Peak Ammonia Research Articles

Paediatric acute liver failure: early outcome and evaluation of transplantation criteria in a Belgian transplantation centre

BackgroundOne of the challenges when caring for children admitted for acute liver failure (ALF) is to quickly identify those who will improve spontaneously and those for whom liver transplantation (LT) is the only therapeutic option.MethodsRetrospective study to review our experience, identify mortality risk factors and update our LT criteria in case of paediatric ALF.Results111 children were admitted between March 1989 and May 2021 (mean age 59.1 months). 28 children never met our LT criteria; 17 had contraindication to LT; 66 were registered on the LT waitlist. 14 of these 66 were subsequently withdrawn because of spontaneous liver function recovery; 11 died before having received a liver; 41 were transplanted. Hospital survival rate was 63% for the whole series, 98% for the children without LT criteria and 71% for the transplanted children. Univariate analysis identified cardiovascular and respiratory failures on admission, and grade 4–5 hepatic encephalopathy (HE) during stay significantly associated with death. Non-survivors also had, on admission and during their stay, significantly higher levels of lactate, ammonia and bilirubin and, during their stay, significantly more frequent prothrombin time ≤ 25% or international normalized ratio ≥ 4.0 than the survivors. Multivariate analysis identified grade 4–5 HE, lactate level on admission and ammonia peak level as significant mortality risk factors.ConclusionOur criteria identified almost all children who had the capacity to spontaneously recover their liver function and suggest that updated criteria should combine biological tests and signs of multiple organ failure.

Continuous renal replacement therapy and therapeutic plasma exchange in pediatric liver failure.

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients.Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1-5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: • Pediatric acute liver failure is associated with high mortality. • Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described.

Real-World Experience of Carglumic Acid for Methylmalonic and Propionic Acidurias: An Interim Analysis of the Multicentre Observational PROTECT Study.

Methylmalonic aciduria (MMA) and propionic aciduria (PA) are organic acidurias characterised by the accumulation of toxic metabolites and hyperammonaemia related to secondary N-acetylglutamate deficiency. Carglumic acid, a synthetic analogue of N-acetylglutamate, decreases ammonia levels by restoring the functioning of the urea cycle. However, there are limited data available on the long-term safety and effectiveness of carglumic acid. Here, we present an interim analysis of the ongoing, long-term, prospective, observational PROTECT study (NCT04176523), which is investigating the long-term use of carglumic acid in children and adults with MMA and PA. Individuals with MMA or PA from France, Germany, Italy, Norway, Spain, Sweden and the UK who have received at least 1 year of carglumic acid treatment as part of their usual care are eligible for inclusion. The primary objective is the number and duration of acute metabolic decompensation events with hyperammonaemia (ammonia level >159 µmol/L during a patient's first month of life or >60 µmol/L thereafter, with an increased lactate level [> 1.8 mmol/L] and/or acidosis [pH < 7.35]) before and after treatment with carglumic acid. Peak plasma ammonia levels during the last decompensation event before and the first decompensation event after carglumic acid initiation, and the annualised rate of decompensation events before and after treatment initiation are also being assessed. Secondary objectives include the duration of hospital stay associated with decompensation events. Data are being collected at approximately 12 months' and 18 months' follow-up. Of the patients currently enrolled in the PROTECT study, data from ten available patients with MMA (n = 4) and PA (n = 6) were analysed. The patients had received carglumic acid for 14-77 (mean 36) months. Carglumic acid reduced the median peak ammonia level of the total patient population from 250 µmol/L (range 97-2569) before treatment to 103 µmol/L (range 97-171) after treatment. The annualised rate of acute metabolic decompensations with hyperammonaemia was reduced by a median of - 41% (range - 100% to + 60%) after treatment with carglumic acid. Of the five patients who experienced a decompensation event before treatment and for whom a post-treatment rate could be calculated, the annualised decompensation event rate was lower after carglumic acid treatment in four patients. The mean duration of hospital inpatient stay during decompensation events was shorter after than before carglumic acid treatment initiation in four of five patients for whom length of stay could be calculated. In this group of patients with MMA and PA, treatment with carglumic acid for at least 1 year reduced peak plasma ammonia levels in the total patient population and reduced the frequency of metabolic decompensation events, as well as the duration of inpatient stay due to metabolic decompensations in a subset of patients. ClinicalTrials.gov, NCT04176523. Registered 25 November, 2019, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04176523 .

