Incidence of surgical procedures for gastrointestinal complications after abdominal wall closure in patients with gastroschisis and omphalocele.

PURPOSE: This study aims to define the extent of additional surgical procedures after abdominal wall closure (AWC) in patients with gastroschisis (GS) and omphalocele (OC) with special focus on gastrointestinal related operations. METHODS: A retrospective chart review was performed including all operations in GS and OC patients in the first year after AWC (2010-2019). The risk for surgery was calculated using the one-year cumulative incidence (CI). RESULTS: 33 GS patients (18 simple GS, 15 complex) and 24 OC patients (12 without (= OCL), 12 OC patients with liver protrusion (= OCL +)) were eligible for analysis. 43 secondary operations (23 in GS, 20 in OC patients) occurred after a median time of 84 days (16-824) in GS and 114.5 days (12-4368) in OC. Patients with complex versus simple GS had a significantly higher risk of undergoing a secondary operation (one-year CI 64.3% vs. 24.4%; p = 0.05). 86.5% of surgical procedures in complex GS and 36.3% in OCL + were related to gastrointestinal complications. Complex GS had a significantly higher risk for GI-related surgery than simple GS. Bowel obstruction was a risk factor for surgery in complex GS (one-year CI 35.7%). CONCLUSION: Complex GS and OCL + patients had the highest risk of undergoing secondary operations, especially those with gastrointestinal complications.

Outcome of esophageal atresia in Germany.

The aim of this study was to evaluate the outcome of esophageal atresia in Germany in a retrospective observational study of a large cohort. Data from the major health insurance company in Germany, which covers approximately 30% of German patients, were analyzed. All patients born and registered between 2009 and 2013 with a diagnosis of esophageal atresia at first admission to the hospital were included. Mortality was analyzed during the first year of life. We identified 287 patients with esophageal atresia, including 253 with and 34 without tracheoesophageal fistula. Associated anomalies were found in 53.7% of the patients; the most frequent were cardiac anomalies (41.8%), anomalies of the urinary tract (17.4%), and atresia of the colon, rectum, and anus (9.4%). Forty-one patients (14.3%) had a birth weight <1500 g. Seventeen patients (5.9%) died before surgery. Gastrostomy was performed during the index admission in 70 patients (25.9%). The reconstruction of the esophageal passage was performed in 247 patients (93.9%). Forty-eight percent of the patients who underwent an operation required dilatation. The mortality rate in the patients who underwent an operation was 10.4%. These results from Germany correspond to the international results that have been reported. The number of dilatations was in the middle of the range of those reported in the literature; the overall mortality rate was in the upper portion of the range of the international rates. Efforts should be made to establish a clinical registry to measure and improve the quality of care for this and other rare conditions.

Steering the azido-tetrazole equilibrium of 4-azidopyrimidines via substituent variation - implications for drug design and azide-alkyne cycloadditions.

This paper focuses on an interesting constitutional isomerism called azido-tetrazole equilibrium which is observed in azido-substituted N-heterocycles. We present a systematic investigation of substituent effects on the isomer ratio within a 2-substituted 4-azidopyrimidine model scaffold. NMR- and IR-spectroscopy as well as X-ray crystallography were employed for thorough analysis and characterization of synthesized derivatives. On the basis of this data, we demonstrate the possibility to steer this valence tautomerism towards the isomer of choice by means of substituent variation. We show that the tetrazole form can act as an efficient disguise for the corresponding azido group masking its well known reactivity in azide-alkyne cycloadditions (ACCs). In copper(I)-catalyzed AAC reactions, substituent-stabilized tetrazoles displayed a highly decreased or even abolished reactivity whereas azides and compounds in the equilibrium were directly converted. By use of an acid sensitive derivative, we provide, to our knowledge, the first experimental basis for a possible exploitation of this dynamic isomerism as a pH-dependent azide-protecting motif for selective SPAAC conjugations in aqueous media. Finally, we demonstrate the applicability and efficiency of stabilized tetrazolo[1,5-c]pyrimidines for Fragment-Based Drug Design (FBDD) in the field of quorum sensing inhibitors.

Parameterization of a reactive force field using a Monte Carlo algorithm.

