Sarcopenia Is More Prevalent Among Inflammatory Bowel Disease Patients Undergoing Surgery and Predicts Progression to Surgery Among Medically Treated Patients.

BACKGROUND: Sarcopenia is common in inflammatory bowel disease (IBD); however, estimates of its prevalence and impact on clinical outcomes are variable. This study sought to compare the prevalence of sarcopenia in IBD patients starting new biologics vs patients undergoing IBD surgeries, and its association with common clinical predictors of nutritional status, adverse events, and clinical outcomes. METHODS: This was a multicenter retrospective cohort study of IBD patients who had a computed tomography (CT) scan within 6 months prior to new biologic initiation (medical cohort) or IBD surgery (surgery cohort). The lowest sex-specific quartile of the total psoas area index at the L3 level defined sarcopenia. Prevalence and predictors of sarcopenia, performance of common clinical nutritional markers, and association with adverse events and clinical outcomes at 1 year were determined. RESULTS: A total of 156 patients were included (48% medical cohort, 52% surgery cohort). Sarcopenia was more common in the surgery cohort (32% vs 16%; P < .02). In the medical cohort, sarcopenia predicted need for surgery at 1 year (odds ratio, 4.75; 95% confidence interval, 1.10-20.57; P = .04). Low albumin and body mass index (BMI) were associated with the presence of sarcopenia; however, 24% of sarcopenic patients had both normal BMI and albumin. CONCLUSIONS: Sarcopenia is more prevalent among IBD patients undergoing surgery and predicts the need for surgery in patients starting new biologic therapy. Low albumin and BMI were similar between cohorts, suggesting a unique role for sarcopenia as a relevant clinical marker of lean muscle mass depletion for surgically and medically treated IBD patients.

Sarcopenia is more common in inflammatory bowel disease surgery patients compared with medical patients, and predicts need for surgery in medical patients. Differences in skeletal muscle measurements compared with albumin and body mass index suggest that sarcopenia may be challenging to detect in routine clinical settings.

Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Clinical Performance of a Novel LIAISON Fecal Calprotectin Assay for Differentiation of Inflammatory Bowel Disease From Irritable Bowel Syndrome.

GOAL: The goal of this study was to assess the clinical performance of an investigational in vitro fecal calprotectin immunoassay for differentiating inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). BACKGROUND: Fecal calprotectin is a stool biomarker that can assist in the detection of intestinal inflammation and is utilized to identify individuals who have a higher chance of having IBD and who require further invasive tests. Current assays exhibit variable performance. MATERIALS AND METHODS: This study was a multicenter, cross-sectional analysis of prospectively collected stool samples from patients 4 years of age or older who presented with gastrointestinal (GI) symptoms and underwent colonoscopy for diagnostic confirmation. IBD was diagnosed based on clinical, endoscopic, and histologic findings. IBS was diagnosed based on Rome III Criteria and negative colonoscopy. Stool samples were extracted and tested on the DiaSorin LIAISON XL using the LIAISON Calprotectin Assay. RESULTS: A total of 240 patients (67% female) were included in the study. In total, 102 patients had IBD (54% ulcerative colitis), 67 had IBS, and 71 had other GI disorders. Median fecal calprotectin levels were significantly higher in patients with IBD [522 µg/g; 95% confidence interval (CI): 354-970 µg/g] compared with IBS (34.5 µg/g; 95% CI: 19.7-44.2 µg/g, P<0.001) and other GI disorders (28.6 µg/g; 95% CI: 18.7-40.3 µg/g, P<0.001). Receiver operating characteristic curve analysis indicated a fecal calprotectin cutoff of 94 µg/g for distinguishing IBD from other GI disorders with an area under the curve of 0.964 (sensitivity=92.2%, specificity=88.4%). CONCLUSION: The automated LIAISON Calprotectin assay brings efficient calprotectin testing to the laboratory with a time to the first result of 35 minutes and is a sensitive marker for distinguishing IBD from IBS with a cutoff of ∼100 µg/g.

Best Practices in Resident Research- A National Survey of High Functioning Internal Medicine Residency Programs in Resident Research in USA.