Conductivity-mediated in situ electrochemical reconstruction of CuOx for nitrate reduction to ammonia.

The electrocatalytic nitrate reduction reaction (NO3RR) is an ideal NH3 synthesis route with ease of operation, high energy efficiency, and low environmental detriment. Electrocatalytic cathodes play a dominant role in the NO3RR. Herein, we constructed a carbon fiber paper-supported CuOx nanoarray catalyst (CP/CuOx) by an in situ electrochemical reconstruction method for NO3--to-NH3 conversion. A series of characterization techniques, such as X-ray diffraction (XRD) and in situ Raman spectroscopy, unveil that CP/CuOx is a polycrystalline-faceted composite copper nanocatalyst with a valence composition containing Cu0, Cu+ and Cu2+. CP/CuOx shows more efficient NO3--to-NH3 conversion than CP/Cu and CP/Cu2O, which indicates that the coexistence of various Cu valence states could play a dominant role. CP/CuOx with a suitable Cu2+ content obtained by adjusting the conductivity during the in situ electrochemical reconstruction process exhibited more than 90% faradaic efficiencies for the NO3RR in a broad range of -0.3 to -1.0 V vs. RHE, 28.65 mg cm-2 h-1 peak ammonia yield, and stable NO3RR efficiencies for ten cycles. These findings suggest that CP/CuOx with suitable copper valence states obtained by fine-tuning the conductivity of the electrochemical reconstruction may provide a competitive cathode catalyst for achieving excellent activity and selectivity of NO3--to-NH3 conversion.

Long-term application of controlled-release urea reduced ammonia volatilization, raising the risk of N2O emissions and improved summer maize yield

ContextWith the extensive promotion of controlled-release urea (CRU), its N-release pattern has been shown to match the crop’s N-demand period and improve crop yield by reducing N losses. Nevertheless, the impacts of CRU on summer maize yield, especially on greenhouse gas emissions, have rarely been reported during its long-term use. ObjectiveIt is necessary through long-term positioning field experiment with CRU application to investigate the regulatory mechanisms of maize yield formation, nitrogen use efficiency (NUE), ammonia volatilization and greenhouse gas emissions. MethodsThe long-term fertilizer positioning experiment for ten years, four treatments were performed: polymeric-coated controlled-release urea (CRF, 42% N, 3-months controlled-release period), sulfur-coated controlled-release urea (SCF, 35% N, 3-months controlled-release period), common urea (CCF, 46% N) and no nitrogen fertilizer (CK). ResultsResults showed that the two coated controlled-release fertilizers significantly increased NUE and dry matter accumulation in summer maize, and ultimately improved grain yield. Compared to CCF, CRF and SCF treatments increased post-silking dry matter accumulation by 16.3% and 13.3%; NUE by 42.3% and 28.9%. The 2-year mean grain yield of CRF and SCF treatment increased 9.0% and 12.4% compared to CCF treatment. CRF treatment significantly increased the NO3--N content in 0–60 cm soil layer; while CRF and SCF treatments showed a significantly higher NH4+-N concentration in the 0–20 cm soil layer than CCF treatment. Compared to CCF treatment, the CRF and SCF treatments significantly reduced peak ammonia volatilization, and the average cumulative emissions of ammonia volatilization of two years were reduced by 80.8% and 53.2%, respectively. CRF treatment had lower peak of N2O emissions but longer N2O emission duration than other N application treatments. The two-year average cumulative N2O emissions from CRF treatment increased by 49.6%, and SCF treatment increased by 61.1% compared to CCF treatment. Compared to CK treatment, total cumulative CH4 uptake was 36.1% lower in CRF treatment, 60.9% in SCF and 78.9% in CCF treatment. The higher cumulative N2O emissions from CRF and SCF treatment resulted in a significantly higher global warming potential (GWP) than CCF treatment. The two-year mean increase in greenhouse gas intensity (GHGI) was 36.2% for CRF treatment and 44.7% for SCF treatment compared to CCF treatment. ConclusionsLong-term application of coated controlled-release fertilizers could achieve high yields and nitrogen use efficiency. However, there is a risk of increased N2O emissions, causing elevated GHGI. SignificanceIn the future, it is necessary to strengthen the research on the comprehensive effects of long-term reduced application of CRU on crop yield and greenhouse gas emissions, in order to promote the wide application of environmentally friendly CRU in the field.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Sludge composting with self-produced carbon source by phosphate buffer coupled hyperthermophilic pretreatment realizing nitrogen retention

