Serological Inflammatory Markers Research Articles

Efficacy of probiotic supplementation and impact on fecal microbiota in patients with inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials.

The aim of this meta-analysis was to evaluate the efficacy of probiotics supplementation in patients with IBD. Randomized controlled trials (RCTs) evaluating the efficacy of probiotics in patients with IBD were searched in PubMed, the Google Scholar database, Web of Science, and CrossRef for the period July 2003 to June 2023. The RCTs were extracted, independently by 2 authors, according to the PICOS criteria. Seven studies, including a total of 795 patients, met the study criteria. Five end points were selected to evaluate the efficacy. Of these, 3 indicators showed a statistically significant difference in efficacy: C-reactive protein (odds ratio [OR]: -2.45, 95% confidence interval [CI]: -3.16, -1.73, P < .01), the number of fecal Bifidobacterium (OR: 3.37, 95% CI: 3.28, 3.47, P < .01), and Lactobacillus(OR: 2.00, 95% CI: 1.91, 2.09, P < .01). The other 2 indicators (disease activity for Crohn's disease and for ulcerative colitis) showed no statistically significant difference, while the OR reflected a positive correlation. Probiotics supplementation may have a positive effect on IBD by reducing clinical symptoms, reducing the serological inflammatory markers, and increasing favorable gut flora in patients with IBD. Additional RCTs are needed to evaluate the therapeutic effect of probiotics in IBD.

Imaging features and clinical value of 18F-FDG PET/CT for predicting airway involvement in patients with relapsing polychondritis

BackgroundThe clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in assessing relapsing polychondritis (RP) with airway involvement remains controversial. This study aimed to investigate PET/CT features of RP with airway involvement and explore its clinical value in predicting disease pattern, severity and prognosis.MethodsRP patients with airway involvement who underwent PET/CT from January 2010 to July 2022 were retrospectively reviewed. PET/CT features were analyzed both visually and semiquantitatively with the maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). Patterns of airway involvement on PET were summarized. Correlations of SUVmax and TLG of the airway were made with spirometric indicators and serological inflammatory markers (CRP and ESR). In addition, long-term follow-up was conducted through questionnaires in regard to symptom control, subjective feeling, pulmonary function, and quality of life.ResultsFifty-two cases were finally included. 18F-FDG PET showed FDG-avid lesions with increased FDG uptake in the airway among 94.2% of the patients. Three patterns (focal, multifocal and diffuse patterns) were identified. TLG of the whole airway was lower in patients with previous therapy (p = 0.046). Bronchoscopy was more sensitive in detecting tracheal abnormalities (90.7% vs.53.5%, p = 0.039) but less sensitive for peripheral airway lesions (65.1% vs. 79.1%, p = 0.046) compared with PET. SUVmax and TLG of the airway positively correlated with spirometry indicators (FEV1%pred, FEV1/FVC, MEF 50%pred, etc.) and serological inflammatory markers. Five patients died during the follow-up, with two deaths related to airway problems. Higher FDG uptake predicted worse subjective feeling, but not with symptom control or pulmonary function.ConclusionPET/CT is a valuable tool for RP with airway involvement, particularly in assessing peripheral airway lesions, and PET/CT related parameters are significantly associated with disease patterns, severity, and long-term outcomes.

The evaluation of antimicrobial stewardship for bacterial meningitis in neonates

AbstractBacterial meningitis (BM) is potentially life threatening in neonates, but the duration of antibiotic therapy is not well established. We aimed to compare the efficacy and safety among neonates suffering from BM of a relatively shortened duration of antibiotic treatment to the currently recommended course. We did a retrospective cohort study in neonates (gestational age [GA] or corrected GA ≥35 weeks) diagnosed with BM. Neonates in the study group were assigned to withdraw the antibiotics on condition that they were clinically stable after taking sufficient antibiotics with normal serological inflammatory biomarkers, whereas the cerebrospinal fluid (CSF) indicators remain abnormal. Neonates in the control group were treated until both serological and CSF indicators returned to normal as recommended. The incidence of recurrent infection after the discontinuation of antibiotics and adverse drug reactions (ADRs) during hospitalization was measured. A total of 233 neonates were enrolled, of whom 160 were assigned to a shortened antibiotic duration and 73 were treated according to the current guidelines. Twelve patients (7.5%) relapsed in the study group, whereas 4 (5.5%) relapsed in the control group (χ2 = 0.320, p = 0.572). The incidences of ADRs were similar in both groups (p &gt; 0.05). The study indicates that antibiotics might be safely discontinued in neonates (GA ≥35 weeks) diagnosed with BM who are clinically stable or improving after antibiotic treatment and feature normal serological inflammatory markers, no severe complications, and no evidence of systemic infection, even if CSF parameters are not completely normal.

