Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

BACKGROUND: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. METHODS: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U-13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2-0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. RESULTS: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m2 [range 41.3-63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U-13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U-13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U-13C3]glycerol trended to be lower in obese adolescents with liver pathology. CONCLUSIONS: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.

Ultrasound-guided erector spinae plane block versus thoracic epidural analgesia: Postoperative pain management after Nuss repair for pectus excavatum.

AIM OF THE STUDY: Postoperative pain management is a significant challenge in patients undergoing Nuss repair for pectus excavatum chest wall deformity. Therapeutic anesthetic options primarily include patient-controlled intravenous analgesia, thoracic epidural analgesia (TEA), and cryoanalgesia. However, TEA is limited to inpatient use and both TEA and cryoanalgesia can result in neurologic injury. The novel technique of ultrasound-guided erector spinae plane regional analgesia has been used recently in our patients undergoing the Nuss repair and has shown impressive pain relief, but without the potential complications of other modalities. Erector spinae plane block (ESPB) postoperative pain management outcomes were studied as compared to TEA. METHODS: Thirty consecutive patients with severe pectus excavatum undergoing Nuss repair and placement of ultrasound-guided ESPB were each paired to a historical cohort control patient with TEA postoperative pain management. The cohort patient match was defined by age (± 2 years), gender, and CT pectus index (± 15%). Study variables included hospital length of stay (LOS), pain scores, and pain medication usage. RESULTS: Pain scores as measured by area under the curve per hour (Day 1: 2.72 (SD = 1.37) vs. 3.90 (SD = 1.81), P = 0.006; Day 2: 2.83 (SD = 1.32) vs. 3.97 (SD = 1.82), P = 0.007) and oral morphine equivalent (OME) pain medication usage (Day 1: 11.9 (SD = 4.9) vs 56.0 (SD = 32.2), P < 0.001; Day 2: 14.7 (SD = 7.1) vs. 38.0 (SD = 21.7), P < 0.001) were higher for the first two postoperative days in the ESPB group. However, mean hospital LOS was nearly one day shorter for ESPB patients (3.78 (SD = 0.82) vs. 2.90 (SD = 0.87), P < 0.001) who were discharged home with the catheter in place until removal, typically at 5-7 days postoperatively. CONCLUSION: Ultrasound-guided ESPB is thus a feasible, safe, and effective alternative to TEA in postoperative pain management after Nuss repair and results in decreased hospital stay. LEVEL OF EVIDENCE: III.

The role of preoperative upper endoscopy in adolescents undergoing laparoscopic vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy (VSG) has been associated with gastroesophageal reflux symptoms and, in adults, with a development of Barrett's esophagus. Adults with Barrett's esophagus identified at baseline before bariatric operation are generally advised against VSG operations. The role of preoperative esophagogastroduodenoscopy (EGD) in adolescents preparing for bariatric surgery is not clearly defined. OBJECTIVE: The goal of this study was to report the frequency of abnormalities identified on EGD performed at baseline in adolescents undergoing VSG for severe obesity. SETTING: Free-standing academic children's hospital. United States. METHODS: A retrospective chart review was conducted to describe findings of EGD performed just before VSG in a cohort of 40 adolescents and young adults (age range 14-25 yr) immediately before VSG. Review of findings from gross and histopathological evaluation of the esophagus, resected stomach, and duodenum was performed. RESULTS: Five individuals reported preoperative symptoms of gastroesophageal reflux. Anatomic findings at EGD were normal in 98% of individuals. Histopathology of the esophagus, stomach, and duodenum was normal in 88%, 70%, and 95%, respectively. Abnormal findings of gastritis (18%), esophagitis (13%), and/or Helicobacter pylori (10%) infection were most common. Those with evidence of H. pylori in gastric resection specimens were treated appropriately with eradication therapy postoperatively. With the exception of 2 patients with incidentally detected esophageal mucosal eosinophilia, EGD findings did not lead to additional changes in medical or surgical management. There were no complications of the EGD procedure. CONCLUSIONS: Routine EGD at the time of VSG was safe but resulted in low yield of abnormal findings requiring a change in clinical management.

Cystic biliary atresia: a wolf in sheep's clothing.

Neonatal obstructive jaundice is frequently explained by biliary atresia (BA) or the presence of a choledochal cyst (CC). Cystic biliary atresia (CBA) has been a proposed as a subtype of BA with projected improved outcomes. We aimed to characterize these lesions further. We conducted an Institutional Review Board-approved review of all patients treated for obstructive jaundice at our tertiary children's hospital over 10 years. Over the decade we evaluated 91 children with obstructive jaundice: 13 CBA, 52 BA, and 26 CC. Patients with isolated CBA and BA were diagnosed significantly earlier than those with CC (15.9, 54, and 281 days, respectively; P = 0.0001). There was a significant delay between diagnosis and surgical intervention for patients with CBA compared with BA: 17 days versus 5.7 days (P = 0.004). There was no difference in rate of transplant between CBA and BA (31 vs. 50%; P = 0.35). The time from surgery until transplant was 13.9 and 18.6 months for CBA and BA, respectively (P = 0.62). Although radiographically similar to CC, CBA behaves similarly to isolated BA. Delay in recognition and surgical treatment may affect outcomes and lead to an increased incidence of liver failure. The presence of a cystic biliary malformation in the setting of neonatal jaundice should be regarded as CBA until proven otherwise.