During sludge composting, ammonia emissions is the main pathway of nitrogen loss. In addition to regulating pH, increasing the carbon source is also important for controlling ammonia emissions. Previous studies have focused on additional carbon sources, while this study used phosphate-buffered saline (PBS) and hyperthermophilic pretreatment (HP) to release difficult-to-utilize carbon sources in extracellular polymeric substance (EPS) for composting. The PBS concentration was 0.22 mmol/g total matter (TM), PBS soaking days were 4.74, HP temperature was 149.46 °C, and the soluble chemical oxygen demand (SCOD) was 45.08 g/kg. Compared with the control check, the peak ammonia emission concentration in the pretreated group was reduced by 8.70 % and the total nitrogen loss was reduced by 18.10 %. Changes in EPS, ammonia assimilation activity, and microbial community composition demonstrated that PBS and HP released the carbon source from the sludge, promoted ammonia assimilation, and enriched bacteria related to ammonia assimilation such as Bacillus (16.52 %). HP treatment made Acinetobacter (12.5 %) the dominant genus in the calefactive phase, and the enrichment of Actinobacteriota (27.27 %) promoted the composting maturity. However, total pretreatment reduced the porosity and permeability of the sludge and affected the activity of microorganisms. Considering the cost of energy consumption, partial pretreatment has more practical application prospects.

Prognostic Markers in Pediatric Acute Liver Failure

Introduction: Acute liver failure (ALF), although rare in children, is a complex progressive pathology, with multisystem involvement and high mortality. Isolated variables or those included in prognostic scores have been studied, to optimize organ allocation. However, its validation is challenging. This study aimed to assess the accuracy of several biomarkers and scores as predictors of prognosis in pediatric ALF (PALF). Methods: An observational study with retrospective data collection, including all cases of ALF, was defined according to the criteria of the Pediatric Acute Liver Failure Study Group, admitted to a pediatric intensive care unit (PICU) for 28 years. Two groups were defined: spontaneous recovery (SR) and non-SR (NSR) – submitted to liver transplantation (LT) or death at PICU discharge. Results: Fifty-nine patients were included, with a median age of 24 months, and 54% were female. The most frequent etiologies were metabolic (25.4%) and infectious (18.6%); 32.2% were undetermined. SR occurred in 21 patients (35.6%). In NSR group (N = 38, 64.4%), 25 required LT (42.4%) and 19 died (32.2%), 6 (15.7%) of whom after LT. The accuracy to predict NSR was acceptable for lactate at admission (AUC 0.72; 95% CI: 0.57–0.86; p = 0.006), ammonia peak (AUC 0.72; 95% CI: 0.58–0.86; p = 0.006), and INR peak (AUC 0.70; 95% CI: 0.56–0.85; p = 0.01). The cut-off value for lactate at admission was 1.95 mmol/L (sensitivity 78.4% and specificity 61.9%), ammonia peak was 64 μmol/L (sensitivity 100% and specificity 38.1%), and INR peak was 4.8 (sensitivity 61.1% and specificity 76.2%). Lactate on admission was shown to be an independent predictor of NSR on logistic regression model. Two prognostic scores had acceptable discrimination for NSR, LIU (AUC 0.73; 95% CI: 0.59–0.87; p = 0.004) and PRISM (AUC 0.71; 95% CI: 0.56–0.86; p = 0.03). In our study, the PALF delta score (PALF-ds) had lower discrimination capacity (AUC 0.63; 95% CI: 0.47–0.78; p = 0.11). Conclusions: The lactate at admission, an easily obtained parameter, had a similar capacity than the more complex scores, LIU and PRISM, to predict NSR. The prognostic value in our population of the promising dynamic score, PALF-ds, was lower than expected.