PURPOSE: Meaningful participation in research for both faculty and residents is generally viewed to be an essential component of residency training. To better understand best practices in residency research, the authors conducted a survey among Internal Medicine (IM) Residency Programs with experience in research. METHODS: Phone interviews were conducted with a convenience sample of Residency Program Directors (PDs). Survey responses were analyzed across the following domains: size and makeup of the residency and research programs, resources for research, role of the PD/research director (RD), profile of trainees doing research, curriculum description, scope of research, role of mentors, career choices and determinants of success. RESULTS: Fifteen programs were included in the study. Across these programs, approximately two-thirds of residents were involved in research during their training . Eighty percent of the programs required an application for residents to engage in research. Ninety-two percent of the programs had a RD but only 58% had a formal research curriculum. Clinical research projects were the most common types of research. On average, two-thirds of residents involved in research submitted abstracts to regional and/or national meetings. The factor most frequently associated with resident research success was an effective faculty research mentor. CONCLUSIONS: Research success during residency is multifactorial. The authors propose that having a robust structure for research that is led by a residency RD, and the presence of effective mentors and strong administrative support are critical for success.

Microscopic Colitis Is Not an Independent Risk Factor for Low Bone Density.

BACKGROUND: Microscopic colitis (MC) is a subtype of inflammatory bowel disease (IBD) with overlapping risk factors for low bone density (LBD). While LBD is a known complication of IBD, its association with MC is not well-established. AIMS: Assess the prevalence of LBD in MC compared to control populations, and evaluate if MC predicts LBD when controlling for confounders. METHODS: Retrospective, observational case control study of adult patients with pathologically confirmed MC from 2005 to 2015. Bone density measurements were abstracted from dual-energy X-ray absorptiometry (DEXA) reports, and bone density was classified using T-score: normal (T ≥ - 1.0), osteopenia (- 1.0 > T > -2.5) or osteoporosis (T ≤ - 2.5). Demographics, disease, medication history and LBD risk factors were obtained from chart review. Prevalence of LBD was compared to national and local controls. A matched control cohort to MC patients without prior diagnosis of LBD was analyzed with logistic regression to assess the relationship of MC to LBD. RESULTS: One hundred and eighteen patients with MC were identified. Osteopenia in women with MC was more prevalent compared to national controls (67% vs. 49%, p = 0.0004), and LBD was more prevalent in MC patients compared to local controls (82% vs. 55%, p < 0.0001). In MC patients without prior diagnosis of LBD matched to controls, there was a higher prevalence of osteopenia (53.2% vs. 36.7%, p = 0.04). However, after controlling for confounders, MC was not associated with LBD (OR 0.83, 95% CI 0.22, 3.16, p = 0.8). CONCLUSIONS: While LBD was more prevalent in MC patients compared to control populations, with adjustment for key confounders (including BMI, steroids, smoking, vitamin D and calcium use), MC was not an independent predictor of LBD.

Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease.

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 µg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 µg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 µg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 µg/mL was 3.7 (95% CI, 1.1-13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

Proactive Vs Reactive Therapeutic Drug Monitoring of Infliximab in Crohn's Disease: A Cost-Effectiveness Analysis in a Simulated Cohort.

BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. METHODS: We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare. RESULTS: The proactive strategy led to fewer flares than the reactive strategy. More patients stayed on IFX in the proactive vs reactive strategy (63.4% vs 58.8% at year 5). From a health sector perspective, a proactive strategy was marginally cost-effective compared with a reactive strategy (incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year), assuming a 40% of the wholesale price of IFX. The results were most sensitive to risk of flaring with a low IFX concentration and the cost of IFX. CONCLUSIONS: Assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective.

