Citations

Seligman’s theory of causal attribution predicts that patients with a pessimistic explanatory style will have less favourable health outcomes. We identified 702 patients who had undergone 894 primary total knee replacements between 1993 and 2005, who responded to follow-up surveys at two (n = 783 knee replacements) and/or five years (n = 443 knee replacements) and had also completed the Minnesota Multiphasic Personality Inventory long before the joint replacement (median = 16.6 and 14.5 years for two- and five-year cohorts, respectively). Scores from the Minnesota Multiphasic Personality Inventory Optimism-Pessimism scale were used to categorise patients as pessimistic (t-score > 60) or non-pessimistic (t-score ≤ 60). Multivariate logistic regression models assessing the effect of pessimistic explanatory style on pain or improvement in knee function were adjusted for gender, age, distance from the place of treatment and depression score. Pessimists reported (a) significantly more moderate or severe pain at two years with odds ratio 2.21 (95% confidence interval (CI) 1.12 to 4.35; p = 0.02), but not at five years when the odds ratio was 1.21 (95% CI 0.51 to 2.83; p = 0.67); and (b) less improvement in knee function at two years when the odds ratio was 0.53 (95% CI 0.30 to 0.96; p = 0.04), but not at five years when the odds ratio was 1.26 (95% CI 0.57 to 2.77; p = 0.57). No significant associations with moderate or severe limitation of activity were seen at two or five years. We conclude that a pessimistic explanatory style is associated with worse pain and functional outcomes two years after total knee replacement.

Abstract Rationale Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. Objectives To compare patient and transfusion risk factors between patients who do and do not develop ALI. Methods In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis. Measurements and Main Results Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37–18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32–17.86) and anti–HLA class II antibodies (OR, 3.08; 95% CI, 1.15–8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI. Conclusions Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.

Abstract Marrow stromal cells can differentiate into osteoblasts, adipocytes, myoblasts, and chondrocytes. Bone morphogenetic protein 2 (BMP-2) is a potent stimulator of osteoblastic differentiation, and identification of the genes regulated by BMP-2 in these cells should provide insight into the mechanism(s) of osteoblastic differentiation. Thus, we used a conditionally immortalized human marrow stromal cell line (hMS) and a gene expression microarray containing probes for a total of 6800 genes to compare gene expression in control and BMP-2-treated cultures. A total of 51 genes showed a consistent change in messenger RNA (mRNA) frequency between two repeat experiments. Seventeen of these genes showed a change in expression of at least 3-fold in BMP-2-treated cultures over control cultures. These included nuclear binding factors (10 genes), signal transduction pathway genes (2 genes), molecular transport (1 gene), cell surface proteins (2 genes) and growth factors (2 genes). Of particular interest were four of the nuclear binding factor genes ID−1, ID−2, ID−3, and ID−4. These encode dominant negative helix-loop-helix (dnHLH) proteins that lack the nuclear binding domain of the basic HLH proteins and thus have no transcriptional activity. They have been implicated in blocking both myogenesis and adipogenesis. Other transcription factors up-regulated at least 3-fold by BMP-2 included Dlx-2, HES-1, STAT1, and JunB. The changes in these nuclear binding factor mRNA levels were confirmed by real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). A further three transcription factors, core binding factor β (CBFβ), AREB6, and SOX4, showed changes in expression of between 2- and 3-fold with BMP-2 treatment. In summary, we have used a gene chip microarray to identify a number of BMP-2 responsive genes in hMS cells. Thus, these studies provide potential candidate genes that may induce osteoblastic differentiation or, in the case of the ID proteins, block differentiation along alternate pathways.

AbstractWe present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 × 109/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2V617F mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.

AbstractThis prospective randomized study examined the acute‐phase response and wound healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a cushingoid porcine model. Repository corticotropin gel was given to 40 pigs for 21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed. The pigs were randomized to undergo LA or PA. In addition to operating time and morbidity, the acute‐phase response was compared by measuring the postoperative white blood cell count, fasting glucose, C‐reactive protein, and nitrogen balance. Wound healing was assessed by (1) scored (1–4) gross appearance at 48 hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength. There was no difference in operating time (mean ± SD) (36 ± 9 minutes open vs. 37 ± 7 minutes laparoscopic), perioperative mortality, degree of leukocytosis, fasting glucose, or C‐reactive protein (p > 0.05). Nitrogen balance, wound scores, and tensile strength at 24 hours and 1 week were more favorable in the LA group than in the PA group (p < 0.05). In the cushingoid porcine model, laparoscopic adrenalectomy was less catabolic and was associated with fewer wound complications than the open posterior adrenalectomy. These findings provide support for continued pursuit of laparoscopic methods for adrenalectomy in the clinical setting.