Days Of Total Parenteral Nutrition Research Articles

Postnatal and diet‐dependent increases in enteric glial cells and VIP‐containing neurones in preterm pigs

A mature enteric nervous system (ENS) is required to ensure a normal pattern of intestinal motility in order to regulate digestion after birth. We hypothesized that neuronal and glial components of the ENS would mature during the first postnatal days in preterm pigs that are a sensitive animal model of food intolerance and necrotizing enterocolitis (NEC). Stereological volume densities of the general neuronal population [assessed by betaIII-tubulin immunoreactivity (IR)] and subsets of neuronal (VIP-IR and nitrergic IR) and glial cells (GFAP-IR and S100-IR) were determined in the small intestine of newborn preterm piglets (93% gestation), after 3 days of receiving total parenteral nutrition (TPN) and after 3 days of TPN plus 2 days of enteral feeding with sow's colostrum or milk formula. Following TPN, VIP in the myenteric and inner submucous plexus and GFAP in the inner submucous plexus increased, while the relative volume of the total neuronal population remained constant. Introduction of enteral food induced variable degrees of food intolerance and NEC, especially after formula feeding, a diet that gave rise to a higher myenteric VIP and GFAP content in the inner submucous plexus than colostrum feeding. However, the ENS seemed unaffected by the presence of NEC-like intestinal lesions. Nevertheless, this study shows that the ENS is highly plastic during the first days after premature birth and adapts in an age- and diet-dependent manner. The observed postnatal adaptation in enteric VIP and GFAP may help to maintain intestinal homeostasis during suboptimal feeding regimens in preterm neonates.

Influence of lung oxidant and antioxidant status on alveolarization: Role of light-exposed total parenteral nutrition

Parenteral multivitamins (MVP) are linked to the generation of peroxides, which cause oxidant injury in lungs associated with alveolar remodelling linked to lung disease of prematurity. This study was to investigate the relationship between alveolar development and lung oxidant-antioxidant status as modulated by the mode of administration of multivitamins with total parenteral nutrition (TPN). Four groups of guinea pig pups received parenteral nutrition differing by 1) mode of MVP admixture: with amino acid solution (AA-MVP) or lipid emulsion (LIP-MVP); 2) light exposure: TPN exposed (LE) or shielded from light (LP). After 2 or 4 days of TPN, vitamins C and E, 8-isoprostaneF 2α and alveolarization index were determined in lungs and GSSG/GSH in lungs and blood. Exposure to light and the mode of MVP admixture did not influence vitamin E and isoprostane levels. Blood glutathione redox potential was more oxidized in LE and LIP-MVP groups after 4-day infusions, whereas lung redox potential was more reduced in LE groups. LP and LIP-MVP had a beneficial effect, with higher number of alveoli. Globally, results indicate that in this model, alveolarization and modifications in lung redox potential are two independent events induced by light exposed TPN.

Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species

We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates. Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000-2001). Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002-2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida-attributable deaths occurred during 2002-2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002-2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis. During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.