Haptoglobin is an independent marker for disease severity and risk for metabolic complications in hidradenitis suppurativa: A prospective study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is highly correlated with obesity. Haptoglobin serum levels have recently been recognized as an important biomarker linking obesity with chronic inflammation. To compare haptoglobin with previously proposed serum biomarkers for the determination of disease severity in HS patients. For this purpose, disease severity of HS patients was determined by a panel of clinical scores as well as several risk factors, such as weight and smoking habits. A prospective, diagnostic accuracy study was performed at the International Centre for Hidradenitis suppurativa/Acne inversa Bochum (ICH). The study included a total of 263 patients, including 131 who had a confirmed diagnosis of HS in Hurley I (n = 16), II (n = 56) and III (n = 59) HS, and 132 healthy controls. The main outcome was to identify serological inflammatory markers for HS disease severity [severe (III) vs. moderate/mild (II/I)] as assessed by Hurley classification. The serum levels of acute phase proteins haptoglobin and CRP, as well as the number of neutrophils in peripheral blood, number of monocytes, the systemic immune-inflammation index and the pan-immune-inflammatory value correlated with disease severity according to established clinical scores (mHSS, SAHS, Hurley, DLQI). HS patients had significantly higher haptologlobin levels compared to healthy controls. Logistic regression analysis revealed haptoglobin as the only independent marker predicting severe HS. In this prospective study, we discovered that the serum levels of the acute phase protein haptoglobin levels serve as an independent marker of disease severity in HS. While this presents the first study in the context of HS. Thus, the present data not only yield a highly promising serum marker to be further validated.

Modern Concepts on the Clinic and Diagnosis of Primary Vasculitis of the Central Nervous System

Primary vasculitis of the central nervous system (PACNS) is a rare form of unknown cause vasculitis that affects the vessels of the brain, spinal cord and meninges without systemic damage. It was found that the average age of the onset of the disease was 50 years. Clinical manifestations depend on the caliber of the affected vessels. The most common initial symptoms are headache and vascular cognitive impairment associated with small vessel involvement. The development of stroke and focal symptoms is interrelated with vascular cognitive impairment and manifests as the lesion of the middle/large cerebral arteries. PACNS is difficult to diagnose, since symptoms of vasculitis outside the central nervous system are rare, serologic markers of inflammation are normal. The analysis of cerebrospinal fluid is usually abnormal due to a moderate nonspecific increase in the level of total protein or the number of leukocytes. Deviations from the norm (cerebral infarction, sometimes tumor-like lesions) are detected according to the data of magnetic resonance imaging of the brain in 97 % of patients with PACNS. Angiography has low sensitivity and low specificity, since it allows to verify vasculitis of only middle and large cerebral arteries, revealing segmental narrowing. To detect inflammation of the blood vessels, as well as to exclude other diseases, it is necessary to perform a biopsy of the substance and the soft membranes of the brain.

Contrast-Enhanced Ultrasonography for the Evaluation of Crohn's Disease in Pediatric Patients.

