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1.
Change in inflammatory parameters in prefrail and frail persons obtaining physical training and nutritional support provided by lay volunteers: A randomized controlled trial.
Haider, S, Grabovac, I, Winzer, E, Kapan, A, Schindler, KE, Lackinger, C, Titze, S, Dorner, TE
PloS one. 2017;(10):e0185879
Abstract
The aim of the study was to compare the effects of home visits with physical training and nutritional support on inflammatory parameters to home visits with social support alone within a randomized controlled trial. Prefrail and frail persons received home visits from lay volunteers twice a week for 12 weeks. Participants in the physical training and nutritional intervention group (PTN, n = 35) conducted two sets of six strength exercises and received nutritional support. The social support group (SoSu, n = 23) received visits only. TNF-α, IL-6, CRP, and total leukocyte count were assessed at baseline and after 12 weeks. Changes over time within groups were analyzed with paired t-tests; differences between groups were analyzed with ANCOVA for repeated measurements. In the PTN group, IL-6 and CRP remained stable, whereas in the SoSu group, IL-6 increased significantly from a median value of 2.6 pg/l (min-max = 2.0-10.2) to 3.0 pg/l (min-max = 2.0-20.8), and CRP rose from 0.2 mg/dl (min-max = 0.1-0.9) to 0.3 mg/dl (min-max = 0.1-3.0) after 12 weeks. In CRP, a significant difference between groups was found. TNF-α and total leukocyte count did not change in either the PTN group or the SoSu group. Persons showing an increase in physical performance (OR 4.54; 95% CI = 1.33-15.45) were more likely to have constant or decreased IL-6 values than persons who showed no improvement. In conclusion, in non-robust older adults, a physical training and nutritional support program provided by lay volunteers can delay a further increase in some inflammatory parameters.
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2.
Growth Improvement with Adalimumab Treatment in Children with Moderately to Severely Active Crohn's Disease.
Walters, TD, Faubion, WA, Griffiths, AM, Baldassano, RN, Escher, J, Ruemmele, FM, Hyams, JS, Lazar, A, Eichner, S, Huang, B, et al
Inflammatory bowel diseases. 2017;(6):967-975
Abstract
BACKGROUND Growth failure is common in children with Crohn's disease. The effect of adalimumab (ADA), a fully human antitumor necrosis factor antagonist, on height velocity in pediatric patients with baseline (BL) linear growth impairment in the IMAgINE 1 trial is presented. METHODS This analysis included female and male patients with growth potential (bone age ≤13 and ≤14 yr, respectively), with BL Pediatric Crohn's disease Activity Index >30, and who failed or were intolerant to conventional therapy. Patients received open-label induction ADA at weeks 0 and 2 by body weight (≥40 kg, 160 and 80 mg and <40 kg, 80 and 40 mg). At week 4, patients were randomized to double-blind high (40 or 20 mg for ≥40 kg or <40 kg) or low dose (20 or 10 mg for ≥40 kg or <40 kg) every other week ADA to week 52. Height velocity z-score was summarized at BL, week 26, and week 52 by patients with BL growth impairment (z-score ≤-1.0) or normal growth (z-score >-1.0). RESULTS ADA therapy significantly improved and normalized growth rate at weeks 26 and 52 in patients with BL growth impairment (median z-score, BL, -3.25; week 26, -0.34; and week 52, 0.21; P < 0.001 versus BL for both), but not in patients with normal growth. Growth improvement was significantly greater at week 26 in week 4 responders to induction therapy compared with nonresponders (median z-score 0.09 versus -2.92; P = 0.02). CONCLUSIONS ADA treatment resulted in growth rate normalization as early as week 26 in children with moderately to severely active Crohn's disease and growth impairment.
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3.
The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial).
