Total Inflammation Score Research Articles

Association between musculoskeletal sonographic features and response to treatment in patients with psoriatic arthritis.

To investigate the association between musculoskeletal sonographic features and clinical features, as well as treatment outcomes, in patients with active psoriatic arthritis (PsA). A prospective cohort study was conducted involving patients with active PsA. Disease activity was assessed clinically at baseline and 3-6 months after initiating therapy, with a Disease Activity Index for PsA (DAPSA) score calculated. A baseline ultrasound examination of 64 joints, 28 tendons and 16 entheses evaluated the following lesions: synovitis, peritenonitis, enthesitis, tenosynovitis, new bone formation and erosions. Total scores for each lesion and total inflammatory and structural scores were calculated. The association between baseline sonographic scores and treatment outcomes was assessed using Cox proportional hazards models (for drug persistence) and generalised estimating equation models for DAPSA change. A total of 135 treatment periods (107 patients) were analysed. Multivariable analysis showed that a greater reduction in DAPSA score at follow-up was associated with higher baseline synovitis (β -3.89), peritenonitis (β -3.93) and enthesitis structural scores (β -2.91). Additionally, the total inflammatory score independently predicted DAPSA change (β -5.23) regardless of the total structural damage score. Drug persistence was analysed in 105 treatment periods, revealing that a higher sonographic erosion score was associated with earlier drug discontinuation (adjusted HR 1.28, 95% CI 1.03 to 1.61). The study results provide preliminary evidence supporting the utility of musculoskeletal ultrasound in predicting treatment response and drug persistence in PsA.

Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration

Introduction: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. Methods: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. Results: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3−54] versus 6 [3−25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. Conclusion: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses.

Perimenstrual worsening of asthma occurs in up to 40% of women with asthma, leading to increased acute exacerbations requiring clinical care. The role of sex hormones during these times remains unclear. In the current study, we used a translational approach to determine whether progesterone exacerbates allergic inflammation in the traditional chicken egg ovalbumin (OVA) model in BALB/c mice. Simultaneously, we used peripheral blood mononuclear cells (PBMC) from healthy human donors to assess the effects of progesterone on circulating group 2 innate lymphoid cells (ILC2). Briefly, lungs of ovariectomized (OVX) or sham-operated female (F-Sham) controls were implanted with a progesterone (P4, 25 mg) (OVX-P4) or placebo pellet (OVX-Placebo), followed by sensitization and challenge with ovalbumin (OVA). Progesterone increased total inflammatory histologic scores, increased hyper-responsiveness to methacholine (MCh), increased select chemokines in the bronchoalveolar lavage (BAL) and serum, and increased ILC2 and neutrophil numbers, along the airways compared with F-Sham-OVA and OVX-Placebo-OVA animals. Lung ILC2 were sorted from F-Sham-OVA, OVX-Placebo-OVA and OVX-P4-OVA treated animals and stimulated with IL-33. OVX-P4-OVA lung ILC2 were more responsive to interleukin 33 (IL-33) compared with F-Sham-OVA treated, producing more IL-13 and chemokines following IL-33 stimulation. We confirmed the expression of the progesterone receptor (PR) on human ILC2, and showed that P4 + IL-33 stimulation also increased IL-13 and chemokine production from human ILC2. We establish that murine ILC2 are capable of responding to P4 and thereby contribute to allergic inflammation in the lung. We confirmed that human ILC2 are also hyper-responsive to P4 and IL-33 and likely contribute to airway exacerbations following allergen exposures in asthmatic women with increased symptoms around the time of menstruation.NEW & NOTEWORTHY There is a strong association between female biological sex and severe asthma. We investigated the allergic immune response, lung pathology, and airway mechanics in the well-described chicken egg ovalbumin (OVA) model with steady levels of progesterone delivered throughout the treatment period. We found that progesterone enhances the activation of mouse group 2 innate lymphoid cells (ILC2). Human ILC2 are also hyper-responsive to progesterone and interleukin 33 (IL-33), and likely contribute to airway exacerbations following allergen exposures in women with asthma.

P013 Magnetic Resonance Imaging-Based Average T2 Signal as A Non-Invasive Measure of Fibrosis In Enteric Crohn’s Disease

