Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases.

Elucidating the molecular pathways active in pathologic tissues has important implications for defining disease subsets, selecting therapy, and monitoring disease activity. The development of therapeutics directed at IFN-α or IFN-γ makes the discovery of probes that report precisely on the activity of different IFN pathways a high priority. We show that, although type I and II IFNs induce the expression of a largely overlapping group of molecules, precise probes of IFN-γ activity can be defined. Used in combination, these probes show prominent IFN-γ effects in Sjögren syndrome (SS) tissues. In contrast, dermatomyositis muscle shows a dominant type I IFN pattern. Interestingly, heterogeneity of IFN signatures exists in patients with SS, with some patients demonstrating a predominant type I pattern. The biochemical patterns largely distinguish the target tissues in patients with SS from those with dermatomyositis and provide a relative weighting of the effects of distinct IFN pathways in specific biopsies. In SS, type I and II IFN effects are localized to the same epithelial cells, surrounded by inflammatory cells expressing IFN-γ-induced proteins, suggesting reinforcing interactions. Precise probes of the different IFN pathways active in tissues of complex rheumatic diseases will be critical to classify disease, elucidate pathogenesis, and select therapy.

Decreasing tobacco use promotes ulcer healing in a patient with Buerger's disease.

Tobacco cessation remains the mainstay treatment for Buerger's Disease; however, limited research exists examining the effect of decreased tobacco use rather than cessation in improving symptoms. We describe a case of a patient with Buerger's disease who experienced ulcer healing and pain improvement through reduced tobacco use.

Isolated elevation of aldolase in the serum of myositis patients: a potential biomarker of damaged early regenerating muscle cells.

OBJECTIVES: Elevated serum aldolase A levels occur in the absence of elevated creatine kinase M (CK) levels in a subset of myositis patients. This study was undertaken to investigate the cell biology of this unexplained clinical observation. METHODS: Cultured human myoblasts were differentiated in vitro. RNA and protein lysates were prepared and used to determine aldolase and CK gene and protein expression by QPCR and immunoblotting. Cardiotoxin was used to induce muscle injury and repair in an experimental mouse model, and aldolase A and CK were immunoblotted in the muscle lysates. Immunohistochemical staining was performed on myositis patient muscle paraffin sections to assess aldolase A and CK staining in vivo. RESULTS: Aldolase A mRNA and protein expression is highest in differentiating myoblasts, and remains robust throughout differentiation. In contrast, CK mRNA and protein levels are low in undifferentiated myoblasts and become strikingly upregulated as differentiation progresses. Aldolase A protein expression is high in regenerating muscle in the mouse model of injury/repair, while CK expression was low. Immunohistochemical staining of human myositis biopsies showed that muscle cells with the highest levels of aldolase and no CK staining have features of regeneration. CONCLUSIONS: In undifferentiated muscle cells, and those early in the differentiation process, aldolase A is expressed in the absence of CK. Thereafter, both are expressed. We propose that isolated serum aldolase A elevation in myositis patients (i) reflects preferential immune-mediated damage of early regenerative cells, and (ii) is a biomarker of damaged early regenerating muscle cells.

Use of drug therapy to manage acute cutaneous necrosis of the skin.

Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue.

Sexual dimorphism in immune response genes as a function of puberty.

BACKGROUND: Autoimmune diseases are more prevalent in females than in males, whereas males have higher mortality associated with infectious diseases. To increase our understanding of this sexual dimorphism in the immune system, we sought to identify and characterize inherent differences in immune response programs in the spleens of male and female mice before, during and after puberty. RESULTS: After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8+ T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production. CONCLUSION: These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.

The readability of original articles in surgical journals.

BACKGROUND: Readability indices have been developed based on sentence length and the use of long words. One such measure is the Reading Ease Scale developed by Rudolf Flesch. Texts that are easy to read have high scores: texts with scores below 30 are similar to legal contracts. This study uses Flesch scores to evaluate the readability of surgical journals. METHODS: Flesch scores were calculated for articles published in the Archives of Surgery, the British Journal of Surgery, and the ANZ Journal of Surgery. The first 30 original articles published in each journal in 2005 were selected for study. Excluded from study were editorials, reviews and case reports. RESULTS: The overall median score was 15.1 (0.0-29.1). The median scores for each of the journals were 12.4 (Archives of Surgery), 14.4 (British Journal of Surgery), and 18.6 (ANZ Journal of Surgery). There was only a minor link between Flesch scores and the use of surgical terms. CONCLUSION: Original articles published in surgical journals contain too many long sentences and complex words. Readability indices are useful tools because they promote the use of simple English. It is realistic for authors to aim for Flesch scores above 30 when creating manuscripts.

