Guidelines for the management of postoperative soiling in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately achieve functional and comfortable stooling, some will experience a variety of problems after pull-through surgery. The most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative soiling in children with Hirschsprung disease. The American Pediatric Surgical Association Hirschsprung Disease Interest Group engaged in a literature review and group discussions. Expert consensus was then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with soiling symptoms following pull-through for Hirschsprung disease. Causes of soiling after pull-through are broadly categorized as abnormalities in sensation, abnormalities in sphincter control, and "pseudo-incontinence." A stepwise algorithm for the diagnosis and management of soiling after a pull-through for Hirschsprung disease is presented; it is our hope that this rational approach will facilitate treatment and optimize outcomes.

Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately do well, many experience a variety of ongoing problems after pull-through surgery. The most common include obstructive symptoms, soiling, enterocolitis and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative obstructive symptoms in children with Hirschsprung disease. The American Pediatric Surgical Association Board of Governors established a Hirschsprung Disease Interest Group. Group discussions, literature review and expert consensus were then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with obstructive symptoms following pull-through for Hirschsprung disease. Causes of obstructive symptoms post-pull-through include mechanical obstruction; persistent or acquired aganglionosis, hypoganglionosis, or transition zone pull-through; internal sphincter achalasia; disordered motility in the proximal intestine that contains ganglion cells; or functional megacolon caused by stool-holding behavior. An algorithm for the diagnosis and management of obstructive symptoms after a pull-through for Hirschsprung disease is presented. A stepwise, logical approach to the diagnosis and management of patients experiencing obstructive symptoms following pull-through for Hirschsprung disease can facilitate treatment. Level of evidence V.

Non-operative treatment versus percutaneous drainage of pancreatic pseudocysts in children.

PURPOSE: The objective of this study was to characterize the clinical course and outcomes of children with pancreatic pseudocysts that were initially treated non-operatively or with percutaneous drainage. METHODS: A retrospective review of children with pancreatic pseudocysts over a 12-year period was completed. Categorical variables were compared using Fischer's exact method and the Student's t test was used to compare continuous variables. Analysis was done using logistic and linear regression models. RESULTS: Thirty-six children met the criteria for pancreatic pseudocyst and 33 children were treated either non-operatively or with percutaneous drainage. Of the 22 children managed non-operatively, 17 required no additional intervention (77 %) and five required surgery. Operative procedures were: Frey procedure (3), distal pancreatectomy (1), and cystgastrostomy (1). Eight of the 11 children treated with initial percutaneous drainage required no additional treatment (72 %). The other three children underwent distal pancreatectomy. Success of non-operative management or percutaneous drainage was not dependent on size or complexity of the pseudocyst Logistic regression did not identify any patient demographic (gender, age, and weight), etiologic (trauma, non-traumatic pancreatitis) or pseudocyst characteristic (size, septations) that predicted failure of non-operative therapy. CONCLUSIONS: In children, pancreatic pseudocysts can frequently be managed without surgery regardless of size or complexity of the pseudocyst. When an intervention is needed, percutaneous drainage can be performed successfully, avoiding the need for major surgical intervention in the majority of patients.

A community challenge to evaluate RNA-seq, fusion detection, and isoform quantification methods for cancer discovery.

The accurate identification and quantitation of RNA isoforms present in the cancer transcriptome is key for analyses ranging from the inference of the impacts of somatic variants to pathway analysis to biomarker development and subtype discovery. The ICGC-TCGA DREAM Somatic Mutation Calling in RNA (SMC-RNA) challenge was a crowd-sourced effort to benchmark methods for RNA isoform quantification and fusion detection from bulk cancer RNA sequencing (RNA-seq) data. It concluded in 2018 with a comparison of 77 fusion detection entries and 65 isoform quantification entries on 51 synthetic tumors and 32 cell lines with spiked-in fusion constructs. We report the entries used to build this benchmark, the leaderboard results, and the experimental features associated with the accurate prediction of RNA species. This challenge required submissions to be in the form of containerized workflows, meaning each of the entries described is easily reusable through CWL and Docker containers at https://github.com/SMC-RNA-challenge. A record of this paper's transparent peer review process is included in the supplemental information.

