INTEGRATED ASSESSMENT OF CLINICAL SEVERITY IN PATIENTS WITH ENDOGENOUS PSYCHOSES BY INFLAMMATORY MARKERS AND INDICATORS OF SYSTEMIC ENDOTOXEMIA

AbstractSeveral cytokines and adipokines are related to clinical severity and progression in knee osteoarthritis. The aim of this study was to evaluate the associations of IL-8 with clinical severity and with local and systemic adipokines and cytokines. This is a Cross-sectional study including 115 women with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, symptoms duration and body mass index were collected. Radiographic severity was evaluated according to Kellgren–Lawrence. Pain and disability were assessed by Lequesne and Knee injury and Osteoarthritis Outcome Score pain, symptoms and function scales. Three inflammatory markers and five adipokines were measured by ELISA in serum and synovial fluid. Partial correlation coefficient (PCC) and corresponding 95% confidence interval were used to evaluate association. Synovial fluid IL-8 was significantly associated with clinical severity scales. After controlling for potential confounders, associations measured by a Partial Correlation Coefficient (PCC) remained essentially unaltered for Lequesne (PCC = 0.237), KOOS pain (PCC = − 0.201) and KOOS symptoms (PCC = − 0.209), KOOS function (PCC = − 0.185), although the later did not reach statistical significance. Also in synovial fluid samples, associations were found between IL-8 and TNF (PCC = 0.334), IL6 (PCC = 0.461), osteopontin (PCC = 0.575), visfatin (PCC = 0.194) and resistin (PCC = 0.182), although significance was not achieved for the later after statistical control for confounders. None of these associations were detected in serum. In conclusion, IL-8 was associated with clinical severity, inflammatory markers and adipokines in synovial fluid, but not in blood. Although the reported associations are weak to moderate in magnitude, these findings reinforce the notion that local and not systemic inflammation is more relevant to clinical severity in knee OA women with joint effusion.

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564. Tocilizumab Induces Rapid, Sustained Improvement of Inflammatory Markers in COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.758 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S346-S347

Author(s):

Robert Colgrove ◽

Scott Morin ◽

Chinmay Jani ◽

Arashdeep Rupal ◽

Daniel L Bourque

Keyword(s):

Clinical Improvement ◽

Inflammatory Markers ◽

Care Facility ◽

Clinical Severity ◽

Ordinal Scale ◽

Partial Recovery ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Severity Scores ◽

Discharge Status

Abstract Background Frequent observation of increasing fever and rising inflammatory markers late after onset of COVID-19 suggests Cytokine Release Syndrome (CRS, “Cytokine Storm”) may contribute to pathophysiology. Tocilizumab (TCZ), a monoclonal antibody targeting the receptor for the pro-inflammatory cytokine, IL-6, is effective in suppressing pathological inflammation in several rheumatological diseases. After administering TCZ to COVID-19 patients with suspected CRS, we observed a sharp fall in inflammatory indices. We analyzed this effect using results from the first 19 COVID-19 patients receiving TCZ at our hospital. Methods Data for all patients with confirmed COVID-19 who received TCZ at our center, a 200 bed community hospital in New England, were extracted from the Electronic Medical Record, including demographics, body temperature, C-Reactive Protein (CRP), IL-6 levels, clinical severity on the Ordinal Scale for Clinical Improvement (OSCI), and clinical outcome (recovery/discharge home, partial recovery/discharge rehab, death). Results were tabulated and statistical significance of changes in indices pre- and post- TCZ assessed by Wilcoxon Signed-Rank Test. Results 19 patients received TCZ: 16 got 400mg x1, 2 got 400 mg x2, 1 got 660 mg x1. Median age was 64 years (range: 44–94), 68% male. Mean interval from symptom onset to receiving TCZ was 11.5 days. Mean IL-6 was 145 pg/mL. Demographics, OSCI scores, and discharge status are shown in Table 1. Average daily peak temperatures (Tmax) pre- and post- TCZ were 100.7 and 98.9°F, p< 0.001. Mean CRP pre- and post- were 234 and 84.6 mg/L, p=0.001 (Fig.1). Decrease in Tmax and CRP was rapid and sustained (Fig. 2, 1st 8 patients shown for clarity.). 58% had improved clinical improvement by OSCI by day 7, 68% by day 14. 7 of 19 of patients were discharged home, 6 to rehab or acute care facility, and 6 died. Table 1: Patient Demographics, Clinical Severity Score, and Discharge Status Conclusion In this cohort of patients with moderate-to-severe COVID-19 and evidence of Cytokine Release Syndrome, tocilizumab was associated with rapid resolution of fever and marked decline in CRP. Most patients showed improvement in clinical severity scores and no adverse reactions were noted. Tocilizumab may be useful in control of pathological inflammation in COVID-19. Controlled trials will be needed to assess overall clinical benefit. Disclosures All Authors: No reported disclosures

