Sustaining the gains: Reducing unnecessary computed tomography scans in pediatric trauma patients.

BACKGROUND/PURPOSE: "Pan-scanning" pediatric blunt trauma patients leads to exposure to harmful radiation and increased healthcare costs without improving outcomes. We aimed to reduce computed tomography (CT) scans that are not indicated (NI) by imaging guidelines for injured children. METHODS: In July 2017, our Pediatric Trauma Center prospectively implemented validated imaging guidelines to direct CT imaging for trauma activations and consultations for children younger than 16 years old with blunt traumatic injuries. Patients with suspected physical abuse, CT imaging prior to arrival, penetrating mechanism, and instability precluding CT imaging were excluded. We compared CT scanning rates for pre-implementation (01/2016-06/2017) and post-implementation (07/2017-08/2021) time periods. Guideline compliance was evaluated by chart review and sustained through iterative process improvement cycles. RESULTS: During the pre-implementation era, 61 patients underwent 171 CT scans of which 87 (51%) scans were not indicated by guidelines. Post-implementation, 363 patients had 531 scans and only 134 (25%) CTs were not indicated. Total CTs performed declined after initiation of guidelines (2.80 vs 1.46 scans/patient, p<0.0001). Total NI CTs declined (1.41 vs 0.37 NI scans/patient, p<0.0001) reflected in significant reductions in all anatomic regions: head, cervical spine, chest, and abdomen/pelvis. Charges related to NI scans decreased from $1,490.31/patient to $408.21/patient, saving $218,000 in charges. Based on prior utilization, 146 children were spared excessive radiation with no clinically significant missed injuries since guideline implementation. CONCLUSIONS: Quality improvement and implementation science methodologies to enhance compliance with imaging guidelines for children with blunt injuries can significantly reduce unnecessary CT scanning without compromising care. This practice reduces harmful radiation exposure in a sensitive patient population and may save healthcare systems money and resources.

Protocol-driven Antibiotic Treatment of Pediatric Empyema After Fibrinolysis.

BACKGROUND: The duration of antibiotic treatment after resolution of empyema in children is variable. We evaluated the efficacy and safety of a protocol-driven antibiotic regimen aimed to decrease antibiotic duration following treatment with fibrinolysis. METHODS: Our institutional protocol consisted of 7 further days of antibiotics upon removal of the thoracostomy tube, with the patient being afebrile, off supplemental oxygen, and having negative cultures. A prospective observational study was then performed between September 2014 and March 2019. Empyema recurrence and antibiotic-related complications were recorded. Results were compared with previously published data from the preprotocol era. RESULTS: A total of 37 patients were included. Mean total duration of antibiotics decreased from 26 ± 6.5 days in the preprotocol group to 22 ± 9.7 days in the postprotocol group (P = 0.004). This resulted in a significant decrease in hospital stay from the preprotocol cohort to the postprotocol cohort, respectively (9.3 ± 4.8 d versus 6.8 ± 3.1 d, P = 0.003). Sixty-two percentage of the patients were intended to treat according to the protocol, with a 50% adherence rate. Patients in which the protocol was followed had an average of 2.8 fewer days of antibiotics after discharge (P = 0.004), although overall duration was not statistically different. Significantly fewer antibiotic-related complications were noted after protocol initiation. There was no difference in empyema recurrence or readmissions. CONCLUSIONS: Institution of a protocol-driven approach to antibiotic duration following resolution of pleural space disease may reduce antibiotic duration and complications without reducing efficacy.

