Limited role of aortic size in the genesis of acute type A aortic dissection

Objective: Increased dimension of the aortic root and proximal aorta is considered a significant risk factor for catastrophic events that involve the ascending aorta. The objective of this study was to determine the possible correlation between pre-dissection aortic diameter and the occurrence of Stanford type A aortic dissection. Methods: Samples of dissected ascending aortas were obtained from 220 patients at the time of their operation. Two groups were identified: patients with connective tissue disorders (Group 1, n = 94) and those without (Group 2, n = 126). Measurements of the true (intimal) lumen were conducted and extrapolated as reliable approximation of pre-dissection aortic diameter. The possible association of intimal diameter with anthropometric and demographic data was analyzed. Results: Median aortic diameter was, respectively, 41.8 and 41.3 mm for patients with and without connective tissue disorders (41.4 mm for the entire cohort). Data analysis indicated that 57% of patients had aortic diameter above 40 mm, while patients with frank aneurysm accounted only for 10%; this proportion was higher in Group 1 compared to Group 2 (17.2% vs 4.7%). Poor or no correlation was demonstrated between aortic size and any of the anthropometric or demographic variables essayed. Significant subgroup differences were found among patients with a history of cigarette smoking, hypertension, diabetes, chronic renal insufficiency, and bicuspid aortic valve. Conclusion: Although aortic diameter remains a strong indication for preventive surgery in patients with inherited connective tissue disorders, acute aortic dissection occurs rarely in the setting of true ascending aortic aneurysms, and despite normal or near-normal aortic size in more than one-third of subjects. Dissection superimposing on small aortic diameters can be regarded as an expression of substantial functional tissue susceptibility to aortic catastrophic events.     

Development and remodeling of engineered cartilage-explant composites in vitro and in vivo

OBJECTIVE: Development and remodeling of engineered cartilage-explant composites were studied in vitro and in vivo. DESIGN: Individual and interactive effects of cell chondrogenic potential (primary or fifth passage bovine calf chondrocytes), scaffold degradation rate (hyaluronan benzyl ester or polyglycolic acid), and adjacent tissue cell activity and architecture (vital trabecular bone (VB), articular cartilage (AC), devitalized bone (DB) or digested cartilage (DC)) were evaluated over 8 weeks in vitro (bioreactor cultures) and in vivo (ectopic implants). RESULTS: In vitro, significant effects of cell type on construct adhesive strength (P<0.001) and scaffold type on adhesive strength (P<0.001), modulus (P=0.014), glycosaminoglycans (GAG) (P<0.001), and collagen (P=0.039) were observed. Chondrogenesis was best when the scaffold degradation rate matched the extracellular matrix deposition rate. In vivo, adjacent tissue type affected adhesive strength (P<0.001), modulus (P<0.001), and GAG (P<0.001) such that 8-week values obtained for bone (VB and DB) were higher than for cartilage (AC). In the AC/construct group, chondrogenesis appeared attenuated in the region of the construct close to the AC. In contrast, in the VB/construct group, a 500 microm thick zone of mature hyaline-like cartilage formed at the interface, and signs of active remodeling were present in the bone that included osteoclastic and osteoblastic activity and trabecular rebuttressing; these features were not present in the DB group or in vitro. CONCLUSIONS: Development and remodeling of composites based on engineered cartilage were mediated in vitro by cell chondrogenic potential and scaffold degradation rate, and in vivo by type of adjacent tissue and time.     

Multimethod Evaluation of Information and Communication Technologies in Health in the Context of Wicked Problems and Sociotechnical Theory

Objective

Few research designs look at the deep structure of complex social systems. We report the design and implementation of a multimethod evaluation model to assess the impact of computerized order entry systems on both the technical and social systems within a health care organization.

Design

We designed a multimethod evaluation model informed by sociotechnical theory and an appreciation of the nature of wicked problems. We mobilized this model to assess the impact of an electronic medication management system via a three-year program of research at a major academic hospital.

Measurements

Model components include measurements relating to three dimensions of system impact: safety and quality, organizational culture, and work and communication patterns.