Contrast-enhanced ultrasonography (CEUS) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn's disease. To demonstrate the feasibility and clinical usefulness of CEUS in the estimation of Crohn's disease activity in children with endoscopy as the reference standard. In this prospective study, 30 pediatric patients with Crohn's disease (24 males and 6 females; median age 14 years) underwent CEUS from December 2020 to August 2021. The simple endoscopic score for Crohn's disease, pediatric Crohn's disease activity index, serologic inflammatory markers, fecal calprotectin and CEUS perfusion parameters were assessed and compared between the inactive and active group based on endoscopic findings. CEUS was performed successfully in all 30 patients. Two patients showed mild adverse side effects such as temporary dysosmia. The active Crohn's disease group showed higher erythrocyte sedimentation rate (mm/hr) (13.0 vs. 2.0, P = 0.003), C-reactive protein (mg/dL) (4.7 vs. 0.55, P = 0.018) and fecal calprotectin (mcg/g) (1,503 vs. 237.5, P = 0.005). Among the quantitative parameters for CEUS, the mean gradient to the peak value was higher in the active group (1.18 vs. 0.93, P = 0.034). The sensitivity and specificity of the mean gradient to the peak value for predicting active Crohn's disease was 55.6% and 83.3%, respectively, with a cut-off of 1.09 (P = 0.015). CEUS can be a safe and specific diagnostic modality for Crohn's disease activity in children. Among quantitative CEUS parameters, the mean gradient to the peak value could be used to differentiate active and inactive Crohn's disease.

NLRP3-Inflammasome Inhibition with IZD334 Does Not Reduce Cardiac Damage in a Pig Model of Myocardial Infarction.

NLRP3-inflammasome-mediated signaling is thought to significantly contribute to the extent of myocardial damage after myocardial infarction (MI). The purpose of this study was to investigate the effects of the NLRP3-inflammasome inhibitor IZD334 on cardiac damage in a pig model of myocardial infarction. Prior to in vivo testing, in vitro, porcine peripheral blood mononuclear cells and whole blood were treated with increasing dosages of IZD334, a novel NLRP3-inflammasome inhibitor, and were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). After determination of the pharmacological profile in healthy pigs, thirty female Landrace pigs were subjected to 75 min of transluminal balloon occlusion of the LAD coronary artery and treated with placebo or IZD334 (1 mg/kg, 3 mg/kg, or 10 mg/kg once daily) in a blinded randomized fashion. In vitro, NLRP3-inflammasome stimulation showed the pronounced release of interleukin (IL)-1β that was attenuated by IZD334 (p &lt; 0.001). In vivo, no differences were observed between groups in serological markers of inflammation nor myocardial IL-1β expression. After 7 days, the ejection fraction did not differ between groups, as assessed with MRI (placebo: 45.1 ± 8.7%, 1 mg/kg: 49.9 ± 6.1%, 3 mg/kg: 42.7 ± 3.8%, 10 mg/kg: 44.9 ± 6.4%, p = 0.26). Infarct size as a percentage of the area at risk was not reduced (placebo: 73.1 ± 3.0%, 1 mg/kg: 75.5 ± 7.3%, 3 mg/kg: 80.3 ± 3.9%, 10 mg/kg: 78.2 ± 8.0%, p = 0.21). In this pig MI model, we did not observe attenuation of the inflammatory response after NLRP3-inflammasome inhibition in vivo. Consecutively, no difference was observed in IS and cardiac function, while in vitro inhibition successfully reduced IL-1β release from stimulated porcine blood cells.

Personal predictive model based on systemic inflammation markers for estimation of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUNDPostoperative pancreatic fistula (PF) is a serious life-threatening complication after pancreaticoduodenectomy (PD). Our research aimed to develop a machine learning (ML)-aided model for PF risk stratification.AIMTo develop an ML-aided model for PF risk stratification.METHODSWe retrospectively collected 618 patients who underwent PD from two tertiary medical centers between January 2012 and August 2021. We used an ML algorithm to build predictive models, and subject prediction index, that is, decision curve analysis, area under operating characteristic curve (AUC) and clinical impact curve to assess the predictive efficiency of each model.RESULTSA total of 29 variables were used to build the ML predictive model. Among them, the best predictive model was random forest classifier (RFC), the AUC was [0.897, 95% confidence interval (CI): 0.370–1.424], while the AUC of the artificial neural network, eXtreme gradient boosting, support vector machine, and decision tree were between 0.726 (95%CI: 0.191–1.261) and 0.882 (95%CI: 0.321–1.443).CONCLUSIONFluctuating serological inflammatory markers and prognostic nutritional index can be used to predict postoperative PF.

Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis.

