Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B.

Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains.IMPORTANCE FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.

Efficiency and outcomes of harmonic device in transanal endoscopic microsurgery compared with monopolar scalpel.

INTRODUCTION: An important fact when facing new technologies is their cost for the Health Publishes. The purpose of this paper is to compare the costs of performing TEM with harmonic scalpel and classic monopolar scalpel and to analyze complications. METHODS: Operation time, blood loss, and hospital stay were recorded to determine the cost of the TEM procedure. We also recorded early and late complications. Patients were divided in two groups: harmonic scalpel group (UC) and monopolar scalpel group (MS). RESULTS: TEM for curative intention was used in 330 rectal tumors from January 1997 to January 2010. A total of 229 patients met the criteria for this study: UC group (n = 87) and MS group (n = 142). Patients from the UC group developed fewer complications (16%) than patients from the MS group (23%). The difference of mean stay between groups was 1.5 days (95% confidence interval, 0.7; 2.2 days; P < 0.001) in favor of the UC group. CONCLUSIONS: Harmonic scalpel provides a safer, easier, and more precise surgical section through clean, bloodless, and better visualized operative field. The additional cost of UC was compensated with the decrease in the health resources (mainly hospital stay).

Metabolic syndrome after bariatric surgery. Results depending on the technique performed.

BACKGROUND: There is a lack of long-term studies for metabolic syndrome after bariatric surgery. Our aim is to show the evolution of the parameters that define the metabolic syndrome after bariatric surgery, up to 10 years of follow-up, in order to clarify what technique gets better results with fewer complications. METHODS: The IDF definition of the metabolic syndrome was used for this study. One hundred twenty-five morbid obese and superobese patients underwent vertical banded gastroplasty. Two hundred sixty-five morbid obese and superobese patients had biliopancreatic diversion (Scopinaro and modified biliopancreatic diversions), and 152 morbid obese patients underwent laparoscopic gastric bypass. A mean follow-up of up to 7 years was done in all groups. RESULTS: Prior to surgery, metabolic syndrome was diagnosed in 114 patients of Scopinaro group (76%), in 85 patients of modified biliopancreatic diversion group (73.9%), in 81 patients of laparoscopic gastric bypass (53.4%), and in 98 patients of vertical banded gastroplasty (78.4%). When metabolic syndrome parameters were evaluated at 7 years of follow-up, owing to weight gain, these results changed nearby to preoperative values in both laparoscopic gastric bypass and vertical banded gastroplasty groups. CONCLUSION: According to our results, the best technique to resolve metabolic syndrome is the modified biliopancreatic diversion. Due to its high morbidity, it only must be considered in superobese patients. In obese patients, the laparoscopic gastric bypass may be a less agressive choice, but it should be coupled with lifestyle changes to keep away from the weight gain in the long run. Restrictive procedures may be indicated only in a few well-selected cases.

Continuum electrostatic calculations of the pKa of ionizable residues in an ion channel: dynamic vs. static input structure.

We have computed the pK(a)'s of the ionizable residues of a protein ion channel, the Staphylococcus aureus toxin alpha-hemolysin, by using two types of input structures, namely the crystal structure of the heptameric alpha-hemolysin and a set of over four hundred snapshots from a 4.38 ns Molecular Dynamics simulation of the protein inserted in a phospholipid planar bilayer. The comparison of the dynamic picture provided by the Molecular Simulation with the static one based on the X-ray crystal structure of the protein embedded in a lipid membrane allows analyzing the influence of the fluctuations in the protein structure on its ionization properties. We find that the use of the dynamic structure provides interesting information about the sensitivity of the computed pK(a) of a given residue to small changes in the local structure. The calculated pK(a) are consistent with previous indirect estimations obtained from single-channel conductance and selectivity measurements.

Critical assessment of OmpF channel selectivity: merging information from different experimental protocols.