Parameterization of a molecular dynamics force field is essential in realistically modeling the physicochemical processes involved in a molecular system. This step is often challenging when the equations involved in describing the force field are complicated as well as when the parameters are mostly empirical. ReaxFF is one such reactive force field which uses hundreds of parameters to describe the interactions between atoms. The optimization of the parameters in ReaxFF is done such that the properties predicted by ReaxFF matches with a set of quantum chemical or experimental data. Usually, the optimization of the parameters is done by an inefficient single-parameter parabolic-search algorithm. In this study, we use a robust metropolis Monte-Carlo algorithm with simulated annealing to search for the optimum parameters for the ReaxFF force field in a high-dimensional parameter space. The optimization is done against a set of quantum chemical data for MgSO4 hydrates. The optimized force field reproduced the chemical structures, the equations of state, and the water binding curves of MgSO4 hydrates. The transferability test of the ReaxFF force field shows the extend of transferability for a particular molecular system. This study points out that the ReaxFF force field is not indefinitely transferable.

[Digital X-ray: interhospital data transfer by CD-ROM. Prospective data evaluation during the import process]. / Digitales Röntgen: interhospitaler Datentransfer auf CD-ROM. Prospektive Datenevaluation während des Arbeitsprozesses.

BACKGROUND: Increasing numbers of radiological imaging diagnostics are archived in digital form. In addition to the results of diagnostics performed in hospital a growing number of patients present with digital results of outpatient radiological investigations. These digitized images represent a challenge for the internal hospital work flow. The aim of the study was to determine the expenditure for the hospital when dealing with digital outpatient diagnostic results. METHOD: Several parameters were observed and analyzed within the import process of nearly 400 CD-ROMs over a time period of 5 months. Only a negligible number of data on CD-ROMs could not be transferred into the hospital archive (1.5%). The duration of the process depended on the amount of data and the time period. RESULTS: During regular hours the import process took on average 13 min per CD and 19 min per patient while the time increased significantly during on-call duties. This study demonstrates the significance of the import of digital outpatient radiological diagnostic results into the hospital archive which can in particular influence patient treatment.

Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in 'herbal mixtures' using LC-MS/MS techniques.

Herbal mixtures, such as 'Spice', containing cannabimimetic compounds are easily available on the Internet and have become increasingly popular among people having to undergo urine drug testing, as these compounds are not detected by current immunochemical tests. For analysis of urine samples, knowledge of the main metabolites is necessary as the unchanged compounds are usually not found in urine after consumption. In this paper, the identification of the major metabolites of the currently most common seven synthetic cannabinoids is presented. Urine samples from patients of psychiatric facilities known to have consumed synthetic cannabinoids were screened by LC-MS/MS and HR-MS/MS techniques, and the major metabolites for each of the following synthetic cannabinoids were identified by their enhanced product ion spectra and accurate mass measurement: JWH-018, JWH-073, JWH-081, JWH-122, JWH-210, JWH-250 and RCS-4. The major metabolic pathway is monohydroxylation either at the N-alkyl side chain, the naphthyl moiety or the indole moiety. In addition, metabolites with carboxylated alkyl chains were identified for some of the compounds. These results facilitate the design of urine screening methods for detecting consumption of synthetic cannabinoids.

Genetic testing in the European Union: does economic evaluation matter?

OBJECTIVE: We review the published economic evaluation studies applied to genetic technologies in the EU to know the main diseases addressed by these studies, the ways the studies were conducted and to assess the efficiency of these new technologies. The final aim of this review was to understand the possibilities of the economic evaluations performed up to date as a tool to contribute to decision making in this area. METHODS: We have reviewed a set of articles found in several databases until March 2010. Literature searches were made in the following databases: PubMed; Euronheed; Centre for Reviews and Dissemination of the University of York-Health Technology Assessment, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database; and Scopus. The algorithm was "(screening or diagnosis) and genetic and (cost or economic) and (country EU27)". We included studies if they met the following criteria: (1) a genetic technology was analysed; (2) human DNA must be tested for; (3) the analysis was a real economic evaluation or a cost study, and (4) the articles had to be related to any EU Member State. RESULTS: We initially found 3,559 papers on genetic testing but only 92 articles of economic analysis referred to a wide range of genetic diseases matched the inclusion criteria. The most studied diseases were as follows: cystic fibrosis (12), breast and ovarian cancer (8), hereditary hemochromatosis (6), Down's syndrome (7), colorectal cancer (5), familial hypercholesterolaemia (5), prostate cancer (4), and thrombophilia (4). Genetic tests were mostly used for screening purposes, and cost-effectiveness analysis is the most common type of economic study. The analysed gene technologies are deemed to be efficient for some specific population groups and screening algorithms according to the values of their cost-effectiveness ratios that were below the commonly accepted threshold of 30,000€. CONCLUSIONS: Economic evaluation of genetic technologies matters but the number of published studies is still rather low as to be widely used for most of the decisions in different jurisdictions across the EU. Further, the decision bodies across EU27 are fragmented and the responsibilities are located at different levels of the decision process for what it is difficult to find out whether a given decision on genetic tests was somehow supported by the economic evaluation results.

