A Case of Intradural Extramedullary Spinal Tuberculosis Diagnosed 8 Years After Treatment of the Primary Infection

Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis, is the second leading killer worldwide from a single infectious agent. Spinal TB is associated with pulmonary disease and may originate from (1) hematogenous spread outside the central nervous system (CNS), (2) sites located within the cranium (meningitis), or (3) secondary extension from vertebral bodies or discs (Pott’s disease).1 Other presentations of tuberculosis include tuberculous arachnoiditis, nonosseous spinal tuberculoma, and spinal meningitis. Of these conditions, spinal tuberculoma can be intradural, extradural, intramedullary, or extramedullary. Intradural extramedullary tuberculosis is the most rare type and is only observed in 1 out of 50,000 cases of tuberculosis.2,3 To date, there has only been one documented intradural extramedullary tuberculoma in a non-HIV-infected patient in North America.4 Intradural spinal tuberculomas often present simultaneously or are preceded by tuberculous meningitis (TBM).5,6 We treated an otherwise healthy 68-yearold male that developed progressive lower extremity pain and weakness from an intradural spinal tuberculoma. While spinal tuberculomas have been previously described, no prior author has reported a tuberculoma several years after successful eradication of the pulmonary infection. In this case report, we present the case, pertinent imaging, operative findings, histopathology, and a review of the literature

Spinal or general anaesthesia for surgical repair of hip fracture and subsequent risk of mortality and morbidity: a database analysis using propensity score‐matching

Around 76,000 people fracture their hip annually in the UK at a considerable personal, social and financial cost. Despite longstanding debate, the optimal mode of anaesthesia (general or spinal) remains unclear. Our aim was to assess whether there is a significant difference in mortality and morbidity between patients undergoing spinal anaesthesia compared with general anaesthesia during hip fracture surgery. A secondary analysis examined whether a difference exists in mortality for patients with pre‐existing cardiovascular disease or chronic obstructive pulmonary disease. This was a clinical database analysis of patients treated for hip fracture in Nottingham, UK between 2004 and 2015. Propensity score‐matching was used to generate matched pairs of patients, one of whom underwent each mode of anaesthesia. Data were analysed using conditional logistic regression, with 7164 patients successfully matched. There was no difference in 30‐ or 90‐day mortality in patients who had spinal rather than general anaesthesia (OR [95%CI] 0.97 [0.8–1.15]; p = 0.764 and 0.93 [0.82–1.05]; p = 0.247 respectively). Patients who had a spinal anaesthetic had a lower‐risk of blood transfusion (OR [95%CI] 0.84 [0.75–0.94]; p = 0.003) and urinary tract infection (OR [95%CI] 0.72 [0.61–0.84]; p [less than] 0.001), but were more likely to develop a chest infection (OR [95%CI] 1.23 [1.07–1.42]; p = 0.004), deep vein thrombosis (OR [95%CI] 2.18 [1.07–4.45]; p = 0.032) or pulmonary embolism (OR [95%CI] 2.23 [1.16–4.29]; p = 0.016). The mode of anaesthesia for hip fracture surgery resulted in no significant difference in mortality, but there was a significant difference in several measures of postoperative morbidity

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine initiative: patient-centred outcomes

BACKGROUND: Patient-centred outcomes are increasingly used in perioperative clinical trials. The Standardised Endpoints in Perioperative Medicine (StEP) initiative aims to define which measures should be used in future research to facilitate comparison between studies and to enable robust evidence synthesis. METHODS: A systematic review was conducted to create a longlist of patient satisfaction, health-related quality of life, functional status, patient well-being, and life-impact measures for consideration. A three-stage Delphi consensus process involving 89 international experts was then conducted in order to refine this list into a set of recommendations. RESULTS: The literature review yielded six patient-satisfaction measures, seven generic health-related quality-of-life measures, eight patient well-being measures, five functional-status measures, and five life-impact measures for consideration. The Delphi response rates were 92%, 87%, and 100% for Rounds 1, 2, and 3, respectively. Three additional measures were added during the Delphi process as a result of contributions from the StEP group members. Firm recommendations have been made about one health-related quality-of-life measure (EuroQol 5 Dimension, five-level version with visual analogue scale), one functional-status measure (WHO Disability Assessment Schedule version 2.0, 12-question version), and one life-impact measure (days alive and out of hospital at 30 days after surgery). Recommendations with caveats have been made about the Bauer patient-satisfaction measure and two life-impact measures (days alive and out of hospital at 1 yr after surgery, and discharge destination). CONCLUSIONS: Several patient-centred outcome measures have been recommended for use in future perioperative studies. We suggest that every clinical study should consider using at least one patient-centred outcome within a suite of endpoints

The structure of iterative methods for symmetric linear discrete ill-posed problems