The ion selectivity of a channel can be quantified in several ways by using different experimental protocols. A wide, mesoscopic channel, the OmpF porin of the outer membrane of E. coli, serves as a case study for comparing and analysing several measures of the channel cation-anion permeability in chlorides of alkali metals (LiCl, NaCl, KCl, CsCl). We show how different insights can be gained and integrated to rationalize the global image of channel selectivity. To this end, reversal potential, channel conductance and bi-ionic potential (two different salts with a common anion on each side of the channel but with the same concentration) experiments are discussed in light of an electrodiffusion model based on the Poisson-Nernst-Planck formalism. Measurements and calculations based on the atomic crystal structure of the channel show that each protocol displays a particular balance between the different sources of selectivity.

Obesity surgery results depending on technique performed: long-term outcome.

BACKGROUND: Many techniques have excellent results at 2 years of follow-up but some matters regarding their long-term efficacy have arisen. This is why bariatric surgery results must be analyzed in long-term follow-up. The aim of this study was to extend the analysis over 5 years, evaluating weight loss, morbidity, and mortality of the surgical procedures performed. METHODS: This was a retrospective cohort study of the different procedures for morbid obesity practiced in our Department of Surgery for morbid obesity. The results have been analyzed in terms of weight loss, morbidity improvement, and postoperative morbidity (Bariatric Analysis And Reporting Outcome System). RESULTS: One hundred twenty-five patients were operated on open vertical banded gastroplasty (VBG), 150 patients of open biliopancreatic diversion (BPD) of Scopinaro, 100 patients of open modified BPD (common limb 75 cm; alimentary limb 225 cm), and 115 patients of laparoscopic Roux-en-Y gastric bypass (LRYGBP). Mean follow-up was: VBG 12 years, BPD 7 years, and LRYGBP 4 years. An excellent initial weight loss was observed at the end of the second year of follow-up in all techniques, but from this time an important regain of weight was observed in VBG group and a discrete weight regain in LRYGBP group. Only BPD groups kept excellent weight results so far in time. Mortality was: VBG 1.6%, BPD 1.2%, and LRYGBP 0%. Early postoperative complications were: VBG 25%, BPD 20.4%, and LRYGBP 20%. Late postoperative morbidity was: protein malnutrition 11% in Scopinaro BPD, 3% in Modified BPD group, and no cases reported either in VBG group or LRYGBP group; iron deficiency 20% VBG, 62% Scopinaro BPD, 40% modified BPD, and 30.5% LRYGBP. A 14.5% of VBG group required revision surgery to gastric bypass or to BPD due to 100% weight regain or vomiting. A 3.2% of Scopinaro BPD with severe protein malnutrition required revision surgery to lengthen common limb to 100 cm. A 0.8% of LRYGBP required revision surgery to distal LRYGBP (common limb 75 cm) due to 100% weight regain. CONCLUSIONS: The most complex bariatric procedures increase the effectiveness but unfortunately they also increase morbidity and mortality. LRYGBP is safe and effective for the treatment of morbid obesity. Modified BPD (75-225 cm) can be considered for the treatment of superobesity (body mass index > 50 kg/m(2)), and restrictive procedures such as VBG should only be performed in well-selected patients due to high rates of failure in long-term follow-up.

Theoretical description of the ion transport across nanopores with titratable fixed charges: analogies between ion channels and synthetic pores.

Recently developed nanometer-sized synthetic pores display several properties so far believed to be distinctive features of a large variety of biological wide ion channels. Thus conductance in the pS-nS range, pH-dependent ion selectivity, fluctuations of current between open and closed states, flux inhibition caused by protons or divalent cations, current rectification, and the ability to perform selective macromolecule sizing and counting are found in synthetic and biological channels alike. Despite other differences such as pore size and geometry, the similarities open a new field for exploring specific technological applications via the chemical modification of synthetic pores with biological molecules. This article reviews some of the basic concepts and theories relevant to ion transport in nanopores with titratable charges stressing the analogies between synthetic pores and biological ion channels. The ultimate goal is to show that continuum theories may account for the essential features of these systems. A simple electrodiffusion model and its comparison with experimental results are chosen as a case study.

