Effect of rest duration between sets on fatigue and recovery after short intense plyometric exercise.

Plyometric training is characterized by high-intensity exercise which is performed in short term efforts divided into sets. The purpose of the present study was twofold: first, to investigate the effects of three distinct plyometric exercise protocols, each with varying work-to-rest ratios, on muscle fatigue and recovery using an incline-plane training machine; and second, to assess the relationship between changes in lower limb muscle strength and power and the biochemical response to the three exercise variants employed. Forty-five adult males were randomly divided into 3 groups (n = 15) performing an exercise of 60 rebounds on an incline-plane training machine. The G0 group performed continuous exercise, while the G45 and G90 groups completed 4 sets of 15 repetitions, each set lasting 45 s with 45 s rest in G45 (work-to-rest ratio of 1:1) and 90 s rest in G90 (1:2 ratio). Changes in muscle torques of knee extensors and flexors, as well as blood lactate (LA) and ammonia levels, were assessed before and every 5 min for 30 min after completing the workout. The results showed significantly higher (p < 0.001) average power across all jumps generated during intermittent compared to continuous exercise. The greatest decrease in knee extensor strength immediately post-exercise was recorded in group G0 and the least in G90. The post-exercise time course of LA changes followed a similar pattern in all groups, while the longer the interval between sets, the faster LA returned to baseline. Intermittent exercise had a more favourable effect on muscle energy metabolism and recovery than continuous exercise, and the work-to-rest ratio of 1:2 in plyometric exercises was sufficient rest time to allow the continuation of exercise in subsequent sets at similar intensity.

Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

External validation of the modified CTP score based on ammonia to predict survival in patients with cirrhosis after TIPS placement.

This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P < 0.0001). The aCTP score showed the best discriminative performance using the C-index compared with other scores at each time point during follow-up, it also showed better calibration in the calibration plot and the lowest Brier scores, and it also showed a higher net benefit than the other scores in the DCA curve. The aCTP score outperformed the other risk scores in predicting survival after TIPS placement in patients with cirrhosis and may be useful for risk stratification and survival prediction.

Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts.

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 µmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Substitution of One Meat-Based Meal With Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet. METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups. RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups. DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.

Intravenous versus oral 'L-ornithine-L-aspartate' in overt hepatic encephalopathy: a randomized comparative study.

Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) L-ornithine-L-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

Effect of residual methane emission on physiological characteristics and carcass performance in Japanese Black cattle.

This study investigated the physiological characteristics and carcass performance associated with residual methane emissions (RME), and the effects of bull differences on CH4-related traits in Japanese Black cattle. Enteric methane (CH4) emissions from 156 Japanese Black cattle (111 heifers and 45 steers) were measured during early fattening using the sniffer method. Various physiological parameters were investigated to clarify the physiological traits between the high, middle, and low RME groups. CH4-related traits were examined to determine whether bull differences affected progeny CH4 emissions. Ruminal butyrate and NH3 concentrations were significantly higher in the high-RME group than in the low-RME group, whereas the propionate content was significantly higher in the low-RME group. Blood urea nitrogen, ß-hydroxybutyric acid, and insulin concentrations were significantly higher, and blood amino acids were lower in the high-RME group than in the other groups. No significant differences were observed in the carcass traits and beef fat composition between RME groups. CH4-related traits were significantly different among bull herds. Our results show that CH4-related traits are heritable, wherein bull differences affect progeny CH4 production capability, and that the above-mentioned rumen fermentations and blood metabolites could be used to evaluate enteric methanogenesis in Japanese Black cattle.

NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.

Critical care management of acute liver failure.

