-
1.
Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: A randomized, controlled trial.
Miyauchi, Y, Furukawa, K, Suzuki, D, Yoshitomi, H, Takayashiki, T, Kuboki, S, Miyazaki, M, Ohtsuka, M
International journal of surgery (London, England). 2019;:69-75
-
-
Free full text
-
Abstract
BACKGROUND We have reported that perioperative and preoperative immunonutrition reduced infectious complications in patients undergoing pancreaticoduodenectomy; however, it is unclear whether perioperative immunonutrition has additional effects compared with preoperative immunonutrition. The present study evaluated whether perioperative, compared with preoperative, immunonutrition has additional effects on cell-mediated immunity and the infection rate after pancreaticoduodenectomy. MATERIALS AND METHODS This was a prospective, randomized clinical trial conducted in our institution. Oral supplementation enriched with arginine, ω-3 fatty acids, and dietary nucleotides was given by enteral infusion to 30 patients before and after surgery (perioperative group); 30 patients received the same enriched formula before surgery and standard enteral nutrition following surgery (preoperative group). The primary endpoint was concanavalin (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation on postoperative day (POD) 7, which is an index of cell-mediated immunity; the secondary endpoint was the postoperative infection rate. RESULTS There were no significant differences in Con A- or PHA-stimulated lymphocyte proliferation on POD 7 between the groups. There was no significant difference in the postoperative infection rate between the two groups. In the post hoc subgroup analysis, with respect to the effect on the infection rate, a significant interaction was found only between a long operative time and perioperative immunonutrition. CONCLUSIONS There were no additional effects of perioperative, compared with preoperative, immunonutrition on postoperative immunity and infectious complications in patients undergoing pancreaticoduodenectomy.
-
2.
Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.
Hamilton-Reeves, JM, Stanley, A, Bechtel, MD, Yankee, TM, Chalise, P, Hand, LK, Lee, EK, Smelser, W, Mirza, M, Wyre, H, et al
The Journal of urology. 2018;(2):292-301
Abstract
PURPOSE Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.
-
3.
Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years.
Puthanakit, T, Huang, LM, Chiu, CH, Tang, RB, Schwarz, TF, Esposito, S, Frenette, L, Giaquinto, C, McNeil, S, Rheault, P, et al
The Journal of infectious diseases. 2016;(4):525-36
-
-
Free full text
-
Abstract
BACKGROUND This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years. METHODS Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety. Limits of noninferiority were predefined as <5% difference in seroconversion rate and <2-fold difference in geometric mean antibody titer ratio. RESULTS One month after the last dose, both 2D regimens in girls aged 9-14 years were noninferior to 3D in women aged 15-25 years and 2D (M0,12) was noninferior to 2D (M0,6). Geometric mean antibody titer ratios (3D/2D) for HPV-16 and HPV-18 were 1.09 (95% confidence interval, .97-1.22) and 0.85 (.76-.95) for 2D (M0,6) versus 3D and 0.89 (.79-1.01) and 0.75 (.67-.85) for 2D (M0,12) versus 3D. The safety profile was clinically acceptable in all groups. CONCLUSIONS The 2D regimens for the HPV-16/18 AS04-adjuvanted vaccine in girls aged 9-14 years (M0,6 or M0,12) elicited HPV-16/18 immune responses that were noninferior to 3D in women aged 15-25 years. CLINICAL TRIALS REGISTRATION NCT01381575.
-
4.
LICHENS' B-OLIGOSACCHARIDES IN THE CORRECTION OF METABOLIC DISORDERS IN TYPE 2 DIABETES MELLITUS.