The utility of endovaginal sonography in the evaluation of fecal incontinence.

OBJECTIVE: The endoanal sonography in female patients with faecal incontinence is sometimes difficult and can lead to diagnostic errors. The aim of this study is to evaluate the value of endovaginal sonography in such cases. MATERIAL AND METHOD: Thirty female patients complaining of faecal incontinence are included in the study. Anal endosonography was performed in all of them in a single ambulatory session, pictures were taken from all along the anal and results were analyzed afterward. Vaginal endosonography was then performed using the same equipment. Result from both techniques were compared. RESULTS: Endoanal sonography was performed in all 30 patients. In 17 cases no anomalies were found. In 3 patients a simple internal anal sphincter defect was found. One case showed a lateral lesion in both sphincters. Six cases presented anterior external defect and in the rest 3 cases a clear view of the anterior wall was impossible. Vaginal endosonography shows a clear image of the anal canal in 23 out of 30 patients. In two cases changed the results of anal endosonography. CONCLUSION: In the study of faecal incontinence, despite of its technical limitations, endovaginal ultrasound could be of help when the anterior wall of the anal canal is not properly defined.

Doppler-guided hemorrhoidal artery ligation in the management of symptomatic hemorrhoids.

OBJECTIVE: The aim of this study is to clinically test the efficacy of a new approach for patients having symptomatic grade III and IV hemorrhoids. MATERIAL AND METHOD: 32 patients (17 females) complaining of grade III or IV hemorrhoids were included in the study. A specially designed proctoscope coupled with a Doppler transducer on its tip was used to identify the hemorrhoidal arteries, which were afterwards suture ligated. Operating time as well as per- and post-operative complications were analyzed. Follow-up was planned following discharge after 1 week, 1 month, 6 months and 1 year. RESULTS: Mean operation time was 27 (range 18-43) minutes, and 5 (range 4-7) arteries were located on average. No patient had severe or moderate postoperative pain, with anal discomfort being the main complaint. Rectal bleeding and tenesmus were the commonest post-operative complications. After one year of follow-up, 19 patients were free of symptoms and 6 of them had significant symptom relief. According to grade, the technique failed in just 3 grade III patients, but in as many as 4 grade IV hemorrhoid cases. CONCLUSIONS: Doppler-guided hemorrhoid artery ligation is an easy-to-perform technique that is well accepted by patients and has good results for grade III hemorrhoids.

Interaction of a polar molecule with an ion channel.

The binding of a polar macromolecule to a large ion channel is studied theoretically, paying special attention to the influence of external conditions (applied voltage and ion strength of solution). The molecule behavior in bound state is considered as random thermal fluctuations within a limited fraction of its phase space. The mean duration of molecule binding (residence time tau r) is represented as the mean first passage time to reach the boundary of that restricted domain. By invoking the adiabatic approximation we reduce the problem to one dimension with the angle between macromolecule dipole and channel axes being the key variable of the problem. The model accounts for experimental measurements of tau r for the antibiotic Ampicillin within the bacterial porin OmpF of Escherichia coli. By assuming that the electrical interaction between Ampicillin dipole and OmpF ionizable groups affects the fluctuations, we find that the biased residence time-voltage dependence observed in experiments is the result of the strong transversal electric field in OmpF constriction with a tilt approximately 30 degrees aside the cis side.

Incidence of incisional hernia following vertical banded gastroplasty.

BACKGROUND: Our aim was to determine which patient-related factors influence the incidence of incisional hernia after vertical banded gastroplasty for morbid obesity. METHODS: We reviewed the medical records of 80 morbidly obese patients operated on between 1986 and 1993. All the operations were performed by only one surgeon, and the midline laparotomy was closed by means of continuous polyglactin 910 suture. Statistical analysis was performed using the Fisher exact test, and significance was assigned for values of P<0.05. RESULTS: Incidence of incisional hernia in: obese 24%, superobese 51% ( P=0.0165), men 40%, women 34% ( P=0.7671), age<50 33%, age>50 50% ( P=0.3137), nondiabetics 31%, diabetics 66% ( P=0.0610), no wound infection 34%, wound infection 37% ( P>0.9999), no anemia 31%, anemia 50% ( P=0.1675), no vomiting 39%, vomiting 32% ( P=0.6350). CONCLUSION: The only patient-related factor that significantly influences the incidence of incisional hernia in morbidly obese patients is body mass index.

Synthetic nanopores with fixed charges: an electrodiffusion model for ionic transport.

Synthetic nanopores with fixed charges exhibit ionic equilibrium and transport properties that resemble those displayed by biological ion channels. We present an electrodiffusion model based on the Nernst-Planck flux equations, which allows for a qualitative description of the steady state ionic transport through a nanopore when the membrane fixed charges and all mobile carriers (including the water ions) are properly taken into account. In particular, we study the current-voltage curve, the electrical conductance, the reversal potential (a measure of the nanopore ionic selectivity), as well as the flux inhibition by protons and divalent cations in the nanopore. The model clearly shows how the changes in the ionization state of the fixed charges with pH and salt concentration dictate the electrical properties of the nanopore. The agreement between the model predictions and previous experimental data allows us to identify which are the main characteristics that permit a simple description of this complex system.

Transanal full-thickness excision of rectal tumours: should the defect be sutured? a randomized controlled trial.

PURPOSE: It is generally recommended that the defect, after full thickness total wall excision of a tumour located in the extraperitoneal part of the rectum, should be sutured. There is a lack of controlled studies however, supporting this approach. The aim of this study was to compare the results obtained in patients after peranal local excision of rectal tumours whose defect were sutured with those that were not. METHODS: 44 patients were prospectively randomized to group A: The defect is closed; Group B: Defect left un-sutured. Pre-operative test were digital examination, proctoscopy and endorectal ultrasound. Local full-thickness excision was performed mainly with the Transanal Endoscopic Microsurgery (TEM) equipment, but for cases near the anal verge a Parks' retractor was used. Data recorded were operation time, blood loss, hospital stay and early and late complications. The first postoperative assessment was planned at 1 month and then every three months until 18 months of follow-up. Result for 40 patients (21 from group A; 19 from group B) were analysed. There were no differences between groups regarding age, sex, location of the tumour and specimen's size. RESULTS: The intra-operative loss of blood was 22 ml for group A and 39 ml for B, the difference was not significant. The mean operation time was slighter longer for group A (93 min) than for group B (77 min) but not statistically significant. For both group the mean hospital stay was of 4[2-7] days. No differences in early or late complications could be demonstrated. CONCLUSION: The present study suggests that there is no difference between these two practices in terms of intra-operative results and outcome.

Alamethicin channel conductance modified by lipid charge.

The membrane surface charge modifies the conductance of ion channels by changing the electric potential and redistributing the ionic composition in their vicinity. We have studied the effects of lipid charge on the conductance of a multi-state channel formed in planar lipid bilayers by the peptide antibiotic alamethicin. The channel conductance was measured in two lipids: in a neutral dioleoylphosphatidylethanolamine (DOPE) and a negatively charged dioleoylphosphatidylserine (DOPS). The charge state of DOPS was manipulated by the pH of the membrane-bathing solution. We find that at high salt concentrations (e.g., 2 M NaCl) the effect of the lipid charge is below the accuracy of our measurements. However, when the salt concentration in the membrane-bathing solution is decreased, the surface charge manifests itself as an increase in the conductance of the first two channel levels that correspond to the smallest conductive alamethicin aggregates. Our analysis shows that both the salt and pH dependence of the surface charge effect can be rationalized within the nonlinear Poisson-Boltzmann approach. Given channel conductance in neutral lipids, we use different procedures to account for the surface charge (e.g., introduce averaging over the channel aperture and take into account Na+ adsorption to DOPS heads), but only one adjustable parameter: an effective distance from the nearest lipid charge to the channel mouth center. We show that this distance varies by 0.3-0.4 nm upon channel transition from the minimal conducting aggregate (level L0) to the next larger one (level L1). This conclusion is in accord with a simple geometrical model of alamethicin aggregation.

