Citations

Study Design. Prospective cohort study. Objective. To characterize the accuracy of patient recollection of preoperative symptoms after lumbar spine surgery. Summary of Background Data. Although patient-reported outcomes have become important in the evaluation of spine surgery patients, the accuracy of patient recall remains unknown. Methods. Patients undergoing lumbar decompression with or without fusion were enrolled. Back and leg Numeric Pain Scores and Oswestry Disability Indices were recorded preoperatively. Patients were asked to recall their preoperative status at a minimum of 1 year after surgery. Actual and recalled scores were compared using paired t tests and relations were quantified using Pearson correlation coefficients. Multivariable linear regression was used to identify factors that affected recollection. Results. Sixty-two patients with a mean age of 66.1 years were included. Compared to their preoperative scores, patients showed significant improvement in back pain (mean difference [MD] = −3.2, 95% CI −4.0 to −2.4), leg pain (MD −3.3, 95% CI −4.3 to −2.2), and disability (MD −25.0%, 95% CI −28.7 to −19.6). Patient recollection of preoperative status was significantly more severe than actual for back pain (MD +2.3, 95% CI 1.5–3.2), leg pain (MD +1.8, 95% CI 0.9–2.7), and disability (MD +9.6%, 95% CI 5.6–14.0). No significant correlation between actual and recalled scores with regards to back (r = 0.18) or leg (r = 0.24) pain and only moderate correlation with disability (r = 0.44) were seen. This was maintained across age, sex, and time between date of surgery and recollection. More than 40% of patients switched their predominant symptom from back pain to leg pain or leg pain to back pain on recall. Conclusion. Relying on patient recollection does not provide an accurate measure of preoperative status after lumbar spine surgery. Recall bias indicates the importance of obtaining true baseline scores and patient-reported outcomes prospectively and not retrospectively. Level of Evidence: 2

Significance Ubiquitin-specific protease 6 (USP6) is a deubiquitylase that is overexpressed by chromosome translocation in two human neoplasms, aneurysmal bone cyst and nodular fasciitis. The relevant substrates of this ubiquitin-specific protease are not clear. Here, we identify the Wnt receptor Frizzled (Fzd) as a key target of the USP6 oncogene. Increased expression of USP6 increases the membrane abundance of Fzd, and hence increases cellular sensitivity to Wnts. USP6 opposes the activity of the ubiquitin ligase and tumor suppressor ring finger protein 43 (RNF43). This study identifies a new mechanism for pathological Wnt pathway activation in human disease and suggests a new approach to regulate Wnt activity therapeutically.

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is lethal cancer whose primary tumor is characterized by dense composition of cancer cells, stromal cells, and extracellular matrix (ECM) composed largely of collagen. Within the PDAC tumor microenvironment, activated pancreatic stellate cells (PSC) are the dominant stromal cell type and responsible for collagen deposition. Lumican is a secreted proteoglycan that regulates collagen fibril assembly. We have previously identified that the presence of lumican in the ECM surrounding PDAC cells is associated with improved patient outcome after multimodal therapy and surgical removal of localized PDAC. Experimental Design: Lumican expression in PDAC from 27 patients was determined by IHC and quantitatively analyzed for colocalization with PSCs. In vitro studies examined the molecular mechanisms of lumican transcription and secretion from PSCs (HPSCs and HPaSteC), and cell adhesion and migration assays examined the effect of lumican on PSCs in a collagen-rich environment. Results: Here we identify PSCs as a significant source of extracellular lumican production through quantitative IHC analysis. We demonstrate that the cytokine, TGF-β, negatively regulates lumican gene transcription within HPSCs through its canonical signaling pathway and binding of SMAD4 to novel SBEs identified within the promoter region. In addition, we found that the ability of HPSCs to produce and secrete extracellular lumican significantly enhances HPSCs adhesion and mobility on collagen. Conclusions: Our results demonstrate that activated pancreatic stellate cells within PDAC secrete lumican under the negative control of TGF-β; once secreted, the extracellular lumican enhances stellate cell adhesion and mobility in a collagen-rich environment. Clin Cancer Res; 22(19); 4934–46. ©2016 AACR.

Abstract Alzheimer's disease research has often focused on the molecular brain changes that promote memory loss and other dementia‐related cognitive impairments. Many studies, for example, have used positron emission tomography (PET) imaging to measure brain levels of the beta‐amyloid protein, a key molecular suspect in Alzheimer's. In recent years, PET scans have become more prominent in clinical settings. Clinicians may use a positive PET scan—that is, a significant presence of beta‐amyloid plaques in the brain—to help determine a diagnosis of Alzheimer's disease. Yet, because beta‐amyloid PET remains a fairly new diagnostic tool, physicians and patients still have many basic questions about how and why it is used. This article addresses some of those questions. It explains what PET scans actually show, how they are employed in research and clinical trials, and when they should and should not be used to help diagnose Alzheimer's in everyday patients. The article also discusses whether cognitively healthy people should request PET scans to assess their risk for developing dementia. Information in the text will be updated in future years, as diagnostic imaging techniques for Alzheimer's disease continue to evolve.

AbstractSVC obstruction is a rare acute complication after bicaval cardiac transplantation and can be catastrophic for the patient. Herein, we report the case of a child who developed SVC thrombosis causing acute SVC syndrome nine days after heart transplantation. Thrombolysis was successfully performed using the AngioJet™ system and subsequent balloon angioplasty with re‐establishment of flow. This procedure allowed for revascularization without repeat sternotomy or stent implantation. The patient is well without recurrence at last follow‐up.

Background: Tibial slope angle is a nonmodifiable risk factor for anterior cruciate ligament (ACL) injury. However, the mechanical role of varying tibial slopes during athletic tasks has yet to be clinically quantified. Purpose: To examine the influence of posterior tibial slope on knee joint loading during controlled, in vitro simulation of the knee joint articulations during athletic tasks. Study Design: Descriptive laboratory study. Methods: A 6 degree of freedom robotic manipulator positionally maneuvered cadaveric knee joints from 12 unique specimens with varying tibial slopes (range, −7.7° to 7.7°) through drop vertical jump and sidestep cutting tasks that were derived from 3-dimensional in vivo motion recordings. Internal knee joint torques and forces were recorded throughout simulation and were linearly correlated with tibial slope. Results: The mean (±SD) posterior tibial slope angle was 2.2° ± 4.3° in the lateral compartment and 2.3° ± 3.3° in the medial compartment. For simulated drop vertical jumps, lateral compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee adduction ( r = 0.60-0.65), flexion ( r = 0.64-0.66), lateral ( r = 0.57-0.69), and external rotation torques ( r = 0.47-0.72) as well as inverse correlations with peak abduction ( r = −0.42 to −0.61) and internal rotation torques ( r = −0.39 to −0.79). Only frontal plane torques were correlated during sidestep cutting simulations. For simulated drop vertical jumps, medial compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee flexion torque ( r = 0.64-0.69) and lateral knee force ( r = 0.55-0.74) as well as inverse correlations with peak external torque ( r = −0.34 to −0.67) and medial knee force ( r = −0.58 to −0.59). These moderate correlations were also present during simulated sidestep cutting. Conclusion: The investigation supported the theory that increased posterior tibial slope would lead to greater magnitude knee joint moments, specifically, internally generated knee adduction and flexion torques. Clinical Relevance: The knee torques that positively correlated with increased tibial slope angle in this investigation are associated with heightened risk of ACL injury. Therefore, the present data indicated that a higher posterior tibial slope is correlated to increased knee loads that are associated with heightened risk of ACL injury.