A population-based comparison of joint survival of hemiarthroplasty versus total shoulder arthroplasty in osteoarthritis and rheumatoid arthritis.

AIMS: Few studies have compared survivorship of total shoulder arthroplasty (TSA) with hemiarthroplasty (HA). This observational study compared survivorship of TSA with HA while controlling for important covariables and accounting for death as a competing risk. PATIENTS AND METHODS: All patients who underwent shoulder arthroplasty in Ontario, Canada between April 2002 and March 2012 were identified using population-based health administrative data. We used the Fine-Gray sub-distribution hazard model to measure the association of arthroplasty type with time to revision surgery (accounting for death as a competing risk) controlling for age, gender, Charlson Comorbidity Index, income quintile, diagnosis, and surgeon factors. RESULTS: During the study period, 5777 patients underwent shoulder arthroplasty (4079 TSA, 70.6%; 1698 HA, 29.4%), 321 (5.6%) underwent revision, and 1090 (18.9%) died. TSA patients were older (TSA mean age 68.4 years (sd 10.2) vs HA mean age 66.5 years (sd 12.7); p = 0.001). The proportion of female patients was slightly lower in the TSA group (58.0% vs 58.4%). The adjusted association between surgery type and time to shoulder revision interacted significantly with patient age. Compared with TSA patients, revision was more common in the HA group (adjusted-health ratio (HR) 1.214, 95% confidence interval (CI) 0.96 to 1.53) but this did not reach statistical significance. CONCLUSION: Although there was a trend towards higher revision risk in patients undergoing HA, we found no statistically significant difference in survivorship between patients undergoing TSA or HA. Cite this article: Bone Joint J 2019;101-B:454-460.

Increased Functional Connectivity After Listening to Favored Music in Adults With Alzheimer Dementia.

BACKGROUND: Personalized music programs have been proposed as an adjunct therapy for patients with Alzheimer disease related dementia, and multicenter trials have now demonstrated improvements in agitation, anxiety, and behavioral symptoms. Underlying neurophysiological mechanisms for these effects remain unclear. METHODS: We examined 17 individuals with a clinical diagnosis of Alzheimer disease related dementia using functional MRI following a training period in a personalized music listening program. RESULTS: We find that participants listening to preferred music show specific activation of the supplementary motor area, a region that has been associated with memory for familiar music that is typically spared in early Alzheimer disease. We also find widespread increases in functional connectivity in corticocortical and corticocerebellar networks following presentation of preferred musical stimuli, suggesting a transient effect on brain function. CONCLUSIONS: Findings support a mechanism whereby attentional network activation in the brain's salience network may lead to improvements in brain network synchronization.

Removing bacteria from hospital surfaces: a laboratory comparison of ultramicrofibre and standard cloths.

We compared the ability of ultramicrofibre-woven cloths with conventional cloths moistened with water only, for their ability to remove several types of organisms relevant to hospital-acquired infections from a variety of surfaces in hospitals. We showed that ultramicrofibre cloths consistently outperformed conventional cloths in their decontamination ability, across all surfaces, and irrespective of whether the bacteria were coated on to the surfaces with phosphate-buffered saline (PBS) or PBS containing horse serum to simulate real-life soiling. The ability of the cloths to remove bacteria from surfaces was assessed by contact plating and colony formation, and by swabbing and measurement of ATP bioluminescence. The results suggest potential for use of ultramicrofibre in healthcare environments. Further studies are required, however, to define accurately how these cloths, which are designed to be used without detergent or biocides, might be capable of safe and effective deployment and recycling in the healthcare environment.

Role of TFIIIA zinc fingers in vivo: analysis of single-finger function in developing Xenopus embryos.

The Xenopus 5S RNA gene-specific transcription factor IIIA (TFIIIA) has nine consecutive Cys2His2 zinc finger motifs. Studies were conducted in vivo to determine the contribution of each of the nine zinc fingers to the activity of TFIIIA in living cells. Nine separate TFIIIA mutants were expressed in Xenopus embryos following microinjection of their respective in vitro-derived mRNAs. Each mutant contained a single histidine-to-asparagine substitution in the third zinc ligand position of an individual zinc finger. These mutations result in structural disruption of the mutated finger with little or no effect on the other fingers. The activity of mutant proteins in vivo was assessed by measuring transcriptional activation of the endogenous 5S RNA genes. Mutants containing a substitution in zinc finger 1, 2, or 3 activate 5S RNA genes at a level which is reduced relative to that in embryos injected with the message for wild-type TFIIIA. Proteins with a histidine-to-asparagine substitution in zinc finger 5 or 7 activate 5S RNA genes at a level that is roughly equivalent to that of the wild-type protein. Zinc fingers 8 and 9 appear to be critical for the normal function of TFIIIA, since mutations in these fingers result in little or no activation of the endogenous 5S RNA genes. Surprisingly, proteins with a mutation in zinc finger 4 or 6 stimulate 5S RNA transcription at a level that is significantly higher than that mediated by similar concentrations of wild-type TFIIIA. Differences in the amount of newly synthesized 5S RNA in embryos containing the various mutant forms of TFIIIA result from differences in the relative number and/or activity of transcription complexes assembled on the endogenous 5S RNA genes and, in the case of the finger 4 and finger 6 mutants, result from increased transcriptional activation of the normally inactive oocyte-type 5S RNA genes. The remarkably high activity of the finger 6 mutant can be reproduced in vitro when transcription is carried out in the presence of 5S RNA. Disruption of zinc finger 6 results in a form of TFIIIA that exhibits reduced susceptibility to feedback inhibition by 5S RNA and therefore increases the availability of the transcription factor for transcription complex formation.

Lessons learned from laparoscopic treatment of gastric and gastroesophageal junction stromal cell tumors.

BACKGROUND: Stromal cell tumors of the gastric and gastroesophageal junction are rare neoplasms that traditionally have been resected for negative margins using an open approach. This study aimed to evaluate the efficacy laparoscopic resection of gastric and gastroesophageal stromal cell tumors and the lessons learned from experience with this method. METHODS: This retrospective review evaluated all patients who underwent laparoscopic resection of gastric or esophageal stromal cell tumors at a tertiary referral center between December 2002 and March 2005. Medical records were reviewed with regard to patient demographics, preoperative evaluation, operative approach, tumor location and pathology, length of operation, complications, and length of hospital stay. RESULTS: A total of 12 consecutive patients with a mean age of 55 +/- 5.9 years were treated. Preoperative endoscopic ultrasound (EUS) was performed for 11 of 12 patients with a diagnostic accuracy of 100%, whereas EUS-guided fine-needle aspiration was performed for 10 of 12 patients with a diagnostic accuracy of 50%. Four patients with symptomatic gastroesophageal junction leiomyomas were treated with enucleation and Nissen fundoplication. Eight patients were treated with laparoscopic wedge resection of gastric lesions. Complete R0 resection was achieved for all the patients undergoing laparoscopic resection. Intraoperative endoscopy was performed for four patients and resulted in shorter operative times. The average operative time for this entire series was 169 +/- 17 min: 199 +/- 24 min for the first six cases and 138 +/- 19 min for the last six cases. The median hospital length of stay was 2 days. One patient with esophageal leiomyoma had persistent dysphagia at the 12-month follow-up assessment. There were no other complications and no deaths in this series of patients. CONCLUSIONS: Laparoscopic resection of gastric and gastroesophageal junction stromal cell tumors may be performed safely with low patient morbidity. This approach can achieve adequate surgical margins and lead to short hospital stays. Improvements in the technique have led to shorter operative times.

Wound oxygen levels during hyperbaric oxygen treatment in healing wounds.