Panel report: best practices for the surgical treatment of obesity.

BACKGROUND: Bariatric surgery is a rapidly growing field. Advances in surgical technologies and techniques have raised concerns about patient safety. Bariatric surgeons and programs are under increased scrutiny from regulatory agencies, insurers, and public health officials to provide high quality and safe care for bariatric patients at all phases of care. METHODS: During the 2009 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), a panel of experts convened to provide updated information on patient safety and best practices in bariatric surgery. The following article is a summary of this panel presentation. RESULTS AND CONCLUSIONS: Weight loss surgery is a field that is evolving and adapting to multiple external pressures. Safety concerns along with increasing public scrutiny have led to a systematic approach to defining best practices, creating standards of care, and identifying mechanisms to ensure that patients consistently receive the best and most effective care possible. In many ways, bariatric surgery and multidisciplinary bariatric surgery programs may serve as a model for other programs and surgical specialties in the near future.

In silico prediction of drug properties.

Drug design has become inconceivable without the assistance of computer-aided methods. In this context in silico was chosen as designation to emphasize the relationship to in vitro and in vivo testing. Nowadays, virtual screening covers much more than estimation of solubility and oral bioavailability of compounds. Along with the challenge of parsing virtual compound libraries, the necessity to model more specific metabolic and toxicological aspects has emerged. Here, recent developments in prediction models are summarized, covering optimization problems in the fields of cytochrome P450 metabolism, blood-brain-barrier permeability, central nervous system activity, and blockade of the hERG-potassium channel. Aspects arising from the use of homology models and quantum chemical calculations are considered with respect to the biological functions. Furthermore, approaches to distinguish drug-like substances from nondrugs by the means of machine learning algorithms are compared in order to derive guidelines for the design of new agents with appropriate properties.

Widespread Occurrence of the Aecial Stage of Sunflower Rust Caused by Puccinia helianthi in North Dakota and Minnesota in 2008.

Sunflower rust caused by Puccinia helianthi (Schw.) is widespread in North America and occurs annually on cultivated sunflower (Helianthus annuus L.) and wild annual and perennial Helianthus spp., although severity on the U.S. sunflower crop has been increasing in recent years (2). P. helianthi is a autoecious, macrocyclic rust, but the aecial stage is rarely observed in the field (1,3,4). In most years, the earliest appearance of sunflower rust in North Dakota (ND) and surrounding states usually occurs in early August as the uredinial stage. Initial inoculum can result from urediniospores that overwinter in the Northern Great Plains, urediniospores blown in from areas south of North Dakota, or basidiospores completing the life cycle. However, aecia have been noted very infrequently and never widespread, indicating initial inoculum is usually urediniospores. Aecia of P. helianthi were first observed on 24 June 2008 in a commercial sunflower field (confection hybrid CHS 3126) near Mohall, ND. Aecia cups measuring 0.2 to 0.3 mm in diameter were observed in clusters that were 1 to 7 mm wide in diameter and containing as many as 150 cups. Aecia cups were bright orange but turned brown-black as they senesced. As many as 15 aecial clusters occurred on individual leaves or cotyledons. Aeciospores were ellipsoid, hyaline, and measured approximately 20 µm in diameter. On 4 July 2008, uredinia were first observed in the same Mohall, ND field. At that time, uredinia, aecia, and senesced aecia could all be found on the same leaves. In a non-fungicide-treated strip of the field, pustule coverage on the lower leaves was 10 to 20% by mid-July, pustule coverage on the upper four leaves of plants in the untreated strip was 56% by 27 August, and yield at harvest was less than 200 kg/ha. The rest of the field was sprayed twice with fungicides and yielded 1,571 kg/ha, which is similar to the statewide yield average of 1,573 kg/ha in 2008. To determine the prevalence of aecia in the primary growing regions of ND and Minnesota (MN), surveys were conducted in 75 sunflower fields in 18 counties between 22 and 24 July in ND and 34 fields in 8 counties between 17 and 31 July in MN. Incidence of aecia and uredinia were determined by visual observation of a minimum of 20 plants scouted in a 'W' pattern in the field. Rust was found in 31 and 53% of fields in ND and MN, respectively. In fields where rust was found, both aecia and uredinia were observed in 37% of the fields, aecia only in 29% of the fields, and uredinia only in 34% of the fields. Although it is uncertain why aecia were widespread in 2008, night temperatures in Mohall, ND, where aecia were first observed, reached the dew point temperature on 51 of 61 days in June and July, suggesting that dew or fog likely formed. Thus, favorable conditions for germination and infection early in the growing season indicate widespread occurrence of rust was likely a result of local inoculum sources. The early appearance of aecia is cause for concern for two reasons: significant yield loss can occur when rust appears early in the growing season; and the presence of aecia suggest that the pathogen completed its sexual cycle. When P. helianthi completes its life cycle it is likely that a greater diversity of races will result (4). References: (1) D. L. Bailey. Univ. Minn. Tech. Bull. 16:1, 1923. (2) D. Berglund. Natl. Sunflower Assoc. Online publication. /Berglund_2007_NSA_Survey_08. 2008. (3) H. S. Jackson. Mem. Torrey Bot. Club 18:1, 1931. (4) G. A. Kong et al. Australas. Plant Pathol. 28:320, 1999.

