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The Impact of Preoperative Immune Modulating Nutrition on Outcomes in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis.
Adiamah, A, Skořepa, P, Weimann, A, Lobo, DN
Annals of surgery. 2019;(2):247-256
Abstract
OBJECTIVE To define the influence of preoperative immune modulating nutrition (IMN) on postoperative outcomes in patients undergoing surgery for gastrointestinal cancer. BACKGROUND Although studies have shown that perioperative IMN may reduce postoperative infectious complications, many of these have included patients with benign and malignant disease, and the optimal timing of such an intervention is not clear. METHODS The Embase, Medline, and Cochrane databases were searched from 2000 to 2018, for prospective randomized controlled trials evaluating preoperative oral or enteral IMN in patients undergoing surgery for gastrointestinal cancer. The primary endpoint was the development of postoperative infectious complications. Secondary endpoints included postoperative noninfectious complications, length of stay, and up to 30-day mortality. The analysis was performed using RevMan v5.3 software. RESULTS Sixteen studies reporting on 1387 patients (715 IMN group, 672 control group) were included. Six of the included studies reported on a mixed population of patients undergoing all gastrointestinal cancer surgery. Of the remaining, 4 investigated IMN in colorectal cancer surgery, 2 in pancreatic surgery, and another 2 in patients undergoing surgery for gastric cancer. There was 1 study each on liver and esophageal cancer. The formulation of nutrition used in all studies in the treated patients was Impact (Novartis/Nestlé), which contains ω-3 fatty acids, arginine, and nucleotides. Preoperative IMN in patients undergoing surgery for gastrointestinal cancer reduced infectious complications [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.38-0.71, P < 0.0001, I = 16%, n = 1387] and length of hospital stay (weighted mean difference -1.57 days, 95% CI -2.48 to -0.66, P = 0.0007, I = 34%, n = 995) when compared with control (isocaloric isonitrogeneous feed or normal diet). It, however, did not affect noninfectious complications (OR 0.98, 95% CI 0.73-1.33, P = 0.91, I = 0%, n = 1303) or mortality (OR 0.55, 95% CI 0.18-1.68, P = 0.29, I = 0%, n = 955). CONCLUSION Given the significant impact on infectious complications and a tendency to shorten length of stay, preoperative IMN should be encouraged in routine practice in patients undergoing surgery for gastrointestinal cancer.
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Short-term probiotic supplementation enhances cellular immune function in healthy elderly: systematic review and meta-analysis of controlled studies.
Miller, LE, Lehtoranta, L, Lehtinen, MJ
Nutrition research (New York, N.Y.). 2019;:1-8
Abstract
Immune function declines with advancing age. Probiotic supplementation has been proposed to slow or reverse these age-related changes. The primary objective of this study was to evaluate the effect of probiotic supplementation on cellular innate immune activity in healthy elderly subjects. We hypothesized that probiotic supplementation would enhance immune function. We performed a systematic review and meta-analysis of controlled trials that reported polymorphonuclear cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following short-term probiotic supplementation in the elderly. Effect size was reported as the standardized mean difference (SMD) between probiotic and control groups, where values of 0.2, 0.5, 0.8, and 1.0 corresponded to small, medium, large, and very large effect sizes, respectively. A total of 17 prospective controlled studies (18 comparisons) of 733 subjects were included. Probiotic supplementation duration ranged from 3 to 12 weeks. Probiotic supplementation increased polymorphonuclear phagocytic capacity (SMD = 1.37, 95% confidence interval: 0.86-1.88, P < .001) and NK cell tumoricidal activity (SMD = 0.55, 95% confidence interval: 0.37-0.73, P < .001) relative to controls. In a subgroup analysis of NK cell activity, heterogeneity among studies was not explained by variability in study design or probiotic characteristics. Main limitations of this research were short-term supplementation durations and unclear clinical benefit of the immune changes. In conclusion, short-term probiotic supplementation enhances cellular immune function in healthy elderly adults.
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Vitamin D for the treatment of multiple sclerosis: a meta-analysis.
McLaughlin, L, Clarke, L, Khalilidehkordi, E, Butzkueven, H, Taylor, B, Broadley, SA
Journal of neurology. 2018;(12):2893-2905
Abstract
OBJECTIVE There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS. METHODS A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing-remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software. RESULTS Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01-0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms. CONCLUSION These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.
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Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases.
Li, X, Chen, Y, Tang, Y, Ding, Y, Xu, Q, Sun, L, Qian, W, Qian, G, Qin, L, Lv, H
European journal of pediatrics. 2018;(8):1279-1292
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Abstract
UNLABELLED The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant. CONCLUSION The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: • Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: • This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.
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Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract Infections in Children: A Meta-analysis of Randomized Controlled Trials.