People with HIV (PWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of clonal hematopoiesis and its association with chronic inflammation and CVD in PWH. Cross-sectional study utilizing archived specimens and data from 118 men (86 PWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers. Clonal hematopoiesis was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database. Clonal hematopoiesis with a variant allele frequency (VAF) greater than 1% was significantly more common in PWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] ( P = 0.035). PWH with clonal hematopoiesis (VAF > 1%) were more likely to have coronary artery stenosis of at least 50% than those without clonal hematopoiesis [6/20 (30%) vs. 6/64 (9%); P = 0.021]. Presence of clonal hematopoiesis was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area. Clonal hematopoiesis was more common in PWH and among PWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of clonal hematopoiesis in PWH.

Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations

BackgroundAlthough autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have...

The Usefulness of Serological Inflammatory Markers in Patients with Rotator Cuff Disease-A Systematic Review.

Background and Objectives: Rotator cuff disease (RCD) is a prominent musculoskeletal pain condition that spans a variety of pathologies. The etiology and precise diagnostic criteria of this condition remain unclear. The current practice of investigating the biochemical status of RCD is by conducting biopsy studies but their invasiveness is a major limitation. Recent biochemical studies on RCD demonstrate the potential application of serological tests for evaluating the disease which may benefit future clinical applications and research. This systematic review is to summarize the results of available studies on serological biochemical investigations in patients with RCD. Methods: An electronic search on databases PubMed and Virtual Health Library was conducted from inception to 1 September 2021. The inclusion criteria were case-control, cross-sectional, and cohort studies with serological biochemical investigations on humans with RCD. Methodological quality was assessed using the Study Quality Assessment Tool for Observational Cohort and Cross-sectional studies from the National Heart, Lung, and Blood Institute. Results: A total of 6008 records were found in the databases; of these, 163 full-text studies were checked for inclusion and exclusion criteria. Nine eligible studies involving 984 subjects with RCD emerged from this systematic review. The quality of the studies found ranged from poor to moderate. In summarizing all the studies, several fatty acids, nonprotein nitrogen, interleukin-1 β, interleukin-8, and vascular endothelial growth factor were found to be significantly higher in blood samples of patients with RCD than with control group patients, while Omega-3 Intex, vitamin B12, vitamin D, phosphorus, interleukin-10, and angiogenin were observed to be significantly lower. Conclusions: This is the first systematic review to summarize current serological studies in patients with RCD. Results of the studies reflect several systemic physiological changes in patients with RCD, which may prove helpful to better understand the complex pathology of RCD. In addition, the results also indicate the possibility of using serological tests in order to evaluate RCD; however, further longitudinal studies are required.

Whole-body MRI in pediatric undefined inflammatory conditions.

Whole-body magnetic resonance imaging (WBMRI) is a multiregional imaging technique suitable for investigating the extent of multisystemic diseases without exposure to radiation, with a high sensitivity to bone alterations. The aim of our study was to evaluate the role of WBMRI in the workup of children with non-specific musculoskeletal features and non-indicative laboratory and instrumental data, who were suspected to have a rheumatologic disease. We retrospectively analyzed medical records, including laboratory tests and radiological data of 34 children who had been evaluated due to non-specific musculoskeletal manifestations, for which a WBMRI was prescribed. We included 34 children, 19 females and 15 males, mean age 10 years (range 2-16 years), with the following clinical features: diffuse arthralgia (12 children), persistent fever (2 children), persistent fever and diffuse arthralgia (20 children). Serologic inflammatory markers were increased in 29/34 patients. Twenty-five children had already received X-ray and / or ultrasound before WBMRI, with a negative / uninformative result. WBMRI was performed 3-6 weeks (median, 3.5 weeks) after the initial presentation of symptoms. In 22/34 (65%) children, WBMRI revealed some abnormalities that supported the final diagnosis. Twelve out of 34 children (35%) were be affected by chronic recurrent multifocal osteomyelitis. WBMRI is helpful in pediatric rheumatology for the differential diagnosis of undefined inflammatory conditions. It appears to be a promising tool, especially in the detection of multifocal bone lesions. The diagnosis that mainly benefits from WBMRI in our series is chronic recurrent multifocal osteomyelitis. WBMRI can also help in excluding neoplastic diseases.

