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PP030-MON TAUROLIDINE SUSCEPTIBILITY OF MICROORGANISMS CAUSING CATHETER SEPSIS IN HOME PARENTERAL NUTRITION PATIENTS USING LONG TERM TAUROLIDINE CATHETER LOCKING
Hormones, mediators and immunity II icantly increased in the CT group (CT: 18.0±4.4/b-actin, V: 6.8±0.40/b-actin, P < 0.05). Moreover, the addition of cystine but not theanine significantly increased LPS-induced IL-18 production in THP-1 cells compared with the control (cystine: 461.8±29.9 pg/ml, control: 101.2±8.1 pg/ml, P < 0.05). Conclusion: Our results suggest that CT administration enhances LPS-induced sNK cell activity at least partly through increasing IL-18 production by cystine in monocytes, and that CT may be effective in preventing immunosuppression in patients after surgery. Disclosure of Interest: None Declared.
PP028-MON SUPPRESSION OF SURGERY-INDUCED HYPERCATABOLISM BY PREOPERATIVE ORAL ADMINISTRATION OF AMINO ACIDS, CYSTINE/THEANINE, IN A MOUSE SURGICAL MODEL T. Shibakusa1 , S. Kurihara1 , Y. Chiba2 , T. Tsuchiya3 , K.A. Tanaka1 , T. Miyachi3 , A. Oyama3 . 1 Institute for Innovation, Ajinomoto Co., Inc, Kawasaki, 2 Nutrition Care Dept., Ajinomoto Co., Inc, Tokyo, 3 Department of Surgery, Sendai City Medical Center, Sendai, Japan Rationale: We previously reported that the preoperative oral administration of cystine/theanine (CT) suppresses inflammatory responses by inhibiting the surgery-induced decrease in glutathione in the small intestine and promotes postoperative recovery (Clin Nutr 2012). Surgical trauma has been reported to enhance the inflammatory response and energy metabolism and to induce muscle protein degradation, known as hypercatabolism. Based on these findings, we examined the effect of CT on the surgery-induced enhancement of energy expenditure (EE) using a mouse surgical model. Methods: CT (70 mg/kg) or a vehicle (V) was orally administered to BALB/c mice aged 12 weeks once a day for 4 days before surgery. On the day of surgery, small intestine manipulation was performed under anaesthesia 2 hours after oral administration. Respiratory gas analysis was performed until 24 hours after surgery. Results: The average EE 1.5 hours before the administration of CT was used as a baseline. The value of EE in the V group gradually increased immediately after surgery and increased approximately 10% 24 hours after surgery compared with the initial value. However, the value of EE in the CT group also gradually increased but was lower compared with the V group during 24 hours. The average value of EE in the latter half of the 24 hours in the CT group was significantly lower than the V group (average of V: 92.55±2.11% vs average of CT: 84.83±2.97%, p < 0.05). Conclusion: These results suggest that the preoperative administration of CT might suppress skeletal muscle proteolysis by inhibiting the surgery-induced enhancement of inflammatory responses and energy metabolism. References Enhancement of postoperative recovery by preoperative oral coadministration of the amino acids, cystine and theanine, in a mouse surgical model., T. Shibakusa, T. Mikami et. al., Clin Nutr. 2012 in press. Disclosure of Interest: None Declared.
149 PP029-MON A 55% REDUCTION IN HOSPITAL ADMISSION RATE OF PATIENTS ON HOME PARENTERAL NUTRITION AFTER INTRODUCTION OF TAUROLIDINE CATHETER LOCKING: A FOLLOW-UP OF NEARLY 200,000 DAYS E.D. Olthof1 , G. Huisman-de Waal1 , R. Vissers1 , G.J. Wanten1 . 1 Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Rationale: Home parenteral nutrition (HPN) patients are at risk for developing catheter-related bloodstream infections (CRBSI). The use of an anti-microbial catheterlock solution containing 2% taurolidine (TauroSept® ) has shown to strongly reduce infectious complications in a pilot study. Our HPN population therefore switched to taurolidine locking in 2008. Methods: We compared population dynamics and hospital admission data in the pre (2006 2007) and post (2008 2011) taurolidine eras, also taking into account new patients who need in-hospital training and patients who use an arteriovenous fistula (AVF) for HPN administration, since the latter do not use a catheter lock. Results: From 2006 towards 2012 the number of HPNrelated admission days at our 15-bed clinical ward remained stable at 1439±167 days/year. Over this period, the population number more than doubled (adult HPN patients from 61 to 133, new patients per year from 13 to 27) and the observation days (patients with a catheter, subcutaneous port or AVF) increased from 21,619 to 44,895 per year (overall 194,559). The number of HPN patients using an AVF decreased from 20 to 12 (33% and 9% of total HPN population, respectively). Most importantly, the ratio of hospital admission days per catheter day decreased by 55% from 0.055 in two pretaurolidine years to 0.025 thereafter, excluding patients who had in-hospital training. During this period all treatment- and educational protocols for HPN patients other than catheter locking remained the same. Conclusion: Our results strongly suggest that catheter locking with 2% taurolidine beneficially alters the course of long-term HPN treatment. These data may have strong implications for the number of patients in whom creation of an AVF for HPN treatment will be considered in the future. Disclosure of Interest: None Declared.
PP030-MON TAUROLIDINE SUSCEPTIBILITY OF MICROORGANISMS CAUSING CATHETER SEPSIS IN HOME PARENTERAL NUTRITION PATIENTS USING LONG TERM TAUROLIDINE CATHETER LOCKING E.D. Olthof1 , R.J. Rentenaar2 , A.J. Rijs2 , G.J. Wanten1 . 1 Gastroenterology and Hepatology, 2 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Rationale: Some home parenteral nutrition (HPN) patients still develop catheter related bloodstream infections (CRBSI), despite the use of an antimicrobial catheter lock solution containing 2% taurolidine (TauroSept® ). The aim of our study was to examine
150 whether CRBSI-causing microorganisms in these HPN patients have decreased susceptibility to taurolidine. Methods: We determined for each CRBSI-causing microorganism, by broth microdilution, the lowest dilution of taurolidine without visible microbial growth after 18 h (bacteria) or 24 h (Candida spp.) of culture, known as the Minimal Inhibitory Concentration (MIC). CRBSI diagnosis was based on clinical symptoms of infection, positive blood culture, and absence of other causes of bloodstream infections. Results: From January 2009 until April 2011, 17 patients in a cohort of 158 HPN patients using a taurolidine catheter lock, developed a single (13 patients) or multiple (4 patients) CRBSIs, resulting in 0.3 infections per 1000 catheter days. Sixty-five percent of CRBSIs were monomicrobial, 35% were polymicrobial. Luminal CRBSIcausing microorganisms were Gram-positive bacteria (59%), Gram-negative rods (22%) or Candida spp. (19%). CRBSI-causing Gram-positive bacteria were mostly coagulase negative Staphylococcus species (n = 9) or S. aureus (n = 3) with taurolidine MIC values of 512 mg/ml or less in 50% of the isolates (MIC50 ). The taurolidine MIC50 for E. coli, the most common CRBSI-causing Gram-negative bacterium, was 512 mg/ml (n = 2). CRBSI-causing C. albicans isolates had higher taurolidine MICs (2048 mg/ml, n = 5) than bacteria. The MIC values found in this study were similar to values reported in the literature. Conclusion: In conclusion, decreased taurolidine susceptibility is not a factor in the pathogenesis of CRBSI in HPN patients using taurolidine catheter locking. Disclosure of Interest: None Declared.
PP031-MON Outstanding abstract ALTERATION OF ENTEROENDOCRINE AND NEUROPEPTIDES IN GRAFT AFTER SMALL BOWEL TRANSPLANTATION IN DOGS H.S. Lai1 , P.H. Lee1 , W.J. Chen1 . 1 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, China Rationale: Two major problems for small bowel transplantation (SBTx), graft rejection and poor graft function, are related to the status of enteroendocrine (Eend), nerve plexuses and ganglions in the graft. We evaluate the alteration of Eend (somatostatin and chromogranin A), and neuropeptides (NP; neurofilament, synaptophysin) markers in the rejected graft after SBTx. Methods: SBTx was performed in male mongrel dogs with the graft intestine preserved by 4ºC UW solution. SMV, SMA end-to-end anastomosis with Modified Mikulicz ileostomy were performed. Blood samples for complete blood cell (CBC) counts, suction biopsies from ileostomy for histopathologic pictures and immunohistochemical staining for NP [neurofilament (Zymed 08-0041, USA) synaptophysin (Zymed 08-0130, USA)], and Eend peptides [chromogranin A (Zymed 08-0094, USA), somatostatin (Zymed 08-0078, USA)] were performed on Days 0, 1, 2, 3, 4, 5 and 7. Results: Successful SBTx in 10 pairs of dogs was shown in Table 1. CBC counts and histopathologic pictures demonstrated a marked rejection on day 5 & 7 after SBTx (p < 0.05). Destruction of the submucosal nerve plexus and ganglion cells were markedly identified by
Poster presentations immunohistochemical staining of NP (neurofilament and synaptophysin) on the 7th postoperative day (p < 0.01). The Eend cells showed no apparent changes, even in a severe rejection status. Table 1. Basic data of small bowel transplantation in dogs Donor/Recipient Bw (kg) Blood loss (ml) Op time (min) Ischemic time (min) Total/Warm Graft length (cm) NP (synaptophysin) d0/d7 Eend (chromatogranin) d0/d7
Range
Medium
Mean±SD
12 24/10.5 15.5 10 50 118 223 40 97/22 51 100 142 10 20/0 5 20 30/18 26
14.5/12 15 151 51/35 120 16/2 24/22
15.5±3.2/12.3±2.8 17±5 142±33 56±9/33±8 112±14 15±3/2±1 (p < 0.01) 24±4/22±4
Conclusion: Monitoring NP (neurofilament and synaptophysin) in nerve fibers demonstrated an useful marker for graft rejection after SBTx. However, the presentation of Eend marker is unclear. Disclosure of Interest: None Declared.
PP032-MON RELATIONSHIP BETWEEN USE OF PROTON PUMP INHIBITORS AND IGF SYSTEM IN OLDER SUBJECTS: THE InCHIANTI STUDY M. Maggio1 , C. Cattabiani1 , F. Lauretani2 , G. Bondi1 , F. De Vita2 , S. Bandinelli3 , A. Corsonello4 , L. Ferrucci5 , G.P. Ceda1 . 1 Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, 2 Geriatric-Rehabilitation, University-Hospital, Parma, 3 Geriatric Unit, Azienda Sanitaria, Firenze, 4 Unit of Geriatric Pharmacoepidemiology, Italian National Research Centres on Aging (INRCA), Cosenza, Italy; 5 National Institute on Aging, National Institutes of Health, Baltimore, United States Rationale: The use of proton pump inhibitors (PPI) is increased worldwide and has been associated with poor clinical outcomes in older subjects [1,2], where PPI may affect adsorption of nutrients, exacerbating the risk of malnutrition [1]. Recent in vitro studies show that PPI may interfere with insulin like-growth factor 1 (IGF-1), an anabolic hormone and nutritional marker whose levels decrease with age [3,4]. However, the relationship between PPI use and IGF system is unknown. Methods: To address this hypothesis we considered 903 older subjects (536 women, 402 men) of InCHIANTI study, with complete information on IGF-1, IGF-binding protein-1 (IGFBP-1) and medications. IGF-1 and IGFBP-1 were measured by immunoradiometric assay. Generalized Linear Models were used to test the association between PPI use (predictor) and IGF-1, IGFBP-1 (outcome). Results: 402 men (388 PPI users and 14 non users) and 536 women (515 PPI non users and 21 users) were considered for this analysis. PPI male users were older (77.7±7.5 vs 74.6±6.9 years ±SD) while women on PPI were younger than non users (74.2.±4.8 vs 76.6±7.8). After adjusting for age, male PPI users (107.0±69.6 vs 127.1±55.8, p < 0.001) and female PPI users (87.6±29.1 vs 107.6±52.3, p = 0.03) had lower levels of IGF-1 than PPI non users. IGFBP-1 was similar in 2 groups in men and women. After adjustment for age, sex, BMI, liver function, caloric intake and IGFBP-1 the relationship between PPI use and IGF-1 was still negative and almost significant (p = 0.06).
PP028-MON SUPPRESSION OF SURGERY-INDUCED HYPERCATABOLISM BY PREOPERATIVE ORAL ADMINISTRATION OF AMINO ACIDS, CYSTINE/THEANINE, IN A MOUSE SURGICAL MODEL T. Shibakusa1 , S. Kurihara1 , Y. Chiba2 , T. Tsuchiya3 , K.A. Tanaka1 , T. Miyachi3 , A. Oyama3 . 1 Institute for Innovation, Ajinomoto Co., Inc, Kawasaki, 2 Nutrition Care Dept., Ajinomoto Co., Inc, Tokyo, 3 Department of Surgery, Sendai City Medical Center, Sendai, Japan Rationale: We previously reported that the preoperative oral administration of cystine/theanine (CT) suppresses inflammatory responses by inhibiting the surgery-induced decrease in glutathione in the small intestine and promotes postoperative recovery (Clin Nutr 2012). Surgical trauma has been reported to enhance the inflammatory response and energy metabolism and to induce muscle protein degradation, known as hypercatabolism. Based on these findings, we examined the effect of CT on the surgery-induced enhancement of energy expenditure (EE) using a mouse surgical model. Methods: CT (70 mg/kg) or a vehicle (V) was orally administered to BALB/c mice aged 12 weeks once a day for 4 days before surgery. On the day of surgery, small intestine manipulation was performed under anaesthesia 2 hours after oral administration. Respiratory gas analysis was performed until 24 hours after surgery. Results: The average EE 1.5 hours before the administration of CT was used as a baseline. The value of EE in the V group gradually increased immediately after surgery and increased approximately 10% 24 hours after surgery compared with the initial value. However, the value of EE in the CT group also gradually increased but was lower compared with the V group during 24 hours. The average value of EE in the latter half of the 24 hours in the CT group was significantly lower than the V group (average of V: 92.55±2.11% vs average of CT: 84.83±2.97%, p < 0.05). Conclusion: These results suggest that the preoperative administration of CT might suppress skeletal muscle proteolysis by inhibiting the surgery-induced enhancement of inflammatory responses and energy metabolism. References Enhancement of postoperative recovery by preoperative oral coadministration of the amino acids, cystine and theanine, in a mouse surgical model., T. Shibakusa, T. Mikami et. al., Clin Nutr. 2012 in press. Disclosure of Interest: None Declared.
149 PP029-MON A 55% REDUCTION IN HOSPITAL ADMISSION RATE OF PATIENTS ON HOME PARENTERAL NUTRITION AFTER INTRODUCTION OF TAUROLIDINE CATHETER LOCKING: A FOLLOW-UP OF NEARLY 200,000 DAYS E.D. Olthof1 , G. Huisman-de Waal1 , R. Vissers1 , G.J. Wanten1 . 1 Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Rationale: Home parenteral nutrition (HPN) patients are at risk for developing catheter-related bloodstream infections (CRBSI). The use of an anti-microbial catheterlock solution containing 2% taurolidine (TauroSept® ) has shown to strongly reduce infectious complications in a pilot study. Our HPN population therefore switched to taurolidine locking in 2008. Methods: We compared population dynamics and hospital admission data in the pre (2006 2007) and post (2008 2011) taurolidine eras, also taking into account new patients who need in-hospital training and patients who use an arteriovenous fistula (AVF) for HPN administration, since the latter do not use a catheter lock. Results: From 2006 towards 2012 the number of HPNrelated admission days at our 15-bed clinical ward remained stable at 1439±167 days/year. Over this period, the population number more than doubled (adult HPN patients from 61 to 133, new patients per year from 13 to 27) and the observation days (patients with a catheter, subcutaneous port or AVF) increased from 21,619 to 44,895 per year (overall 194,559). The number of HPN patients using an AVF decreased from 20 to 12 (33% and 9% of total HPN population, respectively). Most importantly, the ratio of hospital admission days per catheter day decreased by 55% from 0.055 in two pretaurolidine years to 0.025 thereafter, excluding patients who had in-hospital training. During this period all treatment- and educational protocols for HPN patients other than catheter locking remained the same. Conclusion: Our results strongly suggest that catheter locking with 2% taurolidine beneficially alters the course of long-term HPN treatment. These data may have strong implications for the number of patients in whom creation of an AVF for HPN treatment will be considered in the future. Disclosure of Interest: None Declared.
PP030-MON TAUROLIDINE SUSCEPTIBILITY OF MICROORGANISMS CAUSING CATHETER SEPSIS IN HOME PARENTERAL NUTRITION PATIENTS USING LONG TERM TAUROLIDINE CATHETER LOCKING E.D. Olthof1 , R.J. Rentenaar2 , A.J. Rijs2 , G.J. Wanten1 . 1 Gastroenterology and Hepatology, 2 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Rationale: Some home parenteral nutrition (HPN) patients still develop catheter related bloodstream infections (CRBSI), despite the use of an antimicrobial catheter lock solution containing 2% taurolidine (TauroSept® ). The aim of our study was to examine
150 whether CRBSI-causing microorganisms in these HPN patients have decreased susceptibility to taurolidine. Methods: We determined for each CRBSI-causing microorganism, by broth microdilution, the lowest dilution of taurolidine without visible microbial growth after 18 h (bacteria) or 24 h (Candida spp.) of culture, known as the Minimal Inhibitory Concentration (MIC). CRBSI diagnosis was based on clinical symptoms of infection, positive blood culture, and absence of other causes of bloodstream infections. Results: From January 2009 until April 2011, 17 patients in a cohort of 158 HPN patients using a taurolidine catheter lock, developed a single (13 patients) or multiple (4 patients) CRBSIs, resulting in 0.3 infections per 1000 catheter days. Sixty-five percent of CRBSIs were monomicrobial, 35% were polymicrobial. Luminal CRBSIcausing microorganisms were Gram-positive bacteria (59%), Gram-negative rods (22%) or Candida spp. (19%). CRBSI-causing Gram-positive bacteria were mostly coagulase negative Staphylococcus species (n = 9) or S. aureus (n = 3) with taurolidine MIC values of 512 mg/ml or less in 50% of the isolates (MIC50 ). The taurolidine MIC50 for E. coli, the most common CRBSI-causing Gram-negative bacterium, was 512 mg/ml (n = 2). CRBSI-causing C. albicans isolates had higher taurolidine MICs (2048 mg/ml, n = 5) than bacteria. The MIC values found in this study were similar to values reported in the literature. Conclusion: In conclusion, decreased taurolidine susceptibility is not a factor in the pathogenesis of CRBSI in HPN patients using taurolidine catheter locking. Disclosure of Interest: None Declared.
PP031-MON Outstanding abstract ALTERATION OF ENTEROENDOCRINE AND NEUROPEPTIDES IN GRAFT AFTER SMALL BOWEL TRANSPLANTATION IN DOGS H.S. Lai1 , P.H. Lee1 , W.J. Chen1 . 1 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, China Rationale: Two major problems for small bowel transplantation (SBTx), graft rejection and poor graft function, are related to the status of enteroendocrine (Eend), nerve plexuses and ganglions in the graft. We evaluate the alteration of Eend (somatostatin and chromogranin A), and neuropeptides (NP; neurofilament, synaptophysin) markers in the rejected graft after SBTx. Methods: SBTx was performed in male mongrel dogs with the graft intestine preserved by 4ºC UW solution. SMV, SMA end-to-end anastomosis with Modified Mikulicz ileostomy were performed. Blood samples for complete blood cell (CBC) counts, suction biopsies from ileostomy for histopathologic pictures and immunohistochemical staining for NP [neurofilament (Zymed 08-0041, USA) synaptophysin (Zymed 08-0130, USA)], and Eend peptides [chromogranin A (Zymed 08-0094, USA), somatostatin (Zymed 08-0078, USA)] were performed on Days 0, 1, 2, 3, 4, 5 and 7. Results: Successful SBTx in 10 pairs of dogs was shown in Table 1. CBC counts and histopathologic pictures demonstrated a marked rejection on day 5 & 7 after SBTx (p < 0.05). Destruction of the submucosal nerve plexus and ganglion cells were markedly identified by
Poster presentations immunohistochemical staining of NP (neurofilament and synaptophysin) on the 7th postoperative day (p < 0.01). The Eend cells showed no apparent changes, even in a severe rejection status. Table 1. Basic data of small bowel transplantation in dogs Donor/Recipient Bw (kg) Blood loss (ml) Op time (min) Ischemic time (min) Total/Warm Graft length (cm) NP (synaptophysin) d0/d7 Eend (chromatogranin) d0/d7
Range
Medium
Mean±SD
12 24/10.5 15.5 10 50 118 223 40 97/22 51 100 142 10 20/0 5 20 30/18 26
14.5/12 15 151 51/35 120 16/2 24/22
15.5±3.2/12.3±2.8 17±5 142±33 56±9/33±8 112±14 15±3/2±1 (p < 0.01) 24±4/22±4
Conclusion: Monitoring NP (neurofilament and synaptophysin) in nerve fibers demonstrated an useful marker for graft rejection after SBTx. However, the presentation of Eend marker is unclear. Disclosure of Interest: None Declared.
PP032-MON RELATIONSHIP BETWEEN USE OF PROTON PUMP INHIBITORS AND IGF SYSTEM IN OLDER SUBJECTS: THE InCHIANTI STUDY M. Maggio1 , C. Cattabiani1 , F. Lauretani2 , G. Bondi1 , F. De Vita2 , S. Bandinelli3 , A. Corsonello4 , L. Ferrucci5 , G.P. Ceda1 . 1 Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, 2 Geriatric-Rehabilitation, University-Hospital, Parma, 3 Geriatric Unit, Azienda Sanitaria, Firenze, 4 Unit of Geriatric Pharmacoepidemiology, Italian National Research Centres on Aging (INRCA), Cosenza, Italy; 5 National Institute on Aging, National Institutes of Health, Baltimore, United States Rationale: The use of proton pump inhibitors (PPI) is increased worldwide and has been associated with poor clinical outcomes in older subjects [1,2], where PPI may affect adsorption of nutrients, exacerbating the risk of malnutrition [1]. Recent in vitro studies show that PPI may interfere with insulin like-growth factor 1 (IGF-1), an anabolic hormone and nutritional marker whose levels decrease with age [3,4]. However, the relationship between PPI use and IGF system is unknown. Methods: To address this hypothesis we considered 903 older subjects (536 women, 402 men) of InCHIANTI study, with complete information on IGF-1, IGF-binding protein-1 (IGFBP-1) and medications. IGF-1 and IGFBP-1 were measured by immunoradiometric assay. Generalized Linear Models were used to test the association between PPI use (predictor) and IGF-1, IGFBP-1 (outcome). Results: 402 men (388 PPI users and 14 non users) and 536 women (515 PPI non users and 21 users) were considered for this analysis. PPI male users were older (77.7±7.5 vs 74.6±6.9 years ±SD) while women on PPI were younger than non users (74.2.±4.8 vs 76.6±7.8). After adjusting for age, male PPI users (107.0±69.6 vs 127.1±55.8, p < 0.001) and female PPI users (87.6±29.1 vs 107.6±52.3, p = 0.03) had lower levels of IGF-1 than PPI non users. IGFBP-1 was similar in 2 groups in men and women. After adjustment for age, sex, BMI, liver function, caloric intake and IGFBP-1 the relationship between PPI use and IGF-1 was still negative and almost significant (p = 0.06).