Song, T, Hou, X, Yu, X, Wang, Z, Wang, R, Li, Y, Hu, D, Wang, X, Xiao, Z, Sui, Y, et al
Phytotherapy research : PTR. 2016;(7):1095-103
Abstract
This meta-analysis aimed to evaluate the immunomodulating function of Yupingfeng Formula (YPFF) in children with recurrent respiratory tract infections (RRTIs). The PubMed, EMBASE, Cochrane Library, CNKI and WanFang databases were searched for randomized controlled trials comparing with and without YPFF for RRTIs in children. Twelve trials with 1236 patients were identified. Adjuvant treatment with YPFF significantly increased serum levels of IgA (weighted mean difference [WMD] 0.33 mg/mL; 95% confidence interval [CI] 0.20 to 0.45), IgG (WMD 1.36 mg/mL; 95% CI 1.06 to 1.65), IgM (WMD 0.16 mg/mL; 95% CI 0.02 to 0.31), and CD3(+) T-lymphocytes (WMD 10.16%; 95% CI 4.62 to 15.69) but not CD4(+) T-lymphocytes (WMD 3.16%; 95% CI -0.27 to 6.59) and CD8(+) T-lymphocytes (WMD -0.84%; 95% CI -2.50 to 0.81). YPFF also reduced the frequency of RRTIs (WMD -3.80 times; 95% CI -4.86 to -2.74) and increased total effective rates of symptom improvement (risk ratio: 1.44; 95% CI 1.19 to 1.75). Adjuvant treatment with YPFF could improve total clinical effective rate and decrease the frequency of respiratory tract infections in children with RRTIs. The beneficial effects of YPFF may be correlated to its immunomodulating action. More well-designed trials with larger sample sizes are needed to evaluate its efficacy and safety. Copyright © 2016 John Wiley & Sons, Ltd.
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Effect of interferon-β1α therapy on multiple sclerosis based on gadolinium-enhancing or active T2 magnetic resonance imaging outcomes: a meta-analysis.
Lu, Y, Zhao, J, Zhan, Q
Neurological research. 2016;(10):909-15
Abstract
OBJECTIVES Interferon-beta1alpha (IFN-β1α) is widely used to modify the course of relapsing-remitting multiple sclerosis. However, many patients have relapses. The purpose of this study was to evaluate magnetic resonance imaging (MRI) as a predictor of IFN-β1α treatment efficacy in patients with MS. METHODS PubMed, Embase, and the Cochrane Library were searched to identify eligible studies. Manual searches were also conducted. All eligible trials included MS patients who received IFN-β1α based on gadolinium-enhancing or active T2 MRI lesions for determination of relapse rates. RESULTS Of 499 identified studies, we included 10 trials reporting data on 6,037 MS patients. IFN-β1α therapy significantly reduced the risk of relapse (RR: 0.87; 95% confidence intervals (CI): 0.76-0.99; p = 0.032). Furthermore, baseline median T2 lesion volume was found to be related to IFN-β1α therapy and relapse (p = 0.018). Subgroup analysis suggested that IFN-β1α therapy was associated with reduced risk of relapse (RR: 0.82; 95%CI: 0.71-0.94; p = 0.005 versus placebo). However, there was no significant difference in the risk of relapse compared to treatment with low dose IFN-β1α (RR: 0.93; 95%CI: 0.80-1.08; p = 0.337) or glatiramer acetate (RR: 0.93; 95%CI: 0.77-1.14; p = 0.506). Finally, IFN-β1α therapy significantly increased the risk of injection-site disorders, influenza-like syndrome, and alanine transferase elevation. DISCUSSION Effects of IFN-β1α therapy are associated with a statistically significant impact on baseline median T2 lesion volume. However, the safety outcomes are significantly worse in patients who receive IFN-β1α therapy.
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Preoperative standard oral nutrition supplements vs immunonutrition: results of a systematic review and meta-analysis.
Hegazi, RA, Hustead, DS, Evans, DC
Journal of the American College of Surgeons. 2014;(5):1078-87
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Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis.
Mardini, HE, Grigorian, AY
Inflammatory bowel diseases. 2014;(9):1562-7
Abstract
BACKGROUND VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a meta-analysis of studies on its efficacy. METHODS The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated. RESULTS Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7-56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 10 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side effects were reported. CONCLUSIONS VSL#3, when added to conventional therapy at a daily dose of 3.6 × 10 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.
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The efficacy of Chinese herbal medicine as an adjunctive therapy for colorectal cancer: a systematic review and meta-analysis.
Zhong, LL, Chen, HY, Cho, WC, Meng, XM, Tong, Y
Complementary therapies in medicine. 2012;(4):240-52
Abstract
Although Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for colorectal cancer in Asia, its efficacy is not well defined. The purpose of this systematic review is to assess the efficacy of CHM as an adjunctive therapy to chemotherapy for the patients with colorectal cancer. Randomized controlled trials with CHM to treat colorectal cancer were extensively searched in seven databases. Two researchers independently assessed the quality and validity of included trials and extracted outcome data for synthesis. 20 trials were included for analysis. Compared to using chemotherapy alone, CHM combined with chemotherapy significantly increased 1- and 3-year survival rate [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.32-4.41; OR 2.40, 95% CI 1.49-3.87]. The combined therapy significantly slowed colorectal cancer progression (OR 0.50, 95% CI 0.32-0.77) and improved quality of life (OR 3.43, 95% CI 2.35-5.02). It had positive effects in immunoregulation. CHM as an adjunctive therapy also had significant advantages in reducing the adverse effects of chemotherapy. This systematic review suggests that CHM as an adjunctive therapy with chemotherapy versus chemotherapy alone has significant efficacy in terms of prolonging survival, enhancement of tumor response, improvement of quality of life, immunoregulation, and alleviation of acute adverse effects. However, a firm conclusion could not be reached because of the poor quality of the included trials. Further trials with higher quality are required and the efficacy in other forms of advantages remains to be further determined.
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Adverse effects of biologics: a network meta-analysis and Cochrane overview.
Singh, JA, Wells, GA, Christensen, R, Tanjong Ghogomu, E, Maxwell, L, Macdonald, JK, Filippini, G, Skoetz, N, Francis, D, Lopes, LC, et al
The Cochrane database of systematic reviews. 2011;(2):CD008794
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Abstract
BACKGROUND Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. OBJECTIVES To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). METHODS Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. MAIN RESULTS We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. AUTHORS' CONCLUSIONS Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.