IMIA's publication history.

OBJECTIVES: This article lines out the various publications by which IMIA presents its work and the state-of-the art of health and biomedical informatics. METHOD: A short history of IMIA and its publications is presented, a reference list completes the view. RESULTS: IMIA looks back on a long and fruitful publication history of more than a hundred publications. CONCLUSION: Starting from its foundation in 1967, IMIA has continually published the results of its activities and conferences, these publications being one of the most visible proofs of the liveliness and up-to-dateness of the organization and the field.

Modeling the bacterial photosynthetic reaction center. 4. The structural, electrochemical, and hydrogen-bonding properties of 22 mutants of Rhodobacter sphaeroides.

Site-directed mutagenesis has been employed by a number of groups to produce mutants of bacterial photosynthetic reaction centers, with the aim of tuning their operation by modifying hydrogen-bond patterns in the close vicinity of the "special pair" of bacteriochlorophylls P identical with P(L)P(M). Direct X-ray structural measurements of the consequences of mutation are rare. Attention has mostly focused on effects on properties such as carbonyl stretching frequencies and midpoint potentials to infer indirectly the induced structural modifications. In this work, the structures of 22 mutants of Rhodobacter sphaeroides have been calculated using a mixed quantum-mechanical molecular-mechanical method by modifying the known structure of the wild type. We determine (i) the orientation of the 2a-acetyl groups in the wild type, FY(M197), and FH(M197) series mutants of the neutral and oxidized reaction center, (ii) the structure of the FY(M197) mutant and possible water penetration near the special pair, (iii) that significant protein chain distortions are required to assemble some M160 series mutants (LS(M160), LN(M160), LQ(M160), and LH(M160) are considered), (iv) that there is competition for hydrogen-bonding between the 9-keto and 10a-ester groups for the introduced histidine in LH(L131) mutants, (v) that the observed midpoint potential of P for HL(M202) heterodimer mutants, including one involving also LH(M160), can be correlated with the change of electrostatic potential experienced at P(L), (vi) that hydrogen-bond cleavage may sometimes be induced by oxidation of the special pair, (vii) that the OH group of tyrosine M210 points away from P(M), and (viii) that competitive hydrogen-bonding effects determine the change in properties of NL(L166) and NH(L166) mutants. A new technique is introduced for the determination of ionization energies at the Koopmans level from QM/MM calculations, and protein-induced Stark effects on vibrational frequencies are considered.

Thermodynamically consistent incorporation of the Schneider rate equations into two-phase models.