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Markers of systemic inflammation and systemic endotoxinemia in patients with acute endogenous psychoses

Nauchno-prakticheskii zhurnal «Patogenez» ◽

10.25557/2310-0435.2020.01.34-41 ◽

2020 ◽

pp. 34-41

Author(s):

С.А. Зозуля ◽

И.Н. Отман ◽

О.А. Юнилайнен ◽

И.А. Аниховская ◽

Т.П. Клюшник ◽

...

Keyword(s):

Systemic Inflammation ◽

Inflammatory Markers ◽

Clinical Symptoms ◽

Psychometric Evaluation ◽

Pathological Process ◽

Psychotic Symptoms ◽

Control Group ◽

Leukocyte Elastase ◽

Endogenous Psychoses ◽

Icd 10

Актуальность: Современные исследования свидетельствуют о вовлеченности воспаления в патогенез эндогенных психических расстройств. Показано, что активность врождённого иммунитета (высокие показатели лейкоцитарной эластазы (ЛЭ) и а1-протеиназного ингибитора (а1-ПИ)), а также уровень аутоантител к нейроантигенам отражают остроту и тяжесть патологического процесса в мозге. В качестве одного из факторов, инициирующих системное воспаление, рассматривается патогенный формат системной эндотоксинемии (СЭЕ) - эндотоксиновая агрессия (ЭА), - патологический процесс, обусловленный избытком эндотоксина (ЭТ) в кровотоке. Цель: определение взаимосвязи между показателями системного воспаления и СЭЕ у больных с эндогенными психозами, необходимое для оценки роли ЭА в патогенезе изучаемой патологии. Материалы и методы: Обследовано 25 пациентов женского пола в возрасте от 23 до 49 лет (32,6 ± 8,9 лет) с эндогенными психозами (F20, F25 по МКБ-10). Все пациенты находились в остром психотическом состоянии. Психометрическая оценка проведена с помощью шкалы PANSS. Контрольная группа состояла из 25 психически и соматически здоровых женщин соответствующего возраста. В крови пациентов определяли активность воспалительных маркеров ЛЭ и а1-ПИ, а также уровень антител к нейроантигенам S100-B и ОБМ (технология «Нейро-иммуно-тест»), концентрацию эндотоксина (ЭТ) («Микро-ЛАЛ-тест») и активность антиэндотоксинового иммунитета (АЭИ) (технология «СОИС-ИФА»). Данные проанализированы с помощью непараметрических статистических методов (IBM SPSS Statistics 23). Результаты: В сыворотке крови пациентов выявлено статистически значимое повышение активности ЛЭ и а1-ПИ, а в 44% - наличие аутоиммунного компонента к нейроантигенам. У 24% больных на фоне существенного повышения активности маркеров воспаления наблюдалось повышение концентрации ЭТ, сопровождающееся недостаточностью АЭИ (преимущественно к гидрофильной части молекулы ЭТ), что является неблагоприятным фактором, усугубляющим клиническое течение заболевания. У 76% пациентов концентрация ЭТ оставалась в пределах нормативных значений и сопровождалась различным уровнем АЭИ, что, вероятно, может являться следствием ранее перенесённой ЭА. Выявлены корреляции между исследуемыми биологическими показателями, а также их связь с тяжестью клинической симптоматики по PANSS. Выводы: Полученные результаты свидетельствуют о взаимосвязи маркеров системного воспаления и показателей СЭЕ и их вовлеченности в патогенез эндогенных психозов. Background: Recent studies have suggested involvement of inflammation in the pathogenesis of endogenous mental disorders. The activity of innate immunity (increased activities of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI)) and the level of autoantibodies to neuroantigens reflect severity of the pathological process in brain. The pathogenic form of systemic endotoxinemia (SE), that is, endotoxin aggression (EA), a pathological process caused by excessive endotoxin (ET) in the bloodstream, is considered as one of the factors initiating systemic inflammation. Objective: to determine the relationship between markers of systemic inflammation and indexes of systemic endotoxinemia in patients with endogenous psychoses to evaluate the role of EA in the pathogenesis of these disorders. Materials and methods: The study included 25 female patients aged 23 to 49 years with endogenous psychoses (F20, F25 according to ICD-10). All patients experienced exacerbation of psychotic symptoms. Psychometric evaluation was performed using the PANSS scale. The control group consisted of 25 healthy women. LE and a1-PI activities and levels of antibodies to S100-B and MBP (Neuro-Immuno-Test technology), endotoxin concentration (ET) (Micro-LAL-test), and antiendotoxin immunity activity (AIA) (SOIS-IFA technology) were measured in the patients’ blood. Results: The patients had significantly increased serum activities of LE and a1-PI. The autoimmune component to neuroantigens was detected in 44% of cases. In 24% of patients with significantly increased activities of inflammatory markers, ET concentrations were increased, and AIA (mainly to the hydrophilic part of the ET molecule) was deficient, which is an unfavorable factor that aggravates the clinical course of disease. In 76% of patients, the ET concentration remained within reference values; however, AIA levels were variable, which likely resulted from a previous EA. The studied biological indexes were shown to be correlated and linked to severity of clinical symptoms as determined with PANSS. Conclusion: The study demonstrated a relationship between systemic inflammatory markers and SE indexes and their involvement in the pathogenesis of endogenous psychoses.