The management of acute liver failure (ALF) in modern hepatology intensive care units (ICU) has improved patient outcomes. Critical care management of hepatic encephalopathy, cerebral edema, fluid and electrolytes; prevention of infections and organ support are central to improved outcomes of ALF. In particular, the pathogenesis of encephalopathy is multifactorial, with ammonia, elevated intra-cranial pressure and systemic inflammation playing a central role. Although ALF remains associated with high mortality, the availability of supportive care, including organ failure support such as plasma exchange, timely mechanical ventilation or continuous renal replacement therapy, either conservatively manages patients with ALF or offers bridging therapy until liver transplantation. Thus, appropriate critical care management has improved the likelihood of patient recovery in ALF. ICU care interventions such as monitoring of cerebral edema, fluid status assessment and interventions for sepsis prevention, nutritional support and management of electrolytes can salvage a substantial proportion of patients. In this review, we discuss the key aspects of critical care management of ALF.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

INTRODUCTION: Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. METHODS: Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. RESULTS: Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. DISCUSSION: Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

Acceptability of plasma ammonia results when samples are not transported and processed under ideal conditions.

BACKGROUND: It is recommended that samples for plasma ammonia analysis are kept chilled and processed promptly as in vitro metabolism causes falsely elevated results. Rejection of unsuitable samples can cause delayed diagnosis and treatment of hyperammonaemia with potentially serious clinical consequences. The Metabolic Biochemistry Network (MetBioNet) hyperammonaemia guideline recommends analysis of samples not collected under ideal conditions and reporting with appropriate comments. An audit found that some laboratories did not follow this guidance. An investigation was performed into whether storage at controlled room temperature and delayed sample processing affected interpretation of plasma ammonia results. METHODS: Eleven healthy volunteers provided informed consent. Blood was taken from each into 14 paediatric EDTA blood sample tubes, one placed immediately on ice, the others in a rack at room temperature. The chilled and baseline room temperature samples were centrifuged and plasma analysed by the Roche Ammonia (NH3L2) method. Samples stored at room temperature were analysed at 10-min intervals up to 2 h. RESULTS: Baseline room temperature ammonia was higher than in the chilled sample (19 ± 6.6 µmol/L [mean ± standard deviation] and 18 ± 6.6 µmol/L, respectively). Ammonia increased further by 0.09 ± 0.02 µmol/L per minute to 30 ± 8.4 µmol/L at 2 h. No result was above the reference range (50 µmol/L). No healthy subject with normal baseline ammonia would have been erroneously identified as having hyperammonaemia. CONCLUSIONS: Results support MetBioNet guidance that laboratories accept blood samples for ammonia analysis which are not processed under ideal conditions.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04176523. Registered 25 November, 2019, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04176523 .

Inhibition of the urea cycle by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin increases serum ammonia levels in mice.

The aryl hydrocarbon receptor is a ligand-activated transcription factor known for mediating the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. TCDD induces nonalcoholic fatty liver disease (NAFLD)-like pathologies including simple steatosis that can progress to steatohepatitis with fibrosis and bile duct proliferation in male mice. Dose-dependent progression of steatosis to steatohepatitis with fibrosis by TCDD has been associated with metabolic reprogramming, including the disruption of amino acid metabolism. Here, we used targeted metabolomic analysis to reveal dose-dependent changes in the level of ten serum and eleven hepatic amino acids in mice upon treatment with TCDD. Bulk RNA-seq and protein analysis showed TCDD repressed CPS1, OTS, ASS1, ASL, and GLUL, all of which are associated with the urea cycle and glutamine biosynthesis. Urea and glutamine are end products of the detoxification and excretion of ammonia, a toxic byproduct of amino acid catabolism. Furthermore, we found that the catalytic activity of OTC, a rate-limiting step in the urea cycle was also dose dependently repressed. These results are consistent with an increase in circulating ammonia. Collectively, the repression of the urea and glutamate-glutamine cycles increased circulating ammonia levels and the toxicity of TCDD.

[Considering Recurrence Prevention Regimen for Colorectal Cancer Patients with Hyperammonemia Caused by Chemotherapy Containing 5-Fluorouracil].