Hyperbaric oxygen (HBO2) increases wound oxygen delivery, but few data quantify wound oxygen levels over the course of healing. We characterized these changes during and after HBO2 treatment in a rat wound model. The treatment group (n=7) received 2.0 ATA HBO2, 90 minutes BID for 15 days. Control rats (n=5) were only exposed to HBO2 during measurement. On days 5, 10, and 15, wound pO2 was measured before, during, and for an hour after HBO2 treatment. Both the peak pO2 and the pO2 one hour after HBO2 treatment were significantly greater than baseline on all days in both the treatment (p < .01) and control group (p < .05). The peak pO2 during HBO2 exposure and one hour after decreased significantly in the treatment group on day 15 compared to day 5 (p <.01, p <.05 respectively). No significant differences were found in pO2 values between days within the control group. These results demonstrate that both the peak wound oxygen levels and duration of elevation change significantly throughout the course of HBO2 treatment.

Oxidation of 5,8,11,14,17-eicosapentaenoic acid by hepatic and renal microsomes.

Liver and kidney microsomes were isolated from rats raised on high-fat diets. In terms of energy, the high-fat diets contained 4% vegetable and 40% fish, vegetable or coconut oils. Each microsomal preparation was fortified with 1 mM NADPH and incubated with 5,8,11,14,17-eicosapentaenoic acid (20:5(n-3]. The number of metabolites formed was assessed by reverse-phase high-performance liquid chromatography (HPLC). To identify the major metabolites, large-scale incubations were done with 20:5(n-3) and microsomes from phenobarbital-treated rats. After extracts from the phenobarbital and dietary studies were combined, individual products were isolated by reverse- and normal-phase HPLC. The metabolites were identified by mass spectrometry, by chromatographic properties, and by comparing their retention times and mass spectra with those of chemically synthesized standards. For liver microsomes, the major metabolites were: 17,18-, 14,15-, 11,12- and 8,9-dihydroxyeicosatetraenoic acids, 20-hydroxyeicosapentaenoic acid, and 19-hydroxyeicosatetraenoic acid. For renal microsomes, the major metabolites were 20-hydroxyeicosapentaenoic and 19-hydroxypentaenoic acids. Because formation of these metabolites required NADPH and was enhanced by phenobarbital pretreatment, 20:5(n-3) appears to be oxidized by cytochrome P-450 monooxygenases. Based on reverse-phase high performance liquid chromatograms, all three high-fat diets may produce the same types of monooxygenase metabolites from 20:5(n-3). It remains unknown whether fish-oil diets induce the synthesis of monooxygenases to oxidize n-3 fatty acids, because these preliminary studies involved only two animals per dietary group.

Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody.

Patients were entered into a randomized trial of prophylaxis for renal allograft rejection by the administration of an anti-human IL-2 receptor antibody, anti-Tac, during the first ten days posttransplant. Interleukin-2 receptor (IL-2 R) expression was measured using two anti-IL-2 R monoclonal antibodies (moAbs), anti-Tac and 1HT4-4H3. These two antibodies recognize closely spaced epitopes on the 55 kD chain of the IL-2 R. IL-2 R expression was examined on peripheral blood small lymphocytes in three groups of patients who received: (A) cyclosporine CsA and prednisone for baseline immunosuppression (n = 9); (B) anti-Tac with CsA and prednisone as baseline immunosuppression (n = 12); and (C) anti-Tac with azathioprine and prednisone as baseline immunosuppression (n = 5). We found that large numbers of T cells express IL-2 receptors despite the presence of anti-Tac (average of IL-2 R-positive cells at day of peak IL-2 R expression 56.0 +/- 20.8% in group A, 65.2 +/- 26.6% in group B, 21.0 +/- 7.4% in group C). IL-2 R expression did not correlate with clinical activity, and the presence or accessibility of epitopes on the same 55 kD chain varied dramatically from patient to patient.

Comparison of stress digital ventriculography, stress thallium scintigraphy, and digital fluoroscopy in the diagnosis of coronary artery disease in subjects without prior myocardial infarction.

