Randomized Trial of Perfusion-Based Circulatory Management in Infants of Very Low Birth Weight.

OBJECTIVE: To establish the superiority of blood flow (BF)-based circulatory management over conventional blood pressure (BP)-based management strategies used for preventing intraventricular hemorrhage (IVH) in infants of very low birth weight (VLBW). STUDY DESIGN: We conducted a nonblinded, single-centered randomized trial with the aim to prevent IVH by managing BF. Infants with VLBW were assigned randomly to a BF-based group or BP-based (BP group) circulatory management group. The incidence of IVH was the outcome of interest. The IVH also data were compared among healthy patients and patients responsive and unresponsive to the intervention. RESULTS: A total of 219 and 220 infants with VLBW were assigned to the BF and BP groups, respectively. The IVH incidence rate was lower in the BF group, but the difference was not statistically significant (BF group, 6.8% vs BP group, 10.9%; P = .14). In 21% of patients of the BP group and 20% of the BF group, the intervention failed. In BF group, the IVH incidence rate was significantly greater in infants with unsuccessful intervention when compared with healthy individuals (6% vs 23%, P = .001). Multivariate logistic regression analysis revealed a correlation between low blood flow and IVH (aOR 3.24; 95% CI 1.49-7.08, P = .003) but not between low BP and IVH (P = .73). CONCLUSIONS: The BF management protocol did not significantly decrease the incidence of IVH. However, after further optimization, we speculate the treatment strategy holds promise in decreasing the incidence of IVH. Trial registration UMIN-CTR: UMIN000013296.

Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production.

Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1ß, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF.

Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.

BACKGROUND: Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. METHODS: A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. RESULTS: CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. CONCLUSION: ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.

Paradoxical Continuous Left-to-Right Ductal Shunt during Circulatory Collapse due to Ductal Closure in an Infant with Duct-Dependent Systemic Circulation.

Duct-dependent systemic circulation is accompanied by a right-to-left ductal shunt, at least during systole. Although observations of paradoxical continuous left-to-right shunts in duct-dependent systemic circulation have been reported, the mechanism remains unclear. We report a continuous left-to-right ductal shunt throughout the cardiac cycle during the initial recovery phase from circulatory collapse and right ventricular (RV) dysfunction due to ductal closure in an infant with hypoplastic left heart and severe aortic coarctation. Further recovery improved his RV function and changed the ductal flow from continuous left-to-right to bidirectional, which is usually seen in duct-dependent systemic circulation. Marked RV dysfunction may contribute to the continuous left-to-right ductal shunt. A continuous left-to-right ductal shunt should not be used to rule out duct-dependent systemic circulation.

Oxidative and Inflammatory Markers Are Higher in Full-Term Newborns Suffering Funisitis, and Higher Oxidative Markers Are Associated with Admission.

The aim of this study was to assess whether oxidative and inflammatory mediators in the cord blood of newborns with funisitis and chorioamnionitis can serve as indicators of their inflammatory status, and whether there is a positive association between higher mediator levels and an increased risk of admission to the neonatal intensive care unit (NICU). This study was conducted prospectively in a neonatology department of a university hospital. In total, 52 full-term newborns were evaluated, including 17 funisitis cases, 13 chorioamnionitis cases, and 22 control newborns without funisitis or chorioamnionitis. Cord blood samples were measured for oxidative stress and inflammatory status markers. The oxidative stress markers included the total nitric oxide (NO), total hydroperoxide (TH), biological antioxidant potential (BAP), and TH/BAP ratio, comprising the oxidative stress index (OSI). Inflammatory markers included interleukin (IL)-1b, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNFα), interferon γ (IFNγ), and complement component C5a. TH, OSI, IL-1b, IL-6, and IL-8 concentrations were higher in the funisitis group than in the chorioamnionitis and control groups. C5a was higher in the funisitis and chorioamnionitis groups than in the control group. Among all enrolled newborns, 14 were admitted to the NICU. Multiple logistic regression analysis showed that elevated umbilical cord blood levels of OSI and TH were associated with a higher risk of admission to the NICU (OSI: R = 2.3, 95% CI 1.26-4.29, p = 0.007 and TH: R = 1.02, 95%CI = 1.004-1.040, p = 0.015). In conclusion, OSI and TH in cord blood from full-term newborns can provide an index of inflammatory status, and higher levels are associated with the risk of admission to the NICU and, therefore, could serve as an early indicator of inflammatory conditions in newborns.