Effect of coated urea and monensin on rumen metabolism of Nellore cows fed low-quality forage-based diet

ABSTRACT This study investigated the effect of coated urea supplementation associated with monensin on rumen metabolism and fermentation, in cattle consuming a low-quality forage-based diet. Eight ruminally cannulated Nellore cows consuming Brachiaria brizantha cv. Marandu hay were randomly assessed to two 4 × 4 Latin square design, in a 2 × 4 factorial arrangement, with a factorial treatment arrangement with the factors: (i) urea source: (CON) no urea, (URE) common urea, (PCU) polymer-coated urea and (LCU) lipid-coated urea; (ii) monensin: (MON) addition of monensin in the diet; and (NM) no addition of monensin in the diet. Ruminal NH3-N concentration was affected by urea source and there was an interaction between time and the urea source. Rumen acetate molar concentration was lower, while rumen propionate was greater for URE compared to coated urea. The total tract apparent digestibility of crude protein (CP) and non-protein nitrogen (NPN) were greater for URE compared to coated urea treatments and for LCU compared to PCU. Animals fed URE had greater urea excretion compared to coated urea. In conclusion, coated urea generates a lower ammonia peak; however, both coated urea did not promote total nitrogen release. No synergy was observed with the combination of urea and monensin.

Early Predictors of Delayed Respiratory Failure after Glufosinate Ammonium Ingestion

Acute glufosinate ammonium poisoning can cause neurological complications and respiratory failure, which are usually delayed and difficult to predict. Serum ammonia level might be an indicator of severe glufosinate poisoning, but it has not been confirmed. We aimed to investigate the potential predictors of respiratory failure after glufosinate poisoning. We conducted a retrospective review of 21 cases of glufosinate poisoning between 2010 and 2019. Patients were assigned to intubated due to respiratory failure and non-intubated groups. The following characteristics were compared between these two groups; age, sex and period from poisoning to hospital arrival, vital signs, Glasgow coma scale, laboratory parameters and electrocardiogram measurements. Furthermore, the outcomes of morbidity and mortality were analyzed. Totally, 12 cases were be intubated and the other 9 were not intubated. Leukocytosis, hyperglycemia, increased serum creatinine, peak ammonia level and decreased Glasgow coma scale score found at emergency visits were significantly different between these two groups. The white blood cell count (median: 9100 vs. 15 785, p=0.046) and serum creatinine (median: 0.88 vs. 1.20, p=0.019) and blood sugar (median: 114.0 vs. 138.5, p=0.032) levels were higher and the initial Glasgow coma scale score was lower in the intubated group than in the non-intubated group (median: 15 vs. 13, p=0.030). Moreover, six patients who presented with a decreased Glasgow coma scale score and an increased ammonia level developed respiratory failure. In cases of glufosinate poisoning, leukocytosis, hyperglycemia, impaired renal function and decreased Glasgow coma scale score initially can use to predict respiratory failure. Moreover, conscious change combined with an early increase in serum ammonia level implied that, intensive monitoring should be required to prevent lethal complications from delayed onset of respiratory failure.