Results

Application of the evaluation model required the development and testing of purpose-built measurement tools such as software to collect multidimensional work measurement data. The model applied established research methods including medication error audits and social network analysis. Design features of these tools and techniques are described, along with the practical challenges of their implementation. The distinctiveness of doing research within a unique paradigm of complex systems, explicating the wickedness and the dimensionality of sociotechnical theory, is articulated.

Conclusion

Designing an effective evaluation model requires a deep understanding of the nature and complexity of the problems that information technology interventions in health care are trying to address. Adopting a sociotechnical perspective for model generation improves our ability to develop evaluation models that are adaptive and sensitive to the characteristics of wicked problems and provides a strong theoretical basis from which to analyze and interpret findings.     

Clinical Decision Velocity is Increased when Meta-search Filters Enhance an Evidence Retrieval System

Objective

To test whether the use of an evidence retrieval system that uses clinically targeted meta-search filters can enhance the rate at which clinicians make correct decisions, reduce the effort involved in locating evidence, and provide an intuitive match between clinical tasks and search filters.

Design

A laboratory experiment under controlled conditions asked 75 clinicians to answer eight randomly sequenced clinical questions, using one of two randomly assigned search engines. The first search engine Quick Clinical (QC) was equipped with meta-search filters (the combined use of meta-search and search filters) designed to answer typical clinical questions e.g., treatment, diagnosis, and the second ‘library model’ system (LM) offered free access to an identical evidence set with no filter support.

Measurements

Changes in clinical decision making were measured by the proportion of correct post-search answers provided to questions, the time taken to answer questions, and the number of searches and links to documents followed in a search session. The intuitive match between meta-search filters and clinical tasks was measured by the proportion and distribution of filters selected for individual clinical questions.

Results

Clinicians in the two groups performed equally well pre-search. Post search answers improved overall by 21%, with 52.2% of answers correct with QC and 54.7% with LM (χ² = 0.33, df = 1, p > 0.05). Users of QC obtained a significantly greater percentage of their correct answers within the first two minutes of searching compared to LM users (QC 58.2%; LM 32.9%; χ² = 19.203, df = 1, p < 0.001). There was a statistical difference for QC and LM survival curves, which plotted overall time to answer questions, irrespective of answer (Wilcoxon, p = 0.019) and for the average time to provide a correct answer (Wilcoxon, p = 0.006). The QC system users conducted significantly fewer searches per scenario (m = 3.0 SD = 1.15 versus m = 5.5 SD1.97, t = 6.63, df = 72, p = 0.0001). Clinicians using the QC system followed fewer document links than did those who used LM (respectively 3.9 links SD = 1.20 versus 4.7 links SD = 1.79, t = 2.13, df = 72, p = 0.0368). In 6 of the 8 questions, two meta-search filters accounted for 89% or more of clinicians'' first choice, suggesting the choice of filter intuitively matched the clinical decision task at hand.

Conclusions

Meta-search filters result in clinicians arriving at answers more quickly than unconstrained searches across information sources, and appear to increase the rate with which correct decisions are made. In time restricted clinical settings meta-search filters may thus improve overall decision accuracy, as fewer searches that could otherwise lead to a correct answer are abandoned. Meta-search filters appear to be intuitive to use, suggesting that the simplicity of the user model would fit very well into clinical settings.     

Cross‐linked hyaluronic acid filler hydrolysis with hyaluronidase: Different settings to reproduce different clinical scenarios

Skin necrosis is the most severe complication arising from hyaluronic acid (HA) injection. To avoid skin necrosis, hyaluronidase should be injected along the course of the involved artery, to allow blood flow restoration. We evaluated the ability of hyaluronidase to degrade a HA filler in two simulated clinical situations—a compression case and an embolization case—to identify differences in the hyaluronidase injection. In the compression case, a bolus of HA filler was directly soaked in hyaluronidase solution; in the embolization case, a vein harvested from a living patient was filled with the same HA filler and then soaked in hyaluronidase. We then evaluated the quantity of HA remaining after 2 hr. While we found hydrolysis of HA in both cases, in the compression case, we detected almost complete hydrolysis, whereas in the embolization case we observed a reduction of the 60%. Our results support the hypothesis that vessel compression can be resolved with only one injection of hyaluronidase, while in the case of vascular embolization, repeated perivascular injections should be performed owing to the reduction of hyaluronidase activity.     