Edaravone, a hydroxyl radical scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis.

Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

Elevated inflammatory mediators and pulmonary hypertension after applying an extracorporeal circuit in a neonatal sepsis model.

PURPOSE: We aimed to study the changes in cytokines, oxidative mediators, and pulmonary blood pressure in a neonatal sepsis model when applying an extracorporeal circuit (ECC). METHODS: Of 28 anesthetized and mechanically ventilated 3-day-old piglets, 14 underwent cecal ligation and perforation (CLP), of which 7 underwent ECC for 3 h from 3 to 6 h after CLP. The remaining 14 were sham, of which 7 underwent ECC. Serum interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), interferon gamma (IFN-γ), total hydroperoxide (TH), nitric oxide metabolites (NOx), and mean pulmonary arterial blood pressure (mPAP)/mean arterial blood pressure (mABP) ratio were measured at pre-CLP and at 3, 6, and 9 h in the CLP groups, and continued in the sham groups at 12, 15, 18, and 24 h. RESULTS: The CLP group with ECCs compared to the CLP group without it showed higher levels of serum IL-6, IL-10, and NOx at 6 h and higher levels of serum TH at 6 and 9 h. The sham group with ECCs compared to the one without it showed higher levels of serum IL-6 and IL-10 at 12, 15, and 18 h, TH at 6 and 9 h, TNF at 6 h, and IFN-γ at 9 h. The mPAP/mABP ratios in the CLP group with ECCs were higher compared to the CLP group without it at 6 and 9 h. CONCLUSION: Applying ECCs provoked a window of cytokines, free radicals elevation, and pulmonary hypertension which could be hazardous in critically ill newborns.

Pediatric patients receiving ABO-incompatible living related liver transplantation exhibit higher serum transforming growth factor-ß1, interferon-γ and interleukin-2 levels.

BACKGROUND: ABO-incompatible liver transplantation (LTx) is becoming more common in response to the paucity of liver allografts. Several studies have expressed concern about the effect of ABO compatibility on graft survival. PURPOSE: To evaluate the differences in serum cytokine levels between ABO-incompatible (ABO-i) and ABO-compatible (ABO-c; includes ABO-compatible and identical) pediatric LTx recipients during regular outpatient follow-up. Note that, in the field of organ transplantation, transplants are categorized as incompatible, compatible or identical; accordingly, these are the terms we use in the paper. MATERIALS AND METHODS: A clinical outpatient study measuring serum transforming growth factor (TGF)-ß1, interferon (IFN)-γ, interleukin (IL)-2 and IL-10 in 43 living related liver transplantation (LRLT) recipients, of whom 36 received ABO-c LRLT (34 were ABO-identical and 2 were non-identical) and 7 ABO-i LRLT. Serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase and bilirubin were measured as part of the patients' regular follow-up visits. RESULTS: There were no differences between the ABO-c and ABO-i groups in terms of recipient's age [mean 12.6 vs. 11.1 years (y)], post-LTx duration (mean 7.3 vs. 7.3 y), donor's age (mean 35.5 vs. 34.6 y), body weight (28.9 ± 2.9 vs. 27.9 ± 6.9 kg), or gender (19 female and 17 male vs. 4 female and 3 male). Serum TGF-ß1, IFN-γ and IL-2 were significantly higher in the ABO-i group than in the ABO-c group. IL-10, however, did not differ between the two groups. There was a tendency toward higher γGTP levels in the ABO-i group, but this difference did not reach significance. CONCLUSION: ABO-incompatible LRLTx patients have higher serum TGF-ß1, IFN-γ and IL-2 levels as measured at regular outpatient visits. As a result, they face a higher risk of T-helper 1 cell polarization, which could make graft rejection more likely.

Oxidative stress after living related liver transplantation subsides with time in pediatric patients.