Evaluation of the stability of shortcut nitrification-denitrification process based on online specific oxygen uptake rate monitoring

Shortcut nitrification-denitrification (SCND) is widely concerned because of its low energy consumption and high nitrogen removal efficiency. However, the current difficulty lies in the stable maintenance of SCND performance, which leads to the challenge of large-scale application of this new denitrification technology. In this study, the nitrogen removal pathway from complete nitrification-denitrification (CND) to SCND was rapidly realized under high free ammonia (FA), high pH and low dissolved oxygen (DO) conditions. The variations of specific oxygen uptake rate (SOUR) of activated sludge in both processes were investigated by an online SOUR monitoring device. Different curves of SOUR from CND to SCND process were observed, and the ammonia peak obtained based on SOUR monitoring could be used to control aeration time accurately in SCND process. Accordingly, the SOUR ratio of ammonia oxidizing bacteria (AOB) to nitrite oxidizing bacteria (NOB) (SOURAOB/SOURNOB) was increased from 1.40 to 2.93. 16S rRNA Miseq high throughput sequencing revealed the dynamics of AOB and NOB, and the ratio of relative abundance (AOB/NOB) was increased from 1.03 to 3.12. Besides, SOURAOB/SOURNOB displayed significant correlations to ammonia removal rate (P < 0.05), ammonia oxidation rate / nitrite oxidation rate (P < 0.05), nitrite accumulation rate (P < 0.05) and the relative abundance of AOB/NOB (P < 0.05). Thus, a strategy for evaluation the SCND process stability based on online SOUR monitoring is proposed, which provides a theoretical basis for optimizing the SCND performance.

Factors associated with short-term survival in neonates with hyperammonemia.

Hyperammonemia due to inherited metabolic disease can lead to neurological sequelae and death in neonates. Metabolite scavenger (MS) administration and dialysis can be helpful. We aim at analyzing the factors affecting short-term survival in neonates with hyperammonemia. We conducted a retrospective study including all neonates with hyperammonemia admitted to the neonatal intensive care unit (NICU) of the Children's Hospital of Fudan University between April 2013 and June 2020. Sixty-two neonates were enrolled in the study. Of these, 32 neonates were included in the non-survival group, and 30 neonates in the survival group. Compared to the survival group, the non-survival group had a higher peak ammonia level (882.2 vs. 433.4 µmol/L) (P=0.002), a shorter length of stay (5.7 vs. 22.3 d) (P<0.000), and higher rates of acidosis (19 vs. 10) (P=0.047), electrolyte disturbance (15 vs. 6) (P=0.033), coma (12 vs. 2) (P=0.005), and invasive mechanical ventilation (28 vs. 8) (P=0.000). A longer length of stay was the most significant protective factors in the multivariate logistic regression analysis, followed by MS administration. Factors of invasive mechanical ventilation, Δ<0 (Δ= last ammonia level - first ammonia level), coma and electrolyte disturbance established a risk score model that performed well in survival analysis. Area under ROC curve for survival length of hyperammonemia combined with peak ammonia levels was 0.737 (95% CI: 0.603-0.870). MS administration is an effective treatment method for hyperammonemia in neonates, and increasing the length of stay in the NICU could help improve short-term survival. Further intervention should be administered when peak ammonia levels >406.5 µmol/L.

Effect of reed-biochar application on ammonia volatilization from different types of soils

