher in SLE/CP patients than controls/CP. Concentrations of IL-6, IL-17A and IL-33 were increased in SLE/CP individuals when compared to SLE without CP. Multivariate model revealed association of cumulative dose of corticoids with periodontal damage and of IL-33 salivary concentration with SLE activity.
Our findings suggest that long-term therapy with corticoids would contribute with periodontal destruction in SLE patients. Moreover, the increased levels of IL-6, IL-17A and IL-33 in saliva of SLE subjects with CP may signal it as possible inflammatory pathways in this process.
•Acceptance of a COVID-19 vaccine in patients with immune-mediated diseases was high.•COVID-19 vaccine acceptance may be hampered by some comorbidities and treatments.•The short duration of trials ...was the main concern behind COVID-19 vaccine hesitancy.
To identify potential predictors of COVID-19 vaccine hesitancy (C19-VH) in adults with immune-mediated inflammatory diseases (IMID).
A total of 1000 IMID patients were enrolled in this web-based cross-sectional study. A standardised and self-administered survey was designed by members of the Brazilian Society of Rheumatology Steering Committee for Infectious and Endemic diseases and distributed to IMID patients spread across Brazil.
Of the 908 (90.8%) respondents eligible for analysis, 744 (81.9%) were willing to get vaccinated against COVID-19. In our multivariable logistic regression model, concurrent malignancy, fibromyalgia, hydroxychloroquine use, and recent corticosteroid pulse therapy were independently associated with higher odds of C19-VH. The short duration of COVID-19 vaccine clinical trials was the main reason for C19-VH.
We identified novel characteristics potentially associated with C19-VH among adults with IMID. Greater awareness on the safety and efficacy of COVID-19 vaccines is needed for both IMID patients and attending physicians.
Identification of infection in patients with systemic lupus erythematosus (SLE) is a major challenge in clinical practice.
This medical records review study evaluated clinical markers, including the ...performance of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) in the diagnosis of infection in SLE patients.
One hundred four SLE patients hospitalized between 2014 and 2018 were allocated into 3 groups, namely, infection, infection and disease activity, and isolated disease activity. Groups were compared in relation to clinical and laboratory variables. Accuracy measures were calculated for CRP, NLR, and PLR.
C-reactive protein, NLR, and PLR differed between the groups with higher values observed in the infected group, intermediate values in the mixed group, and lower values in the group with isolated activity-CRP (56 vs 26 vs 15 mg/dL, p = 0.002), NLR (7.9 vs 4.0 vs 3.1, p = 0.005), and PLR (270 vs 227 vs 134, p = 0.025). Fever, tachypnea, and PLR were independently associated with infection. The cutoff points of the CRP of 20 mg/L, NLR of 3.5, and PLR of 151.4 presented values of sensitivity and specificity for the prediction of infection equal to 67% and 67%, 65% and 58%, and 71% and 53%, respectively. The developed algorithm showed a sensitivity of 86.6% and specificity of 81% for the diagnosis of infection.
The combined use of clinical and laboratory markers presented superior accuracy than their isolated use, suggesting a great potential for the application of the algorithm in clinical practice.
Schizophrenia etiology is unknown, nevertheless imbalances occurring in an acute psychotic episode are important to its development, such as alterations in cellular energetic state, REDOX homeostasis ...and intracellular Ca
2+
management, all of which are controlled primarily by mitochondria. However, mitochondrial function was always evaluated singularly, in the presence of specific respiratory substrates, without considering the plurality of the electron transport system. In this study, mitochondrial function was analyzed under conditions of isolated or multiple respiratory substrates using brain mitochondria isolated from MK-801-exposed mice. Results showed a high H
2
O
2
production in the presence of pyruvate/malate, with no change in oxygen consumption. In the condition of multiple substrates, however, this effect is lost. The analysis of Ca
2+
retention capacity revealed a significant change in the uptake kinetics of this ion by mitochondria in MK-801-exposed animals. Futhermore, when mitochondria were exposed to calcium, a total loss of oxidative phosphorylation and an impressive increase in H
2
O
2
production were observed in the condition of multiple substrates. There was no alteration in the activity of the antioxidant enzymes analyzed. The data demonstrate for the first time, in an animal model of psychosis, two important aspects (1) mitochondria may compensate deficiencies in a single mitochondrial complex when they oxidize several substrates simultaneously, (2) Ca
2+
handling is compromised in MK-801-exposed mice, resulting in a loss of phosphorylative capacity and an increase in H
2
O
2
production. These data favor the hypothesis that disruption of key physiological roles of mitochondria may be a trigger in acute psychosis and, consequently, schizophrenia.
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