Abstract Background In Crohn’s Disease (CD), 10% of patients present with fibrostenosis with a further 10% progressing from inflammatory to a fibrostenotic disease behaviour over 7 years. 40% of fibrostenotic CD patients need surgery at 5 years compared to ~10% with inflammatory disease. Present non-invasive fibrosis biomarkers lack the required accuracy needed to be used routinely for clinical decision making. T1, T2, diffusion weighted imaging, motility and bowel volumes have shown promise in the non-invasive measure of fibrosis. Methods The primary objective of this study is to undertake biological validation of MRI measures as independent imaging biomarkers of histological fibrosis with the primary outcome being the correlation between MRI measures and histological fibrosis measures. GI-Seg (Motilent, London, UK) is an image analysis tool used to segment the gastrointestinal tract on T2W MRI scans. Patients with CD histological diagnosis and in need of surgical resection for stenosis attended a one-hour 3T MRI scanning session within 12 weeks prior to their intestinal resection surgery. Histological samples were scored by a specialized gastrointestinal pathologist for inflammation, fibrosis, and muscular hypertrophy. An expert radiologist with the help of the histopathologist located the strictures on DWI, quantitative T2&amp;T2 scans, and T2 weighted clinical MRI scans. GI-Seg was used to generate a 3D model of the stricture on T2W scans measuring bowel wall volume and average signal intensity of each stricture. Pearson correlation coefficient was used to quantify the correlation between the variables. Results A total of 10 CD patients, encompassing 20 strictures, were included in the study. The analysis revealed that the average T2 signal has a significant correlation with global fibrosis scores (r(20) = .563, p = .010) (Figure) and total inflammation scores (r(20) = .451, p = .046). Additionally, stricture volume showed a fair correlation with chronic inflammation component scores (r(20) = .453, p = .045). Notably, quantitative T1 values correlated with total inflammation scores (r(17) = .493, p = .045). Conclusion The study reveals fair correlations between the T2 signal average and both global fibrosis and global inflammation scores, as well as between stricture volume and chronic inflammation in CD strictures. While these findings indicate that the GI-seg tool's measurements of bowel wall volume and signal intensity have potential utility as imaging biomarkers for fibrosis and inflammation, the results also underscore the necessity for additional markers that are specifically correlated with fibrosis. Such markers are essential to distinctly identify fibrotic changes, independent of inflammatory processes.

ВЗАИМОСВЯЗЬ ТИПА ЛИЧНОСТИ D И НАРУШЕНИЯ ФУНКЦИИ ЭНДОТЕЛИЯ У ПАЦИЕНТОВ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА

Introduction. Major psychosocial risk factors for acute myocardial infarction include depression, anxiety (various anxiety syndromes and disorders), pessimistic D personality type, work and family stress, anger/hostility, lack of social support, and low socioeconomic status. There are few studies evaluating the association between psychological factors and myocardial infarction. Aim. The aim of the study was to study the relationship of personality type D with the development of endothelial dysfunction in patients with acute myocardial infarction. Material and methods. The study included 158 patients, mean age 58.2±2.5 years, who were admitted to the hospital for ST-segment elevation myocardial infarction. The diagnosis was established according to the clinical guidelines of the Russian Society of Cardiology, 2020. In addition to the traditional clinical and instrumental examination, on the 3rd–7th day after the development of myocardial infarction, patients underwent an assessment of plasma concentrations of inflammatory biomarkers and psychological testing using anxiety and depression rating scales. In the group of patients, individuals with and without personality type D were identified. Results and discussion. Personality type D was found in 29.1% of patients with acute myocardial infarction. Patients with personality type D were significantly younger, employed and married, had a higher body mass index and a significantly greater hereditary burden of arterial hypertension. In patients with personality type D, the values of pro-inflammatory markers were statistically significantly different from the comparison group, which indicates the intensity of subclinical inflammation and cytokine imbalance. Personality type D was significantly associated with total inflammation score and total endothelial dysfunction score. Significant differences were found in the ratio of patients with depressive conditions in subgroups of patients with personality type D. The values of echocardiographic parameters were also associated with the presence of personality type D. Conclusion. Personality type D was associated with impaired endothelial function in men with acute myocardial infarction, they were more likely to have depressive disorders. An adverse effect of personality type D on the cardiovascular system in patients with myocardial infarction was revealed.

Vesicoureteral Reflux Causes Interstitial Inflammation in Pediatric Kidney Allograft: A Clinicopathological Analysis of 1-Year Protocol Biopsies

Introduction: At present, there is limited evidence of the histological impact of vesicoureteral reflux (VUR) on pediatric kidney allografts. In this study, we aimed to investigate the relationship between VUR diagnosed by voiding cystourethrography (VCUG) and 1-year protocol biopsy results. Methods: One hundred thirty-eight pediatric kidney transplantations were performed in Toho University Omori Medical Center between 2009 and 2019. We included 87 pediatric transplant recipients who were evaluated for VUR by VCUG prior to or at the time of the 1-year protocol biopsy and underwent a 1-year protocol biopsy after transplantation. We evaluated the clinicopathological findings of the VUR and non-VUR groups, and histological scores were evaluated using the Banff score. Tamm-Horsfall protein (THP) within the interstitium was identified by light microscopy. Results: Of the 87 transplant recipients, 18 cases (20.7%) were diagnosed with VUR by VCUG. The clinical background and findings were not significantly different between the VUR and non-VUR groups. The pathological findings revealed a significantly higher Banff total interstitial inflammation (ti) score in the VUR group than in the non-VUR group. Multivariate analysis indicated a significant relationship between the Banff ti score and THP within the interstitium, and VUR. The 3-year protocol biopsy results (n = 68) revealed a significantly higher Banff interstitial fibrosis (ci) score in the VUR group than in the non-VUR group. Conclusion: VUR caused interstitial fibrosis in the 1-year pediatric protocol biopsies, and interstitial inflammation at the 1-year protocol biopsy may affect interstitial fibrosis at the 3-year protocol biopsy.

Automated scoring of total inflammation in renal allograft biopsies.

Computer-assisted scoring is gaining prominence in the evaluation of renal histology; however, much of the focus has been on identifying larger objects such as glomeruli. Total inflammation impacts graft outcome, and its quantification requires tools to identify objects at the cellular level or smaller. The goal of the current study was to use CD45 stained slides coupled with image analysis tools to quantify the amount of non-glomerular inflammation within the cortex. Sixty renal transplant whole slide images were used for digital image analysis. Multiple thresholding methods using pixel intensity and object size were used to identify inflammation in the cortex. Additionally, convolutional neural networks were used to separate glomeruli from other objects in the cortex. This combined measure of inflammation was then correlated with rescored Banff total inflammation classification and outcomes. Identification of glomeruli on biopsies had high fidelity (mean pixelwise dice coefficient of .858). Continuous total inflammation scores correlated well with Banff rescoring (maximum Pearson correlation .824). A separate set of thresholds resulted in a significant correlation with alloimmune graft loss. Automated scoring of inflammation showed a high correlation with Banff scoring. Digital image analysis provides a powerful tool for analysis of renal pathology, not only because it is reproducible and can be automated, but also because it provides much more granular data for studies.

Total cortical interstitial inflammation predicts chronic kidney disease progression in patients with lupus nephritis.

End-stage kidney disease (ESKD) from lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Kidney biopsy is the gold standard for diagnosis and prognostication of LN. While interstitial fibrosis and tubular atrophy (IFTA) predict progression to ESKD, the National Institutes of Health (NIH) classification of interstitial inflammation in unscarred cortical parenchyma is not predictive of chronic kidney disease (CKD) progression. The objective of this study was to determine whether total cortical interstitial inflammation that accounts for inflammation in the entire cortical parenchyma could predict CKD progression in patients with LN. Early identification of at-risk patients may improve outcomes. This retrospective cohort study included 125 SLE patients with LN class III, IV, V or mixed (III/V, IV/V) on the index biopsy (2005-2018). Kidney biopsies were reviewed and assigned based on the 2018 NIH Activity Index (AI) and tubulointerstitial lesion categories. Total interstitial inflammation in the entire cortical parenchyma was graded as 0, 1, 2 or 3, corresponding to <10%, 10-25%, 26-50% and >50%, respectively, of the total cortical parenchyma containing an inflammatory infiltrate (similar to the definition used in the Banff total inflammation score). CKD progression was defined as an estimated glomerular filtration rate decrease of ≥30% within 5years after the index biopsy. Kaplan-Meier survival curves and Cox proportional hazards models were performed to compare the two scoring systems, the total cortical intestinal inflammation score and the NIH interstitial inflammation score as predictors of CKD progression. Of 125 patients, 46 experienced CKD progression; 21 of 46 subsequently developed ESKD, 28 (22.4%) had moderate-severe total cortical interstitial inflammation and 8 (6.4%) had moderate-severe NIH interstitial inflammation. There were no differences in baseline characteristics between progressors and nonprogressors. Total cortical interstitial inflammation was associated with CKD progression in time-dependent analyses [hazard ratio 2.45 (95% confidence interval 1.2-4.97)] adjusted for age at biopsy, race, sex, LN class and hypertensive vascular change on kidney biopsy. The NIH interstitial inflammation was not associated with CKD progression. In contrast to the current NIH interstitial inflammation classification, accounting for interstitial inflammation in the entire cortical parenchyma allows identification of patients at risk for CKD progression in LN.

Red propolis reduces inflammation in cyclophosphamide-induced hemorrhagic cystitis in rats.

Introduction. Cyclophosphamide (CP) is used to treat malignant neoplasias and control autoimmune diseases. Still, one of its metabolites, acrolein, is toxic to the urothelium and can lead to hemorrhagic cystitis and severe discomfort.Objective. To evaluate the ability of red propolis to prevent and treat CP-induced hemorrhagic cystitis in rats.Materials and methods. Red propolis was extracted in 1% gum arabic and administered subcutaneously (sc). In the first experiment, groups IA, IIA, and IIIA and groups IB, IIB, and IIIB received water, gum arabic (GA), or propolis, respectively, for 30 days. Then water (controls) or CP (treatment) was administered i.p. In the second experiment, groups IVA, VA, and VIA received water i.p. while groups IVB, VB, and VIB received CP i.p. This was followed by 5 injections at 2-hour intervals with either water, GA, or propolis. Bladder tissue was examined according to Gray’s criteria.Results. The total inflammatory histology score was significantly smaller in group VIB (11.33 ± 2.07). Mild inflammation predominated in group VIB while most of the animals in group IVB had severe inflammation (p=0.0375). Ulcers were predominantly multiple in Groups IVA and VB but rare or absent in Group VIB (p=0.0118). Urothelial cells were mostly absent in groups IVB and VB and present/normal in group VIB (p=0.0052). Fibrin was abundant in groups IVB and VA but mostly absent in group VIB (p=0.0273).Conclusions. Red propolis can reduce inflammation in CP-induced hemorrhagic cystitis in rats.

Magnetic resonance imaging characteristics in patients with spondyloarthritis and clinical diagnosis of heel enthesitis: post hoc analysis from the phase 3 ACHILLES trial

ObjectiveTo investigate the imaging characteristics and clinically assess heel enthesitis in spondyloarthritis (SpA) by applying in a post hoc analysis the Heel Enthesitis Magnetic Resonance Imaging Scoring system (HEMRIS) in blinded and centrally-read MRI data from the ACHILLES trial (NCT02771210).MethodsACHILLES included patients (≥18 years) with active psoriatic arthritis or axial SpA with clinical and MRI-positive heel enthesitis refractory to standard treatment. Patients were randomized to receive subcutaneous secukinumab 150/300 mg or placebo. At week 24, patients on placebo were switched to secukinumab treatment. MRI-positive heel enthesitis was confirmed in all patients by local investigators. MRIs were performed at 3 timepoints: screening and weeks 24 and 52. In the present analysis, all MRIs were re-evaluated by 2 blinded central readers in a consensus read fashion for a priori defined MRI parameters based on HEMRIS.ResultsAt screening, 171/204 (83.8%) of patients presented with entheseal inflammation and/or structural damage, considering both the Achilles tendon and plantar fascia. Pathologies were more evident in the Achilles tendon area compared to the plantar aponeurosis. The most frequent pathologies were intra-tendon hypersignal and retrocalcaneal bursitis. The mean total entheseal inflammation score at screening in the Achilles tendon area was 2.99 (N=204) and the mean change (standard deviation [SD]) from screening to weeks 24 and 52 was − 0.91 (1.99) and − 0.83 (2.12) in the secukinumab group vs − 0.48 (1.86) and − 0.80 (1.98) in the placebo-secukinumab group, respectively. The mean total structural damage score at screening was 1.36 (N=204) and the mean change (SD) from screening to weeks 24 and 52 was 0.00 (0.65) and − 0.06 (0.56) in the secukinumab group vs 0.08 (0.48) and 0.04 (0.75) in the placebo-secukinumab group, respectively.ConclusionsBased on the newly developed HEMRIS, entheseal inflammation and/or structural damage was confirmed in 83.3% of ACHILLES patients. Pathologies were more evident in the Achilles tendon area compared to plantar fascia, with the inflammatory parameters being more responsive with secukinumab treatment compared to placebo. The present analysis, with detailed information on individual MRI parameters, contributes to the scientific debate on heel enthesitis.Trial registrationClinicalTrials.gov NCT02771210.

Bacteriological and pathological investigations on the preputial glands of one-year-old C57BL/6NCrl mice maintained in individually ventilated cages.

Spontaneous infections of the preputial glands represent overlooked health problems in mice that could raise welfare concerns and potentially confound scientific experiments. Agents involved in preputial gland infections have rarely been investigated, with opportunistic pathogens of laboratory animals usually detected in inflamed preputial glands. The aim of this study was to investigate the prevalence of bacterial infection in the preputial glands and the relationship between haematological and pathological changes and infection status. We analysed 40 preputial glands from 20 one-year-old C57BL/6NCrl male mice by using bacteriology, haematology and pathology. Bacteria were isolated from 16/20 (80%) mice, for a total of 32/40 (80%) examined preputial glands. Enterobacter cloacae, Pasteurella spp., Klebsiella spp. and Staphylococcus aureus were identified in 35%, 17.5%, 15% and 12.5% of the examined glands, respectively. Preputial gland inflammation was identified in 29/40 (72.5%) glands and was classified as chronic interstitial adenitis in 27 cases and suppurative adenitis in the remaining two glands. No haematological changes were found in mice with infected glands. Histologically, the presence of intralesional bacteria, intraluminal necrotic material, intraluminal keratin accumulation, interstitial inflammatory cell infiltrate and granulocytes (intraluminal and/or interstitial), along with total inflammatory score and total histopathological score, were significantly increased in infected glands and correlated with the bacterial load. Most severe inflammatory changes were identified after S. aureus infection, while ductal hyperkeratosis was significantly increased in glands infected with Klebsiella spp. In conclusion, preputial gland infection was a common event in one-year-old C57BL/6NCrl mice, and bacterial load correlated with pathological findings, while systemic effects were not highlighted by haematology.

Potential therapeutic effects of ethyl pyruvate in an experimental rat appendicitis model

BackgroundPathophysiology of appendicitis is associated with the underlying inflammatory processes. Ethyl pyruvate (EP) has potent antioxidant and anti inflammatory properties. In this study, we aimed to investigate the effects of EP on the treatment of appendicitis and to examine whether adding EP to the antibiotic treatment could increases the effectiveness of the treatment in a rat appendicitis model. MethodThirty two Wistar rats, which had previously created appendicitis, were randomly divided into 4 groups: Group 1 (0.1 ml saline solution), Group 2 (15 mg/kg ceftriaxone), Group 3 (50 mg/kg EP), Group 4 (EP 50 mg/kg + ceftriaxone 15 mg/kg). In all groups, saline solution, ceftriaxone and EP were administered intraperitoneally and the same procedure was repeated twice a day for the following five days. On day 6, the rats underwent relaparotomy and then intraabdominal findings were recorded. Histopathological examination and interleukin 6 (IL 6) level were performed on appendiceal specimens. ResultsIntra abdominal adhesion score was significantly lower in Group 4 than in Group 1. Total inflammation score was significantly lower in Group 2 than in Group 1 and was significantly lower in Group 4 than in Group 3 and 1. IL 6 level was significantly lower in Group 4 than in Group 3 and 1. ConclusionWe found that adding EP to the antibiotic therapy increased the efficacy of the treatment in the rat appendicitis model. Further studies are required to apply our findings to the clinical setting.

Filgotinib decreases both vertebral body and posterolateral spine inflammation in ankylosing spondylitis: results from the TORTUGA trial.

ObjectivesTo assess the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active AS in the TORTUGA trial.MethodsIn the TORTUGA trial, patients with AS received filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, spine MRIs were evaluated using the Canada–Denmark (CANDEN) MRI scoring system to assess changes from baseline to week 12 in total spine and subscores for inflammation, fat, erosion and new bone formation (NBF) at various anatomical locations. Correlations were assessed between CANDEN inflammation and clinical outcomes and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores and between baseline CANDEN NBF and baseline BASFI and BASMI scores.ResultsMRIs from 47 filgotinib- and 41 placebo-treated patients were evaluated. There were significantly larger reductions with filgotinib vs placebo in total spine inflammation score and most inflammation subscores, including posterolateral elements (costovertebral joints, transverse/spinous processes, soft tissues), facet joints and vertebral bodies. No significant differences were observed for corner or non-corner vertebral body inflammation subscores, spine fat lesion, bone erosion or NBF scores. In the filgotinib group, the change from baseline in the total inflammation score correlated positively with the SPARCC spine score. Baseline NBF scores correlated with baseline BASMI but not BASFI scores.ConclusionsCompared with placebo, filgotinib treatment was associated with significant reductions in MRI measures of spinal inflammation, including in vertebral bodies, facet joints and posterolateral elements.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov), NCT03117270.

Investigating Associations Between Depressive Symptoms and Anti-/Pro-Inflammatory Nutrients in an Elderly Population in Northern China: A Bayesian Kernel Machine Regression Approach.

BackgroudThe potential for dietary inflammation has been shown to be associated with a variety of chronic diseases. The relationship between the potential for dietary inflammation and depression in the elderly is unclear.ObjectiveThis study aimed to exam the relationship between different nutrients and the risk of depression symptoms in the elderly.MethodsIn total, 1865 elderly in northern China were investigated at baseline from 2018 to 2019 and followed up in 2020. We measured the baseline intake of 22 nutrients and used Least Absolute Shrinkage and Selection Operator(LASSO) regression analysis and Bayesian Kernel Machine Regression (BKMR) to explore the association between exposure to a variety of nutrients with different inflammatory potentials and the risk of depressive symptoms.ResultsA total of 447 individuals (24.0%) were diagnosed with depressive symptoms. Through the lasso regression model, it was found that 11 nutrients are significantly related to the risk of depressive symptoms, of which 6 nutrients are pro-inflammatory nutrients (inflammation effect score>0), and 5 are anti-inflammatory nutrients (inflammation effect score<0). We incorporated the inflammatory effect scores of 11 nutrients into the BKMR model at the same time, and found that the overall inflammatory effect of 11 nutrients increased with the increase of total inflammatory scores, suggesting that the overall effect was pro-inflammatory. BKMR subgroup analysis shows that whether in the pro-inflammatory nutrient group or the anti-inflammatory nutrient group, multiple nutrients have a significant combined effect on depressive symptoms. By comparing the overall and group effects, we found that the inflammatory effects of the pro-inflammatory diet and the anti-inflammatory diet in the study’s diet are offset by each other (P<0.005).ConclusionWe determined the combined effect of multiple nutrients of different inflammatory potential classifications on depressive symptoms in the elderly.

PD11-02 PROSTATE INFLAMMATION AND COLLAGEN CONTENT ARE INVERSELY CORRELATED IN HUMAN BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-02 PROSTATE INFLAMMATION AND COLLAGEN CONTENT ARE INVERSELY CORRELATED IN HUMAN BENIGN PROSTATIC HYPERPLASIA Emily Serrell, Andrew Schneider, Matthew Grimes, Sijan Wang, and Wade Bushman Emily SerrellEmily Serrell More articles by this author , Andrew SchneiderAndrew Schneider More articles by this author , Matthew GrimesMatthew Grimes More articles by this author , Sijan WangSijan Wang More articles by this author , and Wade BushmanWade Bushman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate inflammation and fibrosis have been implicated in the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Mouse studies have shown prostate inflammation to produce tissue hyperplasia and an increase in prostatic collagen content (fibrosis). Here we examined the connections of inflammation, age, prostate volume (PV) and collagen content in human BPH surgical specimens. METHODS: Prostate tissue specimens were collected from patients treated by surgery for BPH/LUTS from 2005-2016. Patients were excluded if pathologic examination revealed >5% prostate cancer. PV was determined by transrectal ultrasound or pelvic CT scan. Collagen content was assessed by picrosirius red staining and digitally quantified. Inflammation was assessed by immunostaining with the pan-leukocyte marker CD45 and scored manually by a blinded observer. Associations between PV, age, collagen, and inflammation were evaluated by scatterplot analysis. RESULTS: In 53 men (mean age 65.1 (47-88)), the average PV was 65.5cc (47-88). Collagen content was positively correlated with age (0.34, p=0.01) but was negatively correlated with total inflammation score (r=-0.28, p=0.04). The correlations between increasing PV and both inflammation and collagen content were bimodal with a significant change point at 70 grams (p=0.002). For smaller prostates, inflammation increased (0.49, p=0.002) and collagen decreased (-0.35, p=0.03). For larger prostates, inflammation decreased (-0.29, p=0.30) and collagen increased (0.17, p=0.23). CONCLUSIONS: Our data reveal that age is a strong determinant of collagen content in BPH. In contrast to studies performed in mice, we found an inverse relationship between inflammation and collagen content. This difference may reflect different net effects of inflammation induced collagen degradation and synthesis in the dense stroma of the human prostate versus the more delicate stroma of the mouse. Finally, we found that small and larger prostates have a fundamentally different relationship to inflammation and collagen content, suggesting distinctive molecular or genetic mechanisms for prostate growth and inflammation. Source of Funding: VA Merit Award. I01 BX003454-01 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e197-e198 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emily Serrell More articles by this author Andrew Schneider More articles by this author Matthew Grimes More articles by this author Sijan Wang More articles by this author Wade Bushman More articles by this author Expand All Advertisement Loading ...

POS0257 TOWARDS A SIMPLIFIED FLUID-SENSITIVE MRI-PROTOCOL IN SMALL JOINTS OF THE HAND IN EARLY ARTHRITIS PATIENTS: RELIABILITY BETWEEN MDIXON AND REGULAR FSE FAT SATURATION MRI-SEQUENCES

Background:MRI facilitates early recognition of rheumatoid arthritis (RA) by depicting inflammation. Contrast-enhanced T1-weighted and T2-weighted fat-suppressed sequences have been sensitive and thus recommended, but are hampered by invasiveness, costs and long scan time. Therefore we introduced a modified Dixon-sequence (mDixon) which is more patient-friendly, reduces cost, and scan times by 83%. However, it is not known if this mDixon-sequence is reliable in relation to regular MRI-sequences with and without contrast (T1- and T2-weighted, respectively).Objectives:We determined the reliability between regular MRI-sequences with and without contrast (T1- and T2-weighted, respectively) and mDixon-MRI in early arthritis patients.Methods:29 early arthritis patients underwent regular fat-suppressed-MRI (T1- and T2-weighted) and mDixon-sequences, of metacarpophalangeal-2-5 and wrist-joints. Two readers scored erosions, osteitis, synovitis and tenosynovitis. Intraclass correlation coefficients (ICCs) between readers, and comparing the two sequences, were studied. Spearman correlations were determined.Results:Performance between the two readers with the regular-MRI sequences, was good to excellent (ICCs all ≥0.88). The between reader ICC was also good to excellent for the mDixon-MRI (ICCs all ≥0.76). Next, ICCs between the two sequences was investigated to determine the reliability of mDixon. ICCs were good to excellent for total RAMRIS score 0.87 (95%CI 0.74-0.94), for erosions 0.88 (95%CI 0.69-0.95), and total inflammation score 0.84 (95%CI 0.69-0.82). The individual MRI-inflammation scores, had ICCs for osteitis 0.97 (95%CI 0.93-0.98), for tenosynovitis 0.78 (95%CI 0.58-0.89), and for synovitis 0.57 (95%CI 0.26-0.77). In addition, scores were highly correlated for total RAMRIS, erosions, and total MRI-inflammation score (ρ=0.82, ρ=0.81, ρ=0.80, respectively).Conclusion:Regular-MRI sequences and mDixon-MRI perform equally well, this suggests that mDixon-sequence is reliable to detect joint inflammation. Thus, this is the first step towards an simplified and abridged MRI-protocol in small hand-joints in early arthritis patients. The ultimate goal will be implementation of this mDixon-MRI sequence. Validation in larger studies is warranted.Disclosure of Interests:None declared