30 Years of Flipping the Coin-Heads or Tails?

INTRODUCTION: Swallowed coins are a frequent cause of pediatric emergency department visits. Removal typically involves endoscopic retrieval under anesthesia. We describe our 30-year experience retrieving coins using a Foley catheter under fluoroscopy ("coin flip"). MATERIALS AND METHODS: Patients younger than 18 years who underwent the coin flip procedure from 1988 to 2018 were identified. Failure of fluoroscopic retrieval was followed by rigid endoscopic retrieval in the operating room. Detailed subanalysis of patients between 2011 and 2018 was also performed. RESULTS: A total of 809 patients underwent the coin flip procedure between 1988 and 2018. Median age was 3.3 years; 51% were male. The mean duration from ingestion to presentation was 19.8 hours. Overall success of removal from the esophagus was 85.5%, with 76.5% of coins retrieved and 9% pushed into the stomach. All remaining coins were retrieved by endoscopy. Complication rate was 1.2% with nine minor and one major complications, a tracheal tear that required repair. In our recent cohort, successful fluoroscopic removal led to shorter hospital lengths of stay (3.2 vs. 18.1 hours, p < 0.001). CONCLUSION: Patients who present with a coin in the esophagus can be successfully managed with a coin flip, which can be performed without hospital admission, with rare complications.

Optimization of Pediatric Bowel Management Using an Antegrade Enema Troubleshooting Algorithm.

BACKGROUND: A successful flush is the ability to flush through the appendicostomy or cecostomy channel, empty the flush through the colon, and achieve fecal cleanliness. We evaluated our experience with patients who were having flush difficulties based on a designed algorithm. METHODS: Eight patients with flush difficulties were initially evaluated. Based on the need for additional surgery versus changes in bowel management therapy (BMT), we developed an algorithm to guide future management. The algorithm divided flush issues into before, during, and after flushing. Children aged <20 y who presented with flush issues from September 2018 to August 2019 were evaluated to determine our algorithm's efficacy. Specific outcomes analyzed included changes in BMT versus need for additional surgery. RESULTS: After algorithm creation, 29 patients were evaluated for flush issues. The median age was 8.4 y (interquartile range: 6, 14); 66% (n = 19) were men. Underlying diagnoses included anorectal malformations (n = 17), functional constipation (n = 7), Hirschsprung's disease (n = 2), spina bifida (n = 2), and prune belly (n = 1). A total of 35 flush issues/complaints were noted: 29% before the flush, 9% during the flush, and 63% after the flush. Eighty percent of issues before the flush required surgical intervention, wherease 92% of issues during or after the flush were managed with changes in BMT. CONCLUSIONS: Most flush issues respond to changes in BMT. This algorithm can help delineate which types of flush issues would benefit from surgical intervention and what problems might be present if patients are not responding to changes in their flush regimen.

Intra-abdominal Abscess After Appendectomy-Are Drains Necessary in All Patients?

BACKGROUND: Research has shown that patients who develop a postoperative intra-abdominal abscess (PIAA) after appendectomy have a greater number of health care visits with drain placement. Our institution developed an algorithm to limit drain placement for only abscesses with a size >20 cm2. We sought to determine the adherence to and effectiveness of this algorithm. METHODS: This prospective observational study included patients aged 2-18 y old who developed a PIAA from September 2017 to June 2019. Outcomes were compared between patients with a small or large abscess. Analysis was performed in STATA; P < 0.05 was significant. RESULTS: Thirty patients were included. The median age was 10.6 y (7, 11.7); 60% were men, and 60% were Caucasian. The median duration of symptoms before diagnosis of appendicitis was 3 d (2, 6). Thirteen patients (43%) were diagnosed with a PIAA while still inpatient, and 17 (57%) were readmitted at a later date. After algorithm implementation, 95% (n = 19) of patients with a large abscess had aspiration ± drain placement, whereas 30% (n = 3) with a small abscess underwent drainage. Length of stay after abscess diagnosis, total duration of antibiotics, and number of health care visits were the same between groups. One patient with a small abscess required reoperation for an obstruction, whereas one patient with a large abscess that was drained was readmitted for a recurrent abscess. CONCLUSIONS: Small PIAA can be successfully managed without intervention. Our proposed algorithm can assist in determining which patients can be treated with antibiotics alone.

Same-Day Discharge and Quality of Life for Primary Laparoscopic Rectopexy for Rectal Prolapse in Children: A 10-Year Experience.