NO2/NO3 Plasma Profile under Different Parenteral Nutrition Regimens in Newborns

Objective: Free radical production is increased by the administration of total parenteral nutrition (TPN) and may be linked to its adverse effects. Some of the complications of TPN can be ameliorated by partial enteral feeding. In the present study, we investigated plasma nitrate/nitrite (NO₂/NO₃) levels in newborns under parenteral and enteral plus parenteral nutrition (PN). Study Design: Six categories of patients were studied: (1) 10 term infants receiving enteral feeding, (2) 10 term infants receiving PN plus enteral feeding, (3) 10 term infants receiving TPN, (4) 10 preterm infants receiving enteral feeding, (5) 10 preterm infants receiving PN plus enteral feeding, and (6) 10 preterm infants receiving TPN. Plasma nitrate/nitritelevels were measured in all infants initially and in infants receiving TPN and PN plus enteral feeding on the 1st and 5th days, 3 h after the lipid infusion. Results: There was a statistically significant difference in the weighs of infants between the term and preterm groups. There was no difference in NO₂/NO₃ levels between the term and preterm groups. When the groups of term (groups 1, 2, 3) and preterm (groups 4, 5, 6) infants were compared separately within the groups, no statistically significant difference was found in any parameters. We also made comparison among the six groups’ gestational ages, and we found a difference between all term groups and all preterm groups except between groups 1 and 2; groups 1 and 3; groups 2 and 3; groups 4 and 5, and groups 5 and 6 (p < 0.05). Furthermore, the baseline, 1st and 5th days NO₂/NO₃ levels were compared in the term and preterm groups receiving PN. Plasma NO₂/NO₃levels before TPN were significantly lower in the term infants receiving parenteral fluids compared with NO₂/NO₃levels of 1st day of TPN (p < 0.05). In preterm infants receiving TPN the NO₂/NO₃levels before TPN were significantly lower than the levels on the 5th day of PN (p < 0.05). There was no significant difference among other NO₂/NO₃levels of the patients at baseline, 1st and 5th days in the term and preterm groups. Partial enteral feeding did not change the levels of NO₂/NO₃in term and preterm infants on PN. Conclusion: This study shows that TPN has some impact on nitric oxide (NO) production in newborn and partial enteral nutrition does not reduce this effect. However, since the numbers are very small these findings need to be verified by larger groups of patients.

Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies

To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT). A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM extent and severity were assessed across eight oropharyngeal sites using a validated scale, which was scored as follows: no erythema/ulceration=0; erythema only=I; ulceration, one site=II; ulceration, two sites=III; ulceration, three sites=IV and ulceration, four or more sites=V. OM assessments began on the day of conditioning and continued twice weekly within 28 days or hospital discharge. Analyses examined the relationship between the worst OM grade and selected adverse outcomes, including days with fever, days of total parenteral nutrition (TPN), days of parenteral narcotic therapy, incidence of significant (common terminology criteria (CTC) grade 3 or 4) infection, mortality and inpatient days and charges. The mean age of the study subjects was 41 years. Of the patients, 96% (n = 269) received total body irradiation and 76% (n = 214) experienced an OM grade of > or =II (i.e., ulceration). The worst OM grade was significantly (p < 0.05) associated with the number of days of TPN and parenteral narcotic therapy, number of days with fever, incidence of significant infection, time in hospital and total inpatient charges. OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing allogeneic HSCT.

A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation

Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2) followed by autologous stem cell transplantation were randomly assigned to receive oral cryotherapy or room temperature normal saline rinses 30 min before and for 6 h after high-dose therapy. Patients were evaluated for the development of mucositis using the National Cancer Institute grading system as well as evaluation of secondary measures such as days of total parenteral nutrition (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric intake for 28 days after transplant. Patients self-scored their pain, swallowing, drinking, eating, sleeping and taste alterations for 28 days. The primary end point of this trial was the incidence of grades 3-4 mucositis. Compared to the normal saline group, patients using cryotherapy experienced less grade 3-4 mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had statistically lower uses of narcotics and TPN, although there were no differences in length of hospitalization or weight loss. Patient-reported pain was significantly lower and activities were significantly better in the cryotherapy group.

Congenital Jejunal and Ileal Atresia

The purpose of this study was to describe the prenatal sonographic features and natural course of congenital jejunal and ileal atresia and correlate the findings with neonatal outcomes. We identified all neonates with surgically confirmed jejunal or ileal atresia that had prenatal sonography and neonatal surgery in our center from January 1, 1995, to April 1, 2005. Sonography reports and images were reviewed, without knowledge of neonatal outcomes, for features of intestinal obstruction. Obstetric and neonatal outcomes were evaluated. Fifteen (60%) of 25 offspring with atresias (10 jejunal, 4 ileal, and 1 jejunoileal) had sonography, of which 13 (86.6%) had features of atresia. Findings, number of affected fetuses, and gestational age at recognition included fetal echogenic bowel (n = 8), mean +/- SD, 21.3 +/- 3.8 weeks (range, 17.7-28.4 weeks); enlarged stomach (n = 5), 27.5 +/- 5.0 weeks (range, 22.0-34.3 weeks); dilated bowel (n = 13), 27.8 +/- 5.8 weeks (range, 18.3-35.9 weeks); and polyhydramnios (n = 6), 33.3 +/- 1.7 weeks (range, 31.0-35.6 weeks). No fetus with ileal atresia had an enlarged stomach or polyhydramnios. Delivery occurred at a mean of 34.7 +/- 3.6 weeks, with 9 (60%) cesarean deliveries. Neonatal outcomes of age at surgery, neonatal intensive care unit days, hospital days, total parenteral nutrition days, and death were similar whether or not fetal echogenic bowel, enlarged stomach, dilated bowel, or polyhydramnios was present. Likewise, these outcomes did not vary by type of atresia or time of diagnosis (prenatal or neonatal). Jejunal and ileal atresia have specific sonographic patterns allowing specific prenatal diagnoses in most affected fetuses. Prenatal sonographic findings and time of diagnosis did not affect neonatal outcome.

Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease

Purpose Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN. Methods A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree. Results Neonates (38 studied) required a mean (±SD) of 33 ± 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis ( P = .56), birth weight ( P = .54), gestational age ( P = .18), and duration of TPN ( P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 ± 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology. Conclusions Total parenteral nutrition–associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.

Primary Idiopathic Chylopericardium Associated with Cervicomediastinal Cystic Hygroma

Chylopericardium is a rare clinical entity in which chylous fluid accumulates in the pericardial cavity. We report a case of primary idiopathic chylopericardium associated with multiple, small cervicomediastinal cystic hygromas occurring in an asymptomatic 43-year-old woman with no history of trauma, thoracic surgery, malignancy, infection or tuberculosis. Echocardiography showed a large amount of pericardial effusions and pericardial fluid analysis revealed inappropriately elevated triglyceride. We did not demonstrate communication between the thoracic duct and the pericardial sac by lymphangiography and chest computed tomography. She successfully responded to 30 days of continuous pericardial drainage and 15 days of a medium-chain triglyceride diet after 30 days of total parenteral nutrition. Follow-up echocardiography 6 months after treatment commencement showed a minimal reaccumulation of pericardial fluid without symptom. We conclude that if a patient is asymptomatic and can well tolerate daily life, surgery including pericardiectomy or ligation of the thoracic duct is not necessarily required.

Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule

The differences in toxicity of etoposide following continuous or bolus infusion are unknown. We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I-III was idarubicin 8 mg/m(2) per day days 1-3, cytarabine 2000 mg/m(2) once a day days 1-6, and etoposide 1600 mg/m(2) total dose. Group IV treatment differed by cytarabine given twice daily days 1-6. Patients were randomized to etoposide as a continuous infusion days 1-6 or as a bolus infusion over 10 h on day 7. Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I-III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I-III patients, 51% achieved complete remission, and 11% died from treatment-related complications. The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.

Psoas Abscess: a Rare Complication of Crohn’s Disease

Psoas abscess is a rare complication of Crohn’s disease.Methods and materials: We evaluated the incidence of psoas abscess on 312 patients with Crohn’s disease, seen at our institution between 1992-2001.Results: We encountered three cases of psoas abscess (0.9%). One patient was managed with ileocolic resection and immediate anastomosis, while in two patients a percutaneous drainage was first performed and then, after 12 days of total parenteral nutrition, a resection of the diseased bowel with immediate reconstruction was carried out. Conclusions: A correction of the nutritional deficiencies is mandatory. Percutaneous computed-tomography guided drainage of the abscess with intestinal resection with immediate anastomosis, performed after a parenteral hyperalimentation, should be the method of choice in the management of such patients.

