Factor analysis of the North American Spine Society outcome assessment instrument: a study based on a spine registry of patients treated with lumbar and cervical disc arthroplasty.

BACKGROUND CONTEXT: Studies involving factor analysis (FA) of the items in the North American Spine Society (NASS) outcome assessment instrument have revealed inconsistent factor structures for the individual items. PURPOSE: This study examined whether the factor structure of the NASS varied in relation to the severity of the back/neck problem and differed from that originally recommended by the developers of the questionnaire, by analyzing data before and after surgery in a large series of patients undergoing lumbar or cervical disc arthroplasty. STUDY DESIGN/SETTING: Prospective multicenter observational case series. PATIENT SAMPLE: Three hundred ninety-one patients with low back pain and 553 patients with neck pain completed questionnaires preoperatively and again at 3 to 6 and 12 months follow-ups (FUs), in connection with the SWISSspine disc arthroplasty registry. OUTCOME MEASURES: North American Spine Society outcome assessment instrument. METHODS: First, an exploratory FA without a priori assumptions and subsequently a confirmatory FA were performed on the 17 items of the NASS-lumbar and 19 items of the NASS-cervical collected at each assessment time point. The item-loading invariance was tested in the German version of the questionnaire for baseline and FU. RESULTS: Both NASS-lumbar and NASS-cervical factor structures differed between baseline and postoperative data sets. The confirmatory analysis and item-loading invariance showed better fit for a three-factor (3F) structure for NASS-lumbar, containing items on "disability," "back pain," and "radiating pain, numbness, and weakness (leg/foot)" and for a 5F structure for NASS-cervical including disability, "neck pain," "radiating pain and numbness (arm/hand)," "weakness (arm/hand)," and "motor deficit (legs)." CONCLUSIONS: The best-fitting factor structure at both baseline and FU was selected for both the lumbar- and cervical-NASS questionnaires. It differed from that proposed by the originators of the NASS instruments. Although the NASS questionnaire represents a valid outcome measure for degenerative spine diseases, it is able to distinguish among all major symptom domains (factors) in patients undergoing lumbar and cervical disc arthroplasty; overall, the item structure could be improved. Any potential revision of the NASS should consider its factorial structure; factorial invariance over time should be aimed for, to allow for more precise interpretations of treatment success.

The Hippo Transducer YAP1 Transforms Activated Satellite Cells and Is a Potent Effector of Embryonal Rhabdomyosarcoma Formation.

The role of the Hippo pathway effector YAP1 in soft tissue sarcomas is poorly defined. Here we report that YAP1 activity is elevated in human embryonal rhabdomyosarcoma (ERMS). In mice, sustained YAP1 hyperactivity in activated, but not quiescent, satellite cells induces ERMS with high penetrance and short latency. Via its transcriptional program with TEAD1, YAP1 directly regulates several major hallmarks of ERMS. YAP1-TEAD1 upregulate pro-proliferative and oncogenic genes and maintain the ERMS differentiation block by interfering with MYOD1 and MEF2 pro-differentiation activities. Normalization of YAP1 expression reduces tumor burden in human ERMS xenografts and allows YAP1-driven ERMS to differentiate in situ. Collectively, our results identify YAP1 as a potent ERMS oncogenic driver and a promising target for differentiation therapy.

Engineered aprotinin for improved stability of fibrin biomaterials.

Fibrin has been long used clinically for hemostasis and sealing, yet extension of use in other applications has been limited due to its relatively rapid resorption in vivo, even with addition of aprotinin or other protease inhibitors. We report an engineered aprotinin variant that can be immobilized within fibrin and thus provide extended longevity. When recombinantly fused to a transglutaminase substrate domain from α(2)-plasmin inhibitor (α(2)PI(1-8)), the resulting variant, aprotinin-α(2)PI(1-8), was covalently crosslinked into fibrin matrices during normal thrombin/factor XIIIa-mediated polymerization. Challenge with physiological plasmin concentrations revealed that aprotinin-α(2)PI(1-8)-containing matrices retained 78% of their mass after 3 wk, whereas matrices containing wild type (WT) aprotinin degraded completely within 1 wk. Plasmin challenge of commercial sealants Omrixil and Tisseel, supplemented with aprotinin-α(2)PI(1-8) or WT aprotinin, showed extended longevity as well. When seeded with human dermal fibroblasts, aprotinin-α(2)PI(1-8)-supplemented matrices supported cell growth for at least 33% longer than those containing WT aprotinin. Subcutaneously implanted matrices containing aprotinin-α(2)PI(1-8) were detectable in mice for more than twice as long as those containing WT aprotinin. We conclude that our engineered recombinant aprotinin variant can confer extended longevity to fibrin matrices more effectively than WT aprotinin in vitro and in vivo.

Acute coronary syndrome after levamisole-adultered cocaine abuse

Cocaine is a well known trigger of acute coronary syndromes. Over the last 10 years levamisole, a veterinary anthelminthic drug has been increasingly used as an adulterant of cocaine. Levamisole was used to treat pediatric nephritic syndrome and rheumatoid arthritis before being withdrawn from the market due to its significant toxicity, i.e. hematological complications and vasculitis. The major complications of levamisole-adultered cocaine reported up to now are hematological and dermatological. The case reported here is of a 25 year old man with a history of cocaine abuse who died at home after complaining of retrosternal pain. Postmortem CT-angiography, autopsy, and chemical and toxicological analyses were performed. An eroded coronary artery plaque was found at the proximal segment of the left anterior descending coronary artery. Two myocardial infarct scars were present in the left ventricle. Microscopic examination of the coronary artery revealed infiltration of eosinophils into the adventitia and intima. Toxicological examination confirmed the presence of cocaine and its metabolites in the peripheral blood, and of levamisole in the urine and pericardial fluid. Eosinophilic inflammatory coronary artery pathologies have been clinically linked to coronary dissection, hypersensitivity coronary syndrome and vasospastic allergic angina. The coronary pathology in the presented case could be a complication of levamisole-adultered cocaine use, in which an allergic or immune-mediated mechanism might play a role. The rise in cocaine addiction worldwide and the increase of levamisole adulterated cocaine highlights the importance of updating our knowledge of the effects of adultered cocaine abuse.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes.

The effect of vaccines based on ovalbumin coupled to gas-filled microbubbles for reducing infection by ovalbumin-expressing Listeria monocytogenes.

Gas-filled microbubbles (MB) are a very promising alternative to the currently evaluated lipid- or polymer-based particulate Ag delivery systems. We recently demonstrated the ability of MB to deliver associated Ag to DC, to activate them and thereby induce both humoral and cellular immune responses. We now extended the characterization of MB as antigen-delivery system by appraising the efficiency of MB-associated ovalbumin (OVA-MB) at protecting mice against pathogen infection. Ultrasound-mediated imaging demonstrated that the administration of OVA via MB generates a depot at the injection site that lasts for several hours. We found that OVA-MB injected subcutaneously is far more effective at inducing specific Ab and T cell immunity than immunization with free OVA. Moreover, a covalent link between MB and OVA causes a stronger bias towards a Th1-type of immune response than adsorption of the Ag or its covalent link to liposomes of the same lipid composition. Finally, vaccination of mice with OVA-MB partially protects against a systemic infection with OVA-expressing Listeria monocytogenes. The vaccine induces specific effector CD8 T cell responses capable of decreasing more than 100 fold the bacterial load. MB thus represent a potent Ag delivery system for vaccination against intracellular infectious agents.

Cohort study of trials submitted to ethics committee identified discrepant reporting of outcomes in publications.

OBJECTIVES: To identify factors associated with discrepant outcome reporting in randomized drug trials. STUDY DESIGN AND SETTING: Cohort study of protocols submitted to a Swiss ethics committee 1988-1998: 227 protocols and amendments were compared with 333 matching articles published during 1990-2008. Discrepant reporting was defined as addition, omission, or reclassification of outcomes. RESULTS: Overall, 870 of 2,966 unique outcomes were reported discrepantly (29.3%). Among protocol-defined primary outcomes, 6.9% were not reported (19 of 274), whereas 10.4% of reported outcomes (30 of 288) were not defined in the protocol. Corresponding percentages for secondary outcomes were 19.0% (284 of 1,495) and 14.1% (334 of 2,375). Discrepant reporting was more likely if P values were <0.05 compared with P ≥ 0.05 [adjusted odds ratio (aOR): 1.38; 95% confidence interval (CI): 1.07, 1.78], more likely for efficacy compared with harm outcomes (aOR: 2.99; 95% CI: 2.08, 4.30) and more likely for composite than for single outcomes (aOR: 1.48; 95% CI: 1.00, 2.20). Cardiology (aOR: 2.34; 95% CI: 1.44, 3.79) and infectious diseases (aOR: 1.77; 95% CI: 1.01, 3.13) had more discrepancies compared with all specialties combined. CONCLUSION: Discrepant reporting was associated with statistical significance of results, type of outcome, and specialty area. Trial protocols should be made freely available, and the publications should describe and justify any changes made to protocol-defined outcomes.

Genetic aspects of normal and disturbed sleep.

Sleep disorders commonly involve genetic susceptibility, environmental effects, and interactions between these factors. The heritability of sleep patterns has been shown in studies of monozygotic twins, and sleep electroencephalogram patterns offer a unique genetic fingerprint which may assist in the identification of genes involved in the regulation of sleep. Genetic factors are also thought to play a role in sleep disorders; narcolepsy is a disabling sleep condition and research has revealed the complexity of underlying genetic and environmental influences in the development of this disorder. An understanding of sleep regulation at the molecular level is essential in the identification of new targets for the treatment of sleep disorders, and genome-wide association studies for both normal sleep and sleep disorders may shed new light on the molecular architecture of mechanisms regulating these behaviours.

Acute neurorehabilitation: does a neurosensory and coordinated interdisciplinary programme reduce tracheostomy weaning time and weaning failure?

BACKGROUND/PURPOSE: A new coordinated interdisciplinary unit was created in the acute section of the department of clinical neurosciences, the Acute NeuroRehabilitation (NRA) unit. The objective was to evaluate the impact of the unit and its neurosensory programme on the management of tracheostomy patients in terms of reduction in the average time taken for weaning, weaning success rate and therapeutic efficiency. METHODS: This 49-month retrospective study compares 2 groups of tracheostomy patients before (n = 34) and after (n = 46) NRA intervention. The outcome measures evaluate the benefits of the NRA unit intervention (time to decannulation, weaning and complication rates) and the benefits of the coordination (time to registration in a rehabilitation centre and rate of non-compliance with standards of care). RESULTS: Weaning failure rate was reduced from 27.3% to 9.1%, no complications or recannulations were observed in the post-intervention group after weaning and time to decannulation following admission to our unit decreased from 19.13 to 12.75 days. The rate of non-compliance with patient standards of care was significantly reduced from 45% to 30% (Mann-Whitney p = 0.003). DISCUSSION/CONCLUSIONS: This interdisciplinary weaning programme helped to reduce weaning time and weaning failure, without increased complications, in the sample studied. Coordination improved the efficiency of the interdisciplinary team in the multiplicity and complexity of the different treatments.

Multicenter, Prospective Clinical Evaluation of Respiratory Samples from Subjects at Risk for Pneumocystis jirovecii Infection by Use of a Commercial Real-Time PCR Assay.

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection. Microscopic diagnosis, including diagnosis using the Merifluor-Pneumocystis direct fluorescent antigen (MP-DFA) test, has limitations. Real-time PCR may assist in diagnosis, but no commercially validated real-time PCR assay has been available to date. MycAssay Pneumocystis is a commercial assay that targets the P. jirovecii mitochondrial large subunit (analytical detection limit, ≤3.5 copies/μl of sample). A multicenter trial recruited 110 subjects: 54 with transplants (40 with lung transplants), 32 with nonmalignant conditions, 13 with leukemia, and 11 with solid tumors; 9 were HIV positive. A total of 110 respiratory samples (92% of which were bronchoalveolar lavage [BAL] specimens) were analyzed by PCR. Performance was characterized relative to investigator-determined clinical diagnosis of PCP (including local diagnostic tests), and PCR results were compared with MP-DFA test results for 83 subjects. Thirteen of 14 subjects with PCP and 9/96 without PCP (including 5 undergoing BAL surveillance after lung transplantation) had positive PCR results; sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were 93%, 91%, 59%, and 99%, respectively. Fourteen of 83 subjects for whom PCR and MP-DFA test results were available had PCP; PCR sensitivity, specificity, PPV, and NPV were 93%, 90%, 65%, and 98%, respectively, and MP-DFA test sensitivity, specificity, PPV, and NPV were 93%, 100%, 100%, and 98%. Of the 9 PCR-positive subjects without PCP, 1 later developed PCP. The PCR diagnostic assay compares well with clinical diagnosis using nonmolecular methods. Additional positive results compared with the MP-DFA test may reflect low-level infection or colonization.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

When nightclub security agents assault clients more insight through a qualitative approach.

Between 2007 and 2009, aggressions by security agents of nightclubs on clients increased from 6% to 10% among community violence situations encountered at the Violence Medical Unit (VMU) at the Lausanne University Hospital in Switzerland. Most victims were young men who had been drinking alcohol before the assault. About one quarter (25.7%) presented with one or several fractures, all of them in the head area. (For more details, refer to the previous article "When nightclub security agents assault clients" published in 2012(1).) Following this first study, we performed a second qualitative study in order to bring more information about the context and highlight victims' behaviors and experiences. Four themes emerged: how the assault began; the assault itself; third-party involvement; and the psychological state of victims when they consulted the VMU. The findings of this second study complemented the statistical results of the first study by showing under what circumstances security agents of nightclubs respond with physical violence to situations they consider a threat to security. Furthermore, the study described consequences for the victims that could be quite serious. Our findings support the need for nightclubs to improve selection and training of security staff.

Expression of killer cell immunoglobulin-like receptors (KIRs) by natural killer cells during acute CMV infection after kidney transplantation.

Human cytomegalovirus (CMV) infection may be a serious complication related to immunosuppression after solid organ transplantation. Due to their cytotoxicity, T-cells and natural killer (NK) cells target and clear the virus from CMV-infected cells. Although immunosuppressive drugs suppress T-cell proliferation and activation, they do not affect NK cells that are crucial for controlling the infection. The regulation of NK cells depends on a wide range of activating and inhibitory receptors such as the family of killer-cell immunoglobulin-like receptors (KIRs). Several human genetic studies have demonstrated the association of KIR genes with the clearance of infections. Since the respective activities of the different KIR proteins expressed by NK cells during CMV infection have not been extensively studied, we analyzed the expression of KIRs in a cohort of 22 CMV-IgG(+) renal transplant patients at the time of CMV reactivation, after antiviral therapy and 6 months later. Our data revealed a marked expression of KIR3DL1 during the acute phase of the reactivation. We set up an in vitro model in which NK cells, derived either from healthy donors or from transplanted patients, target allogeneic fibroblasts, CMV-infected or uninfected. Our results demonstrate a significant correlation between the lysis of CMV-infected fibroblasts and the expression of KIR3DL1. Blocking experiments with antibodies to MHC-I, to NKG2D and to NKG2C confirmed the importance of KIR3DL1. Consequently, our results suggest that KIR proteins and especially KIR3DL1 could play an important role during CMV-infection or CMV reactivation in immunosuppressed patients.

Correlates of frailty, prediction of functional decline and preventative approaches - selected results from the lausanne cohort 65+ (lc65+) study (Switzerland) (Lausanne) and the longitudinal urban cohort ageing study (Lucas) (Germany)

Overall introduction.- Longitudinal studies have been designed to investigate prospectively, from their beginning, the pathway leading from health to frailty and to disability. Knowledge about determinants of healthy ageing and health behaviour (resources) as well as risks of functional decline is required to propose appropriate preventative interventions. The functional status in older people is important considering clinical outcome in general, healthcare need and mortality. Part I.- Results and interventions from lucas (longitudinal urban cohort ageing study). Authors.- J. Anders, U. Dapp, L. Neumann, F. Pröfener, C. Minder, S. Golgert, A. Daubmann, K. Wegscheider,. W. von Renteln-Kruse Methods.- The LUCAS core project is a longitudinal cohort of urban community-dwelling people 60 years and older, recruited in 2000/2001. Further LUCAS projects are cross-sectional comparative and interventional studies (RCT). Results.- The emphasis will be on geriatric medical care in a population-based approach, discussing different forms of access, too. (Dapp et al. BMC Geriatrics 2012, 12:35; http://www.biomedcentral.com/1471-2318/12/35): - longitudinal data from the LUCAS urban cohort (n = 3.326) will be presented covering 10 years of observation, including the prediction of functional decline, need of nursing care, and mortality by using a self-filling screening tool; - interventions to prevent functional decline do focus on first (pre-clinical) signs of pre-frailty before entering the frailty-cascade ("Active Health Promotion in Old Age", "geriatric mobility centre") or disability ("home visits"). Conclusions.- The LUCAS research consortium was established to study particular aspects of functional competence, its changes with ageing, to detect pre-clinical signs of functional decline, and to address questions on how to maintain functional competence and to prevent adverse outcome in different settings. The multidimensional data base allows the exploration of several further questions. Gait performance was exmined by GAITRite®-System. Supported by the Federal Ministry for Education and Research (BMBF Funding No. 01ET1002A). Part II.- Selected results from the lausanne cohort 65+ (Lc65 + ) Study (Switzerland). Authors.- Prof Santos-Eggimann Brigitte, Dr Seematter-Bagnoud Laurence, Prof Büla Christophe, Dr Rochat Stéphane. Methods.- The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). Results.- Information is collected about life course social and health-related events, socio-economics, medical and psychosocial dimensions, lifestyle habits, limitations in activities of daily living, mobility impairments, and falls. Gait performance are objectively measured using body-fixed sensors. Frailty is assessed using Fried's frailty phenotype. Follow-up consists in annual self-completed questionnaires, as well as physical examination and physical and mental performance tests every three years. - Lausanne cohort 65+ (Lc65 + ): design and longitudinal outcomes. The baseline data collection was completed among 1422 participants in 2004-2005 through self-completed questionnaires, face-to-face interviews, physical examination and tests of mental and physical performances. Information about institutionalization, self-reported health services utilization, and death is also assessed. An additional random sample (n = 1525) of 65-70 years old subjects was recruited in 2009 (birth year 1939-1943). - lecture no 4: alcohol intake and gait parameters: prevalent and longitudinal association in the Lc65+ study. The association between alcohol intake and gait performance was investigated.