Introduction: Rectal prolapse (RP) in pediatric patients may require surgical intervention. Varying surgical approaches and heterogenous patient populations have resulted in difficulty defining surgical outcomes and superiority of technique. We sought to review our surgical and self-reported outcomes of patients who underwent laparoscopic rectopexy for idiopathic RP. Methods: Records of children <18 years who underwent primary laparoscopic rectopexy between March 2009 and March 2019 were retrospectively reviewed. Patients with redo rectopexy were excluded. Demographics, pre- and postoperative treatment, and outcome data were collected and reported using descriptive statistics. Qualitative analysis of a quality of life (QoL) questionnaire administered to patients and parents 2-10 years postoperatively was performed. Results: Fifteen patients were included. Median age at surgery was 5 years (interquartile range [IQR] 3, 12.5); 60% were male and median weight was 22 kg (IQR 16.4, 39.2). Median length of stay was 6 hours (IQR 4, 22) with 9 (60%) discharged the same day. Perioperatively, 73% were on laxative for constipation, whereas only 33% were on laxative therapy at 6 months postrectopexy. Median follow-up was 19 months (IQR 8, 39). Three patients (20%) suffered recurrent RP (2 required redo rectopexy), and 2 patients self-limited urinary retention. Respondents to the QoL questionnaire indicated improvement in symptoms after surgery. No patient reported fecal incontinence, smearing, or leakage of stool. Conclusion: Laparoscopic rectopexy is a safe minimally invasive approach for children with idiopathic RP that offers high patient satisfaction with same-day discharge, early recovery, and low recurrence.

Declining frequency of thoracoscopic decortication for empyema - redefining failure after fibrinolysis.

BACKGROUND: Primary fibrinolysis for pediatric empyema has become standard of care at our institution. Early study of our protocol revealed a 16% thoracoscopic decortication rate after primary fibrinolysis. We now report the frequency with which children progress to operation with maturation of the protocol. METHODS: A database of patients diagnosed with empyema between September 2014 and March 2019 was examined. Patients who underwent tissue plasminogen activator (tPA) therapy with or without subsequent video-assisted thoracoscopic (VATS) decortication were included. Patients with additional indications for tube thoracostomy or VATS were excluded. RESULTS: Forty-eight patients were included. Median age was 4.5 years [IQR 2-9.3]. Median length of stay (LOS) was 8 days [IQR 6-11]. No patients underwent primary VATS. Median days with a chest tube was 5 [IQR 5-6] and median number of doses of tPA was 3 [IQR 3-3]. Seven patients (14.6%) had a chest tube replaced without undergoing VATS. The VATS rate was 4.2% in the first half of this study but 0% in the last 33 months. CONCLUSION: Thoracoscopic decortication is rarely necessary in children with empyema. Raising the threshold for surgical intervention and utilizing further nonoperative measures can avoid an operation in most children without increasing in-hospital length of stay. LEVEL OF EVIDENCE: IV.

A Prospective, Randomized Cross-over Trial of 2 Low-profile Gastrostomy Buttons to Determine Family Preference.

Low-profile gastrostomy balloon buttons are often used in the pediatric population. We conducted a prospective, randomized crossover trial to determine family preference comparing MIC-KEY (tube A) and MiniONE (tube B) buttons. Patients were randomized to tube A and tube B at placement. At 2 months, patients were given the opposite button. At 4 months, parents indicated their preferred button. A standardized assessment tool was used to assess gastrostomy site skin complications and device malfunction. One hundred fifty-eight patients were randomized, 79 each to receive tube A or tube B first. Sixty-eight with tube A and 60 with tube B completed their first follow-up. Sixty-five with tube A and 43 with tube B completed crossover, 69% of whom preferred tube B (P < 0.001). Including those who preferred their first button and declined to switch at 2 months, 91 of 127 (72%) kept tube B, demonstrating a strong preference for tube B.

Self-reported Outcomes After Cholecystectomy for Pediatric Hyperkinetic Biliary Dyskinesia.