OP0141 EFFECTS OF FILGOTINIB ON SPINAL LESIONS IN ANKYLOSING SPONDYLITIS: MAGNETIC RESONANCE IMAGING DATA FROM THE TORTUGA TRIAL

Background:The oral Janus kinase 1 preferential inhibitor filgotinib (FIL) significantly improved Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) inflammation scores (bone marrow oedema) in the spine and sacroiliac joints vs placebo (PBO) in the Phase 2 TORTUGA trial (NCT03117270) in patients with active ankylosing spondylitis (AS).1Objectives:This post-hoc analysis evaluated the effects of FIL on Canada-Denmark (CANDEN) MRI measures of spinal inflammation and structural lesions in patients from the TORTUGA trial.Methods:TORTUGA was a PBO-controlled, multicentre, double-blind, randomised trial. Patients with active AS (as per modified New York classification criteria, with sacroiliitis confirmed by central reading) were treated with FIL 200 mg (n=58) or PBO (n=58) once daily for 12 weeks. MRI of the total spine was conducted at baseline and at treatment end. Scans were re-evaluated post-hoc by 2 independent experts (blinded to time point and assigned treatment) using the CANDEN method;2 inter-reader discrepancies were resolved by an independent adjudicator. Observed changes from baseline were evaluated using analysis of covariance, with factors for treatment, baseline value, and randomisation stratification by prior tumour necrosis factor inhibitor use. Least-squares (LS) mean changes from baseline and between-group differences with 95% confidence intervals (CI) were calculated; P values are nominal.Results:MRI scans from 88 patients (47 FIL, 41 PBO) with an evaluable scan at baseline and Week 12 (or early termination) were re-evaluated. Baseline characteristics were generally similar between patients with/without an MRI scan. Of those with MRI scans, mean total spine inflammation score (which ranges from 0–614) was higher, and mean ankylosis score (which ranges from 0–460) was lower, in the FIL vs PBO group at baseline. Total spine inflammation scores decreased from baseline with FIL but not with PBO (Figure and Table; P=0.0003 for between-group difference). Cumulative probability plots favoured FIL over PBO for change from baseline in subregion inflammation scores, including posterolateral elements (i.e. sum of lesions in ribs, transverse processes, spinous processes, soft tissue inflammation, and postero-lateral vertebral body), facet joint, and vertebral body. Total spine fat lesion scores numerically increased from baseline in the FIL but not PBO group (P=0.0878 for between-group difference; Table). There were no significant differences between groups for changes in erosion (P=0.1956) or ankylosis (P=0.3888) scores (Table).Table 1.Change from baseline at Week 12 in CANDEN total spine inflammation, total spine fat, total spine bone erosion, and ankylosis scoresTreatment groupnSample mean (SE)LS mean (SE)95% CI of treatment meanLS mean of group difference (SE)95% CI of group differenceBetween-group P valueTotal spine inflammation scoreFilgotinib47–4.98 (0.96)–4.40 (1.13)–6.65, –2.15–4.49 (1.21)–6.85, –2.120.0003Placebo410.29 (0.78)0.09 (1.13)–2.17, 2.34Total spine fat scoreFilgotinib471.01 (0.62)1.09 (0.66)–0.22, 2.401.18 (0.69)–0.18, 2.550.0878Placebo41–0.25 (0.19)–0.09 (0.66)–1.40, 1.21Total spine bone erosion scoreFilgotinib470.01 (0.02)0.07 (0.03)0.00, 0.140.05 (0.04)–0.02, 0.120.1956Placebo41–0.02 (0.03)0.02 (0.03)–0.04, 0.09Total ankylosis scoreFilgotinib470.30 (0.29)0.23 (0.31)–0.40, 0.850.28 (0.34)–0.37, 0.940.3888Placebo41–0.01 (0.08)–0.06 (0.31)–0.68, 0.56SE, standard errorConclusion:This is the first PBO-controlled trial to demonstrate a decrease in inflammatory activity with FIL, not only in the spinal vertebrae but also in the postero-lateral elements of the spine and facet joints. As expected in a 12-week study period, no changes in erosion or ankylosis were seen, while fat lesions showed a tendency to increase with FIL. Larger trials are needed to confirm these results.

