The Obesity Paradox in the Trauma Patient: Normal May not Be Better.

OBJECTIVE: The obesity paradox is the association of increased survival for overweight and obese patients compared to normal and underweight patients, despite an increased risk of morbidity. The obesity paradox has been demonstrated in many disease states but has yet to be studied in trauma. The objective of this study is to elucidate the presence of the obesity paradox in trauma patients by evaluating the association between BMI and outcomes. METHODS: Using the 2014-2015 National Trauma Database (NTDB), adults were categorized by WHO BMI category. Logistic regression was used to assess the odds of mortality associated with each category, adjusting for statistically significant covariables. Length of stay (LOS), ICU LOS and ventilator days were also analyzed, adjusting for statistically significant covariables. RESULTS: A total of 415,807 patients were identified. Underweight patients had increased odds of mortality (OR 1.378, p < 0.001 95% CI 1.252-1.514), while being overweight had a protective effect (OR 0.916, p = 0.002 95% CI 0.867-0.968). Class I obesity was not associated with increased mortality compared to normal weight (OR 1.013, p = 0.707 95% CI 0.946-1.085). Class II and Class III obesity were associated with increased mortality risk (Class II OR 1.178, p = 0.001 95% CI 1.069-1.299; Class III OR 1.515, p < 0.001 95% CI 1.368-1.677). Hospital and ICU LOS increased with each successive increase in BMI category above normal weight. Obesity was associated with increased ventilator days; Class I obese patients had a 22% increase in ventilator days (IRR 1.217 95% CI 1.171-1.263), and Class III obese patients had a 54% increase (IRR 1.536 95% CI 1.450-1.627). CONCLUSION: The obesity paradox exists in trauma patients. Further investigation is needed to elucidate what specific phenotypic aspects confer this benefit and how these can enhance patient care. LEVEL OF EVIDENCE: Level III, prognostic study.

An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model.

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6-7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.

Selective reduction of multifetal pregnancy using high-intensity focused ultrasound in the rabbit model.

OBJECTIVE: High-order multifetal pregnancies carry a significant risk of obstetric complications and poor pregnancy outcome. Selective reduction has traditionally been performed using transabdominal and transvaginal ultrasound-guided intracardiac injection of potassium chloride. We have previously shown that high-intensity focused ultrasound (HIFU) can create a coagulative tissue necrosis in the sheep fetus. The objective of this study was to investigate the feasibility of non-invasive selective fetal reduction using HIFU in a rabbit model. METHODS: A protocol for HIFU-induced tissue coagulation was developed in the rabbit model. The fetal heart was targeted with ultrasound-guided tissue ablation by a HIFU beam. Five time-mated does between 20-29 days' gestation underwent transabdominal fetal cardiac ablation in a total of 11 fetuses. The HIFU system consisted of a 7-MHz high-power transducer, operated at 2000 W/cm2. The fetal heart rate was observed using real-time ultrasound with Doppler flow velocimetry. All lesions were assessed macroscopically and by histological analysis. RESULTS: Severe bradycardia leading to asystole was observed in all targeted fetuses with ultrasound examination. Dissection of fetuses demonstrated a necrotic intrathoracic lesion similar in size to the HIFU focus (approximately 1 x 9 mm). None of the surrounding fetuses was found to have bradycardia during the procedure or a macroscopic lesion on dissection. CONCLUSION: In this pilot study HIFU seems promising to ablate even highly vascularized tissue in the fetus.

Weak correlations between local density and dynamics near the glass transition.

We perform experiments on two different dense colloidal suspensions with confocal microscopy to probe the relationship between local structure and dynamics near the glass transition. We calculate the Voronoi volume for our particles and show that this quantity is not a universal probe of glassy structure for all colloidal suspensions. We correlate the Voronoi volume to displacement and find that these quantities are only weakly correlated. We observe qualitatively similar results in a simulation of a polymer melt. These results suggest that the Voronoi volume does not predict dynamical behavior in experimental colloidal suspensions; a purely structural approach based on local single particle volume likely cannot describe the colloidal glass transition.

Growing correlation length on cooling below the onset of caging in a simulated glass-forming liquid.

We present a calculation of a fourth-order, time-dependent density correlation function that measures higher-order spatiotemporal correlations of the density of a liquid. From molecular dynamics simulations of a glass-forming Lennard-Jones liquid, we find that the characteristic length scale of this function has a maximum as a function of time which increases steadily beyond the characteristic length of the static pair correlation function g(r) in the temperature range approaching the mode coupling temperature from above. This length scale provides a measure of the spatially heterogeneous nature of the dynamics of the liquid in the alpha-relaxation regime.

Water and its energy landscape.

We present an overview of the recent studies on the properties of the potential energy surface for a simple model of water. We emphasize the relations between PES properties and dynamics in supercooled states for the model and discuss possible future application of the PES studies.

