Factors associated with early extubation after superior cavopulmonary connection: analysis from single ventricle reconstruction trial.

BACKGROUND: To evaluate the landscape of early extubation, and identify factors associated with early extubation (≤ 24 h) after superior cavopulmonary connection (stage 2 operation) among children with single ventricle anatomy. METHODS: Patients undergoing stage 2 operation after Norwood operation from the Pediatric Heart Network Single Ventricle Reconstruction (SVR) trial public-use dataset were included. Elastic net regularized logistic regression models were fitted to evaluate the factors associated with early extubation after stage 2 operation. RESULTS: In total, 390 patients from 15 North American centers qualified for inclusion. Of these, 42 patients (10.8%) were extubated in operating room, 151 patients (38.7%) were extubated outside the operating room within the first 24 h after stage 2 operation, and the remaining 197 patients (50.5%) required mechanical ventilation for > 24 h. In adjusted models, factors associated with early extubation after stage 2 operation were elective timing of stage 2 operation, lower incidence of post-Norwood complications, shorter CPB duration for stage 2 operation, and no cardiac catheterization after Stage 2 operation. We also performed multiple other alternative analyses to identify factors associated with early extubation that demonstrated same associations as the primary model. The mean hospital length of stay after Stage 2 operation was 20% shorter among patients with early extubation. CONCLUSIONS: Data from this large multicenter study demonstrate that approximately one-half of the patients undergoing operation for superior cavopulmonary connection are extubated within 24 h after heart operation. Furthermore, early extubation is associated with shorter hospital length of stay.

Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children <18 years undergoing heart surgery for either common atrio-ventricular canal, tetralogy of Fallot, truncus arteriosus or transposition of the great vessels and interrupted aortic arch and requiring ECMO, from 1998-2011. The outcomes evaluated included mortality, ECMO duration and length of hospital stay in patients with del22q11 syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls.

Relationship of ECMO duration with outcomes after pediatric cardiac surgery: a multi-institutional analysis.

BACKGROUND: There are very sparse data on the outcomes of children receiving prolonged extracorporeal membrane oxygenation (ECMO) after cardiac surgery. This study was aimed to evaluate the association of ECMO duration with outcomes in children undergoing surgery for congenital heart disease using the Pediatric Health Information System (PHIS) database. METHODS: Patients aged ≤18 years receiving ECMO after pediatric cardiac surgery (with or without cardiopulmonary bypass) at a PHIS-participating hospital (2004-2013) were included. De-identified data obtained from retrospective, observational dataset included demographic information, baseline characteristics, pre-ECMO risk factors, operation details, patient diagnoses, and center data. Outcomes evaluated included in-hospital mortality, length of mechanical ventilation, length of ICU stay, length of hospital stay, and hospital charges. Cox proportional hazards models were fitted to study the probability of study outcomes as a function of ECMO duration. RESULTS: Nine hundred ninety-eight patients from 37 hospitals qualified for inclusion. The median duration of ECMO run was 4 days (IQR: 1.7). After adjusting for patient and center characteristics, there was 12% increase in the odds of mortality for every 24 hours increase in ECMO duration (OR: 1.12, 95% CI: 1.07-1.18, P<0.001). Patients receiving longer duration of ECMO were associated with longer length of mechanical ventilation, longer length of ICU stay, longer length of hospital stay, and higher hospital charges. CONCLUSION: Data from this large multicenter database suggest that longer duration of ECMO support after pediatric cardiac surgery is associated with worsening outcomes.

Evolution of obesity in a low birth weight cohort.