Exercise thallium scintigraphy is often used for the diagnosis of coronary artery disease (CAD). Exercise digital subtraction ventriculography and digital subtraction fluoroscopy are new diagnostic procedures with roles that have not been determined. To compare the relative accuracies of the digital techniques with thallium scintigraphy, 97 consecutive patients without myocardial infarction underwent all 3 tests on the day before their scheduled coronary angiograms. Forty-two patients had CAD (more than 50% diameter narrowing of 1 major artery). A fixed or reversible perfusion defect defined an abnormal thallium test response and a segmental wall motion abnormality at rest or with exercise defined an abnormal digital ventriculographic response. Any visualized coronary calcific deposit defined an abnormal digital fluorographic response. The sensitivities of digital fluoroscopy (86%) and digital ventriculography (79%) were significantly higher than the sensitivity of thallium (62%) (p less than 0.05). The specificity of thallium (82%) was not significantly higher than that of either digital ventriculography (72%) or fluoroscopy (67%). The diagnostic accuracies of digital fluoroscopy, digital ventriculography, and thallium were 75%, 75% and 73%, respectively. A logistic regression model showed that thallium and digital fluoroscopy were more accurate in younger patients, whereas digital ventriculography was more sensitive in hypertensive persons and in those not taking beta-blocking drugs. The choice of test depends on disease prevalence, clinical variables (such as age and hypertension) and the importance of functional information obtained from stress testing.

Effect of hyperoxia on vascular endothelial growth factor levels in a wound model.

HYPOTHESIS: Hyperbaric oxygen (HBO) therapy increases vascular endothelial growth factor (VEGF) levels in wounds. DESIGN: Wounds were monitored for oxygen delivery during HBO treatment, and wound fluids were analyzed for VEGF and lactate on days 2, 5, and 10 following wounding. SETTING: Experimental animal model. INTERVENTIONS: Rats were randomized to HBO therapy and control groups. The HBO therapy was administered for 90 minutes, twice daily with 100% oxygen at 2.1 atmospheres absolute. Treatment was administered for 7 days following wounding. MAIN OUTCOME MEASURES: Vascular endothelial growth factor, PO(2), and lactate levels in wound fluid were measured on days 2, 5, and 10. RESULTS: Wound oxygen rises with HBO from nearly 0 mm Hg to as high as 600 mm Hg. The peak level occurs at the end of the 90-minute treatment, and hyperoxia of lessening degree persists for approximately 1 hour. The VEGF levels significantly increase with HBO by approximately 40% 5 days following wounding and decrease to control levels 3 days after exposures are stopped. Wound lactate levels remain unchanged with HBO treatment (range, 2.0-10.5 mmol/L). CONCLUSIONS: Increased VEGF production seems to explain in part the angiogenic action of HBO. This supports other data that hypoxia is not necessarily a requirement for wound VEGF production.

Laparoscopy for appendicitis and cholelithiasis during pregnancy: a new standard of care.

BACKGROUND: Subsequent to a report from the authors' institution, the laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy has become the standard of care at LDS Hospital using institutional guidelines. For comparison with previous outcomes described by the authors, 59 additional laparoscopic cases are reported. METHODS: Medical records of all pregnant patients at LDS Hospital who underwent open or laparoscopic cholecystectomy or appendectomy between 1998 and 2002 were reviewed. The outcomes were compared with the authors' previous data. RESULTS: The laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy increased from 54% to 97%. No significant differences in preterm delivery rates, birth weights, or 5-min Apgar scores were found between the two periods. No birth defects or uterine injuries occurred. CONCLUSIONS: With the use of the authors' guidelines, laparoscopy has become the standard of care for managing symptomatic cholelithiasis and appendicitis during pregnancy at LDS Hospital without significant increase in morbidity or mortality.

Prospective comparison of exercise digital subtraction and exercise first pass radionuclide ventriculography.