Tumour necrosis factor: implications for surgical patients.

Tumour necrosis factor alpha (TNF-alpha) is an inflammatory cytokine primarily produced by macrophages. It is a unique protein with contradictive properties; it has the ability to induce cellular death by apoptosis and oncosis, but can also induce cellular regeneration and growth. Genetic polymorphisms in TNFA have been associated with poor outcome in some surgical patients and this may provide a useful tool to screen for high-risk patients. Manipulating TNF-alpha levels in vivo may influence the progression of several pathological conditions. TNF-alpha has anti-cancer properties and has been used to treat cancer patients. Treatment with anti-TNF-alpha drugs and antibodies has been successful in rheumatoid arthritis and other autoimmune diseases, but disappointing in the management of patients with sepsis. This review article focuses on the biological activities, genetic polymorphism of TNFA and the role of TNF-alpha and anti-TNF-alpha treatments, based on animal experiments and clinical trials.

Evolution of trends in risk management.

In the past, the detection and response to adverse clinical events were viewed as an inherent part of professionalism; and, if perceived problems were not sorted out at that level, the ultimate expression of dissatisfaction was litigation. There are now demands for the adoption of more transparent and effective processes for risk management. Reviews of surgical practice have highlighted the presence of unacceptable levels of avoidable adverse events. This is being resolved in two ways. First, attention is being directed to the extent that training and experience have on outcomes after surgery, and both appear to be important. Second, a greater appreciation of human factors engineering has promoted a greater involvement of surgeons in processes involving teamwork and non-technical skills. The community wants surgeons who are competent and health-care systems that minimize risk. In recent times attention has been focused on the turmoil associated with change; but, when events are viewed over a period of several decades, there has been considerable progress towards these ideals. Further advancement would be aided by removing the adversarial nature of malpractice systems that have failed to maintain standards.

Evolution of methodological standards in surgical trials.

BACKGROUND: The Consolidated Standards of Reporting Trials (CONSORT) Statement outlines acceptable ways of performing and reporting clinical trials. The objective of the present study was to identify evolving patterns in the methodological standards of surgical trials. METHODS: Compliance with 12 key standards from the CONSORT statement were evaluated in 490 trials published in either the ANZ Journal of Surgery or the British Journal of Surgery between January 1969 and December 2003. RESULTS: There has been an irregular but progressive improvement in the methodological standards of published trials. The criteria with the greatest improvement related to estimation of sample size, randomization, concealment of the allocated intervention, baseline comparisons, and the method of expressing outcomes. Compliance rates were <50% for three criteria during the last decade of the review, that is, concealment of the allocated intervention, blindness of assessment, and the method of expressing outcomes. CONCLUSION: The results of surgical trials need to be interpreted with care.

Molecular Subsetting of Interferon Pathways in Sjögren's Syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune disease that targets the salivary and lacrimal glands. While all patients demonstrate inflammatory infiltration and abnormal secretory function in the target tissues, the disease features, pathology, and clinical course can vary. Activation of distinct inflammatory pathways may drive disease heterogeneity. The purpose of this study was to investigate whether activation of the interferon (IFN) pathway correlates with key phenotypic features. METHODS: Clinical data and 1 labial salivary gland (stored frozen) were obtained from each of 82 participants (53 patients with primary SS and 29 control subjects) in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Salivary gland lysates were immunoblotted with markers of type I or type II IFN, and patterns of IFN activity were determined by hierarchical clustering. Correlations between SS phenotypic features and IFN activity in the salivary gland were performed. RESULTS: A total of 58% of the SS participants had high IFN activity and differed significantly from those with low IFN activity (higher prevalence of abnormal findings on sialometry, leukopenia, hyperglobulinemia, high-titer antinuclear antibody, anti-SSA, and high focus score on labial salivary gland [LSG] biopsy). Three distinct patterns of IFN were evident: type I-predominant, type II-predominant, and type I/II mixed IFN. These groups were clinically indistinguishable except for the LSG focus score, which was highest in those with type II-predominant IFN. CONCLUSION: The SS phenotype includes distinct molecular subtypes, which are segregated by the magnitude and pattern of IFN responses. Associations between IFN pathways and disease activity suggest that IFNs are relevant therapeutic targets in SS. Patients with distinct patterns of high IFN activity are clinically similar, demonstrating that IFN-targeting therapies must be selected according to the specific pathway(s) that is active in vivo in the individual patient.