OUTCOMES OF COVID-19 INFECTION: COMMUNITY-BASED RETEROSPECTIVE COHORT STUDY

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: COVID-19 infection is associated with a broad-range of clinical presentations from asymptomatic infection to severe pneumonia with multi-system features. Similarly, short- and long-term outcomes vary widely. Although multiple studies have addressed outcomes of patients hospitalized with COVID-19 infection, Community-based studies are sparse and are needed to provide a broader perspective of the lasting impact of this disease, especially lung damage. METHODS: This is a retrospective, Community-based, cohort study of residents of Rochester, Minnesota, who were enrolled in the Mayo Clinic COVID-19 database. Subjects were included if they were diagnosed with COVID-19 infection from March 01, 2020 to May 31, 2020. The clinical presentation, laboratory results, pulmonary function results, and chest imaging findings at the time of presentation and events in the following months until December 31, 2020 were assessed by review of medical records and imaging studies. RESULTS: We identified 570 community patients with COVID-19 infection;median age 38.5 years (range 18-98 years) - 526 patients did not require hospitalization while 44 (7.5%) patients (median age 51.8 years, range 20 - 81) had hypoxemia warranting admission (moderate to severe disease based on WHO clinical progression scale)[i]. At the time of hospitalization, all has undergone chest radiography, and 42 patients (95%) had chest CT with all demonstrating peripheral patchy ground glass opacities (GGOs) bilaterally.Thirteen patients (29.5%) returned for chest radiograph (median interval, 5.9 months);4 of them (13%) had residual parenchymal opacities, of whom nearly all (94%) were 45 years or older. Twenty-five patients had follow-up CT scans three months after initial diagnosis;8 patients (32%) had complete resolution of the CT infiltrates. Seventeen patients (9 females and 8 males) had residual parenchymal opacities with the most common being peripheral and bibasilar GGOs;5 patients had residual reticulonodular scarring and traction bronchiectasis on imaging. 6 patients (13.6%) underwent pulmonary function testing at follow-up visit (median interval 4.6 months), of whom 2 manifested abnormal findings consisting of mild restriction. Overall, 50% of the patients had evidence of residual lung disease (imaging and/or pulmonary function) three months after presentation. Ten patients (59%) with residual disease on chest CT had been hospitalized (six requiring ICU level of care) and manifested significantly elevated inflammatory markers (ferritin, interleukin-6 and C-reactive protein);9 out of these 10 patients with residual disease did not receive steroids at the time of hospitalization. Seven patients (41%) with residual lung infiltrates on CT scan was not hospitalized and didn’t have evidence of severe inflammatory disease. CONCLUSIONS: In our study, we assessed the initial severity and outcomes of subjects diagnosed with COVID-19 in our community and found 3% to manifest persistent lung abnormalities following the acute infection. The residual radiological findings consisted mainly of GGOs affecting the peripheral zones of the lung;however, in a minority of the patients, fibrotic changes were present. Almost two thirds of the patients with persistently abnormal imaging had been hospitalized for at least two days and had high serologic inflammatory markers (C-reactive protein, Ferritin and interleukin-6). This might indicate that the resultant fibrosis is mainly driven by post-inflammatory processes rather than the direct effect of the virus. conversely a considerable number of patients developed interstitial infiltrates without evidence of acute inflammatory reaction which may suggest another non-inflammatory etiology of these findings. Furthermore, most of our patients who manifested lung fibrosis on follow-up CT had not received steroids. Although the long-term course and significance of these residual radiologic findings are not established, prior data of Middle East Respiratory Syndrome and Se ere Acute Respiratory Syndrome suggest that most of these lesions resolve over time among those who survived hospitalization. CLINICAL IMPLICATIONS: The results of this community-based study will provide a broader perspective of the lasting impact of COVID-19 on the lungs. DISCLOSURES: No relevant relationships by Faysal Al-ghoula, source=Web Response Research - industry initiated (clinical relationship with AstraZeneca Pharmaceuticals, LP Please note: 2020 Added 04/27/2021 by Philippe Bauer, source=Web Response, value=Grant/Research Support Research - industry initiated (clinical relationship with Corvus Pharmaceuticals, Inc Please note: 2021 Added 04/27/2021 by Philippe Bauer, source=Web Response, value=Grant/Research Support No relevant relationships by Eva Carmona, source=Web Response No relevant relationships by Tobias Peikert, source=Web Response No relevant relationships by Jay Ryu, source=Web Response

Lower Expression of miR-26a in PBMCs Indicates the Occurrence of Early-Onset Neonatal Sepsis and Is Partly Mediated by the Upregulation of PTEN.