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Alteration of brain temperature and systemic inflammation in Parkinson’s disease

Neurological Sciences ◽

10.1007/s10072-019-04217-3 ◽

2020 ◽

Vol 41 (5) ◽

pp. 1267-1276 ◽

Cited By ~ 1

Author(s):

Hsiu-Ling Chen ◽

Kei Yamada ◽

Koji Sakai ◽

Cheng-Hsien Lu ◽

Meng-Hsiang Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Systemic Inflammation ◽

Inflammatory Markers ◽

Nuclear Dna ◽

Brain Temperature ◽

Age Groups ◽

Clinical Severity ◽

Significant Group

Abstract Objectives Parkinson’s disease (PD) is known to be related to various factors, including neuroinflammation, increased oxidative stress, and brain temperature alteration. We aimed to evaluate the correlation between these factors using diffusion-weighted imaging (DWI) thermometry and blood tests of systemic inflammation. Methods From July 2012 to Jun 2017, 103 patients with PD (44 men and 59 women; mean age, 60.43 ± 9.12 years) and 106 sex- and age-matched healthy volunteers (48 men and 58 women; mean age, 58.16 ± 8.45 years) retrospectively underwent magnetic resonance DWI thermometry to estimate brain intraventricular temperature (Tv). Subjects were divided into three subgroups in light of their ages. The tested inflammatory markers included plasma nuclear DNA, mitochondrial DNA, apoptotic leukocytes, and serum adhesion molecules. The correlations among the Tv values, clinical severity, and systemic inflammatory markers were then calculated. Results The PD patients did not show a natural trend of decline in Tv with age. Comparisons among the different age groups revealed that the younger PD subjects had significantly lower Tv values than the younger controls, but the older subjects had no significant group differences. Overall, the PD patients exhibited lower Tv values than the controls, as well as increased oxidative stress. The brain temperature showed positive correlations with inflammatory markers, including plasma nuclear DNA and L-selectin levels, in all the subjects. Conclusions Possible pathophysiological correlations between systemic inflammation and brain temperature were indicated by the results of this study, a finding which may aid us in investigating the underlying pathogenesis of PD.

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Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis

Cartilage ◽

10.1177/1947603520904776 ◽

2020 ◽

pp. 194760352090477 ◽

Cited By ~ 1

Author(s):

Cristóbal Orellana ◽

Joan Calvet ◽

Antoni Berenguer-Llergo ◽

Néstor Albiñana ◽

María García Manrique ◽

...

Keyword(s):

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Markers ◽

Cross Sectional Study ◽

Clinical Severity ◽

Womac Pain ◽

Obese Women ◽

Cross Sectional ◽

Total Pain ◽

Tnf Α

Objective Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. Design Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. Results Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. Conclusions Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.

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INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2018/51 ◽

2018 ◽

Vol 5 (1) ◽

pp. 248-254

Author(s):

Gopi S ◽

Sharif S.M

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Inflammatory Markers ◽

Clinical Severity ◽

Early Outcome

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Association Of Peripheral Inflammatory Markers With Clinical Severity Following Stroke

International Journal Of Medical Science And Clinical Invention ◽

10.18535/ijmsci/v3i1.01 ◽

2016 ◽

Cited By ~ 1

Author(s):

Kriti Gupta ◽

◽

Sourya Acharya ◽

Samarth Shukla ◽

◽

...

Keyword(s):

Inflammatory Markers ◽

Clinical Severity

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Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers

Scientific Reports ◽

10.1038/s41598-020-77093-z ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Anshul Jain ◽

Rachna Chaurasia ◽

Narendra Singh Sengar ◽

Mayank Singh ◽

Sachin Mahor ◽

...

Keyword(s):

Vitamin D ◽

Serum Ferritin ◽

Inflammatory Markers ◽

Clinical Severity ◽

Medical College ◽

Marked Variability ◽

Group A ◽

The Difference ◽

Vitamin D Supplements ◽

Group B

AbstractCOVID-19 is characterized by marked variability in clinical severity. Vitamin D had recently been reviewed as one of the factors that may affect the severity in COVID-19. The objective of current study is to analyze the vitamin D level in COVID-19 patients and its impact on the disease severity. After approval from Ethics Committee, M.L.B Medical College the current study was undertaken as continuous prospective observational study of 6 weeks. Participants were COVID-19 patients of age group 30–60 years admitted during the study period of 6 weeks. Study included either asymptomatic COVID-19 patients (Group A) or severely ill patients requiring ICU admission (Group B). Serum concentration of 25 (OH)D, were measured along with serum IL-6; TNFα and serum ferritin. Standard statistical analysis was performed to analyze the differences. Current Study enrolled 154 patients, 91 in Group A and 63 patients in Group B. The mean level of vitamin D (in ng/mL) was 27.89 ± 6.21 in Group A and 14.35 ± 5.79 in Group B, the difference was highly significant. The prevalence of vitamin D deficiency was 32.96% and 96.82% respectively in Group A and Group B. Out of total 154 patients, 90 patients were found to be deficient in vitamin D (Group A: 29; Group B: 61). Serum level of inflammatory markers was found to be higher in vitamin D deficient COVID-19 patients viz. IL-6 level (in pg/mL) 19.34 ± 6.17 vs 12.18 ± 4.29; Serum ferritin 319.17 ± 38.21 ng/mL vs 186.83 ± 20.18 ng/mL; TNFα level (in pg/mL) 13.26 ± 5.64 vs 11.87 ± 3.15. The fatality rate was high in vitamin D deficient (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients. As per the flexible approach in the current COVID-19 pandemic authors recommend mass administration of vitamin D supplements to population at risk for COVID-19.

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Monocyte Distribution Width (MDW) as novel inflammatory marker with prognostic significance in COVID-19 patients

10.21203/rs.3.rs-221351/v1 ◽

2021 ◽

Author(s):

Giovanni Riva ◽

Sara Castellano ◽

Vincenzo Nasillo ◽

Anna Maria Ottomano ◽

Giuliano Bergonzini ◽

...

Keyword(s):

Inflammatory Markers ◽

Inflammatory Marker ◽

Clinical Status ◽

Fatal Outcome ◽

Prognostic Significance ◽

Cell Subset ◽

Clinical Severity ◽

Inflammatory Disorder ◽

Cytokine Storm ◽

Distribution Width

Abstract Background: Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring during massive monocyte activation, has recently been described as promising early biomarker of sepsis. Similar to sepsis, in SARS-CoV-2-associated disease (COVID-19) monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder –commonly defined as ‘cytokine storm’– which is part of the complex infection-associated immune dysregulation observed in severe COVID-19 cases (possibly constituting a kind of viral sepsis). Therefore, in this work, we aimed at investigating, for the first time, possible roles of MDW testing in the monitoring of COVID-19 patients.Methods: We longitudinally measured MDW values (readily available along with automated blood cell count) in a cohort of 87 patients with COVID-19 diagnosis, consecutively admitted to our clinics in early 2020, due to aggravation of their clinical status. Statistical analyses were then applied to correlate MDW values with inflammatory markers, disease severity, clinical trajectories and final outcome.Results: We initially found significant direct correlations between MDW and different inflammatory markers routinely assessed during hospitalization, namely CRP (p<0.001), fibrinogen (p<0.001) and ferritin (p<0.01). Moreover, high MDW values resulted remarkably associated with fatal outcome of severe COVID-19 patients (AUC=0.76, 95% CI: 0.66-0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR=4.91, 95% CI: 1.73-13.96; OR=7.14, 95% CI: 2.06-24.71). Furthermore, when evaluating MDW dynamics in COVID-19 cases with longer follow-up, we frequently observed progressive MDW increment in patients with worsening inflammation, while clinical recovery was consistently associated with MDW decrease. Of note, MDW evaluation may also help to assess the response to immunomodulatory treatments, such as tocilizumab. Conclusions: Our pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is (i) easy and rapid to obtain, (ii) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (iii) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (iv) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.

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