A 64-year-old woman was admitted to our hospital because of severe constipation and was diagnosed with unresectable cStage Ⅳb rectal cancer with multiple lung metastases and liver metastases. Because of obstructive symptoms, a laparoscopic sigmoid colostomy was performed. Because of RAS/BRAF wild type, we started the mFOLFOX6 plus panitumumab (Pmab). Ten days after 10 cycles of chemotherapy, she was admitted because of general fatigue, stoma edema, ascites, and leg edema. She became confused(JCSⅢ-200). The laboratory results revealed that her serum ammonia level was 293µg/ dL. We diagnosed 5-FU-induced hyperammonemic encephalopathy. Treatment with branched-chain amino acid solutions resulted in improvement of his mental status and serum ammonia level decreased. After that, the chemotherapy was changed to 5-FU 80% FOLFIRI plus bevacizumab, but hyperammonemia recurred. After improvement of hyperammonemia, the patient has been treated for 4 cycles without becoming unconscious after switching to FTD/TPI plus bevacizumab therapy. In this case, muscle weakness due to sarcopenia was considered to be one of the causes. We believe that oral drugs containing FTD/TPI can be used relatively safely without causing hyperammonemia.

Desflurane and remifentanil anesthesia in a child with citrin deficiency: A case report.

RATIONALE: Hyperammonemia, metabolic derangement, and/or the prolonged effects of anesthetics may lead to delayed emergence from general anesthesia as well as the onset of type 2 citrullinemia, even in compensated patients with citrin deficiency. PATIENT CONCERN: A 5-year-old girl with citrin deficiency was scheduled for blepharoplasty under general anesthesia. She developed hyperammonemia with temporary interruption of medication for a few days before surgery. DIAGNOSIS: The patient was genetically diagnosed as citrin deficiency with a mutation in the SLC25A13 gene via newborn screening for metabolic disorders. Her citrulline and ammonia levels were well-controlled with arginine medication and protein-rich diet. Her elevated ammonia level by temporary interruption of medication was corrected with resumption of arginine medication and protein-rich diet before surgery. INTERVENTIONS: We used desflurane and remifentanil for general anesthesia to avoid hyperammonemia and delayed emergence. End-tidal desflurane concentration and anesthetic depth were carefully monitored to avoid excessive anesthesia. OUTCOMES: She recovered consciousness with slightly increased ammonia level immediately after anesthesia. LESSIONS: General anesthesia of the shortest duration with the least metabolized drugs using desflurane and remifentanil, would be beneficial for rapid emergence in surgical patients with citrin deficiency. Maintenance of nitrogen scavenging medication, a protein-rich diet, and serial measurement of ammonia levels in the perioperative period are also important for avoiding hyperammonemia-related neurological dysfunction.

Two Japanese siblings with arginase-1 deficiency identified using a novel frameshift mutation of ARG1 (p.Lys41Thrfs∗2).

We described two Japanese siblings with arginase-1 (ARG1) deficiency. A 10-year-old girl (the proband and elder sister) was referred to our hospital complaining about her short stature. We diagnosed her with ARG1 deficiency, possibly with elevated levels of blood ammonia and plasma arginine. Her younger sister was found to have spastic paraparesis in her lower extremities and short stature at the age of 4 years. The younger sister also had high levels of plasma arginine, instead of normal levels of blood ammonia. Interestingly, they also prefer to avoid protein-rich foods such as meat, soybeans, cow milk, and dairy products. Genetic testing identified compound heterozygous mutations (c.121_122insCTT [p.Lys41Thrfs∗2] and c.298G>A [p.Asp100Asn]) in the ARG1 gene. The ARG1 mutation of p.Lys41Thrfs∗2 is a novel pathogenic mutation according to open databases and literature.

Prognostic role of serum ammonia in patients with sepsis-associated encephalopathy without hepatic failure.