OBJECTIVE: The objective of this study was to determine the evolution of obesity status (OS) in a longitudinal cohort of low birth weight preterm (LBWPT) infants to an age of 8 years, and to determine whether rapid weight gain in the first year of life independently predicts 8-year OS. STUDY DESIGN: In total, 985 infants (birth weight ≤2500 g, gestation age ≤37 weeks) were recruited from the nursery in an eight-site intervention research program and were evaluated at an age of 3, 5, 6.5 and 8 years. Weight and height were measured by standard protocol at each visit and body mass index was calculated. Obesity status is ≥95% for age and sex. Multiple logistic analyses were performed on 8-year OS with predictor variables including infant race, gender, small for gestational age status, birth weight category, neonatal health index, treatment group and first-year weight gain; maternal education and weight status before conception; and HOME Inventory. RESULT: Overall, 2.3% were OS at an age of 3 years, 6.1% at an age of 5 years, 7.7% at age 6.5 years and 8.7% at an age 8 years. OS varied by birth weight category at each visit. The infants born ≤1500 g had the lowest prevalence of OS at each age. In the logistic regression, maternal race (Hispanic) (adjusted odds ratio=2.8, confidence interval=1.2 to 6.8), maternal obese status (adjusted odds ratio 3.4, confidence interval=1.5 to 7.8) and first-year weight gain (adjusted odds ratio=2.7, confidence interval=1.9 to 3.9), significantly predicted 8-year OS. CONCLUSION: OS is common in LBWPT infants during childhood, and prevalence varies by birth weight category. High weight gain in the first year of life is an important predictor of the development of OS in LBWPT children.

Interactions of inflammatory pain and morphine in infant rats: long-term behavioral effects.

Neonatal rat pups exposed to repetitive acute pain show decreases in pain threshold and altered behavior during adulthood. A model using prolonged inflammatory pain in neonatal rats may have greater clinical relevance for investigating the long-term behavioral effects of neonatal pain in ex-preterm neonates. Neonatal rat pups were exposed to repeated formalin injections on postnatal (P) days 1-7 (P1-P7), with or without morphine pretreatment, and were compared with untreated controls. Behavioral testing during adulthood assessed pain thresholds using hot-plate (HP) and tail-flick (TF) tests, alcohol preference, and locomotor activity (baseline and postamphetamine). Adult rats exposed to neonatal inflammatory pain exhibited longer HP latencies than controls and male rats had longer HP thresholds compared to females. Male rats exposed to neonatal morphine alone exhibited longer TF latencies than controls. Both neonatal morphine treatment and neonatal inflammatory pain decreased ethanol preference, but their effects were not additive. During adulthood, male rats exposed to neonatal inflammatory pain exhibited less locomotor activity than untreated controls. We conclude that neonatal formalin and morphine treatment have specific patterns of long-term behavioral effects in adulthood, some of which are attenuated when the two treatments are combined.

Assessment of indigenous reductive dechlorinating potential at a TCE-contaminated site using microcosms, polymerase chain reaction analysis, and site data.

A combination of microcosm studies, polymerase chain reaction (PCR) analysis, and site data was used to assess the indigenous reductive dechlorinating potential in a trichloroethene (TCE)-contaminated aquifer at Cape Canaveral Air Station, Florida. Sediment and groundwater were obtained from two distinct locations approximately 10 m apart. Microcosm studies were performed to assess dechlorinating activity under a variety of nutrient and electron donor amendment conditions. Most live microcosms constructed using material from the first location, near well 9 (W09), were negative for dechlorination. All live microcosms constructed using material from the second location (W06) exhibited dechlorination of TCE to vinyl chloride (VC) and ethene (ETH). DNA encoding 16S ribosomal RNA (rDNA) with a sequence nearly identical with that from Dehalococcoides ethenogenes strain 195 was detected in the active microcosms and in the sediment from W06 with polymerase chain reaction (PCR) using primers targeted to unique regions of Dehalococcoides 16S rDNA. Dehalococcoides was not detected in the autoclaved microcosms from W06, nor in sediment and most microcosms from W09. The results of the microcosm studies and PCR analysis were supported by field data, which indicated significant accumulation of cis-1,2-dichloroethene (cisDCE) and VC at W06, but not at W09. The different microcosm results obtained for the two locations and the spatial variation of positive PCR results indicates heterogeneous distribution of dechlorinating activity and a specific dechlorinating organism, Dehalococcoides, at the site. As both Dehalococcoides and dechlorination activity were similarly, heterogeneously distributed, this suggests that molecular-probing (which could and should be extended in the future to include virtually all known dechlorinators and/or dehalogenases) can provide a relatively quick and facile method for investigating spatial distributions of dechlorinators on-site.