We formulate a solid-liquid two-phase model including viscous stresses, heat conduction in the two phases, as well as heat exchange through the interface, and a phase change in the structure of nonequilibrium thermodynamics described by a general equation for the nonequilibrium reversible-irreversible coupling (GENERIC). The evolution of the microstructure is studied in terms of the Schneider rate equations introducing the nucleation rate and the radial growth rate of the solid phase. The application of the GENERIC structure shows that this radial growth factor is not an additional, independent material function but is to be expressed in terms of the difference in the chemical potentials, in the temperatures, and in the pressures between the two phases. The contribution due to the pressure difference appears in conjunction with the surface tension in such a way, that a driving force results only if deviations from a generalized version of the Laplace equation occur. Furthermore, it is found that for conditions under which the radial growth rate is zero, the nucleation rate must vanish.

Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors.

Recombinant adeno-associated virus type 2 (rAAV) is a promising vector for in vivo gene therapy. Transduction by rAAV requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. Because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with rAAV transduction. Therefore, we examined the influence of different anticoagulants on rAAV transduction in vitro. rAAV transduction was inhibited by 40.5 +/- 7.9% at heparin concentrations of 0.1 U/ml, and by 81.7 +/- 3.6% at 1.0 U/ml. The low molecular weight (LMW) heparin tinzaparin inhibited rAAV transduction by 20.2 +/- 3.8% at 0.1 U/ml and 37.1 +/- 1.8% at 1.0 U/ml. The inhibitory effect was significantly weaker compared with heparin at 1.0 U/ml, (P < 0.01). The LMW heparinoid danaparoid inhibited rAAV transduction by 8.8 +/- 3.5% at 0.1 U/ml (P < 0.01 compared with heparin). In contrast, recombinant hirudin did not interfere at all with rAAV transduction. In summary, the results demonstrate that inhibition of rAAV transduction by heparin occurs rapidly and at therapeutically used concentrations. LMW heparinoids and above all recombinant hirudin might be alternatives for heparin when vascular gene transfer with rAAV requires transient anticoagulation.

Re-face stereospecificity of methylenetetrahydromethanopterin and methylenetetrahydrofolate dehydrogenases is predetermined by intrinsic properties of the substrate.

Four different dehydrogenases are known that catalyse the reversible dehydrogenation of N5,N10-methylenetetrahydromethanopterin (methylene-H4MPT) or N5,N10-methylenetetrahydrofolate (methylene-H4F) to the respective N5,N10-methenyl compounds. Sequence comparison indicates that the four enzymes are phylogenetically unrelated. They all catalyse the Re-face-stereospecific removal of the pro-R hydrogen atom of the coenzyme's methylene group. The Re-face stereospecificity is in contrast to the finding that in solution the pro-S hydrogen atom of methylene-H4MPT and of methylene-H4F is more reactive to heterolytic cleavage. For a better understanding we determined the conformations of methylene-H4MPT in solution and when enzyme-bound by using NMR spectroscopy and semiempirical quantum mechanical calculations. For the conformation free in solution we find an envelope conformation for the imidazolidine ring, with the flap at N10. The methylene pro-S C-H bond is anticlinal and the methylene pro-R C-H bond is synclinal to the lone electron pair of N10. Semiempirical quantum mechanical calculations of heats of formation of methylene-H4MPT and methylene-H4F indicate that changing this conformation into an activated one in which the pro-S C-H bond is antiperiplanar, resulting in the preformation of the leaving hydride, would require a deltadeltaH(f) of +53 kJ mol-1 for methylene-H4MPT and of +51 kJ mol-1 for methylene-H4F. This is almost twice the energy required to force the imidazolidine ring in the enzyme-bound conformation of methylene-H4MPT (+29 kJ mol-1) or of methylene-H4F (+35 kJ mol-1) into an activated conformation in which the pro-R hydrogen atom is antiperiplanar to the lone electron pair of N10. The much lower energy for pro-R hydrogen activation thus probably predetermines the Re-face stereospecificity of the four dehydrogenases. Results are also presented explaining why the chemical reduction of methenyl-H4MPT+ and methenyl-H4F+ with NaBD4 proceeds Si-face-specific, in contrast to the enzyme-catalysed reaction.

Local Structure Evolution in Particle Network Formation Studied by Brownian Dynamics Simulation.