The application of straw biochar in farmland in Dongting Lake area can realize the resource utilization of straw and reduce environmental risk. In 2020, a rice pot experiment was conducted to investigate the effects of different biochar application levels on ammonia volatilization rate, cumulative ammonia volatilization, pH value, and NH4+-N concentration in surface water. Six levels of reed (Miscanthus lutarioriparius) biochar amount, i.e., 0%, 1%, 2%, 4%, 6% and 8% of soil weight of the 0-20 cm column, were applied in two typical paddy soils in sou-thern China, i.e., reddish clayey soil derived from quaternary red soil and granitic sandy soil derived from granite. Compound fertilizer was applied at a rate of 200 kg N·hm-2. The results showed that biochar application resulted in significant differences in the rate and cumulative amount of ammonia volatilization between the two soils and among different biochar treatments. For the granitic sandy soil, peak ammonia volatilization under different biochar treatments appeared at the second day after fertilization, which was decreased by 23.6%-53.4%. For the reddish clayey soil, peak ammonia volatilization appeared between the 7th to 13th day after fertilization, which increased with biochar addition level. The rate of ammonia volatilization from the granitic sandy soil was generally higher than that from the reddish clayey soil. For the granitic sandy soil, addition of <4% biochar could inhibit the ammonia volatilization and cumulative volatilization amount, with the greatest reduction (46.9%) at the treatment with 2% biochar addition. The addition of biochar did not affect the pH value of surface water at the early stage of rice growth. For the reddish clayey soil, the pH value and NH4+-N concentration in the surface water increased with biochar addition level, resulting in the increases of ammonia volatilization rate and cumulative volatilization amount by 1.3-10.5 times. Biochar addition level was the key factor affecting ammonia volatilization from the two soils. Elovich equation could well fit the variation trend of cumulative ammonia volatilization with time for the two soils, with the correlation reaching extremely significant level for each treatment. Overall, the application of reed biochar could suppress ammonia volatilization from the granitic sandy soil which was nearly neutral in acidity, while would promote ammonia volatilization via increasing pH value and NH4+-N concentration of surface water for the acidic reddish clayey soil. Therefore, appropriate dosages of reed biochar should be selected for different types of soil in order to reduce nitrogen loss.

Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 μmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 μmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.

Multisite Retrospective Review of Outcomes in Renal Replacement Therapy for Neonates with Inborn Errors of Metabolism

To assess the outcomes of neonates in a contemporary multi-institutional cohort who receive renal replacement therapy (RRT) for hyperammonemia. We performed a retrospective analysis of 51 neonatal patients with confirmed inborn errors of metabolism that were treated at 9 different children's hospitals in the US between 2000 and2015. Twenty-nine patients received hemodialysis (57%), 21 patients received continuous renal replacement therapy (41%), and 1 patient received peritoneal dialysis (2%). The median age at admission of both survivors (n=33 [65%]) and nonsurvivors (n=18) was 3days. Peak ammonia and ammonia at admission were not significantly different between survivors and nonsurvivors. Hemodialysis, having more than 1 indication for RRT in addition to hyperammonemia, and complications during RRT were all risk factors for mortality. After accounting for multiple patient factors by multivariable analyses, hemodialysis was associated with a higher risk of death compared with continuous renal replacement therapy. When clinical factors including evidence of renal dysfunction, number of complications, concurrent extracorporeal membrane oxygenation, vasopressor requirement, and degree of hyperammonemia were held constant in a single Cox regression model, the hazard ratio for death with hemodialysis was 4.07 (95% CI 0.908-18.2, P value=.067). To help providers caring for neonates with hyperammonemia understand their patient's likelihood of survival, we created a predictive model with input variables known at the start of RRT. Our large, multicenter retrospective review supports the use of continuous renal replacement therapy for neonatal hyperammonemia.

Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency

PurposeCarbamoyl phosphate synthetase 1 (CPS1) deficiency affects the first step of urea cycle and is a severe form of urea cycle disorder (UCD). The severity of hyperammonemic encephalopathy determines the clinical course of UCDs. Here, we describe the genetic and clinical characteristics of CPS1 deficiency in Korea. Patient and methodsThis study included seven patients with CPS1 deficiency genetically confirmed from January 1992 to September 2020. The peak ammonia level during the first crisis, the half time of peak ammonia level, the initial plasma amino acid levels, and neurological outcomes were compared between CPS1 deficiency and two common UCDs (i.e., 17 patients with argininosuccinate synthetase 1 deficiency and 24 patients with ornithine transcarbamylase deficiency). ResultEleven CPS1 mutations were identified, including 10 novel mutations. Eight mutations were missense. Six patients with CPS1 deficiency had neonatal type. The peak ammonia level, initial glutamate level, and accompanying rate of irreversible neurological damages were highest in patients with CPS1 deficiency. The patient with late-onset CPS1 deficiency responded dramatically to N-carbamylglutamate treatment. ConclusionThe clinical manifestations of CPS1 deficiency were the most severe among UCDs. Considering the high proportion of missense mutations, responsiveness to N-carbamylglutamate would be evaluated in a future study.