Reductive dechlorination of tetrachloroethene to ethene by a two-component enzyme pathway.

Two membrane-bound, reductive dehalogenases that constitute a novel pathway for complete dechlorination of tetrachloroethene (perchloroethylene [PCE]) to ethene were partially purified from an anaerobic microbial enrichment culture containing Dehalococcoides ethenogenes 195. When titanium (III) citrate and methyl viologen were used as reductants, PCE-reductive dehalogenase (PCE-RDase) (51 kDa) dechlorinated PCE to trichloroethene (TCE) at a rate of 20 micromol/min/mg of protein. TCE-reductive dehalogenase (TCE-RDase) (61 kDa) dechlorinated TCE to ethene. TCE, cis-1,2-dichloroethene, and 1,1-dichloroethene were dechlorinated at similar rates, 8 to 12 micromol/min/mg of protein. Vinyl chloride and trans-1,2-dichloroethene were degraded at rates which were approximately 2 orders of magnitude lower. The light-reversible inhibition of TCE-RDase by iodopropane and the light-reversible inhibition of PCE-RDase by iodoethane suggest that both of these dehalogenases contain Co(I) corrinoid cofactors. Isolation and characterization of these novel bacterial enzymes provided further insight into the catalytic mechanisms of biological reductive dehalogenation.

Isolation of a bacterium that reductively dechlorinates tetrachloroethene to ethene.

Tetrachloroethene is a prominent groundwater pollutant that can be reductively dechlorinated by mixed anaerobic microbial populations to the nontoxic product ethene. Strain 195, a coccoid bacterium that dechlorinates tetrachloroethene to ethene, was isolated and characterized. Growth of strain 195 with H2 and tetrachloroethene as the electron donor and acceptor pair required extracts from mixed microbial cultures. Growth of strain 195 was resistant to ampicillin and vancomycin; its cell wall did not react with a peptidoglycan-specific lectin and its ultrastructure resembled S-layers of Archaea. Analysis of the 16S ribosomal DNA sequence of strain 195 indicated that it is a eubacterium without close affiliation to any known groups.

Characterization of an H2-utilizing enrichment culture that reductively dechlorinates tetrachloroethene to vinyl chloride and ethene in the absence of methanogenesis and acetogenesis.

We have been studying an anaerobic enrichment culture which, by using methanol as an electron donor, dechlorinates tetrachloroethene (PCE) to vinyl chloride and ethene. Our previous results indicated that H2 was the direct electron donor for rductive dechlorination of PCE by the methanol-PCE culture. Most-probable-number counts performed on this culture indicated low numbers (< or equal to 10(4)/ml)) of methanogens and PCE dechlorinators using methanol and high numbers (> or equal to 10(6)/ml)) of sulfidogens, methanol-utilizing acetogens, fermentative heterotrophs, and PCE dechlorinators using H2. An anaerobic H2-PCE enrichment culture was derived from a 10(-6) dilution of the methanol-PCE culture. This H2-PCE culture used PCE at increasing rates over time when transferred to fresh medium and could be transferred indefinitely with H2 as the electron donor for the PCE dechlorination, indicating that H2-PCE can serve as an electron donor-acceptor pair for energy conservation and growth. Sustained PCE dechlorination by this culture was supported by supplementation with 0.05 mg of vitamin B12 per liter, 25% (vol/vol) anaerobic digestor sludge supernatant, and 2 mM acetate, which presumably served as a carbon source. Neither methanol nor acetate could serve as an electron donor for dechlorination by the H2-PCE culture, and it did not produce CH4 or acetate from H2-CO2 or methanol, indicating the absence of methanogenic and acetogenic bacteria. Microscopic observatios of the pruified H2-PCE culture showed only two major morphotypes: irregular cocci and small rods.