Strohal, R, Puig, L, Chouela, E, Tsai, TF, Melin, J, Freundlich, B, Molta, CT, Fuiman, J, Pedersen, R, Robertson, D
The Journal of dermatological treatment. 2013;(3):169-78
Abstract
OBJECTIVE To assess the efficacy and safety of two etanercept dose regimens for psoriasis treatment. METHODS Subjects were ≥18 years old with stable moderate-to-severe plaque psoriasis. Subjects were randomised to etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) double-blind for 12 weeks, followed by 50 mg QW open label in all subjects through week 24. Only mild topical corticosteroids were permitted on scalp, axillae and groin for first 12 weeks; topical medications (corticosteroids of all potencies, vitamin D analogues and combination products) were allowed as needed for second 12 weeks at physicians' discretion, consistent with "real-world" therapeutic practice. An independent ethics committee reviewed and approved the study protocol. RESULTS At week 24, 59.9% and 78.2% in the QW/QW and BIW/QW groups achieved PASI 75 improvement. Mean percentage PASI improvement in these groups was 58.5% and 74.1% at week 12 and 70.7% and 81.3% at week 24. Although permitted from weeks 12 to 24, topical agents were used in only 27.7% and 22.6% in the QW/QW and BIW/QW groups by week 24. CONCLUSION Both etanercept regimens were efficacious in moderate-to-severe psoriasis, although the BIW/QW regimen consistently provided higher response rates than the QW/QW regimen. More potent topical medications were used electively in <25% of subjects in each group.
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4.
Effect of treatment with omega-3 fatty acids on C-reactive protein and tumor necrosis factor-alfa in hemodialysis patients.
Tayyebi-Khosroshahi, H, Houshyar, J, Dehgan-Hesari, R, Alikhah, H, Vatankhah, AM, Safaeian, AR, Zonouz, NR
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. 2012;(3):500-6
Abstract
C-reactive protein (CRP), a strong independent risk marker of cardiovascular disease (CVD), and tumor necrosis factor-alfa (TNF-α), a known pro-inflammatory cytokine, are elevated and have damaging effects in patients with chronic renal failure (CRF). Omega-3 fatty acids play an important modulatory role in inflammatory responses. The aim of this study is to review the alterations in serum levels of TNF-α, CRP and other parameters caused by omega-3 supplementation in dialysis patients. The clinical trial was performed in 37 patients with end-stage renal disease undergoing dialysis in hemodialysis centers of three university hospitals in Tabriz. Blood samples were obtained from the study patients for hemoglobin, albumin, ferritin, triglyceride, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol, TNF-α and high specific-CRP (hs-CRP) measurement. The patients received 3 g omega-3 per day for 2 months. The side-effects noticed were nausea, diarrhea and dyspepsia and undesired drug smell. The difference noted in hemoglobin, albumin, ferritin, CRP, triglyceride, total, LDL and HDL-cholesterol before and after supplementation with omega-3 fatty acid was not statistically significant (P > 0.05). However, the use of omega-3 decreased the serum levels of TNF-α significantly. We conclude that the use of 3 g of omega-3 per day caused significant decrease in serum levels of TNF-α in the dialysis population, and its use is recommended in such patients.
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5.
Circulating dendritic cell number and intracellular TNF-α production in women with type 2 diabetes.
Blank, SE, Johnson, EC, Weeks, DK, Wysham, CH
Acta diabetologica. 2012;:S25-32
Abstract
Human dendritic cell (DC) subsets perform specialized functions for surveillance against bacterial and viral infections essential for the management of type 2 diabetes (T2D). Production of tumor necrosis factor-alpha (TNF-α) by DCs acts in autocrine fashion to regulate DC maturation and promotes the inflammatory response. This study was designed to compare circulating DC number and intracellular TNF-α production between post-menopausal women with T2D and healthy women. Blood samples were obtained (n = 21/group) and examined for plasma glucose and TNF-α concentrations, and dendritic cell subset immunophenotype (plasmacytoid, pDC, CD85k(ILT-3)(+)CD123(+)CD16(-)CD14(-) and myeloid, mDC, CD85k(ILT-3)(+)CD33(+)CD123(dim to neg)CD16(-)CD14(dim to neg)). Intracellular production of TNF-α was determined in unstimulated and stimulated DCs. Women with T2D had significantly (P < 0.05) greater plasma glucose and TNF-α concentrations when compared to healthy women. Women with T2D having poor glycemic control (T2D Poor Control, HbA1c ≥ 7%) had fewer circulating pDCs than women with T2D having good glycemic control (T2D Good Control, HbA1c < 7%) and healthy women. A significant interaction (P = 0.011) was observed between the effects of plasma glucose and group for intracellular expression of TNF-α in stimulated pDCs. Intracellular production of TNF-α in pDCs was significantly greater in healthy vs. T2D Poor Control (P < 0.0001) and T2D Good Control (P < 0.0001) but did not differ between T2D subgroups. The mDC number and intracellular production of TNF-α did not differ between groups. These findings indicate that TNF-α production by pDCs was reduced in women with T2D and circulating number of pDCs was associated with glycemic control.