BACKGROUND: Biliary dyskinesia (BD) is a common indication for cholecystectomy in children. Current literature demonstrates an improvement in symptoms after cholecystectomy in most pediatric patients with an EF <35%; however, data supporting the efficacy of cholecystectomy for hyperkinetic BD (EF >65%) is sparse. We sought to determine whether children with hyperkinetic BD (HBD) had resolution of their symptoms after laparoscopic cholecystectomy at our institution. MATERIALS AND METHODS: We conducted a retrospective chart review of children who had undergone laparoscopic cholecystectomy for HBD at our institution between September 2010 and July 2015. Patients completed a phone survey about symptom resolution, whether they were happy to have undergone cholecystectomy, overall satisfaction on a 1-10 scale, and additional workup for those with ongoing pain. Analysis was performed using STATA statistical software with a P-value < 0.05 as statistically significant. RESULTS: Thirteen patients met inclusion criteria. Median gallbladder ejection fraction was 93% [IQR: 90, 97]. Median postoperative follow-up was 59 d [IQR: 25, 151] at which time 50% reported resolution of symptoms. Eight patients participated in the survey at a median follow-up of 45 mo [IQR: 40, 66]. Fifty percent reported ongoing abdominal pain. Frequency of pain varied among patients with pain, occurring from <1 time per week to a few times per day. Five patients (63%), including one patient with ongoing pain, were happy that their gallbladder had been removed and overall satisfaction rating was 5 on a scale of 1-10. CONCLUSIONS: Only half of children with HBD were asymptomatic at long-term follow-up. Cholecystectomy for HBD may or may not improve symptoms.

Postoperative pain control modalities for pectus excavatum repair: A prospective observational study of cryoablation compared to results of a randomized trial of epidural vs patient-controlled analgesia.

BACKGROUND: Pain following bar placement for pectus excavatum is the dominant factor post-operatively and determines length of stay (LOS). We recently adopted intercostal cryoablation as our preferred method of pain control following minimally invasive pectus excavatum repair. We compared the outcomes of cryoablation to results of a recently concluded trial of epidural (EPI) and patient-controlled analgesia (PCA) protocols. METHODS: We conducted a prospective observational study of patients undergoing bar placement for pectus excavatum using intercostal cryoablation. Results are reported and compared with those of a randomized trial comparing EPI with PCA. Comparisons of medians were performed using Kruskal-Wallis H tests with alpha 0.05. RESULTS: Thirty-five patients were treated with cryoablation compared to 32 epidural and 33 PCA patients from the trial. Cryoablation was associated with longer operating time (101 min, versus 58 and 57 min for epidural and PCA groups, p < 0.01), resulted in less time to pain control with oral medication (21 h, versus 72 and 67 h, p < 0.01), and decreased LOS (1 day, versus 4.3 and 4.2 days, p < 0.01). CONCLUSION: Intercostal cryoablation during minimally invasive pectus excavatum repair reduces LOS and perioperative opioid consumption compared with both EPI and PCA. LEVEL OF EVIDENCE: II.

Outcomes Following Dynamic Compression Bracing for Pectus Carinatum.

Introduction: Children with pectus carinatum (PC) are particularly vulnerable to psychosocial effects of poor body image, even though they may not experience physical symptoms. Nonoperative treatment with orthotic bracing is effective in PC correction. We describe our experience with dynamic compression bracing (DCB) for PC patients and their satisfaction with bracing. Materials and Methods: Prospective institutional data of patients undergoing DCB from July 2011 to June 2018 were reviewed and analyzed for those who entered the retainer mode after correction, defined by a correction pressure of <1 psi. A telephone survey was conducted regarding their bracing experience and satisfaction with the outcome on a scale of 1-10. Results: Of 460 PC patients, 144 reached the retainer mode. Median time to retainer mode was 5.5 months. There was no statistically significant relationship between initial correction pressure or carinatum height and time to retainer mode (P = .08 and P = .10, respectively). Fifty-seven percent were compliant with brace use, and median time to retainer mode in this subset was significantly shorter than noncompliant patients (3.5 months versus 10 months, P < .001). Fifty-three percent responded to the survey 13 months [interquartile ratios 3, 33] after the last clinic visit. The main barrier to compliance with wearing the brace was discomfort (37%), while the main motivation for compliance was appearance (58%). All endorsed bracing as worthwhile, with 94% reporting a satisfaction rating of 8 or greater for the correction outcome. Conclusion: DCB is effective in achieving correction of PC in compliant patients. Regardless of time to retainer mode, patients reported high satisfaction with bracing.

