Shimae Fitzgibbons

Mortality of necrotizing enterocolitis expressed by birth weight categories

PURPOSE Low birth weight is the most important risk factor for developing necrotizing enterocolitis (NEC). We aimed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC. METHODS Five hundred eleven centers belonging to the Vermont Oxford Network prospectively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006. The primary outcome variable was in-hospital mortality. RESULTS Birth weight was divided into 4 categories by 250-g increments. The NEC risk (P < .001) and mortality (P < .001) decreased with higher birth weight category. Necrotizing enterocolitis was associated with a significant odds ratio for death for each category (P < .001). Across groups, the odds ratio for NEC mortality increased with higher birth weight category (category 1 = 1.6 vs category 4 = 9.9; P < .001). CONCLUSION The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category. Although the risk and absolute mortality of NEC decrease with higher birth weight, the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight. These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers.

Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure

PURPOSE We sought to determine whether a regimen of 70% ethanol locks could reduce the rate of central venous catheter (CVC) infections in parenteral nutrition-dependent children with intestinal failure. METHODS We performed a retrospective review of 23 parenteral nutrition-dependent children in our multidisciplinary intestinal rehabilitation clinic who started ethanol lock therapy between September 2007 and June 2009. The treatment regimen consisted of a 70% ethanol lock instilled 3 times per week in each catheter lumen. The rate of CVC infections before and after initiation of ethanol lock therapy was compared using the Wilcoxon signed ranks test with significance set at P < .05. RESULTS The most common diagnoses leading to intestinal failure were necrotizing enterocolitis (26.1%), gastroschisis (21.7%), and intestinal atresia (14.3%). Ethanol locks were well tolerated with no reported adverse side effects. The infection rate decreased from 9.9 per 1000 catheter days prior to initiation of ethanol locks to 2.1 per 1000 catheter days during therapy (P = .03). CONCLUSIONS A regimen of ethanol lock therapy administered three days per week appears to be a safe and effective means of reducing the rate of CVC infections in parenteral nutrition-dependent children with intestinal failure.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome.

PURPOSE The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] > or =2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. METHODS After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. RESULTS A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral omega-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). CONCLUSIONS In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.

Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study

BACKGROUND The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy.

Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution

PURPOSE Serial transverse enteroplasty (STEP) is a novel technique to lengthen and taper bowel in patients with intestinal failure. First described in 2003, initial data and reports have demonstrated favorable short-term outcomes, but there is limited published data on long-term outcomes of the procedure. Our aim was to assess clinical and nutritional outcomes after the STEP procedure. METHODS After obtaining institutional review board approval, we reviewed all records of patients (n = 16) who underwent the STEP procedure at our institution from February 2002 to February 2008. Patients were observed for a median time of 23 months (range, 1-71) postoperatively. Analyses of z scores for weight, height, and weight-for-height, and progression of enteral calories were performed using longitudinal linear models with random effects. RESULTS Of the 16 patients (10 male), the median age at time of surgery was 12 months (interquartile range, 1.5-65.0). The mean increase in bowel length was 91% +/- 38%. After the STEP procedure, patients had increased weight-for-age z scores of 0.03 units per month (P = .0001), height for age z scores of 0.02 units per month (P = .004), and weight-for-height z scores of 0.04 units per month (P = .02). Patients had improved enteral tolerance of 1.4% per month (P < .0001). Six patients (38%) transitioned off parenteral nutrition (median, 248 days). Long-term complications included catheter-related bacteremia (n = 5), gastrointestinal bleeding (n = 3), and small bowel obstruction (n = 1). Two patients ultimately underwent transplantation. There were no deaths. CONCLUSIONS In pediatric patients with intestinal failure, the STEP procedure improves enteral tolerance, results in significant catch-up growth, and is not associated with increased mortality.

Relationship between serum citrulline levels and progression to parenteral nutrition independence in children with short bowel syndrome

OBJECTIVE Although bowel length is an important prognostic variable used in the management of children with short bowel syndrome (SBS), reliable measurements can be difficult to obtain. Plasma citrulline (CIT) levels have been proposed as surrogate markers for bowel length and function. We sought to evaluate the relationship between CIT and parenteral nutrition (PN) independence in children with SBS. STUDY DESIGN A retrospective chart review performed for all patients seen in a multidisciplinary pediatric intestinal rehabilitation clinic with a recorded CIT between January 2005 and December 2007 (n = 27). RESULTS Median age at time of CIT determination was 2.4 years. Diagnoses included necrotizing enterocolitis (26%), intestinal atresias (19%), and gastroschisis (22%). Citrulline levels correlated well with bowel length (R = 0.73; P < .0001) and was a strong predictor of PN independence (P Wilcoxon = 0.002; area under the receiver operating characteristic curve = 0.88; 95% confidence interval, 0.75-1.00). The optimal CIT cutoff point distinguishing patients who reached PN independence was 15 micromol/L (sensitivity = 89%; specificity = 78%). CONCLUSION Plasma CIT levels are strong predictors of PN independence in children with SBS and correlate well with a patients recorded bowel length. A cutoff CIT level of 15 micromol/L may serve as a prognostic measure in counseling patients regarding the likelihood of future PN independence.

[13C]Methionine Breath Test to Assess Intestinal Failure-Associated Liver Disease

Oxidation of L[1-13C]methionine ([13C]-Met) in liver mitochondria can be quantified by measuring exhaled 13CO2. We hypothesized that 13CO2 recovery after i.v. administered [13C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-13C]-Met breath tests ([13C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [13C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for 13CO2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO2) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [13C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [13C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [13C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [13C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [13C]-MBT may also help quantify progression or improvement of IFALD.

Novel intravenous 13C-methionine breath test as a measure of liver function in children with short bowel syndrome

UNLABELLED Monitoring hepatic function in children with short bowel syndrome (SBS) and parenteral nutrition-associated liver disease (PNALD) is currently limited to conventional blood testing or liver biopsy. Metabolism of the stable isotope L[1-(13)C]methionine occurs exclusively in liver mitochondria and can be noninvasively quantified in expired breath samples. We hypothesized that the (13)C-methionine breath test ((13)C-MBT) could be a safe, noninvasive, and valid measure of hepatic mitochondrial function in children with SBS and PNALD. METHODS Baseline breath samples were collected in 8 children with SBS before intravenous administration of 2 mg/kg of L[1-(13)C]methionine. Six paired breath samples were obtained at 20-minute intervals. The (13)CO(2) enrichment was analyzed using isotope ratio mass spectrometry. RESULTS All 8 patients (5 males; mean age, 8.9 months) tolerated the (13)C-MBT without adverse events. Two patients underwent serial testing. One patient, tested before and after resolution of cholestasis, demonstrated increased cumulative percentage dose (4.7% to 6.6%) and area under the curve (AUC) (270-303). A second patient with progressive PNALD demonstrated decreased cumulative percentage dose (from 7.8% to 5.9%) and AUC (from 335 to 288). CONCLUSION The (13)C-MBT is a feasible, safe, and potentially clinically relevant measure of hepatic mitochondrial function in children with SBS and PNALD.

Multicenter proficiency benchmarks for advanced laparoscopic suturing tasks

BACKGROUND Advanced laparoscopic suturing (LS) tasks were developed based on a needs assessment. Initial validity evidence has been shown. The purpose of this multicenter study was to determine expert proficiency benchmarks for these tasks. METHODS 6 tasks were included: needle handling (NH), offset-camera forehand suturing (OF), offset-camera backhand suturing (OB), confined space suturing (CF), suturing under tension (UT), and continuous suturing (CS). Minimally invasive surgeons experienced in LS completed the tasks twice. Mean time and median accuracy scores were used to establish the benchmarks. RESULTS Seventeen MIS surgeons enrolled, from 7 academic centers. Mean (95% CI) time in seconds to complete each task was: NH 169 (149-189), OF 158 (134-181), OB 189 (154-224), CF 181 (156-205), UT 379 (334-423), and CS 416 (354-477). Very few errors in accuracy were made by experts in each of the tasks. CONCLUSIONS Time- and accuracy-based proficiency benchmarks for 6 advanced LS tasks were established. These benchmarks will be included in an advanced laparoscopic surgery curriculum currently under development.

Short Bowel Syndrome

Patients with short bowel syndrome, particularly those who are dependent on long-term parenteral nutrition, face serious clinical sequelae that can dramatically impact their quality of life and survival. Over the last few decades, innovations and refinements in nutritional, pharmacologic, and surgical therapies have improved outcomes significantly. An individualized and multidisciplinary management approach is mandatory, and this should ideally take place in specialized centers with the necessary expertise and resources to address these patients’ complex physical and psychosocial issues.