Spatially correlated dynamics in a simulated glass-forming polymer melt: analysis of clustering phenomena.

In recent years, experimental and computational studies have demonstrated that the dynamics of glass-forming liquids are spatially heterogeneous, exhibiting regions of temporarily enhanced or diminished mobility. Here we present a detailed analysis of dynamical heterogeneity in a simulated "bead-spring" model of a low-molecular-weight polymer melt. We investigate the transient nature and size distribution of clusters of "mobile" chain segments (monomers) as the polymer melt is cooled toward its glass transition. We also explore the dependence of this clustering on the way in which the mobile subset is defined. We show that the mean cluster size is time dependent with a peak at intermediate time, and that the mean cluster size at the peak time grows with decreasing temperature T. We show that for each T a particular fraction of particles maximizes the mean cluster size at some characteristic time, and this fraction depends on T. The growing size of the clusters demonstrates the growing range of correlated motion, previously reported for this same system [C. Beneman et al. Nature (London) 399, 246 (1999)]. The distribution of cluster sizes approaches a power law near the mode-coupling temperature, similar to behavior reported for a simulated binary mixture and a dense colloidal suspension, but with a different exponent. We calculate the correlation length of the clusters, and show that it exhibits similar temperature- and time-dependent behavior as the mean cluster size, with a maximum at intermediate time. We show that the characteristic time of the maximum cluster size follows the scaling predicted by mode-coupling theory (MCT) for the beta time scale, revealing a possible connection between spatially heterogeneous dynamics and MCT.

Dynamics of supercooled water in configuration space.

We study the potential energy surface (PES) sampled by a liquid modeled via the widely studied extended simple point charge (SPC/E) model for water. We characterize the curvature of the PES by calculating the instantaneous normal mode (INM) spectrum for a wide range of densities and temperatures. We discuss the information contained in the INM density of states, which requires additional processing to be unambiguously associated with the long-time dynamics. For the SPC/E model, we find that the slowing down of the dynamics in the supercooled region-where the ideal mode coupling theory has been used to describe the dynamics-is controlled by the reduction in the number of directions in configuration space that allow a structural change. We find that the fraction f(dw) of the double-well directions in configuration space determines the value of the diffusion constant D, thereby relating a property of the PES to a macroscopic dynamic quantity; specifically, it appears that square root D is approximately linear in f(dw). Our findings are consistent with the hypothesis that, at the mode coupling crossover temperature, dynamical processes based on the free exploration of configuration space vanish, and processes requiring activation dominate. Hence, the reduction of the number of directions allowing free exploration of configuration space is the mechanism of diffusion implicitly implemented in the ideal mode coupling theory. Additionally, we find a direct relationship between the number of basins sampled by the system and the number of free directions. In this picture, diffusion appears to be related to geometrical properties of the PES, and to be entropic in origin.

Effects of a nanoscopic filler on the structure and dynamics of a simulated polymer melt and the relationship to ultrathin films.

We perform molecular dynamics simulations of an idealized polymer melt surrounding a nanoscopic filler particle. We show that the glass transition temperature T(g) of the melt can be shifted to either higher or lower temperatures by tuning the interactions between polymer and filler. A gradual change of the polymer dynamics approaching the filler surface causes the change in the glass transition. We also find that polymers close to the surface tend to be elongated and flattened. Our findings show a strong similarity to those obtained for ultrathin polymer films.

Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism.

HYPOTHESIS: Use of intraoperative measurement of intact parathyroid hormone (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does not improve overall operative success rates. DESIGN: Case series of patients undergoing parathyroidectomy with or without intraoperative iPTH measurement. SETTING: University teaching hospital. PATIENTS AND INTERVENTIONS: Fifty patients undergoing parathyroidectomy before our institution of intraoperative iPTH sampling in March 1999 (group 1) were compared with 50 patients undergoing parathyroidectomy after this technique was adopted (group 2). Overall, 100 patients underwent operation between December 1996 and May 2000. Serum calcium and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen sections and operative times were also analyzed. RESULTS: Mean preoperative calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2, respectively. One-month postoperative calcium values were identical in both groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20 [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3 patients in group 2 had intraoperative iPTH levels that returned to normal. There was a significant difference in the number of intraoperative frozen sections between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2 (P<.01). There was no significant difference in operative times between groups. CONCLUSIONS: Use of intraoperative iPTH sampling did not significantly affect the overall success of parathyroidectomy, as determined by postoperative normocalcemia. There was, however, a significant decrease in the number of frozen sections sent at operation.

Thermodynamic and structural aspects of the potential energy surface of simulated water.