Safety of perioperative ketorolac administration in pediatric appendectomy.

BACKGROUND: Recent studies in adults undergoing gastrointestinal surgeries show an increased rate of complications with the use of ketorolac. This calls into question the safety of ketorolac in certain procedures. We sought to evaluate the impact of perioperative ketorolac administration on outcomes in pediatric appendectomy. METHODS: The Pediatric Health Information System database was queried for patients aged 5-17 y with a primary diagnosis of appendicitis and a primary procedure of appendectomy during the period 2010-2014. Patients with procedures suggesting incidental appendectomy, those records with data quality issues, deaths, and extracorporeal membrane oxygenation were excluded. Variables recorded included age, sex, race, ethnicity, discharge year, complex chronic conditions, geographic region, intensive care unit admission, mechanical ventilation, and whether appendicitis was coded as complicated. The exposure variable was ketorolac administration on the day of or day after operation. The primary outcomes of interest were any surgical complications during the initial encounter, postoperative length of stay (LOS), total cost for the initial visit, any readmission to ambulatory, observation, or inpatient status within 30 d, and readmission with a diagnosis of peritoneal abscess or other postoperative infection or with transabdominal drainage performed. RESULTS: A total of 78,926 patients were included in the analysis cohort. Mean age was 11.4 y (standard deviation 3.3 y), the majority were males (61%), White (70%), and non-Hispanic (65%). Few had a complex chronic condition (3%) or required mechanical ventilation (2%) or an intensive care unit admission (1%). Patients with complicated appendicitis comprised 28% of the cohort. Most (73%) received ketorolac on postoperative day 0-1; those with complicated appendicitis were more likely to receive ketorolac. In all, 2.6% of the cohort had a surgical complication during the index visit, 4.3% were readmitted within 30 d, and 2% had a postoperative infection or transabdominal drainage (1% in the uncomplicated group and 5% in the complicated group). Median postoperative LOS was 1 d and mean cost was $9811 ± $9509. On bivariate analysis, ketorolac administration was associated with a decrease in same-visit surgical complications (P = 0.004) and cost ($459 decrease, P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. On multivariate analysis, ketorolac administration was associated with a significant decrease in any complication (adjusted odds ratio 0.89, 95% confidence interval 0.80-0.99) and cost (analysis of variance P < 0.001) but was not associated with readmission, postoperative LOS, or postoperative infection. CONCLUSIONS: Based on a large, contemporary data set from children's hospitals, ketorolac administration in the immediate postoperative period after appendectomy for appendicitis is common and was not associated with an increase in postoperative LOS, postoperative infection, or any-cause 30-d readmission. Ketorolac was, however, independently associated with a lower overall rate of postoperative complications and cost in this population.

Intensive care unit admission predicts hospital readmission in pediatric trauma.

BACKGROUND: Hospital readmission in adult trauma is associated with significant morbidity, mortality, and resource utilization. In this study, we examine pediatric intensive care unit (PICU) admission as a risk factor for hospital readmission in pediatric trauma. MATERIALS AND METHODS: This was a retrospective cohort study of patients aged 1 through 19 y in the Pediatric Health Information System database discharged with a trauma diagnosis. Patient and clinical variables included demographics, payer status, length of stay, chronic comorbid conditions, presence of mechanical ventilation, all-patient refined diagnosis-related group and calculated severity of illness, and discharge disposition. The main outcome variable was hospital readmission within 30 d of discharge. Odds ratios (ORs) were calculated in both univariate and multivariate analyses with corresponding 95% confidence intervals (CIs). RESULTS: During the 5-year study period, 90,467 patients were admitted with a trauma diagnosis, of which 16,279 (18.0%) were admitted to the PICU. Hospital readmissions occurred in 3.1% of patients. On univariate analysis, patients admitted to the PICU on the first day of hospital admission (direct PICU admission), and those first admitted to the PICU after the day of hospital admission (delayed PICU admission), had 2-3 times the risk of hospital readmission compared with those never admitted to the PICU (4.8% versus 7.2% versus 2.7%, respectively, P < 0.001). On multivariate analysis, controlling for demographic and clinical variables, the adjusted ORs for hospital readmission in patients with direct and delayed PICU admission were 1.34 (95% CI 1.20-1.50) and 1.88 (95% CI 1.50-2.35) versus no PICU admission, respectively. CONCLUSIONS: PICU admission, either direct or delayed, during hospitalization for trauma care is an independent risk factor for hospital readmission within 30 d of discharge. Further risk stratification may help focus resources on high-risk patients to improve clinical outcomes and reduce readmissions.

