Inflammatory Activity In Patients Research Articles

Evaluation of lacrimal gland vascularisation using superb microvascular imaging: a potential diagnostic tool in Sjögren's syndrome.

To evaluate the superior microvascular imaging (SMI) findings of the lacrimal glands for the sonographic diagnosis of primary Sjögren's syndrome (pSS). 21 patients with pSS and 20 healthy groups were evaluated. Dry eye symptoms and their effects on vision-related functions were evaluated with McMonnies and Ocular Surface Disease Index (OSDI) questionnaires. Lacrimal glands were evaluated by power Doppler ultrasonography (PDUS), colour Doppler ultrasonography (CDUS) and SMI. The diagnostic accuracy of SMI was compared using these techniques. Dry eye symptoms, as determined by McMonnies and OSDI, were significantly more severe in patients with pSS than in control group (p=0.001 and p=0.021, respectively). Lacrimal gland vascular activity rates and hypoechoic areas were significantly higher in pSS patients compared to the control group (p<0.05). It was observed that the detection rates of inflammatory activity in patients with SMI were higher than CDUS and PDUS. In ROC analysis, the SMI technique has the highest accuracy in predicting the probability of pSS in the lacrimal gland compared to the others. In addition, SMI was positively correlated with CDUS, PDUS, OSDI and McMonnies (r=0.809, p<0.001; r=0.773, p<0.001; r=0.756, p=<0.001; r=0.351, p=0.021 respectively). Evaluation of the lacrimal gland by the SMI was found to be excellent in predicting the likelihood of individuals having pSS compared to CDUS and PDUS. This technique may have a role as a reliable and non-invasive adjunctive tool to assess the degree of lacrimal vascularity in pSS.

А COMPREHENSIVE STUDY OF PATIENTS WITH ISCHEMIC HEART DISEASE: AGE, GENDER, AND COMORBIDITY ASPECTS

The purpose of the study was to analyze the clinical characteristics, comorbid status, individual biochemical indicators, and systemic inflammation activity in patients with ischemic heart disease (IHD) depending on age, gender distribution, and diagnosis influence.Materials and methods. The study included 144 patients with IHD, who were divided into two groups – the main and the control. The main group comprised 120 patients with stable angina pectoris (SAP) II-III functional class (FC). The control group consisted of 24 patients with STEMI. All patients underwent a comprehensive examination: general clinical, anthropometric, laboratory (complete blood count, biochemical analysis), and instrumental (office blood pressure measurement, heart rate, and echocardiography). The comorbid profile of patients with IHD was assessed using the Charlson comorbidity index. The severity of systemic inflammation syndrome in the selected patient groups was assessed by the cellular composition of peripheral blood upon admission to the hospital, and based on the obtained data, the values of leukocyte inflammatory markers were calculated.Results. Patients in the main group were younger than those in the control group (54.78 ± 1.11 vs. 63.50 ± 1.82) (p&lt;0.001). A statistically significant predominance of men over women was found among the cohort of IHD patients (63.33% and 36.67%, respectively) (p&lt;0.001), with a tendency towards male predominance among patients with SAP II-III FC compared to those with STEMI (p = 0.074). Patients in the main group compared to those in the control group had significantly higher left ventricular ejection fraction (p&lt;0.001), systolic blood pressure (p&lt;0.001), and diastolic blood pressure (p=0.001). In the control group compared to the main group, more cases of patients with high levels of comorbidity were found (p&lt;0.001). Lower levels of creatinine, fibrinogen, prothrombin time, and glucose were observed in patients in the main group. Patients with SAP II-III FC compared to those with STEMI had lower levels of leukocyte inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR) (p&lt;0.001), systemic immune inflammation index (SII) (p=0.002), systemic inflammation response index (SIRI) (p=0.007), and aggregate index of systemic inflammation (AISI) (p=0.011).Conclusions. The study underscores the need for an individualized approach to each patient with ischemic heart disease, considering their age, gender, and comorbid characteristics, as well as laboratory peculiarities, to improve therapy outcomes and prevent complications.

Evaluation of serum neopterin levels in severe COVID-19 patients: An observational study.

In patients with coronavirus disease (COVID-19), a massive inflammatory response is a significant cause of morbidity and mortality. Inflammatory markers are prognostic indicators of disease severity and the ultimate clinical outcome. Several studies have demonstrated a correlation between serum levels of neopterin, which can be an immune system marker, disease severity, and poor outcomes in COVID-19 patients. Our study aimed to determine the diagnostic significance of neopterin in conjunction with routinely measured inflammatory markers in patients with severe COVID-19. Serum neopterin, C-reactive protein (CRP), albumin levels, and complete blood count were determined in 39 patients with severe COVID-19 and 30 healthy individuals. Demographic characteristics, serum neopterin levels, and other laboratory data were compared between patients and healthy volunteers and statistically analyzed. High neopterin levels were observed in patients with severe COVID-19 compared to healthy volunteers. Furthermore, albumin levels were decreased, while CRP levels were increased in patients, statistically significantly. Also, positive correlations were shown between serum neopterin levels and serum CRP levels, while negative correlations were shown between serum neopterin levels and serum albumin levels. Systemic inflammation markers, CRP/albumin ratio, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio were significantly higher, while lymphocyte/monocyte ratio was also significantly lower in patients with severe COVID-19 than in healthy volunteers. However, serum neopterin levels were not linked to the CRP/albumin ratio, the neutrophil/lymphocyte ratio, or the platelet/lymphocyte ratio. On the other hand, they were linked negatively to the lymphocyte/monocyte ratio. Our findings highlight the association between high neopterin levels and patients with severe COVID-19. Neopterin is correlated with traditional inflammatory biomarkers and may indicate general immune and inflammatory activation in patients with severe COVID-19.

Utility of the Endoscopic Healing Index in Identifying Active Inflammation in Patients with Crohn's Disease: Real World Data from a Tertiary Center.

The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting. This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation. Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32). In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality.

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis

BackgroundChronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. MethodsWhole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). ResultsID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. ConclusionQuantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study.

This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants. While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.

Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease.

Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings. This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE. One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 μg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 μg/g, 69% and 59% for FC = 150 μg/g and 67% and 67% for FC = 200 μg/g. FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.

P078 Inflammatory transcriptomic signatures and cell type compositions in colonic mucosa of ulcerative colitis

Abstract Background Previous studies have explored transcriptomic profiles associated with active inflammation in patients with IBD patients, but consistent characteristics of gene expression and enriched pathways, particularly in Asian patients with UC, remain unconfirmed. Here, we aimed to assess distinctive transcriptomic changes associated with persistent active mucosal inflammation in Asian patients with UC despite of medical treatment. Methods We obtained colonic mucosa biopsies of inflamed and noninflamed tissue from 15 patients with UC and 15 healthy controls and performed RNA sequencing analysis. Utilizing publicly available single cell RNA sequencing (scRNAseq) data, we also identified cell types expressing differentially expressed genes from RNAseq data and performed data deconvolution using CIBERSORTx. Results Transcriptomics profiling revealed that the inflammatory transcriptomic signature was highly enriched in the colonic mucosa of UC-active compared to UC-inactive and controls. By incorporating scRNAseq data, the genes upregulated in UC-active were highly expressed in M cells, inflammatory monocytes, and inflammatory fibroblasts, while downregulated genes were prominent in BEST4+ enterocytes and WNT5B+ fibroblasts. Notably, a sub-cluster of enterocytes associated with SAA1, SLC6A14, and DUOXA2 genes exhibited high expression in UC-active. Deconvolution analysis using CIBERSORTx identified significant enrichment of natural killer cells, inflammatory monocytes, Tuft cells, inflammatory fibroblast, WNT2B+Fos-lo1, and pericytes in UC-active. Conclusion Our RNAseq analysis not only identified significant gene expression changes but also revealed shifts in cell type proportions associated with persistent inflammation. These findings offer valuable insights for developing novel treatment strategies for UC.

Predictive value of serum markers for mucosal healing in patients with inflammatory bowel disease.

To investigate the value of serum markers in assessing mucosal healing (MH) and inflammatory activity in patients with inflammatory bowel disease (IBD). In this retrospective analysis, we examined data from 320 IBD patients, including 176 with ulcerative colitis (UC) and 144 with Crohn's disease (CD), alongside 100 healthy controls during the same period. Serum levels of various markers, including white blood cell (WBC), platelet count (PLT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) were evaluated. These indices were analyzed for their diagnostic value in endoscopic MH in IBD patients. The independent influencing factors affecting MH in IBD patients were identified by univariate and multivariate analyses. The levels of WBC, PLT, ESR, CRP, PLR, and NLR were significantly higher in IBD patients, UC patients, and CD patients than in healthy controls (all P < 0.05). For those achieving MH, their WBC, PLT, ESR, CRP, PLR, and NLR levels were significantly lower than patients who did not achieve MH (all P < 0.05). The AUCs of WBC, PLT, ESR, CRP, PLR, and NLR for the diagnosis of MH were 0.729, 0.756, 0.673, 0.707, 0791, and 0.724, respectively. A multifactorial analysis found that the presence of abdominal pain (OR: 2.155, 95% CI: 1.081-4.297, P < 0.05), higher WBC (OR: 3.927, 95% CI: 2.008-7.681, P < 0.001), higher PLT (OR: 4.181, 95% CI: 2.078-8.412, P < 0.001), higher ESR (OR: 2.221, 95% CI: 1.082-4.562, P < 0.05), higher CRP (OR: 3.874, 95% CI: 1.861-8.065, P < 0.001), higher PLR (OR: 4.087, 95% CI: 1.586-10.534, P < 0.01), and higher NLR ( OR: 2.688, 95% CI: 1.292-5.592, P < 0.01) were independent risk factors for failure in achieving MH. WBC, PLT, ESR, CRP, PLR, and NLR can be used as noninvasive markers for predicting MH in patients with IBD, and they hold promise for clinical application.

Histopathological findings of inflammatory activity in patients with subclinical carditis

In patients with Chronic Rheumatic Carditis, active carditis is an often underdiagnosed condition. Rheumatic attacks promote the aggravation of existing lesions, leading to a deterioration of the patient’s clinical condition. Thus, reducing the morbidity and mortality of the disease depends, in part, on controlling relapses through secondary prophylaxis. Underdiagnosis is due in part to the occurrence of subclinical rheumatic attacks. This study was carried out with data from patients who were diagnosed with Chronic Rheumatic Carditis and who underwent cardiac surgery for valve replacement or repair, without clinical or laboratory evidence of rheumatic outbreak. A fragment of myocardium was sent for histopathological analysis. Data on the frequency of histopathological alterations compatible with a rheumatic outbreak were analyzed. After analysis, 80% of patients showed changes compatible with inflammatory activity. Of these, 87.5% had lymphocytic infiltrate; 25% had Aschoff’s nodules. The most frequent histopathological findings of chronic disease were myocardial hypertrophy in 56.7% of patients and fibrosis in 53.3%.

Liver inflammation activity in patients with autoimmune hepatitis with normal alanine aminotransferase and immunoglobulin G levels

Background and aimsNormal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels. MethodsTwo hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation. ResultsOne hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045–1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138–2.014, P = 0.004) were independent factors associated with advanced inflammation. ConclusionsHigh proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

Гематологические индексы – новые маркеры воспалительной активности у больных с трофическими язвами нижних конечностей в пожилом, старческом возрасте и у долгожителей

Aim. To study the significance of various hematological indices as markers of laboratory inflammatory activity in patients with trophic ulcers of the lower extremities and compare them with similar indices in old patients with coronary artery disease (CAD). Materials and methods. The study enrolled 256 patients; 166 patients with trophic ulcers – in the main group, 90 with CAD, but without ul-cers – in the comparison group. The main group consisted of 31.9% men and 68.1% women. The mean age of patients with trophic ulcers reached 80.8±10.1 years (from 61 to 101 years); 30.1% of patients were centenarians. The ratio of the number of neutrophils to lymphocytes (NLR), neu-trophils to monocytes (NMR), platelets to lymphocytes (PLR), lymphocytes to monocytes (LMR) and systemic immune-inflammation index (SII –platelet count хNLR) were determined. Results. The mean count of leukocytes in patients with trophic ulcers was 7.1±2.6×109/l, neutrophils – 4.7±2.3×109/l, lymphocytes –1.8±2.2×109/l, monocytes – 0.6±0.3×109/l, platelets – 278.5±110×109/l. The mean values of NLR in the group of patients with ulcers reached 3.6, NMR – 15.4, PLR – 214.1, LMR – 5.9, SII – 1102.3. In patients with trophic ulcers, the count of leukocytes (6.7×109/l and 5.9×109/l; p=0.002), neutrophils (4.2×109/l and 3.7×109/l; р=0.002) and platelets (252×109/l and 205×109/л; p&lt;0.0001) was significantly higher than in the group of patients with CAD. NLR (2.7 and 2.1; p=0.003) and PLR (172 and 133; p&lt;0.0001) in patients with trophic ulcers of the lower extremities was higher, but LMR was lower (2.8 and 3.1; p=0.01), than in patients with CAD. In the group of patients with trophic ulcers, the median of the SII reached 452, while in patients with CAD it was 296 (p=0.00003). The median of erythrocyte sedimentation rate in patients with the lower ex-tremities ulcers was 32 mm/h, in patients with CAD – 21 mm/h (p=0.00002).A direct relationship was registered between interleukin-6 level and leukocytes (r=0.32; p=0.01), neutrophils (r=0.36; p=0.005), platelets (r=0.36; p=0.006), NLR (r=0.30; p=0.02), PLR (r=0.27; p=0.03) and SII (r=0.31; p=0.01). Conclusions. The study results suggest that various hematological indices can be used as markers of laboratory inflammatory activity in patients with trophic ulcers of the lower extremities in the old age and centenarians.

Deep learning-based diagnosis of disease activity in patients with Graves’ orbitopathy using orbital SPECT/CT

PurposeOrbital [99mTc]TcDTPA orbital single-photon emission computed tomography (SPECT)/CT is an important method for assessing inflammatory activity in patients with Graves’ orbitopathy (GO). However, interpreting the results requires substantial physician workload. We aim to propose an automated method called GO-Net to detect inflammatory activity in patients with GO.Materials and methodsGO-Net had two stages: (1) a semantic V-Net segmentation network (SV-Net) that extracts extraocular muscles (EOMs) in orbital CT images and (2) a convolutional neural network (CNN) that uses SPECT/CT images and the segmentation results to classify inflammatory activity. A total of 956 eyes from 478 patients with GO (active: 475; inactive: 481) at Xiangya Hospital of Central South University were investigated. For the segmentation task, five-fold cross-validation with 194 eyes was used for training and internal validation. For the classification task, 80% of the eye data were used for training and internal fivefold cross-validation, and the remaining 20% of the eye data were used for testing. The EOM regions of interest (ROIs) were manually drawn by two readers and reviewed by an experienced physician as ground truth for segmentation GO activity was diagnosed according to clinical activity scores (CASs) and the SPECT/CT images. Furthermore, results are interpreted and visualized using gradient-weighted class activation mapping (Grad-CAM).ResultsThe GO-Net model combining CT, SPECT, and EOM masks achieved a sensitivity of 84.63%, a specificity of 83.87%, and an area under the receiver operating curve (AUC) of 0.89 (p < 0.01) on the test set for distinguishing active and inactive GO. Compared with the CT-only model, the GO-Net model showed superior diagnostic performance. Moreover, Grad-CAM demonstrated that the GO-Net model placed focus on the GO-active regions. For EOM segmentation, our segmentation model achieved a mean intersection over union (IOU) of 0.82.ConclusionThe proposed Go-Net model accurately detected GO activity and has great potential in the diagnosis of GO.

Сonnection of immunological markers with morphological manifestations in ulcerative colitis

Background. Inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, are an urgent problem of modern gastroenterology. Therefore, the discovery of new laboratory approaches makes it possible to assess the degree of the disease. Purpose: to reveal the relationship between morphological manifestations and immunological indicators in patients with ulcerative colitis. Materials and methods. The studies were conducted on biological material (blood and colonic biopsy samples) of 90 patients with ulcerative colitis. The thickness of the mucosa, density of the inflammatory infiltrate and its composition, crypt sizes, their architectonics, the presence of crypt abscesses, atrophic and fibrotic changes were calculated in biopsies by morphological and morphometric methods. Immunological studies included the evaluation of mononuclear cells, the levels of B-lymphocytes, interleukin-10, tumor necrosis factor α, immunoglobulins (Ig) A, M, G. Results. The histological activity of the disease was determined by an increased level of inflammatory infiltrate (14,431.4 ± 483.3 per 1 mm2 of stroma) and the presence of many neutrophilic granulocytes (212.2 ± 20.9 per 1 mm2 of stroma) and lymphocytes (2,922.8 ± 76.6 per 1 mm2 of stroma) in it. Also, some patients had crypt abscesses (36.7 % of the total number of patients) and breaches in the epithelial integrity (54.4 % of the total number of patients). A correlation was found between the level of CD22+ lymphocytes and some morphometric parameters: the width of the crypts (r = 0.27; P &lt; 0.01) and the height of the surface epithelium (r = 0.30; P &lt; 0.01); between IgM concentrations and cellular density of mucosal infiltrate (r = 0.29; P &lt; 0.01), neutrophils (r = 0.28; P &lt; 0.01) and basophils (r = 0.24; P &lt; 0.05); level of IgA and macrophages (r = 0.21; P &lt; 0.05), lymphocytes (r = 0.24; P &lt; 0.05), basophils (r = 0.25; P &lt; 0.05). Conclusions. It is shown that some morphological and morphometric indicators are related to immunological parameters. It was found that the elevated level of cytokines correlates with the activity of inflammation in patients with ulcerative colitis. The level of CD22+ lymphocytes and changes in some morphometric indicators (crypt width and surface epithelium height) are directly related to an increase in inflammatory processes in the intestinal mucosa.

Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors.

this is an exploratory study to evaluate calprotectin serum levels in patients with rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) treatment. this is a retrospective observational study including patients with irAEs rheumatic syndromes. We compared the calprotectin levels to those in a control group of patients with RA and with a control group of healthy individuals. Additionally, we included a control group of patients treated with ICI but without irAEs to check calprotectin levels. We also analysed the performance of calprotectin for the identification of active rheumatic disease using receiver operating characteristic curves (ROC). 18 patients with rheumatic irAEs were compared to a control group of 128 RA patients and another group of 29 healthy donors. The mean calprotectin level in the irAE group was 5.15 μg/mL, which was higher than the levels in both the RA group (3.19 μg/mL) and the healthy group (3.81 μg/mL) (cut-off 2 μg/mL). Additionally, 8 oncology patients without irAEs were included. In this group, calprotectin levels were similar to those of the healthy controls. In patients with active inflammation, the calprotectin levels in the irAE group were significantly higher (8.43 μg/mL) compared to the RA group (3.94 μg/mL). ROC curve analysis showed that calprotectin had a very good discriminatory capacity to identify inflammatory activity in patients with rheumatic irAEs (AUC of 0.864). the results suggest that calprotectin may serve as a marker of inflammatory activity in patients with rheumatic irAEs induced by treatment with ICIs.

Commentary: Behçet's uveitis - Expanding treatment horizons.

Behçet’s disease is a complex multisystem disease. A standalone positive typing for HLA-B51 is not considered diagnostic, and the diagnosis of this uveitic entity is based on a myriad of multisystem clinical signs that make up the diagnostic criteria.[1] The genetic predisposition to this disease afforded by HLA-B51 positivity (along with other non-HLA genes) has been postulated to get along with an altered microbiome in the gut of Behçet patients, with an additional possible contribution from infectious agents such as Streptococcus sanguinis, to trigger and then sustain an immune response, which disrupts a previously intact T-cell homeostatic environment. This recent understanding has expanded treatment horizons beyond standard treatment protocols, to include biologic therapy, especially tumor necrosis factor-alpha (TNF-α) antagonists, to achieve control of repeated disrupted immune response.[1] Progressive sight-threatening Behçet’s disease involving the entire uveal tract blinds up to 25% of patients within a course of 10 years, after which the disease progression tends to stabilize.[1,2] This mandates an excellent control of inflammation within this all-important “window period” to save the eye either from the direct inflammatory manifestations of Behçet’s uveitis or its potentially blinding complications.[1] The consensus in uveitis management in Behçet’s disease (according to the European Alliance of Associations of Rheumatology [EULAR] and the American Academy of Ophthalmologists’ guidelines) recommends limitation of steroid administration for control of acute inflammation and substituting steroids with conventional disease-modifying antirheumatic drugs (DMARDs) or biologic therapy. Furthermore, the American Academy of Ophthalmology goes a step further to recommend bypassing the “classic DMARDs” in favor of anti-TNF-α agents in severe, sight-threatening uveitis.[3] Thus, EULAR updated its guidelines in 2018 to recommend administering steroids in posterior segment ocular Behçet’s disease patients, but only in combination with steroid-sparing therapies such as azathioprine (AZA), cyclosporine A (CsA), interferon alpha, or monoclonal anti-TNF antibodies.[3] In the current study[4] of Behçet’s disease with ocular lesions from India, all patients have received steroids and 80% patients have been treated with immunosuppression along with steroids. Randomized controlled trials have shown that the antimetabolite AZA and T-cell inhibitor CsA are effective in the treatment of posterior uveitis in Behçet’s disease. Hence, the updated 2018 EULAR guidelines recommended the use of these two drugs (as against others) in the initial therapy of posterior uveitis.[3] Further, the combined use of AZA and CsA, whether as first- or second-line therapy, has shown efficacy in controlling ocular Behçet’s disease (with more periodic side effect monitoring).[1] In the current study from India, AZA and CsA have been combined in 24% of the patients.[4] In Behçet’s disease, TNF-α production by macrophages, CD4+ and CD8+ T cells, and natural killer cells is increased. The reduction of circulating TNF-α has been shown to result in dramatic improvement in the inflammatory activity of patients with severe pan or posterior uveitis.[1] These anti-TNF-α drugs used are recombinant monoclonal antibodies directed against TNF-α. Due to their potent and fast effects, these agents are now used alone or in combination therapy in refractory ocular Behçet’s cases, or sometimes even as first-line treatment in severe sight-threatening attacks.[3] Adalimumab (ADA) is a fully human monoclonal antibody directed against TNF-α and has been tested against a placebo in both active and quiescent, noninfectious uveitis (VISUAL I and VISUAL II studies, respectively). Ocular Behçet’s disease represented 7% of the uveitic cases enrolled in them.[1] Further, other uncontrolled studies have shown significant results regarding the efficacy of ADA in Behçet’s uveitis.[5] Early initiation of ADA in two children with Behçet’s uveitis succeeded in control of the disease activity, allowing tapering of topical and systemic steroids.[6] Comparative studies have been conducted between ADA and the other agent infliximab (IFX), notably a multicenter study on 177 patients with refractory Behçet’s disease uveitis, which found that both agents gave significantly better control in terms of disease activity as the first-line treatment, but the ADA group had higher percentage of patients with better best corrected visual acuity and fewer drug-related reactions.[7] One must remember that exclusion of tuberculosis and other infectious diseases as well as occult malignancies is mandatory before starting therapy with these agents. Also, an additional immunosuppressant (like methotrexate) may be advisable to prevent anti-chimeric, or antihuman, antibody production, which decreases the efficacy of these agents leading to secondary failure.[1] In the current study from India, biologic agents have been used in 40% of the patients; of which ADA was used in 28% and IFX in 12% of patients.[4] Finally, studies have recently reported success with Janus kinase (JAK) inhibitors in the treatment of noninfectious autoimmune uveitis refractory to conventional DMARDs and anti-TNF-α agents. Successful results have been reported with the JAK inhibitor tofacitinib in refractory Behçet’s disease uveitis,[8] and moving forward, these agents shall most likely further expand our treatment horizons for Behçet’s disease.

Changing Face of Inflammatory Activation in Complex Coronary Artery Disease during the COVID-19 Pandemic

The COVID-19 pandemic has changed the immunological status of the population, indicating increased activation. The aim of the study was to compare the degree of inflammatory activation in patients admitted for surgical revascularization in the period before and during the COVID-19 pandemic. This retrospective analysis included an analysis of inflammatory activation assessed on the basis of whole blood counts in 533 patients (435 (82%) male and 98 (18%) female) with a median age of 66 (61-71) years who underwent surgical revascularization, including 343 and 190 patients operated on in 2018 and 2022, respectively. The compared groups were matched by propensity score matching analysis, obtaining 190 patients in each group. Significantly higher values of preoperative monocyte count (p = 0.015), monocyte-to-lymphocyte ratio (p = 0.004) and systemic inflammatory response index (p = 0.022) were found in the during-COVID subgroup. The perioperative and 12-month mortality rates were comparable, with 1% (n = 4) in 2018 vs. 1% (n = 2) in 2022 (p = 0.911), and 5.6 % (n = 11 patients) vs. 7% (n = 13 patients) (p = 0.413), in the pre-COVID and during-COVID subgroups, respectively. Simple whole blood analysis in patients with complex coronary artery disease performed before and during the COVID-19 pandemic indicates excessive inflammatory activation. However, the immune variation did not interfere with one-year mortality rate after surgical revascularization.

Validation of the simplified magnetic resonance index of activity by using DWI without gadolinium enhancement to evaluate bowel inflammation in Crohn's disease.

To validate the modified simplified magnetic resonance index of activity (sMARIA) score using DWI on non-contrast magnetic resonance enterography (MRE) to evaluate active inflammation in patients with Crohn's disease (CD), compared to the original sMARIA scoring system, with and without contrast enhancement. This retrospective study included 275 bowel segments from 55 CD patients who underwent ileocolonoscopy and MRE within a 2-week period. Two blinded radiologists evaluated original sMARIA on both conventional MRE (CE-sMARIA) and non-contrast MRE (T2-sMARIA). Modified sMARIA was then evaluated using non-contrast MRE, replacing ulcerations with DWI grades. Three scoring systems were compared for diagnostic accuracy of active inflammation, correlation with simple endoscopic score (SES)-CD, and interobserver reproducibility. The AUC of modified sMARIA for detecting active inflammation (0.863, 95% confidence interval [0.803-0.923]) was significantly higher than T2-sMARIA (0.827 [0.773-0.881], p = 0.017), and comparable to CE-sMARIA (0.908 [0.857-0.959], p = 0.122). CE-sMARIA, T2-sMARIA, and modified sMARIA all showed moderate correlation with SES-CD (r = 0.795, 0.722, and 0.777, respectively). Interobserver reproducibility of diffusion restriction (κ, 0.686 [0.602-0.770]) was significantly better than ulcers on conventional MRE (κ, 0.382 [0.212-0.552]; p = 0.001) and T2-weighted image (κ, 0.312 [0.034-0.590]; p = 0.012). Modified sMARIA using DWI can improve the diagnostic performance of sMARIA on non-contrast MRE, showing comparable performance to sMARIA using contrast-enhanced MRE. • DWI can improve the diagnostic performance of non-contrast magnetic resonance enterography (MRE) for assessing active inflammation in patients with Crohn's disease. • Modified simplified magnetic resonance index of activity (sMARIA) using DWI grades in place of ulcers showed comparable diagnostic performance to sMARIA using conventional MRE with contrast-enhanced sequences.

Inflammatory Activity in Patients with Obstructive and Non-obstructive Coronary Artery Disease

Aim. To study the levels of pro-inflammatory biomarkers in patients with obstructive and non-obstructive coronary artery disease (CAD), to identify possible differences for diagnosing the degree of coronary obstruction.Material and methods. The observational study included two groups of patients: with non-obstructive (main group, coronary artery stenosis &lt;50%; n=30) and obstructive (comparison group, hemodynamically significant coronary artery stenosis according to the results of coronary angiography; n=30) CAD. The levels of interleukin-1β (IL-1β) and interleukin 6 (IL-6) were measured in plasma using enzyme immunoassay.Results. IL-6 levels were significantly higher in patients with obstructive CAD (p=0.006) than in patients with non-obstructive CAD. There were no significant differences in the level of IL-1β in both groups (p=0.482). When constructing the ROC curve, the threshold value of IL-6 was 26.060 pg/ml. At the level of IL-6 less than this value, CAD was diagnosed with hemodynamically insignificant stenoses of the coronary arteries.Conclusion. The results of this study confirm that in patients with different types of coronary artery lesions, there are differences in the activity of the inflammation process in the arterial wall. IL-6 was higher in the obstructive lesion group, and IL-1β levels did not differ between groups. Thus, it can be assumed that hemodynamically significant obstruction of the coronary arteries develops as a result of highly active inflammation of the vascular wall. Given the presence of a proven biological basis and the available data on the effectiveness of monoclonal antibodies to IL-1β, one cannot exclude their possible benefit in a cohort of patients with CAD and hemodynamically insignificant stenoses.

P349 Faecal Calprotectin in Ulcerative Colitis - Associations with Mucosal Inflammatory Activity and Disease Extent

Abstract Background In ulcerative colitis (UC), faecal calprotectin (FC) correlates with endoscopic severity and disease extent, and low levels are associated with histological remission [1, 2]. The effect of mucosal inflammatory activity versus disease extent on the FC levels, remains poorly understood. We aimed to compare FC levels in patients grouped by endoscopic and histologic scores of the inflammatory activity. We also grouped patients according to active disease extent based on endoscopic or histological evaluations. Methods This was a post hoc analysis of patients diagnosed with UC or with confirmed UC at Stavanger University Hospital, Norway, from 2012 to 2020. Visits were performed at diagnosis, and after 3 and 11 months. FC was analysed in samples collected from 4 weeks before until 3 days after visits (EliA Calprotectin or EliA Calprotectin 2, Thermo Scientific). At each visit, colonoscopy was performed, and biopsies were collected from three colorectal segments (rectum, left colon, right colon). Mucosal inflammatory activity was scored endoscopically by Mayo Endoscopic Score (MES 0 – 3) and histologically by Nancy Histological Index (NHI 0 – 4). The highest value of the segmental NHI scores were reported. Disease extent was defined by Montreal classification. Distribution of acute inflammation was defined by the number of colorectal segments with NHI ≥ 2 (presence of neutrophilic infiltrates). Results In total 554 visits of 249 patients were analysed. FC levels increased significantly for every stepwise increase in MES, and median FC was 30-fold (range 19-49) higher in MES 3 than in MES 0 subgroups. The largest difference was observed between MES 1 and MES 2 (Figure 1a). FC levels also increased significantly for every stepwise increase in NHI, except between NHI 3 and NHI 4. Median FC level was 54-fold higher in NHI 4 group compared with the NHI 0 group, and the largest difference was observed between NHI 1 and NHI 2 (Figure 1b). Disease extent showed little effect on FC, and significant difference was only observed between proctitis and pancolitis with 3-fold (range 1.6 – 4.5) higher levels in the latter groups (Figure 2a). Median FC level was 3-fold higher in patients with acute inflammation in all 3 segments compared to patients with acute inflammation in only 1 colorectal segment (Figure 2b). Conclusion FC increased significantly by increasing mucosal inflammatory activity, whereas disease extent showed a modest effect on the FC levels. FC is an accurate and useful biomarker of both endoscopic and histological inflammatory activity in patients with ulcerative colitis.