Relations between the thermodynamics and dynamics of supercooled liquids approaching a glass transition is a topic of considerable interest. The potential energy surface of model liquids has been increasingly studied, since it provides a connection between the configurational component of the partition function on the one hand, and the system dynamics on the other. This connection is most obvious at low temperatures, where the motion of the system can be partitioned into vibrations within a basin of attraction and infrequent interbasin transitions. In this work, we present a description of the potential energy surface properties of supercooled liquid water. The dynamics of this model have been studied in great detail in recent years. We locate the minima sampled by the liquid by "quenches" from equilibrium configurations generated via molecular dynamics simulations, and then calculate the temperature and density dependence of the basin energy, degeneracy, and shape. The temperature dependence of the energy of the minima is qualitatively similar to simple liquids, but has anomalous density dependence. The unusual density dependence is also reflected in the configurational entropy, the thermodynamic measure of degeneracy. Finally, we study the structure of simulated water at the minima, which provides insight on the progressive tetrahedral ordering of the liquid on cooling.

Evaluation of local abciximab delivery from the surface of a polymer-coated covered stent: in vivo canine studies.

PURPOSE: To determine the in vitro feasibility of abciximab absorption and elution from a polymer-coated, silicone-covered stent, and to determine the in vivo effect of local delivery of abciximab concerning endothelialization of a polymer-coated, silicone-covered stent in a canine model. MATERIALS AND METHODS: Six polymer-coated, silicone-lined Wallstents were soaked in 2 mg/mL of concentrated solution of I131-labeled abciximab for a period as long as 48 hours. Quantification of abciximab absorption was determined by photon emission. Six maximally drug-loaded devices were then washed continuously with normal saline with use of a pustule pump apparatus. The quantity of residual abciximab was determined by photon emission for a period as long as 16 days. Eight similar devices (as described previously) were then implanted within the iliac arteries of four adult canines. Devices were identical except that four of eight were maximally loaded with abciximab. For each animal, one control implant was placed in the right iliac artery and one experimental implant (drug loaded) was placed in the left iliac artery, via right carotid cutdown. Animals were allowed to recover and no chronic medications were given. After an interval of 6 weeks, the animals were killed. Implants were isolated and perfused with 10% buffered formalin at a pressure of approximately 100 mm Hg for a period of 1 hour. Each implant was encased in methacrylate, sectioned into six equal segments, ground and polished, and stained with hematoxylin and eosin. Each slide was projected on a screen and the thickness of the neointima quantified. The mean neointima was determined for control and experimental groups, and compared for a potential significant difference with a Student t test. RESULTS: Mean absorption of abciximab was 21.53 microg +/- 2.99 per device. Devices were fully saturated at 24 hours. Forty percent was absorbed at 1 hour, and 60% and 80% were absorbed at 4 hours and 12 hours, respectively. Regarding elution, 30% of abciximab was washed out after 1 hour. There was a gradual elution of the drug to 16 days, with approximately 40% remaining at the end of the term. Mean neointimal thickness was 995 microm +/- 597 for the experimental group and 1,738 microm +/- 1,042 for the control group. The difference was significant (P <.05). CONCLUSIONS: Absorption and elution of abciximab from the surface of a covered stent is feasible. Local delivery of abciximab from the surface of this covered stent reduced the thickness of endothelial lining in the canine iliac artery compared to control.

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels.

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.

Structure of supercooled and glassy water under pressure.

We use molecular-dynamics simulations to study the effect of temperature and pressure on the local structure of liquid water in parallel with neutron-scattering experiments. We find, in agreement with experimental results, that the simulated liquid structure at high pressure is nearly independent of temperature, and remarkably similar to the known structure of the high-density amorphous ice. Further, at low pressure, the liquid structure appears to approach the experimentally measured structure of low-density amorphous ice as temperature decreases. These results are consistent with the postulated continuity between the liquid and glassy phases of H2O.

Dynamics of simulated water under pressure.

We present molecular dynamics simulations of the extended simple-point-charge model of water to probe the dynamic properties at temperatures from 350 K down to 190 K and pressures from 2.5 GPa (25 kbar) down to -300 MPa (-3 kbar). We compare our results with those obtained experimentally, both of which show a diffusivity maximum as a function of pressure. We find that our simulation results are consistent with the predictions of the mode-coupling theory for the dynamics of weakly supercooled liquids--strongly supporting the hypothesis that the apparent divergences of dynamic properties observed experimentally may be independent of a possible thermodynamic singularity at low temperature. The dramatic change in water's dynamic and structural properties as a function of pressure allows us to confirm the predictions of MCT over a much broader range of the von Schweidler exponent values than has been studied for simple atomic liquids. We also show how structural changes are reflected in the wave-vector dependence of dynamic properties of the liquid along a path of nearly constant diffusivity. For temperatures below the crossover temperature of MCT (where the predictions of MCT are expected to fail), we find tentative evidence for a crossover of the temperature dependence of the diffusivity from power-law to Arrhenius behavior, with an activation energy typical of a strong liquid.