The effect of solid content and colloidal interactions on the structure of forming networks of colloidal particles is studied by Brownian dynamics simulation. The different situations are compared in terms of the pair distribution function and the distribution of nearest neighbors around each particle. The results indicate that, in fast coagulation, the higher solid contents lead to a freezing-in of the liquid structure. Nevertheless, this effect can be reduced substantially by the introduction of a shallow secondary minimum and an energy barrier in the interaction potential. However, the structures resulting from such slow coagulation show a substantial degree of porosity, larger than those produced at the same solid content but by fast coagulation. It is also shown how the porosity (defined on a few particle diameters) is reflected in the distribution of nearest neighbors around the center particle, i.e., the very local conformation in the particle network. Fractal analysis shows that, at the relatively high volume fractions considered in this study, no intermediate fractal regime exists. Copyright 2000 Academic Press.

NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced pancreatic plasma extravasation.

Substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms regulating this response in the rat pancreas. Anesthetized rats were continuously infused with SP, and plasma extravasation was quantified using Evans blue (EB) dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma extravasation. After 60 min, the NK1-R was desensitized to agonist challenge. Resensitization was first detected at 20 min and increased until full recovery was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase (NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous infusion of SP stimulates plasma extravasation in the rat pancreas via activation of the NK1-R, and these effects are terminated by both desensitization of the NK1-R and the cell-surface protease NEP.

The spectrum and cost of complicated gallstone disease in California.

HYPOTHESIS: We hypothesized that complications of gallstone disease are more common than previously recognized and are related to treatment delay. DESIGN: Retrospective review. PATIENTS: Data for 248 consecutive patients from a university hospital in 1995-1996 and 40,571 patients identified through the 1996 California Office of Statewide Health Planning and Development database who underwent cholecystectomy for gallstone disease were reviewed. MAIN OUTCOME MEASURES: Diagnosis, length of hospital stay, hospital mortality, type of admission, type of surgical procedure, hospital cost, and interval of delay between onset of initial symptoms, ultrasound diagnosis, and cholecystectomy. RESULTS: The spectrum of gallstone disease included biliary colic in 56%, acute cholecystitis in 36%, acute pancreatitis in 4%, choledocholithiasis in 3%, gallbladder cancer in 0.3%, and cholangitis in 0.2%. Community hospitals, public or county hospitals, and academic health centers had a similar distribution of diagnoses. Patients undergoing cholecystectomy for biliary colic had a significantly shorter length of hospital stay, lower operative mortality rate, were more likely to have their operations completed laparoscopically, and had lower hospital charges than patients undergoing cholecystectomy for complications such as acute cholecystitis. Over half of the patients requiring cholecystectomy for complications of gallstones initially presented with biliary colic. Patients with gallstone complications had an average delay from ultrasound confirmation to surgery of 6 months. CONCLUSION: Complications of gallstone disease are (1) common, (2) costly, and (3) potentially preventable.

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

BACKGROUND: The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. METHODS: Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. RESULTS: Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. CONCLUSIONS: Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Does the participation of a surgical trainee adversely impact patient outcomes? A study of major pancreatic resections in California.

BACKGROUND: Some patients have concerns regarding the impact of surgical trainees on the quality of care that they receive in teaching hospitals. No population-based data exist that describe outcomes of surgical procedures in teaching and nonteaching hospitals; however, institutional data suggest that teaching hospitals provide high-quality care. We hypothesized that the presence of a general surgery residency program (GSRP) is associated with superior outcomes for pancreatic resection, a complex surgical procedure. METHODS: A retrospective, population-based, risk-adjusted analysis of 5696 patients who underwent major pancreatic resection compares the outcomes of patients treated at hospitals with a GSRP (GSRP+) and those hospitals without a GSRP (GSRP-). RESULTS: GSRP+ hospitals had a lower operative mortality rate (8.3% vs 11.0%; P <. 001), a lower percentage of patients discharged to another acute care hospital or skilled nursing facility (6.5% vs 13.0%; P <.001), and a longer length of stay compared with GSRP- hospitals (22.1 +/- 0.4 days vs 19.6 +/- 0.3 days; P <.001). The observed difference in hospital mortality rates was not significant after an adjustment was made for patient mix and hospital volume (9.7% vs 10.0%). However, superior outcomes were found in the university teaching hospitals, as compared with the affiliated teaching and the nonteaching hospitals (5.3% [P <.001] vs 11.4% vs 11.0%; risk adjusted, 8.0% [P <.05] vs 10.9% vs 10.0%). CONCLUSIONS: The presence of surgical trainees does not have an adverse impact on the quality of care for One complex procedure, pancreatectomy, and is associated with superior operative mortality rate in university teaching hospitals.