A two institution experience with 226 endoscopically placed jejunal feeding tubes in critically ill surgical patients

Background Early jejunal feeding after surgery or trauma reduces infectious complications. Although not ideal gastric and postpyloric feedings are often used, however, because of difficulty in placing feeding tubes distal to the ligament of Treitz (LOT). Our hypothesis was that feeding tube placement distal to the LOT can be accomplished using a bedside transendoscopic technique. Methods Transendoscopic jejunal (TEJ) tube placement and TEJ tubes inserted simultaneously through percutaneous gastrostomy (PEG) tubes (PEG/TEJ) were attempted to be placed distal to the LOT. Results In all, 226 feeding tubes (185 TEJ, 41 PEG/TEJ) were placed in 179 trauma and 47 nontrauma patients over 3 years (August 20, 1998 to July 15, 2001). Tube location was jejunal in 93.8% of trauma patients, 76.6% of nontrauma patients, and 90.3% of all patients. (Confidence intervals were 89.3% to 96.5%, 62.8% to 86.4%, and 85.7% to 93.5%). Days of total parenteral nutrition were reduced 71.3% in trauma patients, 22.8% in nontrauma patients, and 45% overall at one institution. Conclusions Bedside TEJ and PEG/TEJ placement is safe and successful in placing feeding tubes distal to the LOT in more than 90% of critically ill surgical patients.

Glutamine administration during total parenteral nutrition protects liver adenosine nucleotides during and after subsequent hemorrhagic shock.

Glutamine supplementation of total parenteral nutrition (TPN) in stressed patients has been advocated. To determine whether glutamine supplementation affects the host response to conditions of stress, animals were given TPN with or without glutamine for 7 days. They were then subjected to the acute stress of hemorrhagic shock, which results in marked loss of hepatic adenosine triphosphate (ATP) and adenosine diphosphate (ADP), with accumulation of adenosine monophosphate (AMP) and the metabolites adenosine, inosine, hypoxanthine, and xanthine. This loss of ATP and accumulation of metabolites contributes to subsequent tissue damage. The hypothesis of the study was that glutamine supplementation would significantly improve restoration of hepatic adenosine nucleotides before and after hemorrhagic shock. Sprague-Dawley rats were given TPN for 7 days. One half of the animals (n = 8) received TPN supplemented with glutamine, while one half received TPN with an isonitrogenous mixture of alanine and glycine. Animals were subjected to hemorrhagic shock for 30 minutes and then resuscitated using only heparinized shed blood. Liver biopsies were taken pre- and post-shock, and at 30 and 60 minutes after resuscitation. ATP, ADP, AMP, and their metabolites were measured using gradient high-performance liquid chromatography. After 7 days of TPN, baseline values of ATP, ADP, AMP, and metabolites were similar between the 2 groups before the initiation of shock. Glutamine-treated animals manifested a 40% decrease in ATP level immediately after shock and recovered to 90% of baseline within 60 minutes. By contrast, the control animals manifested a 66% decrease in ATP level after the shock period and recovered only to 60% of baseline at 1 hour postresuscitation. Similar changes were observed in ADP levels and were accompanied by corresponding changes in AMP and adenosine metabolites, all of which rose during shock and fell after resuscitation. Glutamine supplementation significantly protected the liver from tissue damage caused by hemorrhagic shock. ATP levels remained higher during shock and recovered more rapidly after resuscitation. Glutamine supplementation may help to protect cellular energy stores in the stressed organism and may offer opportunities for therapeutic intervention during and after stress.

Prediction of extrauterine growth retardation (EUGR) in VVLBW infants.

Long-term growth failure in very very low birth weight (VVLBW) infants is a common complication of extreme prematurity. Critical illnesses create challenges to adequate nutriture. To identify predictors of extrauterine growth retardation (EUGR) in VVLBW infants and to evaluate their nutritional intake and subsequent growth. A 4-year retrospective chart review of 221 infants <or=1000 g birth weight and <or=29 weeks gestational age who were admitted within 24 hours of birth, were free of major congenital anomalies and survived at least 7 days. Daily intakes and anthropomorphic data were collected and analyzed. Significant events during hospitalization were documented. Mean energy and protein intakes during hospitalization did not reach recommendations of 120 kcal/kg/d and 3.0 g/kg/day. In utero growth rates could not be consistently reached or sustained. As expected, BW (as measured by BW percentile score) was highly predictive of EUGR (p<0.001). When the independent effect of other predictors of EUGR was considered, only days of total parenteral nutrition (p<0.001) and HC percentile at return to birth weight (p<0.001) made a significant contribution to the prediction of EUGR, once the effect of BW was taken into account.

