Reed-Sternberg cell genome expression supports a B-cell lineage.

The malignant Reed-Sternberg cell of Hodgkin's disease, first described a century ago, has resisted in-depth analysis due to its extreme rarity in lymphomatous tissue. To directly study its genome-wide gene expression, approximately 11,000,000 bases (27,518 cDNA sequences) of expressed gene sequence was determined from living single Reed-Sternberg cells, Hodgkin's tissue, and cell lines. This approach increased the number of genes known to be expressed in Hodgkin's disease by 20-fold to 2,666 named genes. The data here indicate that Reed-Sternberg cells from both nodular sclerosing and lymphocyte predominant Hodgkin's disease were derived from an unusual B-cell lineage based on a comparison of their gene expression to approximately 40,000,000 bases (10(5) sequences) of expressed gene sequence from germinal center B cells (GCB) and dendritic cells. The data set of expressed genes, reported here and on the World Wide Web, forms a basis to understand the genes responsible for Hodgkin's disease and develop novel diagnostic markers and therapies. This study of the rare Reed-Sternberg cell, concealed in its heterogenous cellular context, also provides a formidable test case to advance the limit of analysis of differential gene expression to the single disease cell.     

Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. enhanced granulopoietic recovery

Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.     

Systematic review of performance of non‐invasive biomarkers in the evaluation of non‐alcoholic fatty liver disease

This systematic review evaluates the many studies carried out to discover and evaluate non‐invasive markers of non‐alcoholic fatty liver disease (NAFLD). Many different strategies and methods have been used in this task, from the discovery of new markers by global ‘shotgun’ studies to hypothesis‐driven approaches, to the development of algorithm tests based on routinely available clinical and biochemical parameters. We examined the various different approaches, summarising the findings in an attempt to give an overview of the field of non‐invasive markers in NAFLD, encompassing markers of steatosis, necro‐inflammation and fibrosis. The body of literature surrounding this topic is complex and varied, encompassing not only different methodologies but also different patient characteristics, different disease definitions, as well as different end points. This reflects the heterogeneity of NAFLD, which, however, introduces considerably difficulty when trying to draw a conclusion between studies. We have divided this review into three main chapters based on the characteristics of the studies. The Genomics/Proteomics chapter reviews studies using a non‐hypothesis‐driven approach to biomarker discovery. Thereafter, we evaluate studies of association – studies that target‐specific markers, comparing levels between disease and control groups. Finally, we examine the algorithm tests – mathematical systems developed on the basis of previously described markers and assessed, usually, by receiver operator curve analysis. While radiological examination and investigations offer important diagnostic information, such studies are not discussed in this review – the body of literature surrounding blood and anthropological markers is complex and varied, demanding close attention.     

超顺磁性氧化铁（SPIO）对比剂肝脾MR成像的比较研究

目的 比较两种超顺磁性氧化铁（superparamagnetic iron oxide,SPIO)对比剂,Ferumoxides及SHU－555A在肝脾MR成像中的效应。材料与方法 36例已知为肝转移癌患者于SPIO造影前后进行T2WI快速自旋回波成像（T2WI TSE）及T1WI梯度回波快去速相位成像（T1WI FLASH）。扫描伪为1．0T MR机。18例患者行Ferumoxides增强后90分钟进行MR成像;另18例行SHU－55A快速团柱增强,注药后即刻、30秒及480秒行T1WI FLASH成像,10分钟行T2WI TSE成像。测量肝脾、肝转移癌SPIO增强前后的信号强度（signal intensity,SI),计算两种SPIO对比剂在肝脾、肝转移癌增强前后SI变化的百分比（percentage signal intensity change,PSIC)及病灶肝脏对比噪声比（lesion-to-liver contrast-to-noise ratio,CNR)及其变化（ΔCNR）。结果 在T2WI TSE图像上,两种SPIO对比剂造成的肝实质SI下降无显著性差异（P＞0．05）。Ferumoxides引的脾信号下降显著大于SHU－555A（P＜0．05）。两种SPIO对比剂均导致肝实转移癌SNR显著增高。T1WI FLASH图像上,两种对比剂均可导致延迟像上肝脏SI的轻度下降及肝转移癌CNR下降,两者肝脏SIC之间无显著性差异。T1WI上两种对比剂均可导致脾脏SI显著升高,两者脾脏PSIC之间无显著性差异（P＞0．05）。结论 两种SPIO在肝脏的TI及T2增强效应相似,而脾脏的T2增强效应,Ferumoxides强于SHU－555A。     

Impact of Surgeon and Hospital Volume on Mortality,Length of Stay,and Cost of Pancreaticoduodenectomy

Background

Improved mortality rates following pancreaticoduodenectomy by high-volume surgeons and hospitals have been well documented, but less is known about the impact of such volumes on length of stay and cost. This study uses data from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) to examine the effect of surgeon and hospital volume on mortality, length of stay, and cost following pancreaticoduodenectomy while controlling for patient-specific factors.

Methods

Data included 3,137 pancreaticoduodenectomies from the NIS performed between 2004 and 2008. Using logistic regression, the relationship between surgeon volume, hospital volume, and postoperative mortality, length of stay, and cost was estimated while accounting for patient factors.

Results

After controlling for patient characteristics, patients of high-volume surgeons at high-volume hospitals had a significantly lower risk of mortality compared to low-volume surgeons at low-volume hospitals (OR 0.32, p?<?0.001). Patients of high-volume surgeons at high-volume hospitals also had a five day shorter length of stay (p?<?0.001), as well as significantly lower costs (US$12,275, p?<?0.001).

Conclusions

The results of this study, which simultaneously accounted for surgeon volume, hospital volume, and potential confounding patient characteristics, suggest that both surgeon and hospital volume have a significant effect on outcomes following pancreaticoduodenectomy, affecting not only mortality rates but also lengths of stay and costs.

     

Amputation and the assessment of limb viability: perceptions of two hundred and thirty two orthopaedic trainees

INTRODUCTION

The management of complex extremity injury, which may require assessment of limb viability and performance of amputation, is a challenge to those involved in its emergent and definitive care. Concern exists regarding the exposure of orthopaedic trainees to such cases due both to changes in training and centralisation of trauma services.

SUBJECTS AND METHODS

This is a web-based observational study by survey, investigating the confidence and perceived adequacy of training of UK orthopaedic specialist trainees in the assessment of limb viability and amputation surgery. 222 responses from 888 trainees were required to achieve a < 5% error rate with 90% confidence; 232 surveys were completed.

RESULTS

Trainee confidence in dealing with the assessment of limb viability is high despite infrequent exposure to cases. The majority of trainees perceive their training in limb viability assessment as adequate. For performance of amputation, exposure is minimal, confidence is lower and 36% of trainees regard their training as inadequate.

CONCLUSIONS

Limb viability assessment is an area in which trainees feel confident and well trained. There is, however, a perceived training inadequacy in amputation surgery and a corresponding lack of confidence for many trainees, irrespective of training year. This is the first study to offer an insight into specific training experiences of junior orthopaedic surgeons at a national level and it should drive the development of opportunities for trainees to develop skills in amputation surgery.     

Length of Stay and Readmissions in Mastectomy Patients

Interest is growing in preventing readmissions as payers start to link reimbursement to readmission rates. The purpose of this study was to assess factors that contribute to 30‐day readmission rates for women undergoing mastectomy for breast cancer. Data from the Pennsylvania Health Care Cost Containment Council were queried for women undergoing mastectomy for breast cancer during 2011 (n = 2,919). The outcomes measured were length of stay (LOS) and 30‐day readmission. Univariate comparisons between characteristics of readmitted (n = 172) and nonreadmitted patients were performed using t‐tests and chi‐square tests. Readmission was modeled using logistic regression; LOS was modeled using linear regression and controlled for potential confounders. In multivariate analyses, patients with peripheral vascular disease were more likely to be readmitted (OR 4.36, p = 0.002). Increased LOS was also associated with increased odds of readmission (OR 1.26, p = <0.0001). Since LOS was an important predictor of readmission we also estimated determinants of LOS using linear regression. The occurrence of reconstructive surgery (p = <0.0001) and renal disease (p < 0.0001) were highly predictive of longer LOS. This study showed peripheral vascular disease and longer lengths of stay were associated with higher odds of readmission in women undergoing mastectomy. Clinicians should be cognizant that optimizing a patient's vascular status before mastectomy may lead to lower rates of readmission. Additional research is needed to determine whether the relationship between readmissions and length of hospital stay is a causative versus associative phenomenon since LOS is a modifiable factor that may lead to lower readmissions.     

Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP)

Recombinant human interleukin-11 (rhIL-11), a glycoprotein 130 (gp130)-signaling cytokine approved for treatment of thrombocytopenia, also raises von Willebrand factor (VWF) and factor VIII (FVIII) by an unknown mechanism. Desmopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) releases stored VWF and FVIII and is used for treatment of VWF and FVIII deficiencies. To compare the effect of these 2 agents, heterozygous von Willebrand disease (VWD) and normal dogs were treated with either rhIL-11 (50 microg/kg/d subcutaneously x 7 days) or DDAVP (5 microg/kg/d intravenously x 7 days). The rhIL-11 produced a gradual and sustained elevation of VWF and FVIII levels in both heterozygous VWD and normal dogs while DDAVP produced a rapid and unsustained increase. Importantly, rhIL-11 treatment produced a 2.5- to 11-fold increase in VWF mRNA in normal canine heart, aorta, and spleen but not in homozygous VWD dogs, thus identifying a mechanism for elevation of plasma VWF in vivo. Moreover, dogs pretreated with rhIL-11 retain a DDAVP-releasable pool of VWF and FVIII, suggesting that rhIL-11 does not significantly alter trafficking of these proteins to or from storage pools. The half-life of infused VWF is unchanged by rhIL-11 in homozygous VWD dogs. These results show that rhIL-11 and DDAVP raise plasma VWF by different mechanisms. Treatment with rhIL-11 with or without DDAVP may provide an alternative to plasma-derived products for some VWD and hemophilia A patients if it is shown safe in clinical trials.