Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Serial transverse enteroplasty in adults with parenteral nutrition dependence: A case series.

BACKGROUND: Serial transverse enteroplasty is used to treat patients with chronic intestinal failure owing to short bowel syndrome. Current literature lacks discussion of its role for other etiologies of intestinal failure and its impact on adult patients' nutrition support needs and quality of life. METHODS: We performed a case series on adults with parenteral nutrition (PN) dependence who underwent serial transverse enteroplasty at Emory University Hospital, a quaternary referral center between 2011 and 2022. Data collected included demographics, operative technique, and preoperative and postoperative PN requirements. A phone survey was administered to evaluate the impact of PN and the operation on quality of life. RESULTS: Ten patients underwent the procedure of interest during the study period. Indications included short bowel syndrome following multiple abdominal operations or intra-abdominal catastrophe and chronic partial bowel obstruction with dysmotility. Bowel length increased by a median of 83%. All patients were discharged home after a median hospital stay of 21 days. At 1-year follow-up, survival was 100%, two (20%) patients fully weaned from PN, three others (30%) reduced PN frequency, and six (60%) decreased their daily parenteral energy requirement. Two additional patients fully weaned from PN by 18 months postoperatively. CONCLUSION: This represents one of the largest case series of serial transverse enteroplasty in adults. Small intestinal length nearly doubled, and PN dependence was reduced in most patients. Given the low morbidity and good quality of life observed in this series, this procedure should be more widely investigated for patients with chronic intestinal failure.

Laparoscopic-Assisted Pancreatic Necrosectomy: Technique and Initial Outcomes.

BACKGROUND: Necrotizing pancreatitis (NP) may result de novo or following procedures such as ERCP or partial pancreatectomy (post-procedural), and may require surgical debridement. Video-assisted retroperitoneal debridement (VARD) is a standard approach for NP that employs a 5 cm incision with varying degrees of blind and open debridement. We describe our technique and outcomes of a modified VARD called laparoscopic-assisted pancreatic necrosectomy (LAPN) performed through a single 12 mm incision that uses direct laparoscopic visualization during debridement. METHODS: At one medical center, all LAPN patients (2012-2020) were assessed for demographics, disease factors, and outcomes. Bivariate logistic regression analyses were performed to identify factors independently associated with recovery after LAPN for patients with de novo vs post-procedural necrosum. RESULTS: Over 9 years, 60 patients underwent LAPN for NP. Median age was 57 years (IQR: 47-66) and 43 (69%) were men. Pancreas necrosum was de novo in 39 (63%) patients and post-procedural in 23 (37%). NP resolved with a median of 1 LAPN procedure and median hospitalization was 33 days. The LAPN major morbidity rate and in-hospital mortality rate were 47% and 5%. No significant differences were seen between NP etiology cohorts, although post-procedure NP patients trended towards a faster clinical recovery to baseline compared to de novo patients (193 vs 394 days; p-value = .07). CONCLUSIONS: LAPN offers a smaller incision with excellent visualization and non-inferior outcomes, regardless of etiology, with likely faster recovery for patients with post-procedural vs de novo necrotizing pancreatitis.

Preoperative diabetes mellitus and long-term survival after resection of pancreatic adenocarcinoma.

PURPOSE: To assess clinicopathologic features and postresection survival of diabetes mellitus (DM)-associated pancreatic ductal adenocarcinoma (PDAC). METHODS: Records of resected PDAC patients from 2000 to 2007 were reviewed. DM was classified as new-onset (<24 months before PDAC) or longstanding (> or =24 months). Clinicopathologic features were compared by univariate and multivariate analyses. Survival was assessed by Kaplan-Meier method and Cox regression. RESULTS: Of 209 patients, 93 (45%) met criteria for DM (35 longstanding DM, 55 new-onset DM, 3 duration unknown). DM patients were older (DM 66 +/- 9 years, non-DM 63 +/- 12 years, P = 0.06); a majority had additional preoperative comorbidities (DM 64.5%, non-DM 25.9%, P < 0.001). Tumor size was larger in patients with DM (DM 3.8 +/- 1.7 cm, non-DM 3.2 +/- 1.5 cm, P = 0.003). Groups were similar in terms of tumor location, perineural/lymphovascular invasion, and node and margin status. On logistic regression, tumor size >/=3.0 cm was independently associated with both overall DM (odds ratio [OR] 3.60; 95% confidence interval [1.79-7.26]) and new-onset DM (OR 3.69, [1.65-8.24]). Median survival was reduced in patients with DM compared with non-DM (15 versus 17 months, P = 0.015). Multivariate analysis controlling for prognostic variables including age, comorbidities, and tumor size demonstrated that DM was independently associated with reduced survival (hazard ratio [HR] 1.55, [1.02-2.35]). This association was more pronounced for patients with new-onset DM (HR 1.75 [1.10-2.78]) than those with longstanding DM (HR 1.30 [0.75-2.25]). CONCLUSIONS: Preexisting DM is associated with reduced survival in patients undergoing resection for PDAC. PDAC with new-onset DM may exhibit increased tumor size and decreased postresection survival. Additional investigation is needed to clarify etiology and impact of PDAC-associated DM.

Differences in presentation and perioperative outcome after pancreaticoduodenectomy for cancer and benign pancreatitis.

The aim of this study was to examine differences in presentation and outcome in pancreaticoduodenectomy for benign and malignant processes. Pancreaticoduodenectomies performed for pancreatic adenocarcinoma or chronic pancreatitis from 2000 to 2008 were identified from a prospectively maintained database and compared. Pancreaticoduodenectomy revealed adenocarcinoma in 220 patients and benign chronic pancreatitis in 40 patients. Patients with adenocarcinoma were older (64 +/- 10.6 years and 47.6 +/- 10.8 years, respectively, P < 0.001) and more likely to demonstrate jaundice (92 and 13%, respectively, P < 0.001), weight loss (76 and 58%, respectively, P = 0.01), and discrete masses (72 and 55%, respectively, P = 0.03). By contrast, chronic pancreatitis presented with increased pain (98 and 49%, respectively, P < 0.001) and nausea (68 and 32%, respectively, P < 0.001). Patients with pancreatitis experienced reduced blood loss (227 +/- 156 and 571 +/- 626 mL, respectively, P = 0.05) and transfusion (10 and 42%, respectively, P < 0.001). Postoperatively, the groups were similar in risk of fistula, gastroparesis, overall morbidity, and mortality. Infection rates were higher in adenocarcinoma (42 and 20%, respectively, P = 0.01). Forty-nine patients underwent pancreaticoduodenectomy for presumptive chronic pancreatitis, of which nine had adenocarcinoma; logistic regression identified increasing age and jaundice as predictors of malignancy. Compared with patients with adenocarcinoma, those who undergo pancreaticoduodenectomy for chronic pancreatitis are less likely to require preoperative biliary drainage and perioperative transfusion. Infectious complication risk is higher in patients with adenocarcinoma. Increased age and jaundice should raise suspicion of cancer in patients with chronic pancreatitis undergoing evaluation for surgical treatment.

Management of complex abdominal wall defects using acellular porcine dermal collagen.

Multiple techniques have been used for the repair of complex abdominal wall defects after recurrent incisional hernias with varying rates of success. Primary repair has been associated with high recurrence rates, and prosthetic mesh placement is contraindicated in contaminated surgical fields. The development of biologic prostheses has changed the approach to these difficult problems. This study evaluates the management of complex abdominal wall defects using acellular porcine dermal collagen. Between August 2006 and May 2007, 18 patients underwent abdominal wall reconstruction for complex defects with acellular porcine dermal collagen (CollaMend; Bard Inc., Warwick, RI). Patient demographics, preoperative risk factors, previous herniorrhaphy attempts, postoperative complications, recurrences, and long-term results were retrospectively reviewed. Records were reviewed at a mean follow up of 7.3 months; the recurrence rate was 44.4 per cent. A total of 38.9 per cent (seven of 18) developed a postoperative wound complications, including infection in 22.2 per cent (four of 18). All of the patients with infection required prosthesis removal as a result of encapsulation rather than incorporation of the biologic prosthesis. Acellular porcine dermal collagen has the potential for reconstruction of abdominal wall defects with postoperative wound occurrences comparable with other biologic materials. Encapsulation of the material was a major problem in cases with wound infection that required graft removal rather than local wound measures. Hernia recurrence and dehiscence of the graft were problems in noncompromised surgical fields.

Ethanol Lock Therapy Markedly Reduces Catheter-Related Blood Stream Infections in Adults Requiring Home Parenteral Nutrition: A Retrospective Study From a Tertiary Medical Center.