Double layer potential and degree of dissociation in charged lipid monolayers.

One of the contributions to the surface potential in charged phospholipid monolayers at air-water interfaces is the double layer potential. In this note several misconceptions found in the literature concerning the relationship between the double layer potential and the degree of dissociation of the lipid polar headgroups are critically analyzed. The deviations of the double layer potential measurements from the Gouy-Chapman theory observed by several authors are explained by taking into account the dependence of the degree of dissociation with concentration, area per lipid molecule and pH.

Membrane surface-charge titration probed by gramicidin A channel conductance.

We manipulate lipid bilayer surface charge and gauge its influence on gramicidin A channel conductance by two strategies: titration of the lipid charge through bulk solution pH and dilution of a charged lipid by neutral. Using diphytanoyl phosphatidylserine (PS) bilayers with CsCl aqueous solutions, we show that the effects of lipid charge titration on channel conductance are masked 1) by conductance saturation with Cs+ ions in the neutral pH range and 2) by increased proton concentration when the bathing solution pH is less than 3. A smeared charge model permits us to separate different contributions to the channel conductance and to introduce a new method for "bilayer pKa" determination. We use the Gouy-Chapman expression for the charged surface potential to obtain equilibria of protons and cations with lipid charges. To calculate cation concentration at the channel mouth, we compare different models for the ion distribution, exact and linearized forms of the planar Poisson-Boltzmann equation, as well as the construction of a "Gibbs dividing surface" between salt bath and charged membrane. All approximations yield the intrinsic pKain of PS lipid in 0.1 M CsCl to be in the range 2.5-3.0. By diluting PS surface charge at a fixed pH with admixed neutral diphytanoyl phosphatidylcholine (PC), we obtain a conductance decrease in magnitude greater than expected from the electrostatic model. This observation is in accord with the different conductance saturation values for PS and PC lipids reported earlier (, Biochim. Biophys. Acta. 552:369-378) and verified in the present work for solvent-free membranes. In addition to electrostatic effects of surface charge, gramicidin A channel conductance is also influenced by lipid-dependent structural factors.

Access resistance of a single conducting membrane channel.

We have considered the access resistance (AR) of a single conducting channel placed in a membrane bathed by an electrolyte. The classical expression for AR is due to Hall, who modeled the electrolyte as an ohmic conducting homogeneous medium. This approach is discussed in the present paper and it is shown that it is not valid in all cases, but depends on the ion concentration in solution and the ratio between solution and channel resistivities. To get a new expression for AR, we have combined the use of one-dimensional Nernst-Planck and Poisson (NPP) equations for the mouth of the channel and three-dimensional NPP equations for the outside solution. The influence of ion gradients and the channel itself on AR tums out to be considerable in diluted solutions (and also in the case of small channels in any solution). This influence is weaker in concentrated solutions, for which AR is well described by Hall's expression.

A Perturbed Electric Double Layer Near a Soft Polar Interface

A perturbation analysis is applied to a nonequilibrium double electric layer (NDEL) near a membrane with extended soft permeable interfaces (polar zones) under steady-state ion flux conditions. The membrane has been modeled as composed of three layers: an inner hydrophobic layer and two polar zones with fixed charges and dipoles. Ion flux is described according to Nernst-Planck and Poisson equations. A first order approximation of the nonequilibrium electric potential has been obtained, using the electric current as the small parameter. The influence of the ionic flux, the surface dipole density, and the thickness of the polar zone on the NDEL near the membrane has been analyzed. The electric potential and hence the ion concentration profiles in the NDEL change considerably with surface dipole density. A maximum in the electric potential, which is determined by ion flux and polar zone parameters, is predicted in certain cases. The effects shown can help in the interpretation of permselectivity measurements.