A comparative study of postendoscopic sphincterotomy complications with various types of electrosurgical current in patients with choledocholithiasis

BACKGROUND: Whether the type of electrosurgical current used for endoscopic sphincterotomy influences the frequency of postsphincterotomy complications is unknown. METHODS: One hundred eighty-six patients with choledocholithiasis were prospectively randomized to undergo endoscopic sphincterotomy with pure cutting current (n = 62, Group A), blended current (n = 62, Group B), or pure cutting initially followed by blended current (n = 62, Group C). Serum concentrations of amylase and lipase were evaluated in all patients 12 and 24 hours after sphincterotomy. Clinical pancreatitis was classified as mild, moderate, or severe. Postsphincterotomy bleeding was defined as a decrease in hematocrit of greater than 5%. RESULTS: Serum concentrations of amylase and lipase were greater in Groups B and C at 12 and 24 hours after the procedure, as compared with Group A. Clinical mild pancreatitis occurred in 2 patients in Group A (3.2%), 8 in Group B (12.9%), and in 8 in Group C (12.9%). The differences were statistically significant for Group A compared with either Group B or Group C (p = 0.048). Postsphincterotomy bleeding occurred in 3 patients (1.6%), one in each group. CONCLUSION: The use of pure cutting electrosurgical current during endoscopic sphincterotomy in patients with choledocholithiasis is associated with a lesser degree of pancreatic enzyme elevation and lower frequency of pancreatitis, whereas bleeding is not increased compared with blended current. Changing from pure cutting to blended current after the first 3 to 5 mm of the incision is associated with an increased rate of complications compared to the use of pure cutting current for the entire sphincterotomy.     

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators

OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.     

End-inspiratory occlusion maneuver during transesophageal echocardiography for patent foramen ovale detection in intensive care unit patients

Objective Mechanically ventilated patients in the intensive care unit cannot cooperate to perform the Valsalva maneuver during echocardiography for detection of patent foramen ovale. We evaluated the effectiveness of the end-inspiratory occlusion maneuver to enhance detection of patent foramen ovale in this patient population. Design Prospective interventional study. Setting The 40-bed intensive care unit of a university hospital. Patients and participants Twenty five sedated and mechanically ventilated intensive care unit patients referred by their attending physician for bedside transesophageal echocardiography and agitated saline contrast study for detection of patent foramen ovale. Intervention Agitated saline contrast study with end-inspiratory occlusion maneuver. Measurements and results All patients underwent a complete transesophageal echocardiographic study without any complications. Reduction in right atrial cross-sectional area (from 15.80 ± 6.08 cm² to 12.40 ± 4.63 cm²; p < 0.001) and interatrial septum deviation during the maneuver were recorded in all patients. Microbubbles imaged in the left atrium within three cardiac cycles after injection of agitated saline diagnosed patent foramen ovale in three patients. When end-inspiratory occlusion maneuver was added, patent foramen ovale was diagnosed in seven patients (McNemar χ² = 9.33, p = 0.0023). Conclusions The end-inspiratory occlusion maneuver enhances the sensitivity of transesophageal echocardiography with agitated saline contrast study for diagnosing intermittent patent foramen ovale in critically ill mechanically ventilated patients. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Pro‐inflammatory self‐reactive T cells are found within murine TCR‐αβ+CD4−CD8−PD‐1+ cells

TCR‐αβ⁺ double negative (DN) T cells (CD3⁺TCR‐αβ⁺CD4^?CD8^?NK1.1^?CD49b^?) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro‐inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self‐reactive CD8⁺ T cells become DN after activation by self‐antigens, suggesting that self‐reactive T cells may exist within the DN T‐cell population. Here, we demonstrate that programmed cell death 1 (PD‐1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation‐associated markers and a phenotype that strongly suggests they are derived from self‐reactive CD8⁺ cells. We also found that, within DN T cells, the PD‐1⁺ subset generates the majority of pro‐inflammatory cytokines. Finally, using a TCR‐activation reporter mouse (Nur77‐GFP), we confirmed that in the steady‐state PD‐1⁺ DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD‐1⁺ fraction of DN T cells represents self‐reactive cells.     