BACKGROUND: Oxidative stress has been suspected to influence graft survival and prognosis in pediatric recipients of living related liver transplantation (LRLT). PURPOSE: We determined the oxidative status of pediatric LRLT recipients during their regular outpatient follow-up visits, and looked for a relationship between oxidative status and post-liver transplantation (post-LTx) duration. PATIENTS: The study included 43 patients (20 males and 23 females) between the ages of 1.6 and 25.1 years (median 10.7 years) who had undergone LRLT from 5 months to 17.5 years (median 7 years) prior to the study, between the ages of 1.2 and 14.4 years (median 3.5 years). METHODS: Serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), gamma-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), direct bilirubin and choline-esterase were measured as part of the patients' regular follow-up visits. Serum total hydroperoxide (TH) and biological antioxidative potential (BAP) were measured using the free radical analytic system which requires 20 µl of serum and 10 min of processing time for each sample. Oxidative stress index (OSI) was calculated as the ratio of TH to BAP. RESULTS: Serum OSI correlated positively with serum levels of GOT, GPT, LDH, ALP, γ-GTP and direct bilirubin. Serum OSI, TH, LDH, ALP and GOT correlated negatively with post-LTx duration. Serum BAP correlated positively with post-LTx duration. Serum TH correlated positively with serum GOT and γ-GTP, but negatively with serum BAP. CONCLUSIONS: (1) The OSI, which can be calculated based on data acquired through a simple outpatient procedure, can serve as an index of our patients' laboratory results and oxidative status. (2) The LRLT recipients in our study were at risk for oxidative stress early in the post-operative period, but this risk subsided with time.

Improved Survival of Periviable Infants after Alteration of the Threshold of Viability by the Neonatal Resuscitation Program 2015.

Periviable infants (PIs) born at 22-25 weeks gestational age (wGA) have a variable survival rate (49.7-86.2%) among hospitals. One factor involved in this difference may be the definition of the threshold of viability. The American Academy of Pediatrics revised the neonatal resuscitation program in late 2015 (NRP 2015) and altered the threshold of viability from 23 to 22 wGA. The impact on the survival of PIs after the guideline alteration has seldom been discussed. Since 2016, the unit of this study has implemented the renewed guideline for PIs. We retrospectively reviewed and analyzed the survival and clinical variables of PIs before and after implementation of the guideline, which included a 10-year cohort in a single center in Taiwan. There were 168 PIs enrolled between 2010 and 2019 (Epoch-I, 2010-2015; Epoch-II, 2016-2019), after excluding those with congenital anomalies and parent-decided comfort care. Compared to those in Epoch-I, the PIs in Epoch-II had significantly higher odds ratios (2.602) (95% confidence interval: 1.170-5.789; p = 0.019) for survival. Younger gestational age, small size for gestational age, cesarean delivery, low blood pH at birth, and surfactant therapeutic treatment were found to be significant risk factors associated with the survival of PIs (p < 0.05 for each). The altered threshold of viability by NRP 2015 may impact the survival of PIs. However, long-term follow-up for surviving PI is required in the future.

Evaluating patients' outcome post-Kasai operation: a 19-year experience with modification of the hepatic portoenterostomy and applying a novel steroid therapy regimen.

BACKGROUND: We reported a modification of the hepatic portoenterostomy (HPE) for biliary atresia with favorable results. HPE is associated with a risk of hepatic impairment, so we adopted a novel steroid therapy regimen well suited to our procedure. This paper reports the results of our experience. PATIENTS AND METHODS: Between 1991 and 2009, 53 patients (18 boys, 35 girls) underwent modified HPE with novel steroid therapy, which consisted of administering hydrocortisone immediately after surgery, followed by intravenous administration of prednisolone. The number of patients who became normal total bilirubin (TB) levels, frequency of early onset cholangitis and other postoperative complications, and outcomes were retrospectively studied. RESULTS: The TB levels in 43 of the 53 patients became normal. Cholangitis was observed in seven, but all of them recovered. Other postoperative complications were noted in eight, but with no fatal cases. Of the 11 patients who underwent living-donor liver transplantation, 3 died after the transplant. Of the 53 patients, 39 are alive without liver transplantation and 34 have normal TB (range of observation period: 18 years and 9-2 months). CONCLUSIONS: The novel steroid regimen may have contributed to the outcome and appears to be well suited to the modified HPE.

Effect of polymyxin B-immobilized fiber hemoperfusion on respiratory impairment, hepatocellular dysfunction, and leucopenia in a neonatal sepsis model.