Proactive Therapeutic Drug Monitoring of Adalimumab Is Associated With Better Long-term Outcomes Compared With Standard of Care in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Therapeutic drug monitoring [TDM] has proven to be effective for optimising anti-tumour necrosis factor [TNF] therapy in inflammatory bowel disease [IBD]. Nevertheless, the majority of data refer to infliximab and reactive testing or association studies. We aimed to compare the long-term outcome of patients with IBD who received at least one proactive TDM of adalimumab, with standard of care, defined as empirical dose escalation and/or reactive TDM. METHODS: This was a multicentre retrospective cohort study. Patients on maintenance adalimumab therapy from June 2006 to December 2015 were eligible. We analysed time to treatment failure from start of adalimumab until the end of follow-up [July 2016]. Treatment failure was defined as drug discontinuation for secondary loss of response or serious adverse event or need for IBD-related surgery. Serum adalimumab concentrations and antibodies to adalimumab were measured using the Prometheus homogeneous mobility shift assay. RESULTS: A total of 382 patients with IBD [Crohn's disease, n = 311, 81%] were included and received either at least one proactive TDM [n = 53] or standard of care [empirical dose escalation, n = 279; reactive TDM, n = 50]. Patients were followed for a median of 3.1 years [interquartile range, 1.4-4.8 years]. Multiple Cox regression analyses showed that at least one proactive TDM was independently associated with a reduced risk for treatment failure (hazard ratio [HR]: 0.4; 95% confidence interval [CI]: 0.2-0.9; p = 0.022). CONCLUSIONS: This multicentre, retrospective cohort study reflecting real-life clinical practice provides the first evidence that proactive TDM of adalimumab may be associated with a lower risk of treatment failure compared with standard of care in patients with IBD.

Incidence, Admission Rates, and Predictors, and Economic Burden of Adult Emergency Visits for Acute Pancreatitis: Data From the National Emergency Department Sample, 2006 to 2012.

INTRODUCTION: Acute pancreatitis (AP) is the most common gastroenterology-related reason for hospital admission, and a major source of morbidity and mortality in the United States. This study examines the National Emergency Database Sample, a large national database, to analyze trends in emergency department (ED) utilization and costs, risk factors for hospital admission, and associated hospital costs and length of stay (LOS) in patients presenting with AP. METHODS: The National Emergency Database Sample (2006 to 2012) was evaluated for trends in ED visits, ED charges, hospitalization rates, hospital charges, and hospital LOS in patients with primary diagnosis of AP (further subcategorized by age and etiology). A survey logistic-regression model was used to determine factors predictive of hospitalization. RESULTS: A total of 2,193,830 ED visits were analyzed. There was a nonsignificant 5.5% (P=0.07) increase in incidence of ED visits for AP per 10,000 US adults from 2006 to 2012, largely driven by significant increases in ED visits for AP in the 18 to <45 age group (+9.2%; P=0.025), AP associated with alcohol (+15.9%; P=0.001), and AP associated with chronic pancreatitis (+59.5%; P=0.002). Visits for patients aged ≥65 decreased over the time period. Rates of admission and LOS decreased during the time period, while ED and inpatient costs increased (62.1%; P<0.001 and 7.9%; P=0.0011, respectively). Multiple factors were associated with increased risk of hospital admission from the ED, with the strongest predictors being morbid alcohol use [odds ratio (OR), 4.53; P<0.0001], advanced age (age>84 OR, 3.52; P<0.0001), and smoking (OR, 1.75; P<0.0001). CONCLUSIONS: Despite a relative stabilization in the overall incidence of ED visits for AP, continued increases in ED visits and associated costs appear to be driven by younger patients with alcohol-associated and acute on chronic pancreatitis. While rates of hospitalization and LOS are decreasing, associated inflation-adjusted costs are rising. In addition, identified risk factors for hospitalization, such as obesity, alcohol use, and increased age, should be explored in further study for potential use in predictive models and clinical improvement projects.

Incidence and Predictors of 30-Day Readmission Among Patients Hospitalized for Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) hospitalizations along with associated morbidity and costs are increasing. The goal of this study was to use the National Readmission Database to identify the incidence and risk factors for 30-day readmissions among patients with CP. METHODS: We performed a retrospective analysis of National Readmission Database from January 2013 to December 2013 to determine patient demographic and clinical characteristics predictive of 30-day hospital readmission for adult patients (aged >18 years) discharged with a principle diagnosis of CP. A survey logistic regression model was used to determine the predictive value of selected variables for 30-day readmission. RESULTS: In 2013, 12,545 admissions with primary diagnosis of CP were noted, and 30.4% were readmitted within 30 days. Cholecystectomy (odds ratio [OR], 0.53; P = 0.0024) or endoscopic retrograde cholangiopancreatography (OR, 0.70; P = 0.01) during index admission was associated with decreased all-cause readmissions. Pancreatectomy during index admission was associated with reduced (OR, 0.2; P = 0.0005) pancreatitis-related readmissions. CONCLUSIONS: Hospital readmissions for CP are frequent and pose a significant healthcare burden. Performing cholecystectomy, endoscopic retrograde cholangiopancreatography, or pancreatectomy during index admission was associated with reduced odds of readmission.

Incidence and Predictors of Readmissions in Acute Pancreatitis: A Nationwide Analysis.

OBJECTIVES: Acute pancreatitis (AP) is a common cause for hospitalization, and readmission is common, with variable associated risk factors for readmission. Here, we assessed the incidence and risk factors for readmission in AP in a large national database. METHODS: We analyzed data from the National Readmission Database during the year 2013. Index admissions with a primary discharge diagnosis of AP using the International Classification of Diseases, Ninth Revision, Clinical Modification were identified from January to November to identify 30-day readmission rates. Demographic, hospital, and clinical diagnoses were included in multivariate regression analysis to identify readmission risk factors. RESULTS: We identified 243,816 index AP discharges with 39,623 (16.2%) readmitted within 30 days. The most common reason for readmission was recurrent AP (41.5%). Increased odds of all-cause readmission were associated with younger age, nonhome discharge, increasing Charlson Comorbidity Index, and increased length of stay. Cholecystectomy during index admission was associated with reduced all-cause and recurrent AP readmissions (odds ratios of 0.5, and 0.35, respectively). CONCLUSIONS: Readmission for AP is common, most often due to recurrent AP. Multiple factors, including cholecystectomy, during index admission, are associated with significantly reduced odds of all-cause and recurrent AP readmissions.

Out-of-Pocket Cost Is a Barrier to Therapeutic Drug Monitoring in Inflammatory Bowel Disease.

BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed to optimize biologic therapy in inflammatory bowel disease (IBD). However, patients and physicians may be reluctant to perform TDM due to concerns related to potential out-of-pocket costs. AIMS: The aim of this study was to evaluate patient understanding and attitudes toward TDM in different clinical scenarios with and without potential out-of-pocket costs. METHODS: Adult IBD patients at a tertiary gastroenterology clinic were anonymously surveyed from March to September 2016 to assess their understanding of and willingness to undergo TDM in a variety of clinical scenarios, both with and without a potential out-of-pocket cost. Responses were analyzed for associations with changes in attitudes if out-of-pocket costs were involved. RESULTS: Of 118 completed surveys, 68.2% of patients were aware of or had previously undergone TDM. Patient willingness to undergo TDM was high both with and without potential out-of-pocket costs (70 and 98%, respectively); however, patients were significantly less willing with out-of-pocket cost (p < 0.01). Higher disease-related quality of life scores, as measured by the short inflammatory bowel disease questionnaire (SIBDQ), was significantly associated with an increased willingness to assume a potential out-of-pocket cost (p = 0.007). CONCLUSIONS: Overall, patients understand and are willing to undergo TDM in certain potentially beneficial clinical scenarios, however, are significantly less willing if paying out-of-pocket. A higher SIBDQ score was associated with an increase in willingness to undergo TDM when out-of-pocket cost was involved. Physicians should discuss TDM with their patients in order to make an informed and personalized treatment decision.

Does serum procalcitonin aid in the diagnosis of bloodstream infection regardless of whether patients exhibit the systemic inflammatory response syndrome?

BACKGROUND: Physicians frequently rely on the systemic inflammatory response syndrome (SIRS) criteria to detect bloodstream infections (BSIs). We evaluated the diagnostic performance of procalcitonin (PCT) in detecting BSI in patients with and without SIRS. METHODS: We tested the association between BSI, serum PCT levels, contemporaneous SIRS scores and serum lactate using logistic regression in a dataset of 4279 patients. The diagnostic performance of these variables was assessed. RESULTS: In multivariate regression analysis, only log(PCT) was independently associated with BSI (p < 0.05). The mean area under the curve (AUC) of PCT in detecting BSI (0.683; 95% CI 0.65-0.71) was significantly higher than serum lactate (0.615; 95% CI 0.58-0.64) and the SIRS score (0.562; 95% CI 0.53-0.58). The AUC of PCT did not differ significantly by SIRS status. PCT of less than 0.1 ng/mL had a negative predictive value (NPV) of 97.4 and NPV of 96.2% for BSI in the SIRS-negative and SIRS-positive patients, respectively. A PCT of greater than 10 ng/mL had a LR of 6.22 for BSI in SIRS-negative patients. The probability of BSI increased exponentially with rising PCT levels regardless of SIRS status. CONCLUSION: The performance of PCT for the diagnosis of BSI was not affected by SIRS status. Only PCT was independently associated with BSI, while the SIRS criterion and serum lactate were not. A low PCT value may be used to identify patients at a low risk for having BSI in both settings. An elevated PCT value even in a SIRS negative patient should prompt a careful search for BSI.

Optimal delivery of follow-up care after surgery for Crohn's disease: current perspectives.

Despite improvements in medical therapies for Crohn's disease (CD), up to 70% of patients require surgery within 10 years of diagnosis. Surgery is not curative, and almost all patients will experience endoscopic recurrence, and many will go on to clinical recurrence. Identifying patients at high-risk of endoscopic recurrence and standardizing postoperative assessments are essential in preventing clinical recurrence of CD. In this review, we discuss the assessment, monitoring, and treatment of postoperative CD patients. We address the various individual risk factors as well as composite risk factors. Medications used for primary CD treatment can be used in the postoperative setting to prevent endoscopic or clinical recurrence with varying efficacy, although the cost-effectiveness of these approaches are not fully understood. Future directions for postoperative CD management include evaluation of newer biologic agents such as anti-integrin therapy and fecal microbiota transplant for prevention of recurrence. Development of a standard preoperative risk assessment tool to clearly stratify those at high-risk of recurrence is necessary to guide empiric therapy. Lastly, the incorporation of noninvasive testing into disease monitoring will likely lead to early detection of endoscopic recurrence that will allow for tailored treatment to prevent clinical recurrence.

Low Dietary c9t11-Conjugated Linoleic Acid Intake from Dairy Fat or Supplements Reduces Inflammation in Collagen-Induced Arthritis.

Dietary cis-9,trans-11 (c9t11) conjugated linoleic acid (CLA) fed at 0.5 % w/w was previously shown to attenuate inflammation in the murine collagen-induced (CA) arthritis model, and growing evidence implicates c9t11-CLA as a major anti-inflammatory component of dairy fat. To understand c9t11-CLA's contribution to dairy fat's anti-inflammatory action, the minimum amount of dietary c9t11-CLA needed to reduce inflammation must be determined. This study had two objectives: (1) determine the minimum dietary anti-inflammatory c9t11-CLA intake level in the CA model, and (2) compare this to anti-inflammatory effects of dairy fat (non-enriched, naturally c9t11-CLA-enriched, or c9t11-CLA-supplemented). Mice received the following dietary fat treatments (w/w) post arthritis onset: corn oil (6 % CO), 0.125, 0.25, 0.375, and 0.5 % c9t11-CLA, control butter (6 % CB), c9t11-enriched butter (6 % EB), or c9t11-CLA-supplemented butter (6 % SB, containing 0.2 % c9t11-CLA). Paw arthritic severity and pad swelling were scored and measured, respectively, over an 84-day study period. All c9t11-CLA and butter diets decreased the arthritic score (25-51 %, P < 0.01) and paw swelling (8-11 %, P < 0.01). Throughout the study, plasma tumor necrosis factor (TNFα) was elevated in CO-fed arthritic mice compared to non-arthritic (NA) mice but was reduced in 0.5 % c9t11-CLA- and EB-fed mice. Interleukin-1ß and IL-6 were increased in arthritic CO-fed mice compared to NA mice but were reduced in 0.5 % c9t11-CLA- and EB-fed mice through day 42. In conclusion, 0.125 % c9t11-CLA reduced clinical arthritis as effectively as higher doses, and decreased arthritis in CB-fed mice suggested that the minimal anti-inflammatory levels of c9t11-CLA might be below 0.125 %.

Dietary trans-10,cis-12 CLA reduces murine collagen-induced arthritis in a dose-dependent manner.

