Impaired hepatic removal of interleukin-6 in patients with liver cirrhosis

Systemic concentrations of interleukin-6 (IL-6) are elevated in patients with liver cirrhosis, and impaired hepatic uptake of IL-6 was suggested to contribute to higher levels in these patients. To test this hypothesis IL-6 was measured in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 41 patients with liver cirrhosis and four patients with normal liver function. IL-6 was higher in PVS than HVS of all blood donors and about 43% of portal vein derived IL-6 was extracted by the healthy liver, and 6.3% by the cirrhotic liver demonstrating markedly impaired removal of IL-6 by the latter. Whereas in patients with CHILD-PUGH stage A IL-6 in HVS was almost 25% lower than in PVS, in patients with CHILD-PUGH stage C IL-6 was similarly abundant in the two blood compartments. Ascites is a common complication in cirrhotic patients and was associated with higher IL-6 levels in all blood compartments without significant differences in hepatic excretion. Hepatic venous pressure gradient did not correlate with the degree of hepatic IL-6 removal excluding hepatic shunting as the principal cause of impaired IL-6 uptake. Furthermore, patients with alcoholic liver cirrhosis had higher IL-6 in all blood compartments than patients with cryptogenic liver cirrhosis. Aetiology of liver cirrhosis did not affect hepatic removal rate indicating higher IL-6 synthesis in patients with alcoholic liver cirrhosis. In summary, the current data provide evidence that impaired hepatic removal of IL-6 is explained by hepatic shunting and liver dysfunction in patients with liver cirrhosis partly explaining higher systemic levels.

The challenge of triaging chest pain patients: the bernese university hospital experience

Accurate diagnosis of the causes of chest pain and dyspnea remain challenging. In this preliminary observational study with a 5-year follow-up, we attempted to find a simplified approach to selecting patients with chest pain needing immediate care based on the initial evaluation in ED. During a 24-month period were randomly selected 301 patients and a conditional inference tree (CIT) was used as the basis of the prognostic rule. Common diagnoses were musculoskeletal chest pain (27%), ACS (19%) and panic attack (12%). Using variables of ACS symptoms we estimated the likelihood of ACS based on a CIT to be high at 91% (32), low at 4% (198) and intermediate at 20.5-40% in (71) patients. Coronary catheterization was performed within 24 hours in 91% of the patients with ACS. A culprit lesion was found in 79%. Follow-up (median 4.2 years) information was available for 70% of the patients. Of the 164 patients without ACS who were followed up, 5 were treated with revascularization for stable angina pectoris, 2 were treated with revascularization for myocardial infarction, and 25 died. Although a simple triage decision tree could theoretically help to efficient select patients needing immediate care we need also to be vigilant for those presenting with atypical symptoms.

Forced fluid removal in critically ill patients with acute kidney injury

The aim was to test the feasibility of protocol-driven fluid removal with continuous renal replacement therapy (CRRT) in patients in whom standard fluid balance prescription did not result in substantial negative fluid balances.

Enamel loss and adhesive remnants following bracket removal and various clean-up procedures in vitro

This study evaluated the enamel loss and composite remnants after debonding and clean-up. The tested null hypothesis is that there are no differences between different polishing systems regarding removing composite remnants without damaging the tooth surface. Brackets were bonded to 75 extracted human molars and removed after a storage period of 100 hours. The adhesive remnant index (ARI) was evaluated. The clean-up was carried out with five different procedures: 1. carbide bur; 2. carbide bur and Brownie and Greenie silicone polishers; 3. carbide bur and Astropol polishers; 4. carbide bur and Renew polishers; and 5. carbide bur, Brownie, Greenie and PoGo polishers. Silicone impressions were made at baseline (T0) and after debonding (T1) and polishing (T2) to produce plaster replicas. The replicas were analysed with a three-dimensional laser scanner and measured with analytical software. Statistical analysis was performed with the Kruskal-Wallis test and pairwise Wilcoxon tests with Bonferroni-Holm adjustment (α = 0.05). Enamel breakouts after debonding were detectable in 27 per cent of all cases, with a mean volume loss of 0.02 mm(3) (±0.03 mm(3)) and depth of 44.9 μm (±48.3 μm). The overall ARI scores was 3 with a few scores of 1 and 2. The composite remnants after debonding had a mean volume of 2.48 mm(3) (±0.92 mm(3)). Mean volume loss due to polishing was 0.05 mm(3) (±0.26 mm(3)) and the composite remnants had a mean volume of 0.22 mm(3) (±0.32 mm(3)). There were no statistically significant differences in volumetric changes after polishing (P = 0.054) between the different clean-up methods. However, sufficient clean-up without enamel loss was difficult to achieve.

Comparison of dual-energy subtraction and electronic bone suppression combined with computer-aided detection on chest radiographs: effect on human observers' performance in nodule detection

The objective of our study was to compare the effect of dual-energy subtraction and bone suppression software alone and in combination with computer-aided detection (CAD) on the performance of human observers in lung nodule detection.

Impact of image quality, radiologists, lung segments, and Gunnar eyewear on detectability of lung nodules in chest CT

BackgroundDespite the increasingly higher spatial and contrast resolution of CT, nodular lesions are prone to be missed on chest CT. Tinted lenses increase visual acuity and contrast sensitivity by filtering short wavelength light of solar and artificial origin.PurposeTo test the impact of Gunnar eyewear, image quality (standard versus low dose CT) and nodule location on detectability of lung nodules in CT and to compare their individual influence.Material and MethodsA pre-existing database of CT images of patients with lung nodules >5 mm, scanned with standard does image quality (150 ref mAs/120 kVp) and lower dose/quality (40 ref mAs/120 kVp), was used. Five radiologists read 60 chest CTs twice: once with Gunnar glasses and once without glasses with a 1 month break between. At both read-outs the cases were shown at lower dose or standard dose level to quantify the influence of both variables (eyewear vs. image quality) on nodule sensitivity.ResultsThe sensitivity of CT for lung nodules increased significantly using Gunnar eyewear for two readers and insignificantly for two other readers. Over all, the mean sensitivity of all radiologist raised significantly from 50% to 53%, using the glasses (P value = 0.034). In contrast, sensitivity for lung nodules was not significantly affected by lowering the image quality from 150 to 40 ref mAs. The average sensitivity was 52% at low dose level, that was even 0.7% higher than at standard dose level (P value = 0.40). The strongest impact on sensitivity had the factors readers and nodule location (lung segments).ConclusionSensitivity for lung nodules was significantly enhanced by Gunnar eyewear (+3%), while lower image quality (40 ref mAs) had no impact on nodule sensitivity. Not using the glasses had a bigger impact on sensitivity than lowering the image quality.

Prion removal capacity of plasma protein manufacturing processes

BACKGROUND The variant Creutzfeldt-Jakob disease incidence peaked a decade ago and has since declined. Based on epidemiologic evidence, the causative agent, pathogenic prion, has not constituted a tangible contamination threat to large-scale manufacturing of human plasma-derived proteins. Nonetheless, manufacturers have studied the prion removal capabilities of various manufacturing steps to better understand product safety. Collectively analyzing the results could reveal experimental reproducibility and detect trends and mechanisms driving prion removal. STUDY DESIGN AND METHODS Plasma Protein Therapeutics Association member companies collected more than 200 prion removal studies on plasma protein manufacturing steps, including precipitation, adsorption, chromatography, and filtration, as well as combined steps. The studies used a range of model spiking agents and bench-scale process replicas. The results were grouped based on key manufacturing variables to identify factors impacting removal. The log reduction values of a group are presented for comparison. RESULTS Overall prion removal capacities evaluated by independent groups were in good agreement. The removal capacity evaluated using biochemical assays was consistent with prion infectivity removal measured by animal bioassays. Similar reduction values were observed for a given step using various spiking agents, except highly purified prion protein in some circumstances. Comparison between combined and single-step studies revealed complementary or overlapping removal mechanisms. Steps with high removal capacities represent the conditions where the physiochemical differences between prions and therapeutic proteins are most significant. CONCLUSION The results support the intrinsic ability of certain plasma protein manufacturing steps to remove prions in case of an unlikely contamination, providing a safeguard to products.

PVR recurrence and the timing of silicon oil removal

BACKGROUND: Following vitrectomy for PVR-associated retinal detachment, placement of an encircling band, filling with silicone oil (SO) and successful retinal reattachment, a recurrence of PVR can develop. Retinal redetachment after SO removal is usually due to secondary or residual PVR. We wanted to ascertain whether the anatomical and functional outcomes of surgery in patients with a reattached retina and recurrent PVR can be improved by delaying the removal of SO. PATIENTS AND METHODS: 112 consecutive patients with PVR-associated retinal detachment who had undergone vitrectomy with SO filling, were monitored for at least 6 months after SO removal. Prior to SO removal, the retina posterior to the encircling band had to be completely reattached. Patients who developed PVR after SO filling were divided into two groups according to the duration of SO retention: 12 - 18 months (group 2: n = 48); > 18 months (group 3: n = 21). Individuals without PVR recurrence after SO filling and in whom the SO was consequently removed within 4 - 12 months served as control (group 1: n = 43). Anatomical success, intraocular pressure (IOP) and best-corrected visual acuity (BCVA) served as the primary clinical outcome parameters. RESULTS: Six months after SO removal, the anatomical success rates (86.3 %, 88.8 % and 84.6 %, in groups 1, 2 and 3, respectively; log rank = 0.794) and the BCVAs (p = 0.861) were comparable in the three groups. Mean IOP (p = 0.766), and the frequency of complications such as PVR recurrence (p = 0.936), bullous keratopathy (p = 0.981) and macular pucker (p = 0.943) were likewise similar. Patients in whom SO was retained for more than 18 months had the highest IOPs and required the heaviest dosage with anti-glaucoma drugs. CONCLUSIONS: In patients who develop a recurrence of PVR after vitrectomy and SO filling the surgeon can observe and treat retinal changes for up to 18 months without impairing the anatomical and functional outcomes. The retention of SO for more than 18 months does not improve the anatomical outcome. However, it can impair the functional outcome by precipitating the development of a persisting secondary glaucoma.