Active Inflammatory Disease Research Articles

Role of Red Cell Distribution Width in Evaluation of Inflammatory Bowel Disease Activity

Role of Red Cell Distribution Width in Evaluation of Inflammatory Bowel Disease Activity

Largely Accelerated Arterial Aging in Rheumatoid Arthritis Is Associated With Inflammatory Activity and Smoking in the Early Stage of the Disease.

Background: Rheumatoid arthritis (RA) patients have a shorter life expectancy than the general population primarily due to cardiovascular comorbidities. Objectives: To characterize arterial aging in RA. Patients and Methods: Coronary calcium score (CCS) were available from 112 RA patients; out of these patients, follow-up CCS were measured for 54 randomly selected individuals. Control CCS were obtained from the MESA database (includes 6,000 < participants); arterial age was calculated from CCS. Results: RA patients were significantly older (10.45 ± 18.45 years, p < 0.001) in terms of the arterial age than the age-, gender-, and race-matched controls. The proportion of RA patients who had zero CCS was significantly less (p < 0.01) than that of those in the MESA reference group. Each disease year contributed an extra 0.395 years (p < 0.01) on the top of the normal aging process. However, the rate of the accelerated aging is not uniform, in the first years of the disease it is apparently faster. Smoking (p < 0.05), previous cardiovascular events (p < 0.05), and high blood pressure (p < 0.05) had additional significant effect on the aging process. In the follow-up study, inflammatory disease activity (CRP > 5 mg/L, p < 0.05) especially in smokers and shorter than 10 years of disease duration (p = 0.05) had the largest impact. Conclusion: Arterial aging is faster in RA patients than in control subjects, particularly in the first 10 years of the disease. Inflammation, previous cardiovascular events, and smoking are additional contributing factors to the intensified coronary atherosclerosis progression. These data support that optimal control of inflammation is essential to attenuate the cardiovascular risk in RA.

Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID.

Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease. To assess the impact of radiotherapy on IBD course. A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S+1 to S+6) radiotherapy and IBD flare during follow-up. Sixty-one patients (32 women, mean age 59years), with 467 patient semesters of follow-up, treated for digestive (n=31), urinary tract (n=23) and gynaecological cancers (n=7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S+1 to S+3 (P=0.15 vs S-4 to S-1) and 16% (10-25) from S+4 to S+6 (P=0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare. Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period.

Immunological analysis of vitamin D receptor gene expression in Egyptian patients with rheumatoid arthritis: relation to disease activity and functional disability

BackgroundVitamin D (vit D) deficiency has recently been associated with risk of development of rheumatoid arthritis (RA). The aim of this research was to assess vitamin D receptor (VDR) gene expression in Egyptian patients with RA and its relation with the inflammatory state, disease activity, and functional disability.ResultsRA patients had significantly lower vit D level and VDR gene expression compared to controls (mean ± 17.0 ± 6.65, 20.73 ± 8.42 ng/ml, p < 0.05 and 3.29 ± 5.47, 14.22 ± 12.60, p < 0.001 respectively). Receiver operating characteristic (ROC) curve analysis for VDR gene expression in RA patients revealed (area under the curve 0.826, cutoff value for low VDR expression 1.05 ng/ml). Patients with low VDR expression had significantly higher ESR, CRP, double positive RF+ anti-CCP+, DAS28, and MHAQ (p < 0.001, p = 0.001, p < 0.05, p < 0.001, p < 0.001) respectively.ConclusionVitamin D and VDR expression are significantly lower in RA patients than controls. Patients with low VDR gene expression had significantly higher disease activity and disability. This may suggest that apart from low vit D levels, low VDR expression is associated with inflammatory process and it has a potential role in RA pathogenesis and prognosis. Further multicenter studies are needed to confirm these findings.