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6.
Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn's disease - A controlled clinical trial.
Krebs, S, Omer, TN, Omer, B
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2010;(5):305-9
Abstract
Suppression of tumour necrosis factor alpha (TNF-alpha) and other interleukins by wormwood (Artemisia absinthium) extracts were reported recently in in vitro studies. The aim of the present study was to find out if this effect can be also be observed in Crohn's Disease (CD) patients where TNF-alpha appears to play an important role. In a controlled trial, 10 randomly selected patients suffering from CD were given in addition to their basic CD therapy 3x750mg dried powdered wormwood for 6 weeks. Ten patients, also randomly selected who met the inclusion criteria served as control group. Minimum score of 200 on Crohn's Disease Activity Index (CDAI) was required at baseline for inclusion in each group. Patients who received infliximab or similar were excluded from the trial. TNF-alpha level in serum were measured at baseline, and after three and six weeks. During this period all concomitant CD medications was maintained at the baseline dose levels. Average serum TNF-alpha level fell from 24.5+/-3.5pg/ml at baseline to 8.0+/-2.5pg/ml after six weeks. The corresponding levels in the control group were 25.7+/-4.6 (week 0), and 21.1+/-3.2 (week 6). On the clinical side, CDAI scores fell from 275+/-15 to below 175+/-12 in wormwood group with remission of symptoms in eight patients (CDAI score below 170 or reduction by 70 points), compared to only two in the placebo group (CDAI of placebo group 282+/-11 at baseline and 230+/-14 on week 6). IBDQ also reflected accelerated clinical response with wormwood. Of clinical significance were the findings that wormwood also improved mood of the CD patients, as reflected in Hamilton's Depression Scale. These findings provide a base to test wormwood in clinical conditions thought to be mediated by increased production of pro-inflammatory cytokines such as TNF-alpha.
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7.
The prognostic significance of patient-reported outcomes in pancreatic cancer cachexia.
Robinson, DW, Eisenberg, DF, Cella, D, Zhao, N, de Boer, C, DeWitte, M
The journal of supportive oncology. 2008;(6):283-90
Abstract
Data from a clinical study of 86 pancreatic cancer patients with involuntary, significant weight loss (cachexia) were used to explore the relationship between patient-reported outcomes (PROs) and survival. In all, 28 pancreatic cancer patients with cachexia were given gemcitabine (Gemzar) plus 3 mg/kg of infliximab (Remicade), 28 were given gemcitabine plus 5 mg/kg of infliximab, and 30 were given gemcitabine plus placebo in a double-blinded, phase II, multicenter trial. PRO endpoints included scores from the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Anorexia/ Cachexia Therapy (FAACT), Brief Pain Inventory (BPI), and the Short-Form 36 general health survey (SF-36). Population mean scores at baseline indicated fatigue problems (FACIT-F), nutritional health issues (FAACT), and mild-to-moderate pain (BPI "worst pain" score). Baseline normalized SF-36 values for physical functioning, vitality, and mental health indicated substantial impairment. Baseline fatigue and physical-functioning scores predicted survival as well as, or better than, baseline Karnofsky Performance Status or hemoglobin level. A cut-point in the FACIT-F score (median < or = 30) strongly predicted mortality; patients with greater fatigue had a lower median overall survival than did those with less fatigue. These findings supported several features of an a priori clinical-benefit model. Patient-reported fatigue provided powerful prognostic information; tracking of this symptom may be useful for treatment planning and medical monitoring of advanced-stage pancreatic cancer patients with cachexia. These results must be confirmed by larger trials.
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8.
Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis.
Capsoni, F, Sarzi-Puttini, P, Atzeni, F, Minonzio, F, Bonara, P, Doria, A, Carrabba, M
Arthritis research & therapy. 2005;(2):R250-5
Abstract
Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-alpha therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-alpha mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-alpha therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-alpha therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-alpha neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-alpha mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-alpha activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-alpha mAbs in the control of inflammatory arthritis.
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9.
Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors.
Samuelsson, L, Gottsäter, A, Lindgärde, F
Diabetes, obesity & metabolism. 2003;(3):195-201
Abstract
AIM: Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo. METHODS TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily. RESULTS Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001). CONCLUSION Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.