Hyperammonemia syndrome associated with Ureaplasma spp. Infections in immunocompromised patients and transplant recipients: A systematic review and meta-analysis.

Hyperammonemia syndrome (HS) is reported to occur in patients with Ureaplasma spp. infections. We performed a systematic review and meta-analysis of studies reporting HS in patients with Ureaplasma spp. infection. We searched several databases (CINAHL, OVID, ProQuest, and Scopus) from inception to January 2021. We described case reports and series, and performed a meta-analysis for all cohort studies. The pooled risk ratio (RR) for the association between HS and Ureaplasma spp. infections was derived using a random-effects model. The systematic review yielded 18 studies. HS was reported in 53 patients with Ureaplasma spp. infections. The most common clinical manifestations were neurologic. Meta-analysis showed a higher incidence of HS (41.67%) and peak ammonia concentration among Ureaplasma spp.-infected lung transplant recipients compared with Ureaplasma spp.-negative recipients (2.84%). The risk of HS was significantly increased in Ureaplasma spp.-infected recipients compared with Ureaplasma spp.-negative recipients (RR: 14.64; CI: 2.85-75.24). Mortality from Ureaplasma-associated HS was 27.27% compared with 5.24% in those with HS from other causes. The risk of developing HS is higher among Ureaplasma-infected patients compared with uninfected patients. Lung transplant recipients appear to be disproportionally affected, and HS should be suspected in those who present with neurologic symptoms.

A novel ammoniation treatment of barley as a strategy to optimize rumen pH, feed degradability and microbial protein synthesis in sheep.

BACKGROUNDMeeting the energy and nitrogen (N) requirements of high‐performing ruminants at the same time as avoiding digestive disturbances (i.e. rumen acidosis) is a key priority in ruminant nutrition. The present study evaluated the effect of a cereal ammoniation treatment, in which barley grains are combined with urea and enzymes that catalyze the conversion of urea to ammonia to optimize rumen function. Twelve rumen cannulated sheep were randomly divided into two groups and fed a diet containing 60% of ammoniated barley (AMM) or untreated barley supplemented with urea (CTL) to investigate the impact on rumen fermentation and feed utilization.RESULTSAMM had higher total N content and effective rumen degradable N than untreated barely. AMM sheep had a consistently higher rumen pH throughout the day (6.31 versus 6.03) and tended to have a lower post‐prandial ammonia peak and higher acetate molar proportion (+5.1%) than CTL sheep. The rumen environment in AMM sheep favored the colonization and utilization of agro‐industrial by‐products (i.e. orange pulp) by the rumen microbes leading to a higher feed degradability. AMM sheep also had higher total tract apparent N digestibility (+21.7%) and urinary excretion of purine derivatives (+34%), suggesting a higher N uptake and microbial protein synthesis than CTL sheep.CONCLUSIONThe inclusion of AMM in the diet of ruminants represents a valid strategy for maintaining rumen pH within a physiological range and improving N utilization by the rumen microbes, which could have positive effects on the health and productivity of animals in intensive production systems. These findings warrant further studies under conventional farm conditions. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Combining Plasmapheresis with Renal Replacement Therapy: Answer to Hyperammonemia Post Lung Transplantation?