Homocysteine Prevents Total Parenteral Nutrition (TPN)–Induced Cholestasis Without Changes in Hepatic Oxidative Stress in the Rat

The role of oxidative stress in total parenteral nutrition (TPN)-associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow. Three groups of rats (weight, 179-278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot-CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation. After TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. gamma-Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation. This study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.

Homocysteine Prevents Total Parenteral Nutrition (TPN)–Induced Cholestasis Without Changes in Hepatic Oxidative Stress in the Rat

ABSTRACTBackgroundThe role of oxidative stress in total parenteral nutrition (TPN)–associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow.MethodsThree groups of rats (weight, 179–278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot‐CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation.ResultsAfter TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. γ‐Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation.DiscussionThis study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.

Total Parenteral Nutrition in Bone Marrow Transplant: What Is the Appropriate Energy Level?

Objectives: Total parenteral nutrition (TPN), recommended during bone-marrow transplant (BMT), is often withheld following complications. We aim to determine the effective amount of energy supplied and its short-term effects in children requiring BMT. Methods: Twenty children (11 males, 9 females, mean age 8 years, range 1–18 years) receiving 13 allogenic and 7 autologous BMT for malignant (13) and nonmalignant (7) diseases, were retrospectively evaluated for energy/protein intakes, weight changes, time to engraftment and on TPN, occurrence of complications, and metabolic abnormalities. Results: Each child received approximately 72% of the prescribed calories, an average of 0.87 ± 0.2 × basal-metabolic rate, 1.14 ± 0.4 g protein/kg/day, and 176 ± 34:1 nonprotein calories:nitrogen ratio. Body weight improved during the 35 days (range 14–62) of TPN, with loss thereafter. Engraftment occurred in 20 ± 7.5 days. Caloric intake and time to engraftment were related (p = 0.002). Ten central-venous-line and 12 gastrointestinal infections occurred. Among laboratory abnormalities, liver function tests resulted temporarily altered in 10 patients, and permanently in 1 child with cholestasis. Eight children developed graft-versus-host disease. Five died of cancer. Conclusions: The energy supplied with TPN in BMT is less than expected and approximately covers the BMR with mixed effects. Energy intake needs to be calibrated during TPN and adjusted during feeding resumption to expedite recovery.

Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease

Objective: To determine whether tauroursodeoxycholic acid (TUDCA) would prevent or ameliorate the liver injury in neonates treated with total parenteral nutrition (TPN). Study design: Eligible infants were enrolled after surgery when serum direct bilirubin (DB) was <2 mg/dL. TUDCA (30 mg/kg/day) was given enterally to 22 subjects. A concurrent untreated/placebo group was evaluated for comparison (n = 30). Blood chemistries including alanine aminotransferase (ALT), alkaline phosphatase (AP), conjugated bilirubin (CB), and bile acids (BA) were obtained weekly. Results: There was no difference in peak serum CB, ALT, AP, or BA levels between the TUDCA-treated and control infants. When stratified for birth weight (<1500 g and >1500 g), no differences in peak CB, ALT, AP, or BA were noted. Serum CB levels were similar between TUDCA-treated and control infants after 14, 40, 60, 70, and 120 days of TPN. Conclusion: TUDCA appears ineffective in preventing the development or treatment of TPN-associated cholestasis in neonates. Erratic biliary enrichment and prolonged inability to initiate treatment may compromise the utility of enterically administered TUDCA for TPN-treated infants. (J Pediatr 2002;141:237-42)

Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation.

To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients' peak OMAS scores and days with fever (body temperature > 38.0 degrees C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. Patients' peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P <.05) correlated with all of the outcomes of interest except days with fever (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P <.01), (2) a 2.1-fold increase in risk of significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4) 2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001), and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P =.06). Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Is it safe to treat allogeneic stem cell transplant recipients at home during the pancytopenic phase? A pilot trial.

After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital.