Imaging of bone metastasis: An update

Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques which fuse morphological and functional data are the most sensitive and specific, and positron emission tomography (PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.     

Factors affecting perioperative blood loss and transfusion rates in primary total joint arthroplasty: a prospective analysis of 1642 patients

Background

In recent years, the use of low molecular weight heparins such as dalteparin has become attractive because of their ease of administration and superiority in preventing venous thromboembolism (VTE) compared with traditional agents. The primary purpose of our study was to evaluate the impact of dalteparin use on blood loss and transfusion rates in patients undergoing primary total joint arthroplasty. We also evaluated the effect of patient sex, releasing the tourniquet in knee arthroplasty and the turnover of house staff.

Methods

Using our hospital transfusion database, we prospectively studied the mean reduction in hemoglobin and transfusion rates of 1642 consecutive patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) between January 2004 and December 2005. In 2004, warfarin was used exclusively for VTE prevention; however, in 2005, following the release of the 2004 American College of Chest Physicians’ guidelines, our centre began using dalteparin for VTE prophylaxis. We analyzed the impact of dalteparin use and the effect of patient sex, tourniquet release in TKA and house staff turnover months on blood loss and transfusion rates.

Results

The use of dalteparin for postoperative VTE prevention in patients undergoing THA and TKA in 2005 was associated with a significantly greater mean reduction in hemoglobin compared with warfarin use in 2004 (p = 0.014 for patients undergoing THA, p < 0.001 for patients undergoing TKA). The use of dalteparin in 2005 was not associated with a significant increase in allogeneic blood transfusions compared with the use of warfarin in 2004, except in women (p < 0.001). Although we observed no significant differences in mean reduction in hemoglobin between men and women undergoing THA, women undergoing THA had significantly higher transfusion rates regardless of the method of VTE prophylaxis (p = 0.037 for warfarin, p < 0.001 for dalteparin). Intraoperative tourniquet release in patients undergoing TKA was associated with a significantly lower mean reduction in hemoglobin than release after wound closure (p = 0.005). Although house staff turnover months were associated with a significantly greater mean reduction in hemoglobin levels than non-turnover months (p = 0.039), these months were not associated with a significant increase in allogeneic blood transfusions (p = 0.59).

Conclusion

Low molecular weight heparins such as dalteparin are the most common form of VTE prophylaxis in Canada. Our results suggest that dalteparin use, timing of tourniquet release and house staff turnover can all influence transfusion rates and/or blood loss in patients undergoing primary total joint arthroplasty. This study also emphasizes that women undergoing THA are at particularly high risk for blood transfusion.     

Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo

OBJECTIVE

Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.

RESEARCH DESIGN AND METHODS

Healthy human volunteers (n = 14) were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode secreted proteins. Of these, 86 candidates were chosen for validation in adipose from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and for exploration of cellular origin in primary human adipocytes and macrophages in vitro.

RESULTS

Microarray identified 776 adipose genes modulated by LPS; 298 were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96% [95% CI 90–99]) were upregulated (fold changes >1.0) during the lower-dose (LPS 0.6 ng/kg) validation study and 51 of 85 (59% [49–70]) were induced greater than 1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73% of detectable genes, respectively.

CONCLUSIONS

We demonstrate that evoked inflammation of human adipose in vivo modulated expression of multiple genes likely secreted by adipocytes and monocytes. These included established adipocytokines and chemokines implicated in recruitment and activation of lymphocytes, adhesion molecules, antioxidants, and several novel genes with unknown function. Such candidates may represent biomarkers and therapeutic targets for obesity-related complications.Activation of innate and adaptive immunity is a crucial link between adiposity and its metabolic complications (1–4). In rodents, modulation of toll-like receptor-4 (5), tumor necrosis factor (TNF) receptors (6), chemokines, and downstream kinases (7) attenuate diet-induced obesity and insulin resistance. Further, cross talk between immune cells and adipocytes promotes an inflammatory, insulin-resistant state in obesity. A key initiating event in adipose inflammation is recruitment of T-lymphocytes (8,9) and monocyte/macrophages (10,11) with elaboration of inflammatory adipocytokines that modulate metabolic signaling (12–15). Despite experimental evidence in rodent models, most evidence supporting these concepts in humans derives from observational and correlative studies (16–18). Indeed, validated adipokines that mediate, or serve as biomarkers for, complications of human adiposity remain limited.Expression of inflammatory, insulin-signaling, and lipid genes are perturbed in adipose of obese humans (19–21). Recently, the in vitro secretome of subcutaneous and visceral primary human adipocytes was described and includes many unexplored proteins modulated during adipogenesis (1,22). Remarkably, less than half of genes found in the human subcutaneous adipocyte secretome were previously found in the murine 3T3-L1 preadipocyte secretome (22), underscoring the importance of studies in human tissue.Experimental human endotoxemia can provide unique insights into the relationship of inflammation to metabolic disturbance in man (23,24). Others and we have shown that endotoxemia induces acute metabolic, lipoprotein, and oxidant responses that resemble the chronic changes in insulin resistance and metabolic syndrome (25,26). Notably, endotoxemia induces adipose inflammation (27) with activation of several adipose inflammatory cascades, including cytokines, chemokines, and suppressor of cytokine signaling (SOCS) molecules (26) that attenuate insulin signaling and are implicated in obesity and type 2 diabetes (28).We applied microarray mRNA profiling of human adipose during endotoxemia to identify novel inflammation-induced adipose genes. We focused on genes predicted to be secreted and validated our findings in vivo through independent experiments of low-grade human inflammation. Finally, we identified in vitro the likely human adipose cellular source of these top candidates.     

The utilisation of intraosseous infusion in the resuscitation of paediatric major trauma patients

Intraosseous lines are a reliable and rapid tool for obtaining vascular access in emergency situations, particularly in children. Their use is recommended when intravenous access cannot be easily secured and there is a need for fluid or pharmacological resuscitation. Training in this technique is included in the Advanced Trauma Life Support (ATLS) and Advanced Paediatric Life Support course (APLS) provider courses. The objective of this study is to analyse the national use of intraosseous lines in paediatric trauma in England and Wales. Data has been collected from the Trauma Audit and Research Network (TARN) group longitudinally over 14 years from 1988 to 2002. From 23,489 paediatric trauma cases, intraosseous lines were used in only 129 patients. Compared with the remainder of the paediatric data, we found that these were the younger (1-6 years), more severely injured patients (higher ISS, lower GCS, higher head, thorax, and abdominal AIS). The mortality of these patients was high at 64% compared with 4% overall. IO line use was greater in general than in Paediatric hospitals, perhaps due to good intravenous access skills in paediatric centres. We recommend that intraosseous line use should be a skill available to everybody involved in paediatric trauma resuscitation, particularly those who may not have refined paediatric intravenous cannulation skills.     

The role of lymphadenectomy in prostate cancer

It has been shown that an adequate lymphadenectomy for exact staging of prostate cancer consists of removal of all the tissue along the external iliac vein, in the obturator fossa and along the internal iliac artery. Morbidity associated with this procedure is low, if certain technical details are respected. This review discusses in detail the indications for lymphadenectomy and the extent of dissection, based on the localization of the positive nodes. The potential therapeutic impact of extended lymph node dissection in men with prostate cancer is also addressed.     

Sternal wound dehiscence after internal mammary artery harvesting. Logical management. Part 2

Wound breakdown is a serious complication of median sternotomy. This is generally met with a further attempt at surgical apposition using sutures of monofilament surgical steel, following wound debridement. This often fails. The aim of this article is to demonstrate one surgeon's experience in his revised management of sternal wound dehiscence, following internal mammary artery (IMA) harvest, over a 7-year period. Treatment consisted of sternal and soft tissue debridement, and closed irrigation. Wound closure was performed using multiple interrupted deep tension sutures (DTS) only. We believe this article demonstrates that the use of DTS is a safe and effective method of closure, for patients suffering from sternal wound dehiscence following IMA harvest.     

A review of the true methodological quality of nutritional support trials conducted in the critically ill: time for improvement

In this review we sought to appraise the true methodological quality of nutritional support studies conducted in critically ill patients and to compare these findings to the methodological quality of sepsis trials. An extensive literature search revealed 111 randomized controlled trials conducted in critically ill patients evaluating the impact of nutritional support interventions on clinically meaningful outcomes. Compared with sepsis trials, nutritional support studies were significantly less likely to use blinding (32 of 40 versus 35 of 111, P < 0.001) or present an intention-to-treat analysis (37 of 40 versus 64 of 111, P < 0.001). There was a trend toward the less frequent use of randomization methods that are known to maintain allocation concealment (12 of 40 versus 19 of 111, P = 0.10). Although nutritional support studies demonstrated a significant increase in the use of blinding after the publication of the CONSORT statement in 1996 (9 of 47 versus 26 of 64 post-CONSORT, P = 0.023), there were no improvements in other key areas. Previous publications have described the overall methodological quality of sepsis trials as "poor." Nutritional support studies were significantly worse than sepsis trials in all aspects of methodological quality, and there were few improvements noted over time. To detect important differences in clinically meaningful outcomes in critical care, the methodological quality of future studies must be improved.     

Clinical outcomes of keratitis

OBJECTION: To analyse the patient, clinical and microbiological variables associated with poor outcomes from keratitis in patients presenting to a major public hospital in Australia. METHODS: A retrospective audit of the records of all patients who had a corneal scraping in 5 years at Princess Alexandra Hospital (Brisbane, Australia) was carried out. The outcome of a patient's episode of keratitis was classified as poor if they had final visual acuity of 6/60 or worse; had vision loss during treatment; or a complication of keratitis; or needed surgical intervention. RESULTS: A final outcome was established in 207 cases during the 5-year period. Final vision of 6/12 or better was found in 48% (100) of cases while a poor outcome was seen in 28% (58). Linear regression showed poor outcomes were directly associated with age (P < 0.001) and disease severity (P < 0.001). Univariate analysis indicated that poor outcomes were more likely in patients who had had prior ocular surgery (P = 0.005) or ocular surface disease (P = 0.01) and were also associated with presenting visual acuity of worse than 6/60 (P < 0.001) and isolation of Streptococcus pneumoniae (P = 0.002). While patients with traumatic keratitis, contact lens-related keratitis or negative corneal cultures (P = 0.009) were more likely to have good outcomes. Multivariate analysis showed that the relative risk of a patient having a poor outcome was 4.3x (CI 2.0-9.5) if they had severe keratitis, 4.1x (CI 1.8-9.5) if they had keratitis related to ocular surface disease and 3.8x (CI 1.8-8.3) if they were over 50 years old. CONCLUSIONS: An outcome of poor vision, vision loss during treatment, surgical intervention or complication of keratitis is more likely in patients with severe keratitis, keratitis related to prior ocular surface disease or older age.     

Risk and protective factors for wellbeing in older veterans in New Zealand

Objectives: To compare indicators relating to aging and health among veterans and non-veterans, and identify factors associated with subjective wellbeing (SWB) of older New Zealand veterans.

Methods: Self-reported data were obtained from participants in a longitudinal cohort study of New Zealand older adults. Responses from 352 veterans and 1500 non-veterans (age range of 55–86 and gender matched) were selected as a comparison group on indicators related to health and aging. The association of these indicators with veterans’ SWB were assessed using hierarchical regression.

Results: Apart from being older, smoking more, and having more chronic conditions, veterans did not differ from non-veterans on indicators of health and wellbeing. Mental health, physical health, purpose in life, housing satisfaction, and capabilities (choice and freedom) accounted for a significant amount of variance in veterans’ SWB.

Conclusion: Our results suggest that older veterans do not differ greatly on indices of health and aging from their non-veteran peers. Results support previous findings that lower mental and physical health is associated with lower SWB for veterans. Building upon prior findings, the current results demonstrate that interventions focusing on enhancing a sense of purpose in life, supporting one's capability to achieve, and strengthening social and physical environment through social connectedness, may serve as protective factors for SWB in veterans.