Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential. In this report, we elucidate the identity of E-selectin ligands on human metastatic prostate tumor cells and examine their association with prostate tumor progression and metastasis in vivo. To our surprise, we found that the E-selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly, we also found that human prostate tumor cells derived from bone, lymph node, and brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand-1 (ESL-1). Immunohistochemical analysis of PSGL-1 and ESL-1 in normal prostate tissue and in localized and metastatic prostate tumors revealed that ESL-1 was principally localized to intracellular cell membrane and expressed on all normal and malignant prostate tissue, whereas PSGL-1 was notably detected on the surfaces of bone-metastatic prostate tumor cells. These findings implicate a functional role of PSGL-1 in the bone tropism of prostate tumor cells and establish a new perspective into the molecular mechanism of human prostate tumor metastasis. (Cancer Res 2005; 65(13): 5750-60)

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Purpose: We set out to describe the natural history of keratoconus. We included untreated patients, and our key outcome measures were vision, refraction, and corneal curvature. Clinical Relevance: Keratoconus affects 86 in 100 000 people, causing visual loss due to increasing irregular corneal astigmatism, and the quality of life declines in patients. Interventions are used to stabilize the disease or improve vision, including corneal cross-linking (CXL) and grafting, but these carry risks. Detailed knowledge of the natural history of keratoconus is fundamental in making informed decisions on when their benefits outweigh these risks. Methods: We included prospective or retrospective studies of pediatric or adult patients who reported 1 or more of visual acuity, refraction, and corneal curvature measures: steep keratometry (K 2), mean keratometry (K mean), or maximum keratometry (K max), thinnest pachymetry, corneal transplantation rates, corneal scarring incidence, and patient-reported outcome measures (PROMs). Databases analyzed included Medline, Embase, CENTRAL, and CINAHL. Searches were carried out until October 2018. Bias assessment was carried out using the Joanna Briggs Institute model of evidence-based healthcare. Results: Our search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. Younger patients and those with greater K max demonstrated more steepening of K max at 12 months. The meta-analysis for K max demonstrated a significant increase in K max of 0.7 diopters (D) at 12 months (95% confidence interval [CI], 0.31e1.14; P ¼ 0.003). Our meta-regression model predicted that patients had 0.8 D less K max steepening over 12 months for every 10-year increase in age (P ¼ 0.01). Patients were predicted to have 1 D greater K max steepening for every 5 D of greater baseline K max (P ¼ 0.003). At 12 months, there was a significant increase in the average K mean of 0.4 D (95% CI, 0.18e0.65; P ¼ 0.004). Conclusions: We report the first systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes. Younger patients and those with K max steeper than 55 D at presentation have a significantly greater risk of progression of keratoconus. Closer follow-up and a lower threshold for cross-linking should be adopted in patients younger than 17 years and steeper than 55 D K max .

OTA meetings are an excellent source of high-quality information, which is generally subsequently published in peer-reviewed journals. The Journal of Orthopaedic Trauma is the single best source for information presented at the OTA meetings. Allowing more papers to be presented did not affect the publication rate for the meetings.

Purpose: To assess vision-related quality of life using the Impact of Vision Impairment Questionnaire (IVI) in patients with keratoconus enrolled in the Save Sight Keratoconus Registry. Methods: In this cross-sectional study, data on 107 keratoconic patients were collected through a prospectively designed web-based registry from a quaternary referral eye hospital and 2 corneal subspecialty practices. Vision-related quality of life was evaluated using the IVI. Rasch analysis was used to transform the IVI responses into interval-level measures comprising reading, mobility, and emotional well-being subscales. Associations between best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), and pachymetry for each eye and IVI subscale scores were evaluated with univariate (Pearson correlations) and multivariable regression adjusted for age and gender. Results: Of the 107 patients, 37 (34.5%), 41 (38.0%) and 29 (26.9%) had mild, moderate, and severe keratoconus, respectively. On uni- and multivariable analysis, BCVA in the better eye had the strongest association with reading [r = 0.51; 95% confidence interval (CI), 0.35–0.64, P = 0.004] and mobility (r = 0.55; 95% CI, 0.41–0.67, P < 0.001) subscale scores. BCVA in the better and worse eye, both had the joint strongest associations with emotional scores on univariate analysis, but only the latter was significant on multivariable analysis (r = 0.37; 95% CI, 0.20–0.53, P < 0.001). K2 and Kmax in the better eye also displayed significant associations with reading and mobility scores. Conclusions: In patients with keratoconus, BCVA in the better eye had the strongest correlation with reading and mobility scores, whereas BCVA in the worse eye was significantly correlated with emotional scores.

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We demonstrate that the expression of TRAF1 and activated c-Rel, two proteins that function in signaling events downstream of activated CD30 in Reed-Sternberg cells, reliably distinguish classical Hodgkin lymphoma from anaplastic large cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and nonmediastinal diffuse large B-cell lymphoma. By immunohistochemistry, we found strong TRAF1 staining in 21 of 25 cases of classical Hodgkin lymphoma. In contrast, strong TRAF1 staining was present in only 1 of 17 cases of anaplastic large cell lymphoma, 0 of 15 cases of lymphocyte predominant Hodgkin lymphoma, and 2 of 36 cases of nonmediastinal diffuse large B-cell lymphoma. Nuclear staining for c-Rel, a pattern consistent with NFkappaB activation, was observed in the Reed-Sternberg cells in 23 of 25 cases of classical Hodgkin lymphoma but only in 1 of 15 cases of anaplastic large cell lymphoma and 3 of 15 cases of nodular lymphocyte predominant Hodgkin lymphoma. A heterogeneous pattern of subcellular c-Rel localization was found in nonmediastinal diffuse large B-cell lymphoma. Taken together, the combination of strong cytoplasmic TRAF1 expression and nuclear c-Rel was present in 80% of cases of classical Hodgkin lymphoma (n = 25) but in only 3% of cases of the other malignant lymphomas tested (n = 62). Thus, the differential expression patterns of downstream components in the CD30 signaling pathway may prove a useful adjunct in distinguishing cases of classical Hodgkin lymphoma from other malignant lymphomas in routine clinical practice.

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