PURPOSE: Sepsis and septic shock remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Our aim was to study the effects of polymyxin-B direct hemoperfusion (PMX-DHP) therapy on sepsis-induced respiratory impairment, liver dysfunction and leucopenia in a neonatal cecal ligation and perforation (CLP) model. METHODS: Fourteen anesthetized and mechanically ventilated 3-day-old piglets underwent CLP and an arteriovenous extracorporeal circuit from 3 h until 6 h post-CLP, with a PMX column in the PMX-DHP treated group (7 piglets). Changes in oxygen saturation, PCO(2), base excess, white blood cell (WBC) count, platelet count, hematocrit (Hct%), serum glutamate pyruvate transaminase (SGPT), and serum glutamic oxaloacetic transaminase were measured before CLP and at 1, 3 and 6 h after. RESULTS: At 6 h, the PMX-DHP group showed lower Hct%, and SGPT in comparison to the control group, but higher oxygen saturation and WBC count. No effects on the platelet count were found. The survival times of the PMX-DHP group were longer than in control. CONCLUSION: PMX-DHP therapy limited the respiratory impairment, liver dysfunction and leucopenia in a neonatal septic model, which resulted in an improvement of survival time.

Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-kappaB signaling in cultured astrocytes.

Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-kappaB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-kappaB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-kappaB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

Late circulatory dysfunction and decreased cerebral blood flow volume in infants with periventricular leukomalacia.

Periventricular leukomalacia is a major neuropathology in preterm infants associated with adverse motor and cognitive outcome. The cerebral blood flow volume of the internal carotid artery and the vertebral artery was measured by ultrasonography at the neck in 36 low-birth-weight infants with gestational age of 25-34 weeks in order to investigate the pathophysiology of cerebral white-matter injury: 30 infants, normal and 6 infants, diagnosed as PVL. The mean blood flow velocity and diameter of each vessel were measured at postnatal days from day 0 to day 70. The intravascular flow volume was determined by calculating the mean blood flow velocity and the cross-sectional area. The mean blood pressures were recorded and PaCO(2) was determined. The total blood flow volume was significantly lower in infants with PVL than in normal infants on days 0, 1, 21, 28, 35, 42, and 63. The mean blood pressure was significantly lower in infants with PVL than in normal infants on days 7, 14, 21, 28, and 42. We suggest that the total cerebral blood supply is decreased in cases of PVL in the few days after birth and from day 21 to day 42. The results of the present study suggest that a dip in the blood flow volume in the few days after birth might result in subsequent PVL.

Reduction in cerebral blood flow volume in infants complicated with hypoxic ischemic encephalopathy resulting in cerebral palsy.

Hypoxic ischemic brain can result in cerebral palsy, mental retardation, and learning disabilities in surviving children. The purpose of this study was to elucidate the cerebral blood flow volume in infants complicated with brain damage after the birth. Nine term infants with hypoxic ischemic encephalopathy and 41 normal term infants were studied. Four infants with HIE suffered from CP or mental retardation, and the other five infants exhibited normal neurodevelopment. The mean blood flow velocity and diameter of the internal carotid artery and the vertebral artery were measured for 28 days. The intravascular flow volume was determined by calculating the flow velocity and the cross-sectional area. The ejection fraction and cardiac output were obtained, and the mean blood pressures were recorded. The summed flow volumes in both the ICA and VA, and the total CBFV increased after the birth in both the normal infants and the infants diagnosed with HIE with no disability complications. The total blood flow volume was significantly lower in infants with HIE and CP than in normal infants on days 0, 2, 5, 7, 10, 21, and 28, and significantly lower in infants with HIE and CP than in normal infants with HIE on days 2, 4, and 7. The ejection fraction was significantly lower in infants with HIE than in normal infants only on day 0. Our results suggest that the total cerebral blood supply is decreased in infants with HIE in those complicated with brain damage.

The sex differences of cerebrospinal fluid levels of interleukin 8 and antioxidants in asphyxiated newborns.

Newborn males are more sensitive to brain injury than newborn females are. The aim of the present study was to find an explanation for this. We used the neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF) for the classification of 32 newborns (19 males and 13 females) on their fifth postnatal day. The NSE levels were higher than normal (8.4 +/- 1.6 ng/mL) in 10 newborn males and 6 females and were, respectively, considered asphyxiated male and female groups. The remaining newborns, 9 males and 7 females, had normal CSF levels of NSE and were considered normal newborn male and female groups. The CSF samples were measured for 12 cytokines, using a cytokine array kit, and for total hydroperoxide and biological antioxidant potentials (BAPs), using the free radical analytic system. Among the 12 cytokines measured, only interleukin 8 (IL-8) was properly detected. The CSF levels of IL-8 were higher in the asphyxiated newborn females than in the other three groups. The mean CSF levels of BAPs in the asphyxiated newborn females were higher compared with the other three groups, but significance was detected only in comparison with the BAP levels in the CSF samples of the normal newborn males. There were no differences in total hydroperoxide levels among the groups. There are sex-related differences in the CSF levels of IL-8 and antioxidants in asphyxiated newborns, with higher levels in newborn females; this might contribute in the sexual dimorphism regarding the fact that females have better protection from brain injury than the males.

Short-duration ACTH therapy for cryptogenic West syndrome with better outcome.

In this study, seven patients with cryptogenic West syndrome were subjected to short-duration adrenocorticotrophic hormone (ACTH) therapy. ACTH was administered daily for 7 to 12 days (mean 10 days), and then was withdrawn. Daily single dose was 0.022 to 0.027 mg/kg/day (0.024 mg/kg/day, 0.96 IU/kg), total dose was 0.17 to 0.28 mg/kg (0.23 mg/kg, 9.0 IU/kg), and treatment lag was 12 to 105 days (median 14 days). ACTH therapy controlled tonic spasms with no serious side effects in all patients, but two patients still had electroencephalographic abnormality. The intelligence quotients or developmental quotients of six patients with short treatment lag were 79 to 110 at the age of 2 to 6 years; only one patient with long treatment lag had a developmental quotient of 60. This new short-duration ACTH therapy could yield better cognitive outcomes for cryptogenic West syndrome.

Development and characterization of a novel porcine model of neonatal sepsis.

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

Biliary atresia type I cyst and choledochal cyst [corrected]: can we differentiate or not?

BACKGROUND/PURPOSE: It is difficult to discriminate between choledochal cyst[corrected]with obstructive jaundice and biliary atresia with a cyst at the porta hepatis in neonates or young infants. This review evaluates whether it is possible to differentiate between these two diseases. We here also provide an overview of our experience with type I cyst biliary atresia patients. METHODS: Among all the biliary atresia infants who we treated, the infants who were diagnosed with type I cyst biliary atresia were identified and reviewed for their management and outcome. The clinical course and management in different reports were reviewed and compared to the cases presented to our institution. RESULTS: Among the 220 biliary atresia cases, 11 (5 %; male/female: 4/7) were diagnosed to be type I cyst biliary atresia. Two received hepaticoenterostomy and nine received hepatic portoenteros. Three patients had severe late complications; overall, nine (81.8 %) were alive with their native liver and without jaundice. CONCLUSIONS: Patient with choledochal cyst [corrected] are likely to represent larger cysts and inversely, smaller, static, anechoic cysts are more likely to represent cystic biliary atresia. However, exceptional cases were yet presented, and a definitive diagnosis may not be reached. Thus a complete differentiation between choledochal cyst [corrected] from type I cyst biliary atresia is yet hard to reach.

Children undergoing liver transplantation for treatment of inherited metabolic diseases are prone to higher oxidative stress, complement activity and transforming growth factor-ß1.

BACKGROUND: Main indications for liver transplantation in the pediatric population include biliary atresia and inherited metabolic diseases. The present study evaluated whether there are differences between pediatric patients undergoing living-related liver transplantation due to the two diseases in terms of their oxidative and immunological status during their regular outpatient follow-up visits. MATERIAL AND METHODS: A clinical outpatient study measuring serum oxidative stress index (calculated as serum oxidant/antioxidant ratio, in the form of serum total hydroperoxide/serum biological antioxidative potential), serum terminal complement component 5a, as an indicator of complement activity and immunological status, and transforming growth factor-ß1, as a marker of liver fibrosis, in 16 patients (6 males and 10 females, 2.5-15 years old) who received living-related liver transplantation due to inherited metabolic diseases (n=6; in the form of propionic acidemia [n=1], methylmalonic acidemia [n=1], arginase deficiency [n=1], tyrosinemia [n=2], and glycogen storage disease type 1b [n=1], with an age range of 2.4-14.6 years old) and due to biliary atresia ([n=10], with an age range of 2.9-14.5 years old). RESULTS: Serum oxidative stress index, complement component-5a, and transforming growth factor-ß1 were significantly higher in the inherited metabolic diseases group than in the biliary atresia group. In all patients, serum oxidative stress index correlated positively with complement component-5a and transforming growth factor-ß1. CONCLUSIONS: Patients who receive living-related liver transplantation due to inherited metabolic diseases are prone to higher oxidative stress, complement activity, and serum transforming growth factor-ß1.