BACKGROUND: The use of central venous catheter (CVC) access for home parenteral nutrition (HPN) is associated with catheter-related bloodstream infections (CRBSIs). There are limited data on the use of ethanol lock therapy (ELT) to prevent CRBSI in adult HPN patients. Our aim was to determine whether the routine institution of ELT decreased the incidence of CRBSI compared with historic controls at Emory University Hospital (EUH) in Atlanta, Georgia, USA. METHODS: EUH medical records of adult HPN patients discharged with a tunneled, silicone CVC on ELT were retrospectively studied during a pre-hoc determined 14-month observation period (n = 87; 13,386 catheter days) and compared with clinically similar HPN patients from the same institution before institution of the ELT protocol for all appropriate patients. The ELT protocol involved instilling 2 mL of 70% ethanol into each catheter lumen daily after the HPN cycle, following initial flushing with normal saline. RESULTS: Only 5 of 87 patients (5.7%) who received ELT were diagnosed with a CRBSI (0.45/1000 catheter days) during observation. We compared these data with our previously published clinically matched patient population from EUH (n = 22) receiving HPN via a silicone CVC without ELT. Of these historical controls, 45.5% were diagnosed with 1 or more CRBSIs (8.7/1000 catheter days) during observation (P < .001 vs the current ELT cohort). CONCLUSIONS: In this retrospective study with historical controls from the same academic center, institution of ELT in adults requiring HPN via a silicone CVC was associated with a marked (19-fold) reduction in CRBSI.

Prospective analysis of serum carotenoids, vitamin A, and tocopherols in adults with short bowel syndrome undergoing intestinal rehabilitation.

OBJECTIVE: Carotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program. METHODS: Twenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg . kg(-1) . d(-1); n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12. RESULTS: A significant percentage of subjects exhibited low serum concentrations for carotenoids and alpha-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while alpha-tocopherol levels rose. Serum alpha-tocopherol concentration was negatively associated with PN lipid dose (r = -0.34, P < 0.008). CONCLUSION: Patients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum alpha-tocopherol concentrations.

Important prognostic factors in adenocarcinoma of the ampulla of Vater.

Ampullary adenocarcinoma (AmpCA) carries a better overall survival (OS) rate than other periampullary cancers. We examined clinicopathologic features in AmpCA for impact on OS. Records of patients undergoing pancreaticoduodenectomy from 2000 to 2007 for AmpCA were reviewed and histological specimens were reanalyzed. Of 302 patients undergoing pancreaticoduodenectomy for malignancy, 45 (14.9%) had AmpCA. Mean age was 61.3 +/- 12.2 years, mean tumor size was 2.6 +/- 1.3 cm, 57 per cent were > or = T3 tumors, 42 per cent were N1 stage, 13 (49%) had perineural invasion (PNI), and 29 (64%) had lymphovascular invasion (LVI). Thirteen were intestinal (29%), 14 were pancreaticobiliary (31%), and 18 were mixed (40%). Median OS was 42 months (range 4-80 mos). On log rank testing, > or = T3 (24 vs 65 mos, P < 0.01), N1 (25 vs 61 mos, P < 0.01), poor differentiation (24 vs 44 mos, P = 0.01), pancreaticobiliary subtype (23 vs 44 mos, P = 0.01), and PNI (23 vs 44 mos, P < 0.01) were significant for worse survival. By multivariate analysis, N1 disease (hazard ratio [HR] 4.50, 95% confidence interval [CI] 1.16-17.40) and PNI (HR 4.62, CI 1.11-19.21) maintained associations with worse survival, whereas histological subtype did not. N1 disease and presence of PNI demonstrated independent associations with worse survival. Given high percentage of mixed histology, PNI may be more informative than the subtype in predicting outcome for patients with AmpCA.

Comparison of central and extended left pancreatectomy for lesions of the pancreatic neck.

BACKGROUND: Central pancreatectomy (CP) is a parenchyma-sparing alternative to extended left pancreatectomy (ELP) for tumors of the pancreatic neck. We compared short- and long-term outcomes for the two approaches. METHODS: Patients who underwent CP or ELP from 2000-2007 for neoplasms of the neck were identified. Charts were reviewed for patient, treatment, and outcome data. Long-term and quality-of-life (QoL) data were gathered through Institutional Review Board (IRB)-approved telephone interviews and questionnaires European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and QLQ-PAN26. RESULTS: 31 patients were identified; 13 underwent CP and 18 underwent ELP. Median follow-up was 29 months (range 5-90). Groups did not differ in age, American Society of Anesthesiologists (ASA) class, or preexisting diabetes mellitus (DM). CP patients had less gland resected (5.7 +/- 2.1 cm versus 10.8 +/- 2.8 cm) and lower postoperative mean blood glucose levels (120 +/- 15 mg/dl versus 136 +/- 24 mg/dl). CP patients experienced more complications (92% versus 39%), but no significant difference in major complications (38%, CP versus 17%, ELP; P = 0.17) or hospital stay (9 +/- 3 days, CP versus 7.5 +/- 4 days, ELP). There was one perioperative death in the CP group, unrelated to surgical technique. Questionnaire analysis showed no differences in functional or symptom scales. New-onset exocrine insufficiency was not significantly different between the groups (10%, CP versus 27%, ELP; P = 0.62), but the ELP group had a higher rate of new-onset DM (57% versus 11%; P = 0.04). CONCLUSION: CP is associated with more complications than ELP, but no difference in long-term QoL. Due to the lower incidence of postoperative DM, CP can be recommended for healthy patients with indolent tumors of the pancreatic neck.

Nutrient intake from habitual oral diet in patients with severe short bowel syndrome living in the southeastern United States.

OBJECTIVES: Little data are published on the habitual home oral diet of patients with short bowel syndrome (SBS). METHODS: We assessed nutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the southeastern United States. Intestinal absorption of energy, fat, nitrogen (N), and carbohydrate (CHO) was determined in a metabolic ward. RESULTS: We studied 12 women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm residual small bowel). The patients demonstrated severe malabsorption of energy (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%). Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day ( approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only seven patients (37%) were taking oral multivitamin-mineral supplements and only six subjects (32%) were taking oral iron and calcium supplements, respectively. CONCLUSION: In these SBS patients, an oral diet provided a significant proportion of daily nutrient intake. The types of foods and fluids consumed are likely to worsen malabsorption and thus increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of these individuals.

Depletion of plasma antioxidants in surgical intensive care unit patients requiring parenteral feeding: effects of parenteral nutrition with or without alanyl-glutamine dipeptide supplementation.

OBJECTIVES: Antioxidant depletion is common in critically ill patients. This study was designed to determine the effects of parenteral nutrition (PN), with or without glutamine (Gln) supplementation, on systemic antioxidant status in adult patients after major surgery who required PN in the surgical intensive care unit (SICU) setting. METHODS: Fifty-nine patients in the SICU who required PN after pancreatic surgery or cardiac, vascular, or colonic (non-pancreatic) surgery were randomized in a double-blinded study to receive standard PN (Gln-free) or Gln-supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide. Conventional PN vitamin and mineral doses were administered to all subjects. Plasma concentrations of the antioxidant glutathione (GSH) and the antioxidant nutrients alpha-tocopherol, vitamin C, and zinc were determined at baseline (initiation of study PN) and again after 7 d of study PN. Data were analyzed for the total study cohort and within the pancreatic surgery and non-pancreatic (cardiac, vascular, and colonic) surgery patient subgroups. RESULTS: Mean plasma antioxidant concentrations were within or slightly below the normal ranges at baseline. However, a larger percentage of patients demonstrated below-normal baseline plasma concentrations of GSH (59%), vitamin C (59%), and zinc (68%), respectively. A smaller percentage of patients exhibited below-normal plasma alpha-tocopherol levels (21%). Study PN significantly improved plasma zinc levels in the entire study group and in each surgical subgroup. Gln-PN significantly improved the change in plasma levels of reduced GSH from baseline to day 7 in the non-pancreatic surgery patients (PN -0.27 microM versus Gln-PN +0.26 microM, P < 0.03). CONCLUSION: Low plasma levels of key antioxidants were common in this group of patients in the SICU despite administration of PN containing conventional micronutrients. Compared with standard PN, Gln-supplemented PN improved plasma GSH levels in patients in the SICU after cardiac, vascular, or colonic operations.

Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.

BACKGROUND: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.

BACKGROUND: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Development and Validation of a Risk Calculator for Renal Complications after Colorectal Surgery Using the National Surgical Quality Improvement Program Participant Use Files.

Postoperative acute renal failure is a major cause of morbidity and mortality in colon and rectal surgery. Our objective was to identify preoperative risk factors that predispose patients to postoperative renal failure and renal insufficiency, and subsequently develop a risk calculator. Using the National Surgical Quality Improvement Program Participant Use Files database, all patients who underwent colorectal surgery in 2009 were selected (n = 21,720). We identified renal complications during the 30-day period after surgery. Using multivariate logistic regression analysis, a predictive model was developed. The overall incidence of renal complications among colorectal surgery patients was 1.6 per cent. Significant predictors include male gender (adjusted odds ratio [OR]: 1.8), dependent functional status (OR: 1.5), preoperative dyspnea (OR: 1.5), hypertension (OR: 1.6), preoperative acute renal failure (OR: 2.0), American Society of Anesthesiologists class ≥3 (OR: 2.2), preoperative creatinine >1.2 mg/dL (OR: 2.8), albumin <3.5 g/dL (OR: 1.8), and emergency operation (OR: 1.5). This final model has an area under the curve (AUC) of 0.79 and was validated with similar excellent discrimination (area under the curve: 0.76). Using this model, a risk calculator was developed with excellent predictive ability for postoperative renal complications in colorectal patients and can be used to aid clinical decision-making, patient counseling, and further research on measures to improve patient care.

Parenteral glutamine increases serum heat shock protein 70 in critically ill patients.

OBJECTIVE: Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients. DESIGN AND SETTING: Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital. PATIENTS: 29 patients admitted to the SICU and requiring PN for more than 7 days. INTERVENTIONS: Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined. RESULTS: HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay. CONCLUSIONS: Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.

Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome.

BACKGROUND: Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS). OBJECTIVE: The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT1 in adults with or without SBS. DESIGN: Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry. RESULTS: The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes; and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01). CONCLUSIONS: Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.

Improving quality of surgical care and outcomes: factors impacting surgical site infection after colorectal resection.

Surgical site infections (SSIs) result in patient morbidity and increased costs. The purpose of this study was to determine reasons underlying SSI to enable interventions addressing identified factors. Combining data from the American College of Surgeons National Surgical Quality Improvement Project with medical record extraction, we evaluated 365 patients who underwent colon resection from January 2009 to December 2012 at a single institution. Of the 365 patients, 84 (23%) developed SSI. On univariate analysis, significant risk factors included disseminated cancer, ileostomy, patient temperature less than 36°C for greater than 60 minutes, and higher glucose level. The median number of cases per surgeon was 36, and a case volume below the median was associated with a higher risk of SSI. On multivariate analysis, significant risks associated with SSI included disseminated cancer (odds ratio [OR], 4.31; P < .001); surgery performed by a surgeon with less than 36 cases (OR, 2.19; P = .008); higher glucose level (OR, 1.06; P = .017); and transfusion of five units or more of blood (OR, 3.26; P = .029). In this study we found both modifiable and unmodifiable factors associated with increased SSI. Identifying modifiable risk factors enables targeting specific areas to improve the quality of care and patient outcomes.

Characterization of post-hospital infections in adults requiring home parenteral nutrition.

OBJECTIVE: Limited data are available on the incidence and risk factors for infection in patients requiring home parenteral nutrition (HPN). METHODS: A retrospective study was conducted in 101 consecutive adults (63 female, 38 male) discharged on HPN from the Emory University Hospital, Atlanta, GA. New bloodstream infections (BSIs) requiring rehospitalization and other infections were evaluated. RESULTS: Most infections (75%) developed during the initial 6 mo after hospital discharge; rates of BSI were particularly high during the first 4 mo. Fifty-six patients (55.4%) developed 102 BSIs (11.5 BSIs/1000 catheter-days). Most BSIs were attributed to gram-positive organisms (46%), including coagulase-negative Staphylococcus, Staphylococcus aureus, Enterococcus species, and others, followed by Candida species (20%) and gram-negative organisms (13%). Twenty-one percent of BSIs were polymicrobial. The BSI incidence rate ratio was significantly increased for patients with mean prehospital discharge blood glucose concentrations in the highest quartile versus the lowest quartile (incidence rate ratio 2.4, P = 0.017). Patients with a peripherally inserted central catheter versus non-peripherally inserted central catheter central venous catheters had significantly higher rates of BSI (P = 0.018). Thirty-nine patients (38.6%) developed 81 non-BSIs, including pneumonia, urinary tract infections, and surgical site infections. Postdischarge PN dextrose, lipid, and total calorie doses were unrelated to BSI but were variably related to the rate of non-BSIs. CONCLUSIONS: Adult patients on HPN exhibit a very high incidence of post-hospital infections. Higher mean blood glucose levels during predischarge hospitalization and the use of peripherally inserted central catheters at discharge are associated with an increased risk of BSI in the postdischarge home setting.