Kershengolts, BM, Sydykova, LA, Sharoyko, VV, Anshakova, VV, Stepanova, AV, Varfolomeeva, NA
Wiadomosci lekarskie (Warsaw, Poland : 1960). 2015;(4):480-2
Abstract
INTRODUCTION Lichens of the genus Cladonia are used as medicinal plants in folk medicine. Biologically active food supplement (BAFS) on the basis of lichens p. Cladonia was derived by mechanical-chemical biotechnology in the Educational-Research-Engineering Laboratory "Mechanical-Chemical Biotechnology" of the North-Eastern Federal University (NEFU). As a result of biotech impact, the solid β-glycoside bonds are destructed on β-oligosaccharide molecules, and other groups of lichen BAS is mobilized. The content of hydrolysable carbohydrates in samples of lichen increased 8 times after mechanical activation. AIM: The aim of investigation was to study the effects of BAFS "Yagel-Detox" in patients with type 2 diabetes mellitus (DM 2). MATERIALS AND METHODS The 150 patients (group 1--100 patients receiving "Yagel-Detox", group 2--50 patients receiving placebo) with a diagnosis DM 2 were examined. The research included: general clinical and instrumental examination, biochemical and clinical blood tests. "Yagel-Detox" was used 1 capsule 3 times a day, the rate of admission was 3 months. RESULTS Clinical trials have shown that 3-month intake of BAFS "Yagel-Detox" reduces the concentration of blood glucose 1.3 1.6 times (in the control group--1.2 ÷ 1.4 times), glycosylated hemoglobin--from 9.8 ÷ 11.4% to 7.6% (in the control group--1.0%). The concentration of low-density lipoprotein (LDL) reduced on 1.3% through 6 months. Patients of both groups were on the similar tablet glucose-lowering therapy (randomized treatment), which have not been adjusted. CONCLUSIONS The obtained results allow us to recommend BAFS "Yagel-Detox" as an additional remedy to normalize blood glucose concentration in patients with DM 2.
-
5.
Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver.
Jo, J, Tan, AT, Ussher, JE, Sandalova, E, Tang, XZ, Tan-Garcia, A, To, N, Hong, M, Chia, A, Gill, US, et al
PLoS pathogens. 2014;(6):e1004210
Abstract
The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161(Bright) mucosal-associated invariant T (MAIT) and CD56(Bright) NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies.
-
6.
An observer-blind, randomized, multi-center trial assessing long-term safety and immunogenicity of AS03-adjuvanted or unadjuvanted H1N1/2009 influenza vaccines in children 10-17 years of age.
Poder, A, Simurka, P, Li, P, Roy-Ghanta, S, Vaughn, D
Vaccine. 2014;(9):1121-9
Abstract
BACKGROUND Vaccination is an effective strategy to prevent influenza. This observer-blind, randomized study in children 10-17 years of age assessed whether the hemagglutination inhibition (HI) antibody responses elicited by H1N1/2009 vaccines adjuvanted with AS03 (an adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion) or without adjuvant, met the European regulatory immunogenicity criteria at Days 21 and 182. METHODS Three hundred and ten healthy children were randomized (3:3:3:5) to receive one dose of 3.75 μg hemagglutinin (HA) AS03A-adjuvanted vaccine, one or two doses of 1.9 μg HA AS03B-adjuvanted vaccine, or one dose of 15 μg HA pandemic vaccine. All children received a booster dose of the allocated vaccine at Day 182. Serum samples were tested for HI antibody response at Days 21, 42, 182 and 189. RESULTS All vaccination regimens elicited HI antibody responses that met the European regulatory criteria at Days 21 and 42. HI antibody responses fulfilling European regulatory criteria were still observed six months after the first vaccine dose in all study vaccines groups. Two doses of 1.9 μg HA AS03B-adjuvanted vaccine elicited the strongest HI antibody response throughout the study. The non-adjuvanted 15 μg HA vaccine elicited a lower HI antibody response than the AS03-adjuvanted vaccines. At Day 189, the European regulatory criteria were met for all vaccines with baseline HI antibody titers as reference. An anamnestic response for all vaccines was suggested at Day 189, based on the rapid increase in HI antibody geometric mean titers (1.5-2.5-fold increase). Injection site reactogenicity was higher following the AS03-adjuvanted vaccines compared with the non-adjuvanted vaccine. No safety concerns were identified for any study vaccine. CONCLUSION All study vaccines elicited HI antibody responses that persisted at purported protective levels through six months after vaccination and fulfilled the European regulatory criteria.
-
7.
Immunogenicity and efficacy in hemodialysis patients of an AS03(A)-adjuvanted vaccine for 2009 pandemic influenza A(H1N1): a nonrandomized trial.
Dikow, R, Eckerle, I, Ksoll-Rudek, D, Hampel, H, Schwenger, V, Zeier, M, Schnitzler, P, Sommerer, C
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2011;(5):716-23
Abstract
BACKGROUND Hemodialysis patients have a reduced response to vaccinations because of uremia-related immune dysfunction. To increase the immunogenicity of vaccines, antigens can be formulated with adjuvants. The new tocopherol-containing adjuvant system AS03(A) has not been tested yet in patients with end-stage renal disease. STUDY DESIGN Nonrandomized trial. SETTING & PARTICIPANTS 291 hemodialysis patients from 3 dialysis units co-operating with the Department of Nephrology at the University Hospital Heidelberg, Germany: 169 patients were vaccinated using either 1 (64 patients) or 2 doses (105 patients); 123 patients refused the vaccination and served as controls. INTERVENTION Intramuscular immunization with 3.75 μg of an inactivated split-virion A/California/7/2009 H1N1v pandemic vaccine adjuvanted with AS03(A) in a single- or double-dose regimen. OUTCOMES A pandemic influenza A immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) response >11 AU (arbitrary units) was defined as a positive response. MEASUREMENTS Quantitative antibody testing using the pandemic influenza A IgG ELISA. Antibody titers were tested 3 months after vaccination and compared with nonimmunized dialysis patients. RESULTS After vaccination against 2009 pandemic influenza A(H1N1), 41 of 64 (64.1%) patients with 1 vaccination and 93 of 105 (88.6%) with 2 vaccinations showed a protective immune response compared with 43 of 123 (34.9%) unvaccinated patients (P < 0.001). Logistic regression analysis confirmed vaccination dose as an independent factor for response to pandemic H1N1 vaccination. No episode of pandemic H1N1 illness occurred in any group within the study period of 6 months after vaccination. No serious adverse events occurred, and local symptoms ranged from mild to moderate in 143 of 169 (84.6%) patients. LIMITATIONS Nonrandomized assignment; use of nontreated patients as controls; no comparison to nonadjuvanted vaccines; dose variation in the intervention group. CONCLUSIONS Pandemic H1N1 vaccine adjuvanted with AS03(A) is immunogenic, effective, and safe in hemodialysis patients.
-
8.
Modulation of serum gastric parietal cell antibody level by levamisole and vitamin B12 in oral lichen planus.
Lin, HP, Wang, YP, Chia, JS, Chiang, CP, Sun, A
Oral diseases. 2011;(1):95-101
Abstract
OBJECTIVES The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti-gastric parietal cell autoantibody (GPCA) level in GPCA-positive oral lichen planus (OLP) patients. MATERIALS AND METHODS Of 147 GPCA-positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. RESULTS Treatment with levamisole plus vitamin B12 for a period of 2-50 months and treatment with vitamin B12 only for a period of 4-44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2-50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA-negative remission period. CONCLUSION For GPCA-positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life.
-
9.
A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems.
Precioso, AR, Miraglia, JL, Campos, LM, Goulart, AC, Timenetsky, Mdo C, Cardoso, MR, Luna, E, Mondini, G, Guedes, Jda S, Raw, I
Vaccine. 2011;(48):8974-81
Abstract
METHODS We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. RESULTS A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene. CONCLUSIONS Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.
-
10.
Oral supplementation with a nutraceutical containing Echinacea, methionine and antioxidant/immunostimulating compounds in patients with cutaneous viral warts.
Cassano, N, Ferrari, A, Fai, D, Pettinato, M, Pellè, S, Del Brocco, L, Ligori, P, Romano, I, Curia, S, Carbonara, M, et al
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2011;(3):191-5
Abstract
AIM: The aim of thos paper was to determine the effect of oral supplementation (OS) with a nutraceutical, containing methionine, Echinacea, zinc, probiotics and other antioxidant and immunostimulating compounds, on the response of cutaneous warts to conventional standard therapy (CST). METHODS This was an open-label study in adults and adolescents aged 14 years or more and with a body weight ≥40 kg, who had at least one cutaneous viral wart. Eligible patients were consecutively allocated to CST (topical therapy with a preparation containing salicylic acid and lactic acid or liquid nitrogen cryotherapy) alone or CST combined with nutraceutical OS for 4 months. RESULTS A total of 172 patients were enrolled: 83 received CST alone and 89 CST+OS. During the 6-month observation period, a statistically significant reduction of the mean number of warts was obtained in each treatment group and subgroup. The addition of nutraceutical OS was associated with a significantly lower number of warts at 6 months as compared to CST alone. Complete remission was obtained in 54.5% and 86% of patients in the CST group and CST+OS arm, respectively (P<0.001). The influence of the nutraceutical on the response rate appeared to be more prominent in the subgroup of patients treated with topical therapy. The development of new warts during the study period occurred significantly less frequently with CST+OS compared to CST (9% versus 25%; P=0.004). No adverse events possibly related to the nutraceutical administration were observed. CONCLUSION Our pilot experience seems to suggest that nutraceutical OS is safe and beneficial in patients with cutaneous warts, and capable of enhancing the response to CST.