Intestinal absorption of Mn-mesoporphyrin in a small bowel sac system: effect of oleic acid.

RATIONALE AND OBJECTIVES: The authors investigated the effect of oleic acid (cis-9-octadecenoic acid) (OA), a lipidic carrier, on the intestinal absorption rate and T1 relaxation time of manganese (III) mesoporphyrin (Mn-mesoporphyrin), a prototype hepatobiliary contrast agent for magnetic resonance imaging. METHODS: Mn-mesoporphyrin was formulated with OA at various concentrations. Small bowel sacs were created in 36 rats and filled with complexed and free Mn-mesoporphyrin. Intestinal absorption of Mn-mesoporphyrin was measured with spectrophotometry at 364 nm. T1 relaxation times were measured in samples of Mn-mesoporphyrin solutions, bowel wall, liver, and bile. RESULTS: Absorption rates ranged from 4.2%/cm2/h to 13%/cm2/h. Absorption was greatest (13%/cm2/h) when a combination of 1 mmol/L Mn-mesoporphyrin and 26.5 mmol/L OA was used. The T1 of bile decreased from 2,480 to 248 msec (maximum decrease) in rats that received Mn-mesoporphyrin. CONCLUSION: Mn-mesoporphyrin is absorbed from the small bowel in both the lipid-associated and free form, resulting in substantial shortening of the T1 in bile.

Renal perfusion: pharmacologic changes depicted with power Doppler US in an animal model.

PURPOSE: To evaluate the ability of power Doppler ultrasonography to depict changes in renal perfusion after pharmacologic manipulations. MATERIALS AND METHODS: Six domestic swine were intubated and anesthetized. The right renal artery was catheterized for injection of epinephrine (100 micrograms) and papaverine (2 mg/kg). Intraarterial blood pressure, heart rate, and oxygen saturation were measured continuously. Longitudinal images of the kidney were obtained, and the power Doppler color map was analyzed subjectively and by computer at baseline and at the time of maximum drug effect. RESULTS: Epinephrine produced vasoconstriction with a diminished power Doppler color map and a decrease in both subjective and computer scores. After papaverine-induced vasodilatation, the power Doppler map was enhanced, as reflected by increased subjective and computer scores. CONCLUSION: The power Doppler color map reflects anticipated changes in renal perfusion after alterations in blood flow by vasoactive drugs.

Magnetic resonance imaging of the hepatobiliary system: intestinal absorption studies of manganese mesoporphyrin.

RATIONALE AND OBJECTIVES: We studied the intestinal absorption of manganese mesoporphyrin (Mn-mesoporphyrin), a potential oral hepatobiliary contrast agent. METHODS: Mn-mesoporphyrin was complexed with monoolein and taurocholate (mixed micelles). Portal venous delivery and biliary excretion were measured after intestinal administration in rats and rabbits, and the mechanism of intestinal transport was studied in a combined lymph-bile fistula model in rats. T1-weighted magnetic resonance (MR) images of the liver were obtained in rats and domestic pigs before and after gastric administration of Mn-mesoporphyrin in mixed micelles. RESULTS: A 2.2-fold increase of portal venous Mn concentration was found 90 min after intestinal administration of the complex. None was found in the lymph collected from the thoracic duct, indicating a transcellular transport mechanism through the intestinal mucosa with portal venous delivery. Mn-mesoporphyrin levels in bile peaked between 240 and 270 min after administration (200-fold increase). The greatest liver enhancement (20-90%) was measured 360 min after administration. CONCLUSION: The feasibility of intestinal delivery of Mn-mesoporphyrin, a lipophilic hepatobiliary contrast agent was demonstrated.

Blood back flow into angiographic catheters.

PURPOSE: Because of a potential impact on thrombus formation, this study determines the degree of blood back flow into catheters filled with different fluids. MATERIALS AND METHODS: Catheters filled with saline or non-ionic or ionic contrast medium were placed in pulsatile circulating human blood in vitro. Catheter orientation was varied, and blood back flow was recorded. RESULTS: When the leading end of the catheter was angled downward, blood back flow into a contrast material-filled catheter was far greater than that into a saline-filled catheter (7.0 vs 0.5 cm). Conversely, when the leading end of the catheter was horizontal, blood back flow was much greater when the catheter contained saline versus contrast media (3.6 vs 0.4 cm). Ionicity of contrast material did not affect back flow. CONCLUSION: Back flow of blood into a catheter can be considerable and is dependent on the type of fluid within the catheter and orientation of the leading end of the catheter. Angiographic techniques adjusted to these findings are important to maintain patient safety.