Dietary trans-10,cis-12 (t10c12) conjugated linoleic acid (CLA) has been shown to reduce inflammation in a murine collagen-induced arthritis (CA) model. To understand the anti-inflammatory potential of t10c12-CLA in the diet, the minimum dose of pure dietary t10c12-CLA capable of reducing CA was investigated. Because plasma inflammatory cytokines often do not reflect the progression of late-stage arthritis, inflamed tissue cytokine concentrations were also investigated in relation to increasing dietary t10c12-CLA amounts. Mice were randomly assigned to the following dietary treatments upon the establishment of arthritis: corn oil (CO) or 0.125%, 0.25%, 0.375%, or 0.5% t10c12-CLA (wt:wt) for 84 d. Sham mice (no arthritis) were fed CO and served as controls. Arthritic paw score, based on subjective assessment of arthritic severity, and paw thickness decreased linearly overall [16-65% (P < 0.001) and 0.5-12% (P < 0.001), respectively] as dietary t10c12-CLA increased (P < 0.001, R(2) < 0.81). Increasing dietary t10c12-CLA was associated with a decrease in plasma interleukin (IL)-1ß at days 21 and 42 compared with CO-fed arthritic mice, such that mice fed ≥0.25% t10c12-CLA had IL-1ß concentrations that were similar to sham mice. Plasma cytokines returned to sham mice concentrations by day 63 regardless of treatment; however, an arthritis-induced elevation in paw IL-1ß decreased linearly as dietary t10c12-CLA concentrations increased at day 84 (P = 0.007, R(2) = 0.92). Similarly, increasing dietary t10c12-CLA linearly decreased paw tumor necrosis factor (TNF)-α (P = 0.05, R(2) = 0.70). In conclusion, ≥0.125% t10c12-CLA dose-dependently reduced inflammation in a murine CA model.

Third ventricle, cerebral aqueduct, and fourth ventricle mixed ependymal neurocytoma: a case report and review of the literature.

PURPOSE: A case report of an 8-year-old female who underwent interhemispheric transcallosal approach to the third ventricle, cerebral aqueduct, and fourth ventricle for resection of a mixed ependymal neurocytoma and review of the literature was evaluated. METHODS: An Ovid MEDLINE review of the literature was conducted starting in 1946 to current using search terms as described in our keywords. RESULTS: A total of 16 neurocytoma have been described in the literature as either posterior third ventricle or posterior fossa in origin. Of these lesions, five have been described as mixed glial-neuronal and all of these were located in the fourth ventricle. To our knowledge, this is the first described mixed glial-neuronal tumor located in the posterior third ventricle and aqueduct.

Individual isomers of conjugated linoleic acid reduce inflammation associated with established collagen-induced arthritis in DBA/1 mice.

Previously, dietary conjugated linoleic acid [(CLA), an equal mixture of cis-9, trans-11 (c9t11) and trans-10, cis-12 (t10c12) CLA isomers], was found to reduce inflammation in the murine collagen antibody-induced arthritis model, but less so in the murine collagen-induced arthritis (CIA) model, an arthritic model dependent upon acquired immunity. Because CLA is known to alter the acquired immune response, it was hypothesized that feeding CLA after the establishment of arthritis would reduce paw swelling in the CIA model. In this study, upon the establishment of arthritic symptoms, mice were randomized to the following dietary treatments: corn oil (CO) control (n = 6), 0.5% c9t11-CLA (n = 8), 0.5% t10c12-CLA (n = 6), or 1% combined CLA (1:1 c9t11:t10c12-CLA, n = 6). Paws were scored for severity of arthritis and measured for changes in thickness during an 84-d study period. Dietary c9t11- and combined-CLA similarly decreased the arthritic score (29%, P = 0.036, P = 0.049, respectively, when normalized to initial score) and paw thickness (0.11 mm, P = 0.027, P = 0.035, respectively) compared with CO. Dietary t10c12-CLA reduced the arthritic score (41%, P = 0.007 when normalized) and paw thickness (0.12 mm, P = 0.013) relative to CO. Reduced interleukin-1beta on d 7 and 21 for all CLA treatments (n = 3) relative to CO suggested that antiinflammatory effects of CLA isomers might work by common mechanisms of known pathways involved in chronic inflammation. In conclusion, dietary CLA reduced inflammation associated with CIA, and both c9t11-CLA and t10c12-CLA exhibited antiinflammatory effects.