High Sensitive C- Reactive Protein in Patients with Angiographically Proved Coronary Artery Disease

Introduction: Atherosclerosis is associated with increased inflammatory activity and risk of vascular disease. The hypothesis is that, the hs-CRP testing might have prognostic usefulness for patients with CAD. Considering a major role of hs-CRP in atherothrombosis, its measurements can provide a novel method to detect individuals at high risk of rupture of plaque.&#x0D; Aim of the Work: This study was performed to find out the relation of high sensitive CRP (hs-CRP) with angiographically proved coronary artery disease (CAD) and its severity.&#x0D; Methodology: Total 125 patients underwent CAG in present study, of them 36% were females and 64% were males, predominated by male sex (‘p’ &lt;0.001.&#x0D; Results: The mean for hs-CRP levels was 1.67(±0.85) mg/L and significantly high in patient with CAD. Strong correlation was formed between age ≥ 45 years and hs-CRP 1-3 mg/ L in present cohort of CAD. About one third of population with CAD had dyslipidemia of them majority (2/3rd) had hs-CRP 1-3 mg/L. Two-third of patients with CAD with tobacco consumption in any form had hs-CRP 1-3 mg/L and was significant than &lt; 1 mg/L and &gt;3 mg/L hs-CRP level. The hs-CRP level associated favorably with the frequency and extent of the CAD in present study (r=0.664).&#x0D; Conclusion: High sensitive CRP offers better risk stratification, predictive and prognostic value, in patients with CAD. Further studies and interventions are mandatory to identify the independent role of hs-CRP as a CAD risk factor and its cost effectiveness in a population of a developing country like India.

Hysteroscopy in Abnormal Uterine Bleeding

Aims: To evaluate the role of hysteroscopy in abnormal uterine bleeding in women of reproductive age group and to correlate the hysteroscopic findings with histopathology.&#x0D; Methods: The study was carried out in the Department of Obstetrics and Gynecology at Patan Academy of Health Sciences, Kathmandu. Thirty patients of age group 20-61years with abnormal uterine bleeding were included. Demonstrable pelvic pathology like cancer of cervix, vagina or endometrium and active pelvic inflammatory disease (PID) were excluded. All patients were assessed using hysteroscopy and findings were correlated with histopathology.&#x0D; Results: On hysteroscopy, endometrium was normal in 30%, hyperplastic in 30%, polyps found in 20% and atrophic in 10%. Endometrial polyp and submucous fibroid was seen in 6.7% cases and 3.3% cases each. On confirmation by histopathology the findings were: normal endometrium in 40% cases, hyperplastic in 40%, polyp in 16.7% and atrophic in 3.3%. Submucous fibroid and suspicious endometrium came to be endometrial hyperplasia on histopathology.&#x0D; Conclusions: Hysteroscopy has more than 90% diagnostic accuracy to diagnose endometrial morphology and diagnostic agreement of endometrial finding is 63.33%.&#x0D; Keywords: abnormal uterine bleeding, hysteroscopy, predictive value

Arterial stiffness could reflect increased cardiac load and reduced pulmonary function in the general population

Abstract Background Pulmonary function is known to decrease with age and reduced pulmonary function has been reported to be associated with all-cause mortality and cardiovascular death. The association between pulmonary impairment and atherosclerosis was reported previously but has not been investigated sufficiently in the general population. Purpose We hypothesized that arterial stiffness could reflect increase of cardiac load and reduced pulmonary function. The present study aimed to investigate whether increased cardiac load and reduced pulmonary function could affect arterial stiffness in the general population. Methods Subjects undergoing their health check-up were enrolled. Plasma B-type natriuretic peptide (BNP) levels and serum high-sensitivity cardiac troponin I (hs-cTnI) levels were measured to evaluate cardiac load and myocardial damage. Radial augmentation index (rAI) was measured to investigate arterial stiffness using HEM-9000AI device. Subjects with an ST-T segment abnormality on the electrocardiogram, renal insufficiency, cancer, active inflammatory disease, or a history of cardiovascular events and pulmonary disease were excluded. Pulmonary function was assessed using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in 1 second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC). Results A total of 1100 subjects aged 57 years were enrolled and their median values of BNP and hs-cTnI were 15.5 and 2.3 pg/ml. The levels of rAI were significantly associated with the levels of BNP after adjustment for possible confounders in multivariate regression analysis, but were not with the levels of hs-TnI. While the parameters of pulmonary function were inversely associated with the levels of rAI and hs-cTnI after adjustment for possible confounders in the multivariate regression analysis, but not with the levels of BNP. The other multivariate regression analyses where BNP, hs-cTnI, parameters of pulmonary function, and the other possible factors were simultaneously included as independent variables revealed that the BNP levels and the FVC%-predicted or FEV1%-predicted, besides age, gender, smoking status, body mass index, blood pressure, heart rate, creatinine, fasting plasma glucose, and triglyceride, were significantly associated with the levels of rAI. Conclusions The significant associations of rAI with BNP and pulmonary function were revealed in the general population. These findings support that arterial stiffness could reflect increased cardiac load and reduced pulmonary function, in apparently healthy individuals. Funding Acknowledgement Type of funding source: None

