Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

The evolution of clinical audit as a tool for quality improvement.

Clinical auditing practices are recognized universally as a useful tool in evaluating and improving the quality of care provided by a health service. External auditing is a regular activity for mental health services in Australia but internal auditing activities are conducted at the discretion of each service. This paper evaluates the effectiveness of 6 years of internal auditing activities in a mental health service. A review of the scope, audit tools, purpose, sampling and design of the internal audits and identification of the recommendations from six consecutive annual audit reports was completed. Audit recommendations were examined, as well as levels of implementation and reasons for success or failure. Fifty-seven recommendations were identified, with 35% without action, 28% implemented and 33.3% still pending or in progress. The recommendations were more likely to be implemented if they relied on activity, planning and action across a selection of service areas rather than being restricted to individual departments within a service, if they did not involve non-mental health service departments and if they were not reliant on attitudinal change. Tools used, scope and reporting formats have become more sophisticated as part of the evolutionary nature of the auditing process. Internal auditing in the Barwon Health Mental Health Service has been effective in producing change in the quality of care across the organization. A number of evolutionary changes in the audit process have improved the efficiency and effectiveness of the audit.

Aspectos clínico e cirúrgicos do tumor mamário canino: clinical and surgical evolution

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6%, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60% evoluíram para o controle, 32% melhoraram, 9% mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is frequent in stroke patients. Risk factors, treatment response, short-term and long-term outcome of SDB in stroke patients are poorly known. METHODS: We prospectively studied 152 patients (mean age 56+/-13 years) with acute ischemic stroke. Cardiovascular risk factors, Epworth sleepiness score (ESS), stroke severity/etiology, and time of stroke onset were assessed. The apnea-hypopnea index (AHI) was determined 3+/-2 days after stroke onset and 6 months later (subacute phase). Continuous positive airway pressure (CPAP) treatment was started acutely in patients with SDB (AHI > or =15 or AHI > or =10+ESS >10). CPAP compliance, incidence of vascular events, and stroke outcome were assessed 60+/-16 months later (chronic phase). RESULTS: Initial AHI was 18+/-16 (> or =10 in 58%, > or =30 in 17% of patients) and decreased in the subacute phase (P<0.001). Age, diabetes, and nighttime stroke onset were independent predictors of AHI (r2=0.34). In patients with AHI > or =30, age, male gender, body mass index, diabetes, hypertension, coronary heart disease, ESS, and macroangiopathic etiology of stroke were significantly higher/more common than in patients with AHI <10. Long-term incidence of vascular events and stroke outcome were similar in both groups. CPAP was started in 51% and continued chronically in 15% of SDB pts. Long-term stroke mortality was associated with initial AHI, age, hypertension, diabetes, and coronary heart disease. CONCLUSIONS: SDB is common particularly in elderly stroke male patients with diabetes, nighttime stroke onset, and macroangiopathy as cause of stroke; it improves after the acute phase, is associated with an increased poststroke mortality, and can be treated with CPAP in a small percentage of patients.

The evolution of urine analysis : an historical sketch of the clinical examination of urine: lecture memoranda, American Medical Association, Los Angeles, 1911.

Foreword signed: Henry S. Wellcome.

Evolution of vocational rehabilitation competencies in Australia

Over the past decade, there has been growth in the delivery of vocational rehabilitation services globally, as countries seek to control disability-related expenditure, yet there has been minimal research outside the United States on competencies required to work in this area. This study reports on research conducted in Australia to determine current job function and knowledge areas in terms of their importance and frequency of use in the provision of vocational rehabilitation. A survey comprising items from the Rehabilitation Skills Inventory-Amended and International Survey of Disability Management was completed by 149 rehabilitation counselors and items submitted to factor analysis. T-tests and analyses of variance were used to determine differences between scores of importance and frequency and differences in scores based on work setting and professional training. Six factors were identified as important and frequently used: (i) vocational counseling, (ii) professional practice, (iii) personal counseling, (iv) rehabilitation case management, (v) workplace disability case management, and (vi) workplace intervention and program management. Vocational counseling, professional practice and personal counseling were significantly more important and performed more frequently by respondents in vocational rehabilitation settings than those in compensation settings. These same three factors were rated significantly higher in importance and frequency by those with rehabilitation counselor training when compared with those with other training. In conclusion, although ‘traditional’ knowledge and skill areas such as vocational counseling, professional practice, and personal counseling were identified as central to vocational rehabilitation practice in Australian rehabilitation agencies, mean ratings suggest a growing emphasis on knowledge and skills associated with disability management practice.

Cerclage, evolution and potential of a Cinderella Technology : an overview with reference to periprosthetic fractures

Periprosthetic fractures are increasingly frequent. The fracture may be located over the shaft of the prosthesis, at its tip or below (21). The treatment of explosion fractures is difficult because the shaft blocks the application of implants, like screws, which need to penetrate the medullary cavity. The cerclage, as a simple periosteal loop, made of wire or more recently cable, does not only avoid the medullary cavity. Its centripetal mode of action is well suited for reducing and maintaining radially displaced fractures. Furthermore, the cerclage lends itself well for minimally invasive internal fixation. New insight challenges the disrepute of which the cerclage technology suffered for decades. The outcome of cerclage fixation benefits from an improved understanding of its technology, mechano-biology and periosteal blood supply. Preconceived and generally accepted opinions like "strangulation of blood supply" need to be re-examined. Recent mechanical evaluations (22) demonstrate that the wire application may be improved but cable is superior in hand- ling, maintenance of tension and strength. Beside the classical concepts of absolute and relative stability a defined stability condition needs consideration. It is typical for cerclage. Called "loose-lock stability" it specifies the situation where a loosened implant allows first unimpeded displacement changing abruptly into a locked fixation preventing further dislocation.

Comparative study of coagulase negative Staphylococci (CoNS) from clinical isolates, skin and nasal sources

Staphylococci are important pathogenic bacteria responsible for a range of diseases in humans. The most frequently isolated microorganisms in a hospital microbiology laboratory are staphylococci. The general classification of staphylococci divides them into two major groups; Coagulase-positive staphylococci (e.g. Staphylococcus aureus) and Coagulase-negative staphylococci (e.g. Staphylococcus epidermidis). Coagulase-negative staphylococcal (CoNS) isolates include a variety of species and many different strains but are often dominated by the most important organism of this group, S. epidermidis. Currently, these organisms are regarded as important pathogenic organisms causing infections related to prosthetic materials and surgical wounds. A significant number of S. epidermidis isolates are also resistant to different antimicrobial agents. Virulence factors in CoNS are not very clearly established and not well documented. S. epidermidis is evolving as a resistant and powerful microbe related to nosocomial infections because it has different properties which independently, and in combination, make it a successful infectious agent, especially in the hospital environment. Such characteristics include biofilm formation, drug resistance and the evolution of genetic variables. The purpose of this project was to develop a novel SNP genotyping method to genotype S. epidermidis strains originating from hospital patients and healthy individuals. High-Resolution Melt Analysis was used to assign binary typing profiles to both clinical and commensal strains using a new bioinformatics approach. The presence of antibiotic resistance genes and biofilm coding genes were also interrogated in these isolates.

Ross River virus evolution : implications for vaccine development

Ross River virus is a mosquito-borne alphavirus that causes approximately 5000 cases of epidemic polyarthritis in Australia each year and has direct medical-associated costs of approximately US$15 million annually. While mosquito control programs are able, at best, to contain rather than prevent this disease, natural infection with Ross River virus confers lifelong protection against subsequent clinical infection. A killed-virus vaccine has been developed, which is in Phase III clinical trials. Analyses of intra-host genetic diversity and of long-term evolutionary changes in Ross River virus populations suggest that antigenic variation is unlikely to pose a threat to the efficacy of this vaccine.