Chloroform degradation in methanogenic methanol enrichment cultures and by Methanosarcina barkeri 227.

The effects of methanol addition and consumption on chloroform degradation rate and product distribution in methanogenic methanol enrichment cultures and in cultures of Methanosarcina barkeri 227 were investigated. Degradation of chloroform with initial concentrations up to 27.3 microM in enrichment cultures and 4.8 microM in pure cultures was stimulated by the addition of methanol. However, methanol consumption was inhibited by as little as 2.5 microM chloroform in enrichment cultures and 0.8 microM chloroform in pure cultures, suggesting that the presence of methanol, not its exact concentration or consumption rate, was the most significant variable affecting chloroform degradation rate. Methanol addition also significantly increased the number of moles of dichloromethane produced per mole of chloroform consumed. In enrichment cultures, the number of moles of dichloromethane produced per mole of chloroform consumed ranged from 0.7 (methanol consumption essentially uninhibited) to 0.35 (methanol consumption significantly inhibited) to less than 0.2 (methanol not added to the culture). In pure cultures, the number of moles of dichloromethane produced per mole of chloroform consumed was 0.47 when methanol was added and 0.24 when no methanol was added. Studies with [14C]chloroform in both enrichment and pure cultures confirmed that methanol metabolism stimulated dichloromethane production compared with CO2 production. The results indicate that while the addition of methanol significantly stimulated chloroform degradation in both methanogenic methanol enrichment cultures and cultures of M. barkeri 227, the prospects for use of methanol as a growth substrate for anaerobic chloroform-degrading systems may be limited unless the increased production of undesirable chloroform degradation products and the inhibition of methanol consumption can be mitigated.

Reductive dechlorination of tetrachloroethene by a high rate anaerobic microbial consortium.

Tetrachloroethene (PCE) and other chloroethenes are major contaminants in groundwater, and PCE is particularly resistant to attack by aerobes. We have developed an anaerobic enrichment culture that carries out reductive dechlorination of chloroethenes to ethene at high rates, thereby detoxifying them. Although the electron donor added to the culture is methanol, our evidence indicates that H2 is the electron donor used directly for dechlorination. We have recently obtained a culture from 10(-6) dilution of the original methanol/PCE culture that uses H2 as an electron donor for PCE dechlorination. Because the culture can be transferred indefinitely and the rate of PCE dechlorination increases after inoculation, we suggest that dechlorinating organisms in the culture use the carbon-chlorine bonds in chloroethenes as electron acceptors for energy conservation.

Hydrogen as an electron donor for dechlorination of tetrachloroethene by an anaerobic mixed culture.

Hydrogen served as an electron donor in the reductive dechlorination of tetrachloroethene to vinyl chloride and ethene over periods of 14 to 40 days in anaerobic enrichment cultures; however, sustained dechlorination for more extended periods required the addition of filtered supernatant from a methanol-fed culture. This result suggests a nutritional dependency of hydrogen-utilizing dechlorinators on the metabolic products of other organisms in the more diverse, methanol-fed system. Vancomycin, an inhibitor of cell wall synthesis in eubacteria, was found to inhibit acetogenesis when added at 100 mg/liter to both methanol-fed and hydrogen-fed cultures. The effect of vancomycin on dechlorination was more complex. Methanol could not sustain dechlorination when vancomycin inhibited acetogenesis, while hydrogen could. These results are consistent with a model in which hydrogen is the electron donor directly used for dechlorination by organisms resistant to vancomycin and with the hypothesis that the role of acetogens in methanol-fed cultures is to metabolize a portion of the methanol to hydrogen. Methanol and other substrates shown to support dechlorination in pure and mixed cultures may merely serve as precursors for the formation of an intermediate hydrogen pool. This hypothesis suggests that, for bioremediation of high levels of tetrachloroethene, electron donors that cause the production of a large hydrogen pool should be selected or methods that directly use H2 should be devised.