Objectives: Our previous study shows that serum ammonia in sepsis patients without hepatic failure is associated with a poor prognosis. The relationship between serum ammonia level and the prognosis of sepsis-associated encephalopathy (SAE) patients without hepatic failure remains unclear. We aimed to explore the relationship between serum ammonia levels and the prognosis of patients with SAE. Materials and methods: This study is a retrospective cohort study. We collected 465 patients with SAE admitted to the intensive care unit (ICU) from Medical Information Mart for Intensive Care IV (MIMIC IV) from 2008 to 2019. Patients with SAE were divided into a survival group (369 patients) and a non-survival group (96 patients). We used the Wilcoxon signed-rank test and the multivariate logistic regression analysis to analyze the relationship between serum ammonia levels and the prognosis of patients with SAE. R software was used to analyze the dataset. Results: The primary outcome was the relationship between serum ammonia level and hospital mortality of SAE. The secondary outcomes were the relationship between serum ammonia level and hospital stays, simplified acute physiology score (SAPS II), Charlson, Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), and lactate level of SAE. The mortality of patients with SAE was 20.6%. The serum ammonia level was not significantly associated with hospital mortality, longer hospital stays, higher SAPS II and Charlson scores, and lower GCS of patients with SAE. The serum ammonia level was associated with higher SOFA scores and lactate levels in patients with SAE. The SAPS II and Charlson scores were independent risk factors for death in patients with SAE. Conclusion: Serum ammonia level was associated with higher SOFA scores and lactate levels in patients with SAE. In addition, the SAPS II and Charlson scores can be used to assess the prognosis of patients with SAE. Therefore, we should closely monitor serum ammonia, SAPS II, and Charlson levels in patients with SAE.

Long-Term Carbohydrate-Containing Late-Evening Snack Significantly Improves the Ratio of Branched Chain Amino Acids to Aromatic Amino Acids in Adults with Liver Cirrhosis due to Hepatitis B.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Optimization of an ammonia assay based on transmembrane pH-gradient polymersomes.

Reliable ammonia quantification assays are essential for monitoring ammonemia in patients with liver diseases. In this study, we describe the development process of a microplate-based assay for accurate, precise, and robust ammonia quantification in biological fluids, following regulatory guidelines on bioanalytical method validation. The assay is based on transmembrane pH-gradient polymersomes that encapsulate a pH-sensitive ratiometric fluorophore, the fluorescence signal of which correlates with the ammonia concentration in the sample. Using a four-parameter logistic regression, the assay had a large quantification range (30-800 µM ammonia). As for selectivity, the presence of amino acids or pyruvate (up to clinically relevant concentrations) showed no assay interference. In samples with low bilirubin levels, polymersomes containing the fluorophore pyranine provided accurate ammonia quantification. In samples with high bilirubin concentrations, billirubin's optical interference was alleviated when replacing pyranine with a close to near-infrared hemicyanine fluorophore. Finally, the assay could correctly retrieve the ammonia concentration in ammonia-spiked human plasma samples, which was confirmed by comparing our measurements with the data obtained using a commercially available point-of-care device for ammonia.

Prediction of minimal hepatic encephalopathy by using an radiomics nomogram in chronic hepatic schistosomiasis patients.

OBJECTIVE: To construct an MR-radiomics nomogram to predict minimal hepatic encephalopathy (MHE) in patients with chronic hepatic schistosomiasis (CHS). METHODS: From July 2017 to July 2020, 236 CHS patients with non-HE (n = 140) and MHE (n = 96) were retrospective collected and randomly divided into training group and testing group. Radiomics features were extracted from substantia nigra-striatum system of a brain diffusion weighted images (DWI) and combined with clinical predictors to build a radiomics nomogram for predicting MHE in CHS patients. The ROC curve was used to evaluate the predicting performance in training group and testing group. The clinical decisive curve (CDC) was used to assess the clinical net benefit of using radiomics nomogram in predicting MHE. RESULTS: Low seralbumin (P < 0.05), low platelet count (P < 0.05) and high plasma ammonia (P < 0.05) was the significant clinical predictors for MHE in CHS patients. The AUC, specificity and sensitivity of the radiomics nomogram were 0.89, 0.90 and 0.86 in the training group, and were 0.83, 0.85 and 0.75 in the training group. The CDC analysis showed clinical net benefits for the radiomics nomogram in predicting MHE. CONCLUSIONS: The radiomics nomogram combining DWI radiomics features and clinical predictors could be useful tool to predict MHE in CHS patients.