Frequency of Intradialytic Hypotension Events Do Not Increase with Oral Nutritional Supplementation during Hemodialysis Treatment: A Randomized Controlled Trial

This study aimed to compare the effect of the use of a renal-specific oral nutritional supplement (RS-ONS) during hemodialysis sessions and the use of RS-ONS at home on the incidence of intradialytic hypotension. A single-center, 12-week, open-label, randomized controlled clinical trial was conducted. The intervention was a RN-ONS divided into two portions: 100 and 137mL. The first portion was given after 1hour of hemodialysis (HD) treatment, while the second portion was given 45minutes before the end of HD. The research staff registered the baseline and final nutritional parameters and systolic arterial pressure (SAP) from the screen of the HD device during 36 HD sessions. Hypotension symptoms were also recorded every hour during each HD session. The nutritional and functional status was also assessed. We registered a total of 16 hypotensive events during 1082 HD sessions: 9 were in patients supplemented at home (551 HD sessions) and 7 occurred in patients supplemented during HD P=.668. Incidence of intradialytic hypotension (IH) during 1082 HD sessions was 1.4%. The total malnutrition inflammation score (MIS) decreased in both groups (P<.01), and the percentage of cachexia improved in the supplemented-during-HD group (P<.05). In this randomized controlled trial, intradialytic hypotension events did not increase with the RS-ONS during HD treatment. This strategy appears to be a safe anabolic nutritional strategy for the prevention of PEW, selecting stable patients and administering a fractioned volume of the supplement after the first hour of HD treatment. More studies with larger samples size are required to confirm these findings.

Integration of eHealth Into Pediatric Inflammatory Bowel Disease Care is Safe: 3 Years of Follow-up of Daily Care.

The aim of the study was to evaluate integration of an eHealth solution, www.young.constant-care.com, into daily care (I-eHealth). The I-eHealth solution was offered to inflammatory bowel disease (IBD) patients ages 10 to 17 years old in nonbiological treatment. The application was used monthly and in case of flare-ups. Blood and fecal calprotectin (FC) were tested every 3 months and during flare-ups. A total inflammation score (based on symptoms and FC) was visualized for the patient in a traffic light curve. An IBD nurse followed up on the registrations every 2 weeks. Patients had 1 yearly planned visit at the hospital. On-demand visits were arranged depending on the total inflammation. I-eHealth results were compared with data from a previous randomized clinical trial (RCT)-eHealth study (the control group of which had 4 planned annual visits). Thirty-six IBD patients were followed by I-eHealth, mean age 14.7 years (SD 7.75). The median (interquartile range [IQR]) duration of using I-eHealth was 1.9 years (0.29-2.51), equal to 66.11 patient-years, compared with 40.45 in the RCT-eHealth group and 46.49 in the RCT-control group. On-demand visits per patient-year did not differ between the groups: 1.13 (I-eHealth), 1.16 (RCT-eHealth), and 0.84 (RCT-control) (P = 0.84/0.85). Hospitalizations and acute outpatient visits per patient-year did not differ between the groups: 0.11 and 0.11 (I-eHealth), 0.05 and 0.02 (RCT-eHealth), 0.11 and 0.11 (RCT-control) (P = 0.17/0.81 and 0.12/0.81). Time to first escalation of medication, and time to first on-demand visit, did not differ between the I-eHealth group and data from the clinical trial (Log rank: P = 0.25 and P = 0.61). I-eHealth is comparably with results from eHealth under RCT supervision.

Single-snip paralimbal incision: A quick approach to rectus muscles.

INTRODUCTION:Less invasive and quicker surgeries have become common. We compared two conjunctival incisional approaches in strabismus, namely Follow standard paralimbal approach for (SPLA) and single-snip paralimbal (SSPLA).MATERIALS AND METHODS:Forty-four patients with horizontal strabismus qualifying for uniocular recession–resection surgeries were randomized to SPLA and SSPLA. SSPLA involved a single v-shaped incision, with the apex of the V near the limbus, and the limbs facing away: by pinching up the conjunctiva with a forceps and delivering the single snip with a spring scissors. We compared the postoperative grades of redness, congestion, chemosis, foreign body sensation, and drop intolerance at day 1, 2 weeks, and 6–8 weeks; scar visibility, as yes or no, at 6–8 weeks; success rates, considered to be within 10 prism diopters of orthophoria, at 6–8 weeks; and operation duration in minutes.STATISTICAL ANALYSIS:Statistical analysis was done using Mann–Whitney U-test, for inflammatory grades, Chi-square for proportions, and t-test for parametric measures. Statistical significance was set at P < 0.05.RESULTS:On postoperative day 1, congestion (P = 0.02), foreign-body sensation (P = 0.04), and total inflammatory score (P = 0.003) were statistically significantly favoring the SSPLA group. While at 2 weeks, only congestion (P = 0.02) was found to be significantly less in the SSPLA group. There were no significant differences in the proportions of scar visibility (5/22 in the SPLA vs. 3/22 in the SSPLA) and success rate: 20/22 vs. 18/22. The SSPLA was quicker on an average by 6 min (P < 0.001, 95% confidence interval: 3.2–8.7).CONCLUSION:Compared to the SPLA, the SSPLA is quicker and results in lesser inflammation in the immediate postoperative period.