Purpose Hyperammonemia is a fatal complication post lung transplantation. There are no guidelines for treating hyperammonemia and hence various treatment protocols have been tried. We present a short case series of Hyperammonemia post LTx from India with focusing on Plasmapheresis with Renal Replacement Therapy (RRT) as a combination treatment option apart from routine standard measures leading to survival. Methods We conducted a retrospective study of patients who underwent LTx between April 1 2017 and March 1 , 2020. Patients who developed hyperammonemia syndrome in the post transplantation period, which was defined as symptoms of encephalopathy and plasma ammonia level exceeding 200 μmol/L , excluding hepatic dysfunction were included. Data including demographics, antimicrobial, immunosuppression , ammonia levels , and outcomes were noted. Results 4 of 132 lung transplant recipients developed hyperammonemia syndrome postoperatively during this time period. Median time to peak Ammonia level was 7 days, and median peak ammonia level was 336 μmol/L. All 4 patients were treated with bowel decontamination measures like Metronidazole, Lactulose, Rifaximin . 3 patients received SLED and 1 patient received CRRT. Prompt discontinuation of CNIs was done in all 4 patients. Sodium benzoate infusions were also initiated. 1 patient was also treated with Plasmapheresis with SLED which helped in recovery and survival. Same patient had also received ATG after CNI discontinuation. 3 of the 4 patients died. All 3 patients who expired had poor Tacrolimus Metaboliser status while the patient who recovered had Intermediate Tacrolimus Metaboliser status. Conclusion Hyperammonemia post lung transplantation is often a fatal complication. A multipronged approach is required to achieve survival. Combining Plasmapheresis with SLED /CRRT apart from other standard measures like Bowel decontamination, Prompt discontinuation of CNIs, treating Urease splitting organisms, etc might be an answer to recovery and survival for Hyperammonemia post LTx. Further research is required to determine efficacy of combining Plasmapheresis with RRT along with other treatment options . Also recipient's Tacrolimus Metaboliser status might correlate for developing Hyperammonemia and response to treatment which would warrant further research.

Treatment Strategy for Hyperammonemia in Lung Transplantation

Purpose Idiopathic hyperammonemia syndrome (IHS) is a rare, often fatal complication following lung transplantation. Multiple treatment strategies have been documented including dialysis, although no definite treatments exist so far, and mortality remains high. In this study, we analyzed the current treatment strategy to determine the better treatment option in patients with hyperammonemia. Methods 283 patients who underwent lung transplantation from January 2013 to June 2020 were retrospectively reviewed. We defined non-severe hyperammonemia as serum ammonia >38umol/L, severe hyperammonemia as >75umol/L, and HIS >200umol/L at least one occasion. Elevated serum ammonia was detected in 134 patients. For the assessment of the treatment response, patients with severe hyperammonemia were divided into subgroups; the resolved group in which was treated successfully, and the failed group in which had failed to resolve. Results Among 134 patients with hyperammonemia, 38 (28.4%) showed severe hyperammonemia and 10 of 38 have failed to resolve. Mean peak ammonia level was 52.7umol/L in non-severe patients, 111.6umol/L in resolved patients, and 356.6umol/L in the failed group (p=0.001). The peak level was detected on median postoperative 16.7day in non-severe patients, 42.8day in the resolved group, and 25.4day in the failed group (p=0.001). 16 (16.8%) were symptomatic in non-severe patients, 12 (46.2%) in the resolved group and all patients in the failed group were symptomatic (p=0.001). Total amount of transfusion within postoperative 48 hours is greater in the failed group (2912.5ml) than the resolved group (1655.7ml, p=0.040), especially, the tendency was remarkable for red blood cell transfusion (1945.0ml vs. 799.0ml; p=0.018). The proportions of applying renal replacement, nitrogen scavengers, and bowel decontaminant were not significantly different. Although not statistically significant, only the resolved group patients had received empirical antibiotics such as fluoroquinolone (37.5%, p=0.063). All the patients in the failed group died during follow up, 4 of them died due to IHS. Conclusion None of the current treatment was optimally effective for hyperammonemia. However, certain combinations of antibiotics might have potential to lower serum ammonia, which is consistent with recent findings that microbes such as Ureaplasma spp. can cause hyperammonemia after lung transplantation.