The iterative solution of large linear discrete ill-posed problems with an error contaminated data vector requires the use of specially designed methods in order to avoid severe error propagation. Range restricted minimal residual methods have been found to be well suited for the solution of many such problems. This paper discusses the structure of matrices that arise in a range restricted minimal residual method for the solution of large linear discrete ill-posed problems with a symmetric matrix. The exploitation of the structure results in a method that is competitive with respect to computer storage, number of iterations, and accuracy.Acknowledgments We would like to thank the referees for comments. The work of F. M. was supported by Dirección General de Investigación Científica y Técnica, Ministerio de Economía y Competitividad of Spain under grant MTM2012-36732-C03-01. Work of L. R. was supported by Universidad Carlos III de Madrid in the Department of Mathematics during the academic year 2010-2011 within the framework of the Chair of Excellence Program and by NSF grant DMS-1115385

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Discovering joint associations between disease and gene pairs with a novel similarity test

Genes in a functional pathway can have complex interactions. A gene might activate or suppress another gene, so it is of interest to test joint associations of gene pairs. To simultaneously detect the joint association between disease and two genes (or two chromosomal regions), we propose a new test with the use of genomic similarities. Our test is designed to detect epistasis in the absence of main effects, main effects in the absence of epistasis, or the presence of both main effects and epistasis. Results: The simulation results show that our similarity test with the matching measure is more powerful than the Pearson's chi(2) test when the disease mutants were introduced at common haplotypes, but is less powerful when the disease mutants were introduced at rare haplotypes. Our similarity tests with the counting measures are more sensitive to marker informativity and linkage disequilibrium patterns, and thus are often inferior to the similarity test with the matching measure and the Pearson 's chi(2) test. Conclusions: In detecting joint associations between disease and gene pairs, our similarity test is a complementary method to the Pearson's chi(2) test

Marjolin's ulcers: theories, prognostic factors and their peculiarities in spina bifida patients

<p>Abstract</p> <p>Background</p> <p>Due to improved care, more and more children born with spina bifida in rural Kenya are surviving into adulthood. This improved survival has led to significant challenges in their lifestyles, especially the need to ensure pressure ulcer prevention and treatment. Malignant degeneration of pressure ulcers in spina bifida patients is very rare. The author describes the clinical presentation of two pressure ulcer carcinomas that are at variance from classical descriptions.</p> <p>Materials and methods</p> <p>An internet/Medline/PubMed search of English literature for theories on Marjolin's ulcer evolution and prognostic features of Marjolin's ulcers was performed.</p> <p>A chart review of two young adults with spina bifida who had presented to the author's hospital between 2004 and August 2010 with chronic pressure ulcers found to be Marjolin's ulcers on histo-pathological examination was performed, and the clinical features are reported.</p> <p>Results</p> <p>The two ulcers appeared clinically benign: one was a deep ulcer, while the other was shallow; both had normal, benign-appearing edges, and a foul smelling discharge. The two ulcers were surrounded by induration and multiple communicating sinuses, with no evidence of chronic osteomyelitis. The internet search revealed a total of nine theories on Marjolin's ulcer development, as well as seven clinical and four histological prognostic features.</p> <p>Discussion</p> <p>The multifactorial theory, a coalescence of a number of proposed theories, best explains the evolution of Marjolin's ulcers. Poor prognostic features include pressure ulcer carcinomas, lesions and location in the lower limbs/trunks, all present in the two patients making their prognosis dim: this is despite the surgical margins being clear of tumor. Benign appearance, induration and presence of multiple communicating sinuses are features that have not been previously described as presenting features of pressure ulcers carcinomas.</p> <p>Conclusion</p> <p>There is need for spina bifida patients and their guardians/caretakers to receive a close follow-up throughout life; health education focused on pressure ulcer prevention as well as early treatment of pressure ulcers when they occur, will avert the development of Marjolin's ulcers, and save lives.</p

Practical and Theoretical Considerations in Study Design for Detecting Gene-Gene Interactions Using MDR and GMDR Approaches

Detection of interacting risk factors for complex traits is challenging. The choice of an appropriate method, sample size, and allocation of cases and controls are serious concerns. To provide empirical guidelines for planning such studies and data analyses, we investigated the performance of the multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) methods under various experimental scenarios. We developed the mathematical expectation of accuracy and used it as an indicator parameter to perform a gene-gene interaction study. We then examined the statistical power of GMDR and MDR within the plausible range of accuracy (0.50∼0.65) reported in the literature. The GMDR with covariate adjustment had a power of>80% in a case-control design with a sample size of≥2000, with theoretical accuracy ranging from 0.56 to 0.62. However, when the accuracy was<0.56, a sample size of≥4000 was required to have sufficient power. In our simulations, the GMDR outperformed the MDR under all models with accuracy ranging from 0.56∼0.62 for a sample size of 1000–2000. However, the two methods performed similarly when the accuracy was outside this range or the sample was significantly larger. We conclude that with adjustment of a covariate, GMDR performs better than MDR and a sample size of 1000∼2000 is reasonably large for detecting gene-gene interactions in the range of effect size reported by the current literature; whereas larger sample size is required for more subtle interactions with accuracy<0.56