In order to test the comparative sensitivities of first-pass radionuclide and digital subtraction ventriculography in detecting wall motion abnormalities during exercise, 29 patients referred for coronary angiography were submitted to both types of stress ventriculograms. Resting and exercise ventriculograms by both techniques were reviewed by independent observers and the five equal ventricular wall segments were graded as normal, mildly, moderately, severely hypokinetic, akinetic, or dyskinetic. Of the 29 patients, 24 had arteriographically defined ischemic potential (at least greater than 50% obstruction of a major coronary artery supplying viable myocardium). Exercise digital subtraction ventriculography correctly identified 17 (71%) of these by a worsening of wall motion during exercise, while radionuclide ventriculography identified only eight (33%) by the wall motion response. When either a worsening of wall motion or the failure to increase ejection fraction by at least 5 points were used as criteria for an abnormal test, the sensitivities of digital and radionuclide ventriculographies were 96% and 79%, respectively. Though the number of patients without ischemic potential (5 patients) was too small to judge the relative specificities, digital subtraction ventriculography appears to be more sensitive than radionuclide ventriculography in identifying exercise-induced wall motion abnormalities and in predicting coronary occlusions.

Oxygen derepresses deacetoxycephalosporin C synthase and increases the conversion of penicillin N to cephamycin C in Streptomyces clavuligerus.

When dissolved oxygen (DO) was maintained at saturation level during batch fermentations of Streptomyces clavuligerus (NRRL 3585), the accumulation of the intermediate penicillin N was lowered while formation of the end product cephamycin C was increased relative to fermentations without DO control. The specific activity of the penicillin ring-expansion enzyme deacetoxycephalosporin C synthase (DAOCS) was increased 2.3-fold under oxygen saturated conditions, whereas the penicillin ring-cyclizing enzyme isopenicillin N synthase (IPNS) showed only a 1.3-fold increase. Thus oxygen derepression of DAOCS appears to be an important regulatory mechanism in the conversion of penicillin N to cephamycin C in S. clavuligerus. IPNS, an early acting enzyme in cephamycin C biosynthesis, and DAOCS, which acts late in the pathway, both disappeared from cell extracts at 60 h, just prior to cessation of cephamycin production.

Transabdominal oxygenation using perfluorocarbons.

PURPOSE: Evaluation of the intraabdominal (intraperitoneal and intraluminal) administration of oxygen-saturated perfluorocarbon on both portal and arterial blood oxygenation. METHODS: Eight male rabbits were divided into the test (n = 5) and control (n = 3) groups. Each underwent intrajejunal, intraperitoneal, and intravascular (artery, portal vein) catheter placements along with ligation of the duodenum and the terminal ileum under general anesthesia. The test group received oxygen-saturated perfluorotripropylamine (FTPA), and the control group received oxygen desaturated FTPA. The oxygen delivery was assessed by serial blood gas measurements before and after the administration of FTPA. RESULTS: The administration of oxygen-saturated FTPA significantly increased the partial pressure of oxygen within both the arterial and the portal venous blood (PaO2, PpVO2) without significant changes in PCO2 values. Oxygen desaturated FTPA failed to show any effects on blood gas values. Compared with oxygen desaturated FTPA, oxygen-saturated FTPA increased PaO2, PpVO2, and oxygen saturation (artery, portal vein) significantly at some, but not all of the time-points measured. CONCLUSIONS: The intraabdominal administration of saturated FTPA improved both the portal venous and the arterial oxygenation. This new mode of oxygenation may be helpful as an adjunct to conventional oxygen delivery systems.

Characterization of antigens from mycoplasmas of animal origin.

Alcholeplasma laidlawii, Mycoplasma gallisepticum, M mycoides subsp mycoides, M agalactiae, M bovirhinis, mycoplasmal strain ST-6, and culture medium were compared with M bovis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay (ELISA), and gel electrophoresis-derived ELISA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated there were areas of homology and areas of heterology among the species tested. Sera from rabbits hyperimmunized with the mycoplasma organisms and noninoculated culture medium demonstrated ELISA reactivity with M bovis antigens immobilized on polystyrene. Absorption of the serum from a rabbit hyperimmunized with M bovis reduced 65.9% of its reactivity with culture medium, 29.7% to 32.7% of its reactivity with the heterologous species, and 21.1% of its reactivity with the homologous species. Gel electrophoresis-derived ELISA performed on immobilized M bovis antigens separated by molecular weight, using sera from rabbits hyperimmunized with the mycoplasmal species under study and noninoculated culture medium revealed antigenic components which are shared among species or with the culture medium and several components which may be unique to M bovis.