Epidemiological, clinal and allergological observations on pompholyx

We have studied a group of 104 patients with pompholyx, to investigate the relationship between allergological factors and its etiopathogenesis. The following examinations were performed: blood sampling (routine tests and IgE levels), allergological tests (patch, prick, intradermal, and oral provovation tests with nickel sulphate), skin biopsy to exclude pemphigus vulgaris or bullous pemphigoid. An accurate history of familial and personal allergic diathesis was enquired for and various possible aggravating factors (season, microclimate, perspiration and emotional stress) were considered. The results were age and sex-matched with a healthy control group (208 subjects). We found familial and personal atopic diathesis in 50% of patients versus 11.5% of controls (p less than 0.001); 39 patients (37.49%) also had high levels of IgE. Nickel sulphate was the allergen with the highest positivity on patch testing: 20.19% versus 6.25% of the control group (p less than 0.001). The % of patients allergic to nickel reached 26%, including those (6 patients) reacting to the oral provocation test. Season (43 patients) and hyperhidrosis (38) were the aggravating factors most commonly claimed. We detected no correlation between age, sex, grading of pompholyx and the allergological parameters investigated. Though several different allergological findings have previously been reported in dyshidrosis, their role in its pathogenesis has not yet been fully explained. We think that different haptens or antigens can produce the same clinical and histological picture of pompholyx in predisposed subjects.     

Spectral fluorescence lifetime detection and selective melanin imaging by multiphoton laser tomography for melanoma diagnosis

Abstract:  Multiphoton excited tissue fluorescence summarises the emission of all naturally occurring endogenous fluorescent bio-molecules with their often overlapping fluorescence spectra. Common fluorescence intensity measurements could not be utilised to distinguish between different fluorophores or metabolic states. To overcome this limitation, we investigated new procedures of selective melanin imaging and spectral fluorescence lifetime imaging in combination with high resolution multiphoton laser tomography. Overall 46 melanocytic lesions of human skin were analysed. We suggested that fluorescence light, detected in such a way, may yield additional information for melanoma diagnostics. Remarkable differences in lifetime behaviour of keratinocytes in contrast to melanocytes were observed. Fluorescence lifetime distribution was found in correlation with the intracellular amount of melanin. Spectral analysis of melanoma revealed a main fluorescence peak around 470 nm in combination with an additional peak close to 550 nm throughout all epidermal layers. Excitation at 800 nm shows a selectively observable fluorescence of melanin containing cells and offers the possibility of cell classification. Procedures of selective imaging as well as spectral fluorescence lifetime imaging by means of multiphoton laser tomography support diagnostic decisions and may improve the process of non-invasive early detection of melanoma.     

Assessment of EtQxBox complexation in solution by steady-state and time-resolved fluorescence spectroscopy

Reliable chemical sensors with high selectivity and sensitivity toward specific target molecules require rational synthesis of receptors, in-depth characterization of their complexation abilities and highly efficient transduction of the molecular recognition event. Here we report a steady-state and time-resolved fluorescence investigation of EtQxBox, a fluorescent conformationally blocked quinoxaline-based cavitand, aimed at assessing its selectivity toward aromatic versus non-aromatic analytes in solution. Fluorescence quenching of the EtQxBox in acetone is observed at increasing concentration of both aromatic (i.e. benzonitrile) and aliphatic (i.e. acetonitrile) compounds. The combination with fluorescence lifetime measurements permits to discriminate the predominantly static quenching of the aromatic analyte, due to non-fluorescent host–guest complex formation, from the mostly dynamic quenching of the non-aromatic compound, resulting from aspecific diffusive collisions between the fluorophore and the quencher. The equilibrium association constants for both the complexes have been estimated using Stern–Volmer model.

We investigate the role of combined static and dynamic quenching in fluorescence transduction of benzonitrile and acetonitrile complexation by a rigid quinoxaline-based cavitand.