Tory A. Meyer

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.

Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid concentrations and concentrations in urine of 3-methylhistidine (3-MH), creatinine, and cortisol were measured at the time of surgery to assess the catabolic state of the patients. A three- to fourfold increase in mRNA levels for ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased by approximately 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in urine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that sepsis is associated with increased mRNAs of the ubiquitin-proteasome pathway in human skeletal muscle.

Endotoxemia in mice stimulates production of complement C3 and serum amyloid A in mucosa of small intestine

We examined the effect of endotoxemia in mice on protein and mRNA levels for the acute phase proteins complement C3 and serum amyloid A (SAA) in jejunal mucosa. Endotoxemia was induced in mice by the subcutaneous injection of 250 μg lipopolysaccharide per mouse. Control mice were injected with saline. C3 and SAA were measured by ELISA. Messenger RNA levels were determined by Northern blot analysis or competitive PCR. Immunohistochemistry was performed to determine in which cell type(s) C3 and SAA were present. Mucosal C3 and SAA protein and mRNA levels were increased in endotoxemic mice. Immunohistochemistry showed that C3 was present in both enterocytes and cells of the lamina propria, whereas SAA was seen mainly in lamina propria cells. Results suggest that endotoxemia stimulates production of C3 and SAA in small intestinal mucosa. The response may be regulated at the transcriptional level and probably reflects increased synthesis of the acute phase proteins in both enterocytes and cells of the lamina propria.We examined the effect of endotoxemia in mice on protein and mRNA levels for the acute phase proteins complement C3 and serum amyloid A (SAA) in jejunal mucosa. Endotoxemia was induced in mice by the subcutaneous injection of 250 microg lipopolysaccharide per mouse. Control mice were injected with saline. C3 and SAA were measured by ELISA. Messenger RNA levels were determined by Northern blot analysis or competitive PCR. Immunohistochemistry was performed to determine in which cell type(s) C3 and SAA were present. Mucosal C3 and SAA protein and mRNA levels were increased in endotoxemic mice. Immunohistochemistry showed that C3 was present in both enterocytes and cells of the lamina propria, whereas SAA was seen mainly in lamina propria cells. Results suggest that endotoxemia stimulates production of C3 and SAA in small intestinal mucosa. The response may be regulated at the transcriptional level and probably reflects increased synthesis of the acute phase proteins in both enterocytes and cells of the lamina propria.

Extracorporeal life support for the treatment of viral pneumonia: Collective experience from the ELSO registry

Abstract Viral pneumonia is the most common indication for pediatric extracorporeal life support (ECLS). Despite this fact, no previous studies have directly stratified patient outcome according to vival etiology. Methods: Using the Extracorporeal Life Support Organization (ELSO) registry database, the authors reviewed the national experience of patients undergoing ECLS with culture or serologically demonstrated viral pneumonia and compared outcome parameters according to viral etiology. Results: Patients differed with respect to age and weight according to the viral type. Patients with respiratory syncytial virus (RSV, median age 3 months), herpes simplex virus (HSV, 0.13 months), cytomegalovirus (CMV, 2.5 months), and adenovirus (0.6 months) were younger than those with other viruses (5.5 months). The patient groups did not significantly differ with respect to pre-ECLS Pao 2 mean airway pressure (MAP), oxygenation index (OI), mode, or duration of ECLS. The overall survival of patients with viral pneumonia was 57%, although patients with RSV or CMV were found to have a 67% survival. Patients infected with HSV and adenovirus had a significantly lower survival rate (31% and 25%, respectively) when compared with those with RSV. In addition RSV pneumonia was associated with fewer cardiovascular complications than several of the other viral types. When comparison was made between survivors and nonsurvivors, a higher last pre-ECLS MAP and increased incidence of elevated creatinine and renal failure requiring dialysis were noted among nonsurvivors. Conclusion: ECLS remains an important modality in the treatment of neonatal and pediatric patients with respiratory failure secondary to viral pneumonia. The survival rate of these patients varies according to the type of viral infection.

Usefulness of surveillance cultures in neonatal extracorporeal membrane oxygenation

Sepsis is difficult to identify in patients treated with extracorporeal membrane oxygenation (ECMO). This study evaluates the usefulness of surveillance cultures obtained during ECMO. We retrospectively reviewed the records of 187 patients from four ECMO centers with birth weights 1,574 to 4,900 gm and gestational ages 33–43 weeks, over a 4 year interval. Most patients had surveillance blood cultures daily, and tracheal aspirates and urine culture every other day. Charts were reviewed for culture results before, during, and for the 7 days after ECMO, and clinical response to the culture results. A total of 2,423 cultures were obtained during 1,487 days of ECMO, of which 155 were positive (6.4%): 13 of 1,370 blood cultures (0.9%), 137 of 850 tracheal aspirate cultures (16%), and 5 of 203 urine cultures (2.3%). After 72 hours, tracheal aspirate cultures became positive with nosocomial organisms in 33 of 131 patients. None of 153 bacterial urine cultures were positive, and only one of 34 viral urine cultures were positive (CMV). We conclude that routine daily blood cultures are not useful in neonatal ECMO. Tracheal aspirate cultures may be helpful in the management of antibiotic therapy in patients on ECMO for more than 5 days. Routine bacterial urine cultures did not provide useful information.

Utility of daily head ultrasonography for infants on extracorporeal membrane oxygenation

BACKGROUND/PURPOSE Intracranial hemorrhage (ICH) is a major concern during extracorporeal membrane oxygenation (ECMO). Daily cranial ultrasonography has been used by many ECMO centers as a diagnostic tool for both detecting and following ICH while infants are on bypass. The purpose of this patient review was to look at the usefulness of performing daily cranial ultrasonography (HUS) in infants on ECMO in detecting intraventricular hemorrhage of a magnitude sufficient to alter patient treatment. METHODS The authors reviewed retrospectively all of the records of all neonates treated with ECMO at the Hermann Childrens Hospital, Wilford Hall USAF Medical Center, Cincinnati Childrens Hospital, The University of Texas Medical Branch at Galveston, and Texas Childrens Hospital between February 1986 to March 1995. Two hundred ninety-eight patients were placed on ECMO during this period. All patients had HUS before, and daily while on ECMO, and all were reviewed by the staff radiologists. A total of 2,518 HUS examinations were performed. RESULTS Fifty-two of 298 patients (17.5%) had an intraventricular hemorrhage seen on ultrasound scan. Nine of 52 patients (17.3%) had an ICH seen on the initial HUS examination before ECMO, all of which were grade I, and 43 of 52 patients (82.7%) had ICH while on ECMO. Of these ICH, 15 were grade I, 10 were grade II, 10 were grade III, and eight were grade IV. Forty of these ICH (93%) were diagnosed by HUS during the first 5 days of the ECMO course. Seven hundred eighty-six HUS were performed after day 5, at an estimated cost of

Sepsis increases putrescine concentration and protein synthesis in mucosa of small intestine in rats.

300,000 to

Duodenal transection in child abuse.

450,000 (charges), demonstrating three new intraventricular hemorrhages, one grade I, and one grade IV on day 7 and one grade I on day 8. Eight patients were taken off ECMO because of ICH diagnosed within the first 5 days. One patient was taken off ECMO because of ICH diagnosed after 5 days. This patient had clinical symptoms suggestive of ICH. CONCLUSIONS Almost all ICH occur during the first 5 days of an ECMO course. Unless there is a clinical suspicion, it is not cost effective to perform HUS after the fifth day on ECMO, because subsequent HUS examinations are unlikely to yield information significant enough to alter management.

Decreasing Exposure to Radiation, Surgical Risk, and Costs for Pediatric Complicated Pneumonia: A Guideline Evaluation

Recent studies suggest that sepsis stimulates mucosal polyamine and protein synthesis. It is not known in which cell type polyamine biosynthesis is increased during sepsis and if polyamines regulate mucosal protein synthesis. We examined the effect of sepsis in rats on polyamine biosynthesis in isolated jejunal enterocytes and measured mucosal protein synthesis following inhibition of ornithine decarboxylase (ODC) activity with difluoromethylornithine. ODC and S-adenosylmethionine decarboxylase (SAMDC) activities and putrescine concentrations were increased in isolated jejunal enterocytes 16 h after induction of sepsis by cecal ligation and puncture. Enterocyte spermidine and spermine levels were not influenced by sepsis. Mucosal ODC and SAMDC activities and polyamine levels were increased following treatment of rats with interleukin-1 but not tumor necrosis factor. Treatment of rats with difluoromethylornithine prevented the sepsis-induced increase in mucosal ODC activity, putrescine concentration, and protein synthesis rate. The results suggest that sepsis increases ODC and SAMDC activities and putrescine concentrations in enterocytes of the small intestine. This metabolic response to sepsis may be regulated by interleukin-1 although other mechanisms may also be involved. Increased mucosal protein synthesis during sepsis may at least in part be regulated by increased putrescine levels.

Endotoxin Stimulates Interleukin-6 Production in Intestinal Epithelial Cells: A Synergistic Effect With Prostaglandin E2

A n estimated 702 000 children were victims of maltreatment in the United States in 2009, with 17.8% being subject to physical abuse. This estimate translates to a rate of 9.3 maltreated children per 1000 in the population. Three-quarters of the victims had no history of prior victimization. The youngest children had the highest victimization rate, with 20.6 per 1000 children from birth to 1 year. Given that the rate of abuse in infants is double that of older children, one must be suspicious when an infant is diagnosed with a small intestine injury, especially with a duodenal transection. One percent of nonaccidental trauma in children involves intra-abdominal injury. The number of children affected may seem low; however, this injury is associated with signifi cant morbidity and mortality. With a 50% mortality rate, abdominal trauma is the second most common injury associated with fatal child abuse. Therefore, rapid assessment, diagnosis, and treatment are imperative in decreasing the morbidity and mortality of these children.

Protein synthesis in isolated enterocytes from septic or endotoxaemic rats: regulation by glutamine.

OBJECTIVES This report describes the creation and successful implementation of a complicated pneumonia care algorithm at our institution. Outcomes are measured for specific goals of the algorithm: to decrease radiation exposure, surgical risk, and patient charges without adversely affecting clinical outcomes. METHODS We describe steps involved in algorithm creation and implementation at our institution. To depict outcomes of the algorithm, we completed a retrospective cohort study of hospitalized pediatric patients with a diagnosis of complicated pneumonia at a single institution between January 2010 and April 2016 who met criteria for the algorithm. Charts were manually reviewed and data were analyzed via Wilcoxon rank sum, χ2, and Fishers exact tests. RESULTS Throughout the algorithm creation process, our institution began to see a change in practice. We saw a statistically significant decrease in the number of patients who underwent a chest computed tomography scan and an increase in patients who underwent a chest ultrasound (P < .001). We also saw an increase in the use of chest tube placement with fibrinolytics and a decrease in the use of video-assisted thoracoscopic surgery as the initial chest procedure (P ≤ .001) after algorithm implementation. These interventions reduced related charges without significantly affecting length of stay, readmission rate, or other variables studied. CONCLUSIONS The collaborative creation and introduction of an algorithm for the management of complicated pneumonia at our institution, combined with an effort among physicians to incorporate evidence-based clinical care into practice, led to reduced radiation exposure, surgical risk, and cost to patient.