Aim: It is difficult to identify neonatal sepsis early due to the lack of specific markers. The aim of the present study was to explore whether miR-26a expression in peripheral blood mononuclear cells (PBMCs) could be used as a diagnostic marker of the disease and whether phosphatase and tensin homolog (PTEN) was involved in suppressing miR-26a expression.Methods: A total of 51 early-onset septic newborns and 102 healthy newborns were included. Blood specimens were collected from septic newborns at the time of clinical diagnosis (baseline) and again between 72 and 96 h after birth. Blood specimens were collected from healthy newborns on admission. The expressions of miR-26a and PTEN in PBMCs were measured using real-time quantitative PCR (RT-qPCR). Other data, including hemoculture, were collected from medical records.Results: In septic newborns with and without a positive hemoculture, a lower baseline level of miR-26a in PBMCs was associated with a higher risk of disease. Additionally, at baseline, there was a certain linear relationship between the levels of miR-26a and two serological inflammatory markers (i.e., white blood cell count and C-reactive protein level) in septic newborns. In addition, the baseline expressions of miR-26a and PTEN showed a reverse linear relationship. Compared with those at baseline, the expression of miR-26a was higher and the expression of PTEN was lower in septic newborns starting at 72 h after birth.Conclusion: A lower baseline miR-26a expression in PBMCs indicated the occurrence of early-onset neonatal sepsis, and a reduced miR-26a expression might be partly related to the inflammatory process and PTEN upregulation.

Arterial wall inflammation in rheumatoid arthritis is reduced by anti-inflammatory treatment

BackgroundRheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD), partly due to an increased prevalence of cardiovascular risk factors, but also due to chronic systemic inflammation inducing atherosclerotic changes of the arterial wall. The aim of this study was to determine whether anti-inflammatory therapy for the treatment of RA has favorable effects on arterial wall inflammation in RA patients. MethodsArterial wall inflammation before and after 6 months of anti-inflammatory treatment was assessed in 49 early and established RA patients using 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (18F-FDG-PET/CT). Arterial 18F-FDG uptake was quantified as maximum standardized uptake value (SUVmax) in the thoracic aorta, abdominal aorta, carotid, iliac and femoral arteries. Early RA patients (n = 26) were treated with conventional synthetic disease modifying anti-rheumatic drugs with or without corticosteroids, whereas established RA patients (n = 23) were treated with adalimumab. ResultsIn RA patients, overall SUVmax was over time reduced by 4% (difference −0.06, 95%CI −0.12 to −0.01, p = 0.02), with largest reductions in carotid (-8%, p = 0.001) and femoral arteries (−7%, p = 0.005). There was no difference in arterial wall inflammation change between early and established RA patients (SUVmax difference 0.003, 95%CI −0.11 to 0.12, p = 0.95). Change in arterial wall inflammation significantly correlated with change in serological inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). ConclusionArterial wall inflammation in RA patients is reduced by anti-inflammatory treatment and this reduction correlates with reductions of serological inflammatory markers. These results suggest that anti-inflammatory treatment of RA has favorable effects on the risk of cardiovascular events in RA patients.

Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT.

Introduction: Sarcoidosis is a T-helper cell mediated disease characterized by granulomatous inflammation. We posited that unsupervised clustering of various features in sarcoidosis would establish phenotypes associated with inflammatory activity measured by 18FDG-PET/CT. Our goal was to identify unique features capable of distinguishing clusters and subsequently examine the relationship with FDG avidity to substantiate their potential use as markers for sarcoidosis inflammation.Methods: We performed a retrospective study of a diverse, but primarily African American, cohort of 58 subjects with biopsy proven sarcoidosis followed at the University of Illinois Bernie Mac Sarcoidosis Center and Center for Lung Health who underwent 18FDG-PET/CT scan. Demographic, therapeutic, radiographic, and laboratory data were utilized in unsupervised cluster analysis to identify sarcoidosis phenotypes. The association between clusters, their defining features, and quantitative measurements on 18FDG-PET/CT was determined. The relevance of these features as markers of 18FDG-PET/CT inflammatory activity was also investigated.Results: Clustering determined three distinct phenotypes: (1) a predominantly African American cluster with chronic, quiescent disease, (2) a predominantly African American cluster with elevated conventional inflammatory markers, advanced pulmonary disease and extrathoracic involvement, and (3) a predominantly Caucasian cluster characterized by reduced lymphocyte counts and acute disease. In contrast to the chronic quiescent cluster, Clusters 2 and 3 were defined by significantly greater FDG avidity on 18FDG-PET/CT. Despite similarly increased inflammatory activity on 18FDG-PET/CT, Clusters 2, and 3 differed with regards to extrathoracic FDG avidity and circulating lymphocyte profiles, specifically CD4+ T-cells. Notably, absolute lymphocyte counts and CD4+ T-cell counts were found to predict 18FDG-PET/CT inflammatory activity by receiver operating curve analysis with a 69.2 and 73.42% area under the curve, respectively.Conclusions: Utilizing cluster analysis, three distinct phenotypes of sarcoidosis were identified with significant variation in race, disease chronicity, and serologic markers of inflammation. These phenotypes displayed varying levels of circulating inflammatory cells. Additionally, reduction in lymphocytes, specifically CD4+ T-cells, was significantly related to activity on 18FDG-PET/CT. Though future studies are warranted, these findings suggest that peripheral lymphocyte counts may be considered a determinant of sarcoidosis phenotypes and an indicator of active inflammation on 18FDG-PET/CT.

Utility of magnetic resonance imaging in Crohn's associated sacroiliitis: A cross‐sectional study

Prevalence of sacroiliitis in Crohn's disease (CD) is variable depending on defining criteria. This study utilized standardized sacroiliac joint (SIJ) magnetic resonance imaging (MRI) to identify sacroiliitis in CD patients and its association with clinical and serological markers. Consecutive adult subjects with CD prospectively enrolled from an inflammatory bowel disease clinic underwent SIJ MRI. Data collected included CD duration, history of joint/back pain, human leukocyte antigen-B27 status, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index, Harvey Bradshaw Index (HBI) for activity of CD, Ankylosing Spondylitis Disease Activity Score, and various serologic markers of inflammation. Three blinded readers reviewed MRIs for active and structural lesions according to the Spondyloarthritis Research Consortium of Canada modules. Thirty-three CD patients were enrolled: 76% female, 80% White, median age 36.4years (interquartile range 27.2-49.0), moderate CD activity (mean HBI 8.8±SD 4.5). Nineteen subjects (58%) reported any back pain, 13 of whom had inflammatory back pain. Four subjects (12%) showed sacroiliitis using global approach and 6 (18%) met Assessment of SpondyloArthritis international Society MRI criteria of sacroiliitis. Older age (mean 51.2±SD 12.5 vs. 37.2±14; P=.04), history of dactylitis (50.0% vs. 3.4%, P=.03) and worse BASMI (4.1±0.7 vs. 2.4±0.8, P≤.001) were associated with MRI sacroiliitis; no serologic measure was associated. There were 12%-18% of CD patients who had MRI evidence of sacroiliitis, which was not associated with back pain, CD activity or serologic measures. This data suggests that MRI is a useful modality to identify subclinical sacroiliitis in CD patients.