The clinical value of multimodal ultrasound for the evaluation of disease activity and complications in inflammatory bowel disease.

Inflammatory bowel disease (IBD) has the characteristics of chronic relapse and remission, which makes early diagnosis and effective evaluation of disease activity especially crucial. With the development of ultrasound technology, its role in the diagnosis and treatment of IBD is increasing. This study aimed to explore the value of multimodal ultrasound in the assessment of disease activity and complications in IBD. Patients with clinically confirmed IBD were selected and examined with two-dimensional ultrasound, Doppler ultrasound, contrast-enhanced ultrasound (CEUS), elastography, endoscopy with biopsies, and whole-abdominal enhanced computed tomography (CT). Collect relevant laboratory data, including C-reactive protein, erythrocyte sedimentation rate, etc. Endoscopy is used as the gold standard for disease activity assessment, and the diagnostic value of each ultrasound parameter is compared separately, and correlation analysis is made. Intestinal maximum wall thickness in patients in the disease activity group (active group) was significantly thicker than that in patients in remission group (7.93±2.65 vs. 4.16±1.08 mm, P<0.001). The mean values of Peak Enhancement (PE) and the area under the receiver operating characteristic (ROC) curve (AUC) were higher in the active stage than in remission, with a significant difference (-40.66±4.81 vs. -50.47±5.03 db, 356.44±170.67 vs. 194.42±92.09 dBsec, both P<0.05). Time To Peak (TTP) showed no significant difference between the active stage and remission (20.04±8.74 vs. 20.09±11.13 s, P>0.05). Twenty cases of intestinal stricture were detected by ultrasound, and no fistula or abscesses were detected. CEUS and elastography could distinguish inflammatory bowel stenosis and fibrous bowel stenosis in patients with IBD. In the fibrosis group and inflammation group, the mean shear wave velocity, Young's modulus, TTP, PE, and AUC were statistically significantly different (P<0.05). The mean maximum wall thickness and disease extent assessed by ultrasound and CT were strongly correlated (r=0.799, 0.831). Wall thickness showed a moderate positive correlation with CRP and ESR and a strong positive correlation with Mayo score (P<0.05), but no significant correlation with CDAI (P>0.05). Multimodal ultrasound provides more detailed clinical reference values for the comprehensive evaluation of IBD.

Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy

ObjectivesTo define fatigue trajectories in patients with rheumatoid arthritis (RA) who initiate biological DMARD (bDMARD) treatment, and explore baseline predictors for a trajectory of continued fatigue.MethodsOne-hundred and eighty-four patients with...

Rapid weight gain in infliximab treated Crohn’s disease patients is sustained over time: real-life data over 12 months

Background Infliximab (IFX) is used in active Crohn’s disease for induction and maintenance of remission. There are scanty data on weight gain in IBD-patients under anti-TNF treatment. We investigated changes in weight and blood chemistry in anti-TNF-naïve Crohn’s disease patients during their first course of IFX. Methods Retrospective analysis of 110 patients (77 men, 33 women) aged 34 years (range 14–73), 54 with luminal and 56 with fistulising disease, given at least 3 infusions of IFX (range 3–11). Data regarding body weight, height, C-reactive protein (CRP), haemoglobin and S-albumin at baseline, before the third infusion, at three months and at 12 months were collected. Results At 6 weeks, 65 (59%) increased in weight, 73% and 76% at three and 12 months, respectively. There was an increase in median weight (1.7 kg, IQR = 3.1 kg) and BMI (0.5 kg/m2, IQR = 1.2 kg/m2) at 6 weeks, which persisted at three and 12 months (all p < .001). There was no difference between men and women. Young patients, patients with underweight or fistulising disease increased most in weight. Disease activity assessed by PGA and SES-CD decreased at all time points (p < .05). Increases in weight and BMI correlated with an increase in serum albumin and a decrease in CRP. Conclusion Approximately 60% of Crohn’s disease patients experience weight gain within the first six weeks of infliximab treatment. The weight increment correlates with improvements in inflammatory markers and disease activity. The causes of weight gain may be related to treatment induced metabolic changes and reduced inflammatory burden.

IL6 genetic variants haplotype is associated with susceptibility and disease activity but not with therapy response in patients with inflammatory bowel disease.

The aim of the present study was to evaluate the IL6 -174 G>C (rs1800795) and -572 G>C (rs1800796) genetic variants and their association with inflammatory bowel diseases (IBDs), disease activity, and response to TNF-α inhibitors. The study included 178 patients with IBD and 224 healthy controls. Among the IBD patients, 66 of them were in use of TNF-α inhibitors therapy and were followed during 48weeks and categorized as responders and non-responders. In total, 89 (50.0%) had ulcerative colitis (UC) and 89 (50.0%) had Crohn's disease (CD). The IL6 -572 CC genotype presented a protective effect in CD patients in codominant and recessive models, while the IL6 -174 CC genotype was associated with susceptibility to UC and CD. The presence of G/C haplotype in the recessive model (GCGC) was associated with UC. The Crohn's disease endoscopic index of severity was low in those patients carrying the GCGC haplotype. It was observed that there was no association between the IL6 genetic variants and TNF-α inhibitor therapy response. The G/C haplotype (recessive model) was associated with susceptibility to UC but not to CD. However, the G/C haplotype (dominant model) was associated with the endoscopic activity of CD. Moreover, these IL6 variants did not predict the TNF-α inhibitor therapy response.

S0654 Association of Enteric Infections and Disease Activity in Inflammatory Bowel Disease

S0654 Association of Enteric Infections and Disease Activity in Inflammatory Bowel Disease

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64Cu-Macrin in Mice, Rabbits, and Pigs.

Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases. We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64Cu-Macrin-a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose. PET imaging using 64Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle (VT680Macrin) primarily in tissue macrophages. In 5-day-old mice, 64Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of 64Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that 64Cu-Macrin is safe for use in humans. Taken together, these results indicate 64Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. 64Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.

Effect of tobacco use on disease activity and DMT discontinuation in multiple sclerosis patients treated with dimethyl fumarate or fingolimod.

BackgroundTobacco exposure is a modifiable risk factor for multiple sclerosis (MS). Studies evaluating the relationship between tobacco, disease activity, and disease modifying therapy (DMT) persistence yielded conflicting results. We sought to address this issue with data from clinical practice.ObjectiveTo compare 24-month disease outcomes in tobacco versus non-tobacco users treated with dimethyl fumarate (DMF) or fingolimod (FTY) in clinical practice.MethodsWe retrospectively identified 659 MS patients treated with DMF or FTY, stratified by patient-reported tobacco use. DMT discontinuation and measures of disease activity at 24 months were assessed using propensity score (PS) weighting. Outcome estimates were calculated as tobacco vs non-tobacco use.Results164 tobacco users (DMF n = 101; FTY n = 63) and 495 non-tobacco users (DMF n = 294; FTY n = 201) were identified. Tobacco (39.4%) and non-tobacco (34.4%) users were equally likely to discontinue DMT (OR = 1.17, 95% CI 0.79, 1.75), but tobacco users discontinued therapy earlier (HR = 1.53, 95% CI 1.06, 2.43). There were no differences in ARR (rate ratio = 1.39, 95% CI 0.97, 1.96). However, tobacco users had decreased odds of NEDA-2 (OR = 0.61, 95% CI 0.44, 0.83).ConclusionOur findings suggest that tobacco is a negative risk factor for inflammatory disease activity and earlier DMF and FTY discontinuation.

S2306 Bad to the Bone: A Rare Case of Fistulizing Disease Extending to the Sacrum

INTRODUCTION: Fistula formation commonly occurs between intestines and other epithelial-lined hollow organs such as the bladder, skin, vagina, or other regions of the gastrointestinal tract. Infrequently, a connection can form between the bowel and the vertebral column and lead to vertebral osteomyelitis. We present the case of a young male with significant abdominal pathology found to have sacral osteomyelitis in the setting of fistula formation between the small bowel and sacrum. CASE DESCRIPTION/METHODS: A 27-year-old male with a history of opioid dependence and abdominal gunshot wound requiring subtotal colectomy with ileo-rectal anastomosis presented with progressive, bloody diarrhea and poor appetite. The patient reported history of previous colonoscopies with balloon dilations of strictures but never diagnosed with inflammatory bowel disease (IBD) or started on any therapies. On exam, the patient was emaciated with multiple clean abdominal scars and diffuse, mild abdominal tenderness. Labs showed microcytic anemia with hemoglobin of 8, elevated fecal calprotectin (402) and CRP (15.1) without leukocytosis, and negative tissue transglutaminase. His stool studies and gastrointestinal pathogen panel were negative for Clostridium difficile or other pathogens. Computed Tomography of the abdomen found enteritis and proctocolitis and concern for possible osteomyelitis of the sacrum and coccyx. Magnetic resonance enterography found multiple entero-colonic fistulas and active inflammatory disease of the small bowel, inflammation of the sacral nerve roots, and concern for fistulization between the small bowel and sacrum. Subsequent flexible sigmoidoscopy found ulcerated friable mucosa and pseudomembranes in the rectum. Pathology showed nonspecific chronic inflammation and was negative for Clostridium difficile. He was started on Rifaximin for empiric treatment of small intestinal bacterial overgrowth with improvement in diarrhea and is planned for further IBD workup to assess the status of his fistulizing disease. DISCUSSION: While most enteric fistulas occur due to prior abdominal surgery complications, 10-15% occur from inflammation and infection associated with Crohn’s disease. Rarely, fistulas can develop between bowel and vertebra, and osteomyelitis may result due to translocation of gut flora from the intestine to the spine via the fistula as seen in our patient. Ultimately, this uncommon presentation should prompt investigation into etiology and use imaging to guide aggressive management.Figure 1.: Rectal ulcer seen on flexible sigmoidoscopy.Figure 2.: MRE showing evidence of a fistula from the small bowel to the sacrum.

Comparison of LABORAS with static incapacitance testing for assessing spontaneous pain behaviour in surgically-induced murine osteoarthritis

ObjectiveEvoked responses following mechanical or thermal stimulation are typically used to assess pain behaviour in murine osteoarthritis (OA). However, there is no consensus on how best to measure spontaneous pain behaviour. MethodOA by partial meniscectomy (PMX), or sham surgery was performed in 10-week old C57BL/6 male mice. Collagen-induced arthritis (CIA) was induced in 10 week old DBA1 male mice. Spontaneous pain behaviour, either at the time of active inflammatory disease (CIA), or over the 12 weeks after induction of OA, was assessed by static incapacitance testing (measuring percentage of weight placed through each hindlimb), and Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS) (translating cage vibrations of singly house animals into specific activities). Data were analysed by repeated measures two way ANOVA with post hoc testing comparing experimental groups with either sham operated or naïve controls. ResultsBy incapacitance testing, two phases of painful behaviour were evident after PMX: a transient, post-operative phase, which resolved within one week, and a late OA pain phase starting 8 weeks post surgery and reaching statistical significance at week 12 (95% CI: sham 89.51–98.19, PMX 76.18–98.16). LABORAS, was able to detect pain behaviour in mice with CIA, but no statistically significant pain behaviour was observed in OA mice either post operatively (once analgesia had been controlled for) or at any later time points for any activity compared with the sham group. ConclusionStatic incapacitance testing is superior to LABORAS for measuring spontaneous pain behaviour in surgically induced murine OA.

Exploring the performance of outcome measures in MS for predicting cognitive and clinical progression in the following years

The demand for better outcome measures in multiple sclerosis (MS) management has been increasingly recognized. Nevertheless, the prognostic impacts of available outcome measures for long-term clinical and especially cognitive disability have not been thoroughly investigated. We, therefore, aimed to explore the sustainability and long-term predictive value of outcome measures in MS. We studied a cohort of 42 relapsing-remitting MS patients and 30 healthy subjects. Evaluations were performed at baseline and after two (Y2) and six years (Y6), and included neurological and neuropsychological evaluation (BRBN), MRI (3T), and quality of life assessment. Combined clinical and cognitive measures were evaluated, such as minimal and no evidence of disease activity (MEDA and NEDA, respectively). We performed logistic regression with bootstrapping and calculated the diagnostic properties to identify patients who reached six-year clinical and/or cognitive worsening. NEDA status was observed in up to 30.8% of patients at Y2, but only in 5% at Y6, and did not preclude cognitive decline (SDMT and BRBN). The absence of MRI activity and MEDA status at Y2 were associated with less EDSS worsening in the following years but without impact on cognition. The absence of deterioration on combined clinical/cognitive measures at Y2 (e.g., T25W+ 9HPT+BRBN) was associated with better outcomes in the following years (clinical and cognitive), with moderate to large effect sizes. For the identification of clinical worsening at Y6, best accuracies were found for MEDA (70.6%), and clinical worsening (71.4%), but only MEDA remained in the final model after multivariable logistic regression analysis (OR=6.81, p=0.017). For combined clinical and cognitive worsening at Y6, only T25W+ 9HPT+BRBN remained in the final model (OR=8.5, p=0.017). Early MS inflammatory disease activity is associated with future clinical disability. Nevertheless, NEDA was difficult to sustain in the long-term and did not preclude cognitive deterioration. Clinical and cognitive measures combined predicted outcomes better than each one isolated. Our data suggest that the evaluation of more than one cognitive domain yields a better predictive outcome measure.

Review article: how the intestinal microbiota may reflect disease activity and influence therapeutic outcome in inflammatory bowel disease.

Intestinal bacteria produce metabolites and by-products necessary for homeostasis. Imbalance in this equilibrium is linked to multiple pathologies including inflammatory bowel disease (IBD). The role of the gut microbiota in determining treatment response is becoming apparent, and may act as biomarker for efficacy. To describe knowledge about the intestinal microbiota on disease severity and treatment outcomes in IBD METHODS: Descriptive review using PubMed to identify literature on the intestinal microbiota in IBD RESULTS: Severe IBD has a less diverse microbiota with fewer commensal microbiota communities and more opportunistic pathogenic bacteria originating from the oral cavity or respiratory tract. IBD treatments can alter gut microbiota composition, but in vitro/in vivo studies are needed to prove causation. A diversification of the microbiota is observed during remission. Patients with a more diverse baseline microbiome and higher microbial diversity show better response to anti-tumour necrosis factor-α, vedolizumab and ustekinumab therapy. Higher abundance of short chain fatty acid-producing bacteria, fewer mucus-colonising bacteria and lower abundance of pro-inflammatory bacteria have also been associated with a favourable outcome. Predictive models, based on a combination of microbiota, clinical data and serological markers, have good accuracy for treatment outcome and disease severity. The intestinal microbiota in IBD carries a set of promising biomarkers of disease activity and prediction of therapeutic outcome. Current insights may also help in designing microbiota modulation strategies to improve outcomes in IBD.

MRI activity in MS and completed pregnancy: Data from a tertiary academic center.

ObjectiveTo evaluate postpartum MRI activity in patients with MS and a completed pregnancy and to compare these results to an age-matched untreated nonpregnant MS cohort.MethodsPatient with MS from a tertiary care MS center between 2006 and 2015, with prepartum and postpartum neurologic follow-ups and MRI scans were analyzed. Clinical activity and inflammatory brain MRI activity (new T2-hyperintense or gadolinium-enhancing [Gd+] lesions) were assessed peripartum. The results were compared with untreated reproductive-age patients with MS from the placebo arm of the clinical trials.ResultsA total of 123 pregnancies in 123 women (median Expanded Disability Status Scale 1.0) were analyzed. Approximately 7.2% relapsed during pregnancy and 48.7% relapsed postpartum. Of pregnancies with prepartum and postpartum gadolinium (Gd)-enhanced MRI (n = 112), 8% had Gd+ lesions prepartum and 33% had new Gd+ lesions postpartum. Overall, 54.4% had either new T2 or Gd+ lesions postpartum. Seventy-nine percent of subjects with postpartum relapse had new MRI activity compared with 37.1% without relapse (p < 0.001). Twenty-five percent had both clinical and radiographic activity and only 24.9% maintained no evidence of disease activity status postpartum. There was no association between postpartum MRI activity and disease-modifying treatments (DMTs) (p > 0.5). MRI and clinical outcomes were also assessed for 126 nonpregnant untreated female patients with MS. Comparing pregnancy and no pregnancy groups, there was no difference in MRI activity at follow-up.ConclusionsThere was a high level of inflammatory radiographic disease activity which was related to relapses in postpartum patients with MS. Further studies are needed to determine whether hormonal fluctuations vs extended time off DMTs may be the underlying cause of our observations.

Selective Increment of Synovial Soluble TYRO3 Correlates with Disease Severity and Joint Inflammation in Patients with Rheumatoid Arthritis.

Objective To investigate the role of TAM receptors in rheumatoid arthritis (RA) by determining synovial tissue TAM receptor expression, synovial fluid levels of soluble TAM receptors, and the relationship between soluble TAM receptors, joint inflammation and disease activity. Methods TAM receptor expression was determined by immunohistochemistry on the synovium from RA and osteoarthritis (OA) patients. Soluble (s) Tyro3, sAxl, sMer, and their ligand Gas6 were measured by ELISA in the synovial fluid of RA (n = 28) and OA (n = 12) patients and cytokine levels by multiplex immunoassay in RA samples. Correlation analyses were performed among sTAM receptors with local cytokine levels; systemic disease parameters like erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (ACPA); and disease activity scores (DAS28-ESR) in RA patients. Results TAM receptors were expressed on different locations in the synovial tissue (lining, sublining, and blood vessels), and a similar expression pattern was observed in RA and OA patients. Synovial fluid sTyro3 and sMer were significantly enhanced in RA compared to OA patients, whereas no significant differences in sAxl and Gas6 levels were found. In RA samples, sTyro3 levels, but not sMer, correlated positively with proinflammatory local cytokines and the systemic factor erythrocyte sedimentation rate. Moreover, stratification analysis showed high sTyro3 levels positively correlated with higher DAS28-ESR and in RF and ACPA double positive RA patients. Conclusion sTyro3 in the synovial fluid of RA patients correlates with local inflammatory molecules and systemic disease activity. These findings suggest that the reduced negative control of cell activation by TAM receptors due to their shedding in the synovial fluid, mainly sTyro3, favoring joint inflammation in RA patients.