Evaluation of medical decision support systems (DDX generators) using real medical cases of varying complexity and origin.

BACKGROUND: Medical decision support systems (CDSSs) are increasingly used in medicine, but their utility in daily medical practice is difficult to evaluate. One variant of CDSS is a generator of differential diagnoses (DDx generator). We performed a feasibility study on three different, publicly available data sets of medical cases in order to identify the frequency in which two different DDx generators provide helpful information (either by providing a list of differential diagnosis or recognizing the expert diagnosis if available) for a given case report. METHODS: Used data sets were n = 105 cases from a web-based forum of telemedicine with real life cases from Afghanistan (Afghan data set; AD), n = 124 cases discussed in a web-based medical forum (Coliquio data set; CD). Both websites are restricted for medical professionals only. The third data set consisted 50 special case reports published in the New England Journal of Medicine (NEJM). After keyword extraction, data were entered into two different DDx generators (IsabelHealth (IH), Memem7 (M7)) to examine differences in target diagnosis recognition and physician-rated usefulness between DDx generators. RESULTS: Both DDx generators detected the target diagnosis equally successfully (all cases: M7, 83/170 (49%); IH 90/170 (53%), NEJM: M7, 28/50 (56%); IH, 34/50 (68%); differences n.s.). Differences occurred in AD, where detection of an expert diagnosis was less successful with IH than with M7 (29.7% vs. 54.1%, p = 0.003). In contrast, in CD IH performed significantly better than M7 (73.9% vs. 32.6%, p = 0.021). Congruent identification of target diagnosis occurred in only 46/170 (27.1%) of cases. However, a qualitative analysis of the DDx results revealed useful complements from using the two systems in parallel. CONCLUSION: Both DDx systems IsabelHealth and Memem7 provided substantial help in finding a helpful list of differential diagnoses or identifying the target diagnosis either in standard cases or complicated and rare cases. Our pilot study highlights the need for different levels of complexity and types of real-world medical test cases, as there are significant differences between DDx generators away from traditional case reports. Combining different results from DDx generators seems to be a possible approach for future review and use of the systems.

[Metabolic acidosis : Diagnosis and treatment]. / Metabolische Azidose : Diagnostik und Therapie.

Acid-base disorders and in particular metabolic acidosis are very common in critically ill patients and contribute significantly to morbidity and mortality. We shed light on the most common causes, the pathophysiology and treatments. Particular attention will be paid to the common practice of substituting sodium bicarbonate in the light of recent study results.

Renal complications of cancer therapies.

Cancer patients often exhibit preexisting renal impairment and are simultaneously at risk for developing further kidney injury due to direct or indirect complications of oncological therapies. The nature of kidney injury is highly dependent on the therapy regimen used, and the spectrum of possible kidney stressors has widened as a result of the development of new therapeutic modalities such as molecular therapy or immunotherapy. Indirect renal complications are often due to volume depletion or other therapy-related side effects. Direct toxicity from "classic" chemotherapy treatments such as cisplatin usually leads to acute tubular necrosis, whereas treatment with protein kinase inhibitors is more likely to cause disorders such as thrombotic microangiopathy. Immunotherapy often affects kidneys through the development of acute interstitial nephritis. Because of the high risk of nephrological complications in oncological patients, close monitoring of renal function and the early involvement of a nephrologist are strongly recommended.

Block copolymer arrangement and composition effects on protein conformation using atomic force microscope-based antigen-antibody adhesion.

The conformational changes of fibronectin (FN) deposited on various block copolymers where one block is composed of poly(methyl methacrylate) (PMMA) and the other block is either poly(acrylic acid) (PAA) or poly(2-hydroxyethyl methacrylate) (PHEMA) were investigated using a functionalized atomic force microscope (AFM) tip. The tip was modified with an antibody sensitive to the exposure of the arginine-glycine-aspartic acid (RGD) groups in FN. By studying the adhesive interactions between the antibody and the proteins adsorbed on the block copolymer surface and phase imaging, it was found that the triblock copolymers PAA-b-PMMA-b-PAA and PMMA-b-PHEMA-b-PMMA, which both have large domain sizes, are conducive to the exposure of the FN RGD groups on the surface. On the basis of these results, it is concluded that the surface chemistry as well as the nanomorphology dictated by the block copolymer arrangement could both tune protein conformation and orientation and optimize cell adhesion to the biomaterial surface.

Morphology and protein adsorption characteristics of block copolymer surfaces.

Biocompatible polymers are known to act as scaffolds for the regeneration and growth of bone. Block copolymers are of interest as scaffold materials because novel, structurally diverse polymers can be synthesized from biocompatible blocks. Block copolymer nanostructure and surface morphology is easily tunable with synthetic techniques and the diverse nanostructures can be used to affect cell and tissue behaviour. In this paper, we present atomic force microscopy studies on the morphology and corresponding protein adsorption behaviour of a novel class of methyl methacrylate and acrylic acid diblock and triblock copolymers. The topography, phase angle and adhesion maps were obtained to study the morphology. Atomic force microscopy imaging reveals that the diblock and triblock copolymers present distinct nanomorphologies, although their chemical composition is the same. This has implications on the role of nanomorphology in cell-polymer interactions independent of chemical composition. Protein adsorption on a biomaterial surface is critical to understanding its biocompatibility and bovine serum albumin was used to model that behaviour on the block copolymer surfaces. An increase in the adhesive force of the surface was observed to correlate with the adsorption of bovine serum albumin on the block copolymer surfaces investigated.

Fracture toughness of modified dental resin systems.

This study compared the relative fracture toughness of a Bis-GMA//TEGDMA (50:50 wt%)-based resin system modified by 5, 10, and 15 wt% of a methacrylate-terminated poly(butadiene-acrylonitrile-acrylic acid) terpolymer toughening agent. After storage in distilled water at 37 +/- 2 degrees C for 7 days, plane strain fracture toughness (KIC) was determined on an Instron testing machine at a 0.5-mm min-1 displacement rate. The glass transition temperature (Tg) in degrees C was determined after 7 days (dry and wet) storage by thermomechanical analysis. The results of this study showed significantly improved fracture toughness and lowered water sorption with the modified resin systems which was indicated by higher wet glass transition temperatures.

Influence of hyperbranched multi-methacrylates for dental neat resins on proliferation of human gingival fibroblasts.

We have previously shown that hyperbranched multi-methacrylate (H-MMA)-modified dental resins have VLC activities, lower polymerization shrinkage, and improved mechanical properties, compared to the 2,2-bis[4-(2-hydroxy-3-methacryloyolxypropoxy)phenyl]propane/triethyleneglycol dimethacrylate (BisGMA/TEGDMA) neat resin. The results are due to the unique molecular structure and high molecular weight of H-MMA intermediates. The purpose of this study was to evaluate the biocompatibility of H-MMA-modified dental neat resins. The cell proliferation of three human gingival fibroblast strains on either H-MMA, BisGMA/TEGDMA, or a polystyrene disk was examined. Following 10 days of cell proliferation, there was no statistical difference in cell number between H-MMA-modified and unmodified resin disks. H-MMA-modified resins had less free monomer leaching than the unmodified resin but showed similar properties in water sorption and contact angle values. All these results suggest that the biocompatibility of H-MMA-modified dental neat resins is as good as that of commercially used BisGMA/TEGDMA resin and H-MMA has potential applications in dental composites.

von Willebrand factor: an endothelial marker to monitor in-vitro fertilization patients with ovarian hyperstimulation syndrome.

A retrospective study was conducted to evaluate the possible role of endothelial and extracellular factors in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Plasma changes in von Willebrand-Jürgen factor were correlated with the clinical condition of hyperstimulated patients, since the rise of capillary permeability is the central event in all subsequent morbidity. The corresponding oestradiol levels and ultrasound parameters were assessed. In-vitro fertilization patients designated as 'high responders' and with oestradiol values > 2500 pg/ml and > 8 pre-ovulatory follicles at the time of human chorionic gonadotrophin (HCG) injection were assessed. Among 62 patients, 37 fulfilled these criteria and 18 developed OHSS, indicating the low predictive ability of ultrasound and oestradiol values alone. The remaining 19 patients served as control group. von Willebrand factor-associated antigen in plasma was measured using enzyme-linked immunosorbent assay and ristocetin co-factor activity by an aggregatometric test. Basal values of the two groups of patients did not differ but there were large inter-individual variations. A slight increase occurred in the control group until the day of HCG although individual cycles showed 'no change of pattern' or a 'decreasing tendency' from the start. Some patients allocated to the non-hyperstimulated type showed a steep increase of values followed by a decline. A consistent increase in the OHSS group lasted after embryo transfer even to the late corpus luteum phase. These subtle changes of capillary permeability or damage always preceded the clinical signs, such as ascites, haemoconcentration, hypoproteinaemia and pleural effusion. Mean values differed in the two groups from the day preceding ovum retrieval.(ABSTRACT TRUNCATED AT 250 WORDS)

Charge and acidity compensation during proton-sugar symport in Chlorella: The H(+)-ATPase does not fully compensate for the sugar-coupled proton influx.

This study was undertaken in order to demonstrate the extent to which the activity of the plasmalemma H(+)-ATPase compensates for the charge and acidity flow caused by the sugar-proton symport in cells of chlorella vulgaris Beij.. Detailed analysis of H(+) and K(+) fluxes from and into the medium together with measurements of respiration, cytoplasmic pH, and cellular ATP-levels indicate three consecutive phases after the onset of H(+) symport. Phase 1 occurred immediately after addition of sugar, with an uptake of H(+) by the hexoseproton symport and charge compensation by K(+) loss from the cells and, to a smaller degree, by loss of another ion, probably a divalent cation. This phase coincided with strong membrane depolarization. Phase 2 started approximately 5 s after addition of sugar, when the acceleration of the H(+)-ATPase caused a slow-down of the K(+) efflux, a decrease in the cellular ATP level and an increase in respiration. The increased respiration was most probably responsible for a pronounced net acidification of the medium. This phase was inhibited in deuterium oxide. In phase 3, finally, a slow rate of net H(+) uptake and K(+) loss was established for several further minutes, together with a slight depolarization of the membrane. There was hardly any pH change in the cytoplasm, because the cytoplasmic buffering capacity was high enough to stabilize the pH for several minutes despite the net H(+) fluxes. The quantitative participation of the several phases of H(+) and K(+) flow depended on the pH of the medium, the ambient Ca(2+) concentration, and the metabolic fate of the transported sugar. The results indicate that the activity of the H(+)-ATPase never fully compensated for H(+) uptake by the sugar-symport system, because at least 10% of symport-caused charge inflow was compensated for by K(+) efflux. The restoration of pH in the cytoplasm and in the medium was probably achieved by metabolic reactions connected to increased glycolysis and respiration.