Novel use of porcine urinary bladder matrix for pediatric pilonidal wound care: preliminary experience.

BACKGROUND: Extracellular matrix is used in various applications. We present our preliminary experience using a new device that consists of a porcine extracellular matrix with an epithelial basement membrane (MatriStem(®), ACell, Inc. Columbia, MD, USA) for adolescent pilonidal disease. METHODS: A retrospective review of four patients with pilonidal disease was undertaken. Three occurred in the gluteal cleft, and the fourth in the umbilicus. In the first patient, the wound deficit was filled with lyophilized MicroMatrix powder and a sheet of Multilayer Wound Matrix was placed to cover the wound. In the second patient, two sinus tracts were debrided, packed with MicroMatrix, and a sheet of fenestrated Burn Matrix was applied. In the third patient, MicroMatrix and Surgical Matrix PSMX (six-layer) was applied as a roll filling the dead space. In the last patient, an umbilical sinus 3 cm deep was packed with MicroMatrix powder followed by a rolled sheet of 2-ply Surgical Matrix RS. Patients were evaluated weekly post-operatively, and more MicroMatrix and sheet material was added if a wound deficit was still present. Measurements were taken in two dimensions, diameter and depth, to characterize wounds. RESULTS: Resolution of wound deficit was graphed versus time. Pain was assessed by scoring 0-10. Rapid wound closure was achieved. Two of the patients had failed wound healing with saline dressing changes prior to MatriStem application. These two patients in particular were highly satisfied with the comfort of the MatriStem approach relative to their time with saline dressings. Most had no pain after 1 week when bolster sutures were removed. CONCLUSION: In the treatment of open pilonidal wounds in adolescents, porcine urinary bladder matrix wound care devices offer closure times and cost similar to well-established methods while offering a substantial advantage in terms of patient comfort and convenience. This preliminary experience supports a prospective study.

Trends in treatment of infectious parapneumonic effusions in U.S. children's hospitals, 2004-2014.

PURPOSE: The purpose of this study was to examine trends in the treatment of patients with infectious parapneumonic effusions in U.S. children's hospitals over the past decade. METHODS: The PHIS database was queried for patients younger than 18years old with pneumonia and pleural effusion in three yearlong periods over the past decade. Variables included age, gender, payer, race/ethnicity, hospital region, hospital type, markers of illness severity, and treatment group (antibiotics alone, chest tube thoracostomy±thrombolytics, video-assisted thoracoscopy (VATS), or thoracotomy). RESULTS: 5569 patients were included in the final analysis. The proportion of patients treated with antibiotics alone increased from 62% to 74% from 2004 to 2014 (p<0.001). Among patients requiring pleural space drainage, the frequency of VATS peaked in 2009 (50.8%), dropping to 36.4% in 2014 (p<0.001), while tube thoracostomy, usually with fibrinolytics, rose from 39.0% in 2009 to 53.2% in 2014 (p<0.001). CONCLUSION: In a select cohort of free-standing, tertiary care U.S. children's hospitals, antibiotic administration alone remains the most common treatment approach to infectious parapneumonic effusions. VATS treatment for those patients requiring pleural space drainage is being gradually supplanted by thoracostomy tube placement with instillation of fibrinolytics.

Repair of esophageal atresia with proximal fistula using endoscopic magnetic compression anastomosis (magnamosis) after staged lengthening.

We describe the treatment of a patient with long-gap esophageal atresia with an upper pouch fistula, mircogastria and minimal distal esophageal remnant. After 4.5 months of feeding via gastrostomy, a proximal fistula was identified by bronchoscopy and a thoracoscopic modified Foker procedure was performed reducing the gap from approximately 7-5 cm over 2 weeks of traction. A second stage to ligate the fistula and suture approximate the proximal and distal esophagus resulted in a gap of 1.5 cm. IRB and FDA approval was then obtained for endoscopic placement of 10-French catheter mounted magnets in the proximal and distal pouches promoting a magnetic compression anastomosis (magnamosis). Magnetic coupling occurred at 4 days and after magnet removal at 13 days an esophagram demonstrated a 10 French channel without leak. Serial endoscopic balloon dilation has allowed drainage of swallowed secretions as the baby learns bottling behavior at home.

Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue.

BACKGROUND: Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue. METHODS: To evaluate this hypothesis, 16 obese individuals were studied before and 7-8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls. RESULTS: Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p < 0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis. CONCLUSIONS: These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB.

Effects on GLP-1, PYY, and leptin by direct stimulation of terminal ileum and cecum in humans: implications for ileal transposition.

BACKGROUND: We do not have a unified, scientifically tested theory of causation for obesity and its co-morbidities, nor do we have explanations for the mechanics of the metabolic/bariatric surgery procedures. Integral to proffered hypotheses are the actions of the hormones glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin. The objective of this study was to obtain blood levels of GLP-1, PYY, and leptin after stimulation of the terminal ileum and cecum by a static infusion of a food hydrolysate in morbidly obese patients undergoing a duodenal switch procedure. SETTING: University Hospital. METHODS: Plasma levels of GLP-1, PYY, and leptin were obtained at 0, 30, 60, 90, and 120 minutes after instillation of 240 mL of a food hydrolysate into the ileum or cecum. RESULTS: The mean±SD GLP-1 values by cecal stimulation for 0, 30, 60, 90, and 120 minutes were: 41.3±23.2; 39.6±21.8; 38.9±19.1; 47.4±22.3; 51.7±27.3 pM, and by ileal stimulation: 55.0±32.8; 83.4±16.1; 78.7±23.8; 84.7±23.5; 76.4±25.6. The mean±SD PYY values by cecal stimulation were: 62.1±24.8; 91.1±32.8; 102.1±39.6; 119.6±37.5; 130.3±36.7, and by ileal stimulation: 73.8±41.6; 138.1±17.7; 149.5±23.3; 165.7±24.3; 155.5±29.1. Percent change in PYY levels increased ~150%, GLP-1 increased ~50%, and leptin decreased ~20%. CONCLUSION: Direct stimulation of the human terminal ileum and cecum by a food hydrolysate elicits significant plasma GLP-1 and PYY elevations and leptin decreases, peaking at 90-120 minutes. The ileal GLP-1 and PYY responses exceed those of the cecum, and the PYY effect is about 3-fold that of GLP-1. The results of this study question the satiety premise for ileal transposition.

NGF induces the expression of group IIA secretory phospholipase A2 in PC12 cells: the newly synthesized enzyme is addressed to growing neurites.

We proposed that group IIA secretory phospholipase A(2) (GIIA) participates in neuritogenesis based on our observations that the enzyme migrates to growth cones and neurite tips when PC12 cells are induced to differentiate by nerve growth factor (NGF) (Ferrini et al., Neurochem Res 35:2168-2174, 2010). The involvement of other secretory PLA(2) isoforms in neuronal development has been suggested by others but through different mechanisms. In the present study, we compared the subcellular distribution of GIIA and group X sPLA(2) (GX) after stimulation of PC12 cells with NGF. We found that GIIA, but not GX, localized at the neuritic tips after treatment with NGF, as demonstrated by immunofluorescence analysis. We also found that NGF stimulated the expression and the activity of GIIA. In addition, NGF induced the expressed myc-tagged GIIA protein to migrate to neurite tips in its active form. We propose that GIIA expression, activity, and subcellular localization is regulated by NGF and that the enzyme may participate in neuritogenesis through intracellular mechanisms, most likely by facilitating the remodelling of glycerophospholipid molecular species by deacylation-reacylation reactions necessary for the incorporation of polyunsaturated fatty acids.