Altered structure of autoantigens during apoptosis.

The clustering and concentration of autoantigens at the surface of apoptotic cells, in combination with the striking tolerance-inducing function of apoptotic cells, have focused attention on abnormalities in apoptotic cell execution and clearance as potential susceptibility and initiating factors in systemic autoimmunity. Structural changes that occur during cell death may influence the immunogenicity of self antigens. This article discusses the modifications that autoantigens undergo during cell death, identifies certain proimmune forms of apoptotic death in which autoantigen structure is frequently modified, and reviews the mechanisms through which such structural changes might lead to initiation of an autoimmune response.

Randomization in surgical trials.

BACKGROUND: There are concerns that use of the term "randomized" conveys a form of legitimacy to surgical trials that may sometimes be inappropriate. The objective of this study was to review the nature and use of randomization techniques in surgical trials. METHODS: We evaluated aspects of the randomization process in 619 surgical trials published within 10 prestigious journals between January 1990 and December 1999. RESULTS: Only 33% of the published trials (202/619) adequately described a valid randomization process. Furthermore, 78% (484/619) did not declare the use or extent of a blinding technique and almost two-thirds of the published trials failed to state how they concealed the randomization process. CONCLUSIONS: Our study indicates that many published surgical trials ignore basic aspects of the randomization process. It is difficult for surgeons to have faith in trials that fail to demonstrate an unbiased allocation of patients and ignore the need to maintain some confidentiality about the allocation of patients into groups.

A prospective randomized trial of enteral glutamine in critical illness.

OBJECTIVE: To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients. DESIGN: This two-armed clinical trial was triple blind (patients, attending staff, research nurse). SETTING: The 10 bed general ICU at Royal Perth Hospital, Western Australia. PATIENTS: This trial evaluated 363 patients requiring mechanical ventilation (median APACHE II score=14); of these, 85 had trauma. INTERVENTION: The intervention solution contained 20 g/l glutamine and the control solution was isojoulic and isonitrogenous. MEASUREMENTS AND RESULTS: The groups had similar characteristics at baseline, and they also received equivalent amounts of protein and energy. Patients in the glutamine group received a median of 19 g/glutamine per day and 91% (332 of 363) of the patients were fed via a nasogastric tube (median duration=10 days). The outcomes were similar in the two groups: (a) death within 6 months: glutamine group 15% (27 of 179) vs control group 16% (30 of 184); p=0.75; relative risk, 0.95 (95% confidence interval, 0.71-1.28); and (b) severe sepsis: glutamine group 21% (38 of 179) vs control group 23% (43 of 184); p=0.62; relative risk, 0.94 (95% confidence interval, 0.72-1.22). There was also no discernable difference in the secondary outcomes relating to infections, febrile period, antimicrobial therapy, and consumption of inotropes. CONCLUSION: This clinical trial did not support the use of enteral glutamine supplements in similar cohorts of critically ill patients.

One surgeon's philosophy of surgical education.

The concept of a philosophy of surgical education provides a vehicle for ensuring that there is a united and comprehensive approach to surgical training. This is important because none of the current approaches to higher education provides a suitable model for surgical training and it is dangerous to uncritically adopt every prevailing fashion in education.

Imagery practice and the development of surgical skills.

BACKGROUND: The purpose of this review is to explore the potential role of imagery practice during the acquisition of surgical skills, imagery practice being the mental rehearsal of a skill. METHODS: The core of this review is derived from a literature search of a computer database (Medline). FINDINGS: The cognitive processing that occurs during times of intense learning involves processes such as dream enactment behavior and imagery practice. These processes complement and augment the more usual forms of practice. CONCLUSIONS: Imagery practice provides a mechanism for the explicit learning of surgical skills.

The management of patients with the short bowel syndrome.

The surgeon is invariably the primary specialist involved in managing patients with short bowel syndrome. Because of this they will play an important role in co-ordinating the management of these patients. The principal aims at the initial surgery are to preserve life, then to preserve gut length, and maintain its continuity. In the immediate postoperative period, there needs to be a balance between keeping the patient alive through the use of TPN and antisecretory agents and promoting gut adaptation with the use of oral nutrition. If the gut fails to adapt during this period, then the patient may require therapy with more specific agents to promote gut adaptation such as growth factors and glutamine. If following this, the patient still has a short gut syndrome, then the principal options remain either long term TPN, or intestinal transplantation which remains a difficult and challenging procedure with a high mortality and morbidity due to rejection.