Persistent pain as an indicator of infection from low virulence organisms compared to serological inflammatory markers

Persistent pain as an indicator of infection from low virulence organisms compared to serological inflammatory markers

THU0174 ANTI-IL-6 RECEPTOR ANTIBODY AMELIORATES DISEASE ACTIVITY OF RHEUMATOID ARTHRITIS PATIENTS WITH KNEE JOINT INVOLVEMENT -ANSWER COHORT STUDY-

Background:It has been reported that rheumatoid arthritis (RA) patients who have large joint involvement associated with higher serological inflammatory markers and more functional disability1. Moreover, a previous report showed that these patients were more difficult to achieve clinical remission. However, it remains unclear which biologics are effective in the patients with RA who have large joint involvement.Objectives:The aim of this study is to investigate the efficacy of anti-IL-6 receptor antibody (aIL-6) or TNF-inhibitor (TNFi) in the treatment of RA patients who have knee joint involvement.Methods:We enrolled the 784 patients who visited our hospitals in 2003 to 2019 and were treated with aIL-6 or TNFi more than 12 weeks. We divided the patients into 2 groups with or without knee joint involvement for further analysis. Knee joint involvement was defined as the patients had at least one swelling joint of knee at baseline. We investigated the CDAI levels at baseline and 12 weeks after the initiation of biologics.Results:Interestingly, the patients who had knee joint involvement with aIL-6 significantly ameliorated ΔCDAI (n=95, 15.0±10.8; mean±SD) compared to those with TNFi (n=148, 11.4±10.3) at 12 weeks (P=0.003). aIL-6 group consists of 95 tocilizumab treated patients. TNFi group includes 25 adalimumab, 25 certolizumab pegol, 14 etanercept, 54 golimumab and 30 infliximab treated patients. Baseline clinical characteristics of the 243 RA patients who had knee joint involvement were shown in Table 1. Mean ages, sex and disease durations were not significantly different between the two groups. Baseline CDAI levels of aIL-6 group (24.8±11.8) were slightly elevated compared to those of TNFi group (21.7 ±10.9). Multivariate analysis adjusted for age, gender and baseline CDAI levels revealed that aIL-6 significantly improved ΔCDAI levels compared to TNFi (P=0.04). By contrast, in the RA patients who had no swelling of knee joints, there was no significant difference of ΔCDAI improvement between aIL-6 group (n=156, 5.5±7.4) and TNFi group (n=385, 6.7±8.9).Table 1.Baseline clinical characteristics of 243 RA patients who had knee joint involvementaIL-6 group(n=95)TNFi group(n=148)p ValueAge (mean±SD)60.7±15.261.9±14.40.58Gender (female, %)80.079.10.97Duration (year)9.3 ±10.38.4±10.50.56DAS28ESR (mean±SD)5.3±1.25.2 ±4.80.03CDAI (mean ±SD)24.8±11.821.7 ±10.90.04MTX use, (%)45.462.20.02MTX dose (mg/day)8.7 ±3.39.0 ±3.50.61PSL use, (%)44.345.60.74PSL dose (mg/day)5.5 ±3.55.1 ±2.90.55Conclusion:Thus, these findings suggest that anti-IL-6 receptor antibody was more effective in the RA patients with knee joint involvement compared to TNF- inhibitor.

CD28- Cells Are Increased in Early Rheumatoid Arthritis and Are Linked With Cytomegalovirus Status.

Objective: CD3+CD8+CD28− cells are higher in Rheumatoid Arthritis (RA). The aim of this study was to assess CD3+CD8+CD28− cells in patients with early RA and assess the effects of cytomegalovirus (CMV) seropositivity.Method: In this prospective observation study, 50 RA patients were recruited from Cardiff University Hospital of Wales (UHW) rheumatology outpatient, 25 patients with early disease (disease duration 0–6 months) and 25 patients with established disease (>2 years). These were compared with 25 healthy controls. Clinical and serological markers of inflammation were noted, and peripheral blood mononuclear cells were analyzed using flow cytometry.Results: The percentage of the CD8+CD28− T cells was increased in RA patients and was associated with disease duration. The percentage of CD8+CD28− T cells was increased in CMV positive early and established RA grouped and early RA patients in comparison to CMV negative patients (p < 0.05). There is a weak but statistically significant correlation between the percentage of CD3+CD8+CD28− cells and CRP in CMV positive RA patients (r = 0.227, p < 0.05).Conclusion: The percentage of CD8+CD28− T cells is higher in RA patients and correlates with disease duration, highlighting a potential role early in the disease process. These cells were also higher in CMV positive early RA patients which may suggest a role of CMV in disease development.