Biodegradation of dichloromethane and its utilization as a growth substrate under methanogenic conditions.

Biodegradation of dichloromethane (DCM) to environmentally acceptable products was demonstrated under methanogenic conditions (35 degrees C). When DCM was supplied to enrichment cultures as the sole organic compound at a low enough concentration to avoid inhibition of methanogenesis, the molar ratio of CH4 formed to DCM consumed (0.473) was very close to the amount predicted by stoichiometric conservation of electrons. DCM degradation was also demonstrated when methanogenesis was partially inhibited (with 0.5 to 1.5 mM 2-bromoethanesulfonate or approximately 2 mM DCM) or completely stopped (with 50 to 55.5 mM 2-bromoethanesulfonate). Addition of a eubacterial inhibitor (vancomycin, 100 mg/liter) greatly reduced the rate of DCM degradation. 14CO2 was the principal product of [14C]DCM degradation, followed by 14CH4 (when methanogenesis was uninhibited) or 14CH3COOH (when methanogenesis was partially or completely inhibited). Hydrogen accumulated during DCM degradation and then returned to background levels when DCM was consumed. These results suggested that nonmethanogenic organisms mediated DCM degradation, oxidizing a portion to CO2 and fermenting the remainder to acetate; acetate formation suggested involvement of an acetogen. Methanogens in the enrichment culture then converted the products of DCM degradation to CH4. Aceticlastic methanogens were more easily inhibited by 2-bromoethanesulfonate and DCM than were CO2-reducing methanogens. When DCM was the sole organic-carbon and electron donor source supplied, its use as a growth substrate was demonstrated. The highest observed yield was 0.085 g of suspended organic carbon formed per g of DCM carbon consumed. Approximately 85% of the biomass formed was attributable to the growth of nonmethanogens, and 15% was attributable to methanogens.

Reductive dechlorination of high concentrations of tetrachloroethene to ethene by an anaerobic enrichment culture in the absence of methanogenesis.

Tetrachloroethene, also known as perchloroethylene (PCE), is a common groundwater contaminant throughout the United States. The incomplete reductive dechlorination of PCE--resulting in accumulations of trichloroethene, dichloroethene isomers, and/or vinyl chloride--has been observed by many investigators in a wide variety of methanogenic environments. Previous mixed-culture studies have demonstrated that complete dechlorination to ethene is possible, although the final dechlorination step from vinyl chloride to ethene is rate limiting, with significant levels of vinyl chloride typically persisting. In this study, anaerobic methanol-PCE enrichment cultures which proved capable of dechlorinating high concentrations PCE to ethene were developed. Added concentrations of PCE as high as 550 microM (91-mg/liter nominal concentration; approximately 55-mg/liter actual aqueous concentration) were routinely dechlorinated to 80% ethene and 20% vinyl chloride within 2 days at 35 degrees C. The methanol level used was approximately twice that needed for complete dechlorination of PCE to ethene. The observed transformations occurred in the absence of methanogenesis, which was apparently inhibited by the high concentrations of PCE. When incubation was allowed to proceed for as long as 4 days, virtually complete conversion of PCE to ethene resulted, with less than 1% persisting as vinyl chloride. An electron balance demonstrated that methanol consumption was completely accounted for by dechlorination (31%) and acetate production (69%). The high volumetric rates of PCE dechlorination (up to 275 mumol/liter/day) and the relatively large fraction (ca. one-third) of the supplied electron donor used for dechlorination suggest that reductive dechlorination could be exploited for bioremediation of PCE-contaminated sites.

Tetrachloroethene transformation to trichloroethene and cis-1,2-dichloroethene by sulfate-reducing enrichment cultures.

Tetrachloroethene, also known as perchloroethylene, was reductively dechlorinated to trichloroethene and cis-1,2-dichloroethene by laboratory sulfate-reducing enrichment cultures. The causative organism or group was not identified. However, tetrachloroethene was dechlorinated to trichloroethene in 50 mM bromoethane-sulfonate-inhibited enrichments and to trichloroethene and cis-1,2-dichloroethene in 3 mM fluoroacetate-inhibited enrichments. Overall transformation varied from 92% tetrachloroethene removal in 13 days to 22% removal in 65 days, depending on conditions of the inoculum, inhibitor used, and auxilliary substrate used. Neither lactate, acetate, methanol, isobutyric acid, valeric acid, isovaleric acid, hexanoic acid, succinic acid, nor hydrogen appeared directly to support tetrachloroethene dechlorination, although lactate-fed inocula demonstrated longer-term dechlorinating capability.

Biological reductive dechlorination of tetrachloroethylene and trichloroethylene to ethylene under methanogenic conditions.

A biological process for remediation of groundwater contaminated with tetrachloroethylene (PCE) and trichloroethylene (TCE) can only be applied if the transformation products are environmentally acceptable. Studies with enrichment cultures of PCE- and TCE-degrading microorganisms provide evidence that, under methanogenic conditions, mixed cultures are able to completely dechlorinate PCE and TCE to ethylene, a product which is environmentally acceptable. Radiotracer studies with [14C]PCE indicated that [14C]ethylene was the terminal product; significant conversion to 14CO2 or 14CH4 was not observed. The rate-limiting step in the pathway appeared to be conversion of vinyl chloride to ethylene. To sustain reductive dechlorination of PCE and TCE, it was necessary to supply an electron donor; methanol was the most effective, although hydrogen, formate, acetate, and glucose also served. Studies with the inhibitor 2-bromoethanesulfonate suggested that methanogens played a key role in the observed biotransformations of PCE and TCE.

A kinetic model for anaerobic digestion of biological sludge.

The principal objective of this study was the development and evaluation of a comprehensive kinetic model capable of predicting digester performance when fed biological sludge, preliminary conversion mechanisms such as cell death, lysis, and hydrolysis responsible for rendering viable biological sludge organisms to available substrate were studied in depth. The results of this study indicate that hydrolysis of the dead, particulate biomass-primarily consisting of protein-is the slowest step, and therefore kinetically controls the overall process of anaerobic digestion of biological sludge. A kinetic model was developed which could accurately describe digester performance and predict effluent quality.

Alkaline treatment of wheat straw for increasing anaerobic biodegradability.

Wheat straw was treated with NaOH and anaerobically digested for methane production. Alkaline treatment resulted in a greater than 100% increase in biodegradability of wheat straw. The potential of a process flow scheme employing high alkali concentration at ambient temperature with solids separation and recycle of filtrate containing residual alkali was explored. The effect of NaOH on the solubilization of cell wall constituents and potential problems of toxicity are discussed. A solubilization model was developed which is used to predict biodegradability of whole samples based on solids and filtrate biodegradabilities. Energy requirements and chemical costs are also addressed.

Modeling alkali consumption and digestibility improvement from alkaline treatment of wheat straw.

The alkali consumption during alkaline treatment of wheat straw at ambient temperature was measured as a function of time, solids concentration, and alkali concentration. The maximum measured alkali consumption was 5.5 g NaOH/100 g TS over a period of 30 days of treatment. Chemical functional groups (e.g., acyl and carboxyl groups) were measured and compared with the observed alkali consumption. The kinetics of alkali consumption were studied and a model was developed which predicts alkali consumption reasonably well. Use of this model was made to predict biodegradability of alkali-treated wheat straw, since a strong correlation was found to exist between alkali consumption and observed biodegradability. The method of bioconversion used was anaerobic digestion for methane production.