The effect of angulation in abdominal aortic aneurysms: fluid–structure interaction simulations of idealized geometries

Abdominal aortic aneurysm (AAA) represents a degenerative disease process of the abdominal aorta that results in dilation and permanent remodeling of the arterial wall. A fluid structure interaction (FSI) parametric study was conducted to evaluate the progression of aneurysmal disease and its possible implications on risk of rupture. Two parametric studies were conducted using (i) the iliac bifurcation angle and (ii) the AAA neck angulation. Idealized streamlined AAA geometries were employed. The simulations were carried out using both isotropic and anisotropic wall material models. The parameters were based on CT scans measurements obtained from a population of patients. The results indicate that the peak wall stresses increased with increasing iliac and neck inlet angles. Wall shear stress (WSS) and fluid pressure were analyzed and correlated with the wall stresses for both sets of studies. An adaptation response of a temporary reduction of the peak wall stresses seem to correlate to a certain extent with increasing iliac angles. For the neck angulation studies it appears that a breakdown from symmetric vortices at the AAA inlet into a single larger vortex significantly increases the wall stress. Our parametric FSI study demonstrates the adaptation response during aneurysmal disease progression and its possible effects on the AAA risk of rupture. This dependence on geometric parameters of the AAA can be used as an additional diagnostic tool to help clinicians reach informed decisions in establishing whether a risky surgical intervention is warranted.     

Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia

Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to possess antioxidant properties, which may explain some of their beneficial effects in reducing atherosclerosis. We sought to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels differ between subjects with isolated hypercholesterolemia and combined hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL according to the type of dyslipidemia. Twenty-five subjects with total cholesterol >200 mg/dl and triglycerides <150 mg/dl, and 22 subjects with total cholesterol >200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox-LDL, and free radicals were measured at baseline and after 3 months of treatment. In both groups studied, simvastatin significantly improved lipids, and reduced C-reactive protein and fibrinogen levels. Free radicals were significantly reduced only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia had significantly higher baseline levels of ox-LDL compared to those with hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In conclusion, subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia. Simvastatin significantly reduced circulating ox-LDL in both groups, but whether this reduction is related to clinical outcomes remains to be shown.     

Fever of unknown origin: Discrimination between infectious and non-infectious causes

ObjectiveThe present study aimed to develop and evaluate a simple diagnostic model that could aid physicians to discriminate between infectious and non-infectious causes of fever of unknown origin (FUO).Design/Setting/SubjectsPatients with classical FUO were studied in two distinct, prospective, observational phases. In the derivation phase that lasted from 1992 to 2000, 33 variables regarding demographic characteristics, history, symptoms, signs, and laboratory profile were recorded and considered in a logistic regression analysis using the diagnosis of infection as a dependent variable. In the validation phase, the discriminatory capacity of a score based on the derived predictors of infection was calculated for FUO patients assessed from 2001 to 2007.ResultsData from 112 individuals (mean age 56.5 ± 11.2 years) were analyzed in the derivation cohort. The final diagnoses included infections, malignancies, non-infectious inflammatory diseases, and miscellaneous conditions in 30.4%, 10.7%, 33% and 5.4% of subjects, whereas 20.5% of cases remained undiagnosed. C-reactive protein > 60 mg/L (odds ratio 6.0 [95% confidence intervals 2.5, 9.8]), eosinophils < 40/mm³ (4.1 [2.0, 7.3]) and ferritin < 500 μg/L (2.5 [1.3, 5.2]) were independently associated with diagnosis of infection. Among the 100 patients of the validation cohort, the presence of ≥ 2 of the above factors predicted infection with sensitivity, specificity, and positive and negative predictive values of 91.4%, 92.3%, 86.5%, and 95.2%, respectively.ConclusionsThe combination of C-reactive protein, ferritin and eosinophil count may be useful in discriminating infectious from non-infectious causes in patients hospitalised for classical FUO.     

Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial

Purpose  

Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting ⁹⁰Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of ⁹⁰Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide ²¹³Bi with a mean tissue range of 81 μm may have a more favourable toxicity profile. Therefore, we evaluated locally injected ²¹³Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality.