Abnormalities of the pericruciate fat pad: Correlations with the location and severity of chondral lesions of the knee.

PURPOSE: The aim of this study was to evaluate the relationship between the grade of signal change of the pericruciate fat pad (PCFP) and the location and severity of cartilage alterations in the knee on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study included 234 patients (M:F = 96:138, mean: 51 years) who underwent knee MRI. Two experienced musculoskeletal radiologists assessed any PCFP alterations (as grades 0-3) and chondral lesions using the modified Outerbridge grade (as grades 0-4). Bone marrow lesions (BMLs), meniscal status, anterior cruciate ligament alterations, and effusion-synovitis were also evaluated on the MRI. The relationships between PCFP alteration and MR findings (including the grade of chondral lesion) were evaluated. RESULTS: Signal changes in the PCFP were detected in 150 cases by Reader 1 (grade 0, 67 cases; grade 1, 53 cases; grade 2, 21 cases; grade 3, 9 cases) and in 154 cases by Reader 2 (grade 0, 59 cases; grade 1, 61 cases; grade 2, 24 cases; grade 3, 10 cases). The grade of PCFP signal change was statistically significantly correlated with the grade of the chondral lesion of the medial femoral condyle (MFC) (p = 0.029 and p = 0.003, respectively) and the medial tibial plateau (MTP) (p = 0.045, p = 0.002, Readers 1 and 2, respectively). The grade of PCFP signal change was significantly correlated with the grade of the BMLs of the MFC, MTP, and lateral femoral condyle (p < 0.05) for both readers. PCFP alteration was related to effusion-synovitis and tears of the medial meniscus. CONCLUSIONS: The grade of PCFP signal change was correlated with the severity of the cartilage alteration in the medial compartment of the knee joint and was also correlated with BMLs in the medial compartment, medial meniscal tears, and synovitis. Therefore, signal change in the PFCP seen on MRI can be an additional clue of the presence of osteoarthritis in the knee, particularly in the medial compartment.

The reproducibility of shear wave and strain elastography in epidermal cysts.

PURPOSE: This study evaluated epidermal cyst elasticity using multiple parameters of strain elastography (SE) and shear wave elastography (SWE) and assessed the reproducibility of each parameter. METHODS: This retrospective study included 73 patients with epidermal cysts who underwent SE and SWE. SE scores were classified as 1-4 according to elasticity. The strain ratio was evaluated using the elasticity ratio of lesions and adjacent subcutaneous fat tissue. For SWE, the shear wave velocity (m/s), elasticity (kPa) according to the Young modulus, velocity ratio, and elasticity ratio were evaluated. All values were measured twice. The reproducibility of SE and SWE measurements was assessed. The relationships among SE and SWE measurements were evaluated. RESULTS: The strain ratio on SE images showed good reproducibility (intra-class correlation coefficient [ICC]=0.789), and SE scores showed substantial reproducibility (kappa=0.753 and kappa=0.758 for readers 1 and 2, respectively). Moderate reproducibility was found for shear wave velocity and elasticity (ICC=0.750 and ICC=0.648, respectively), as well as for the shear wave velocity of the reference tissue and velocity ratio (ICC=0.747 and ICC=0.713, respectively). All SE scores were positively correlated with the strain ratio (P<0.001). The strain ratio in the second SE session was significantly correlated with the elasticity ratio and velocity ratio in the first SWE session (r=0.245, P=0.037; r=0.243, P=0.038, respectively). Other variables were not correlated. CONCLUSION: SE and SWE parameters of epidermal cysts showed moderate to good reproducibility. The strain ratio on SE showed good reproducibility and could provide relatively objective and consistent measurements of epidermal cyst elasticity.

Factors of Hospitals Associated With an Independent Hospice Care Unit: A Quantitative Empirical Study.

Few studies have examined why some hospitals operate independent hospice units (IHUs) and others do not. This study aims to investigate the organizational factors of hospitals having IHU. The units of analysis were individual hospitals. The study had a cross-sectional design and used health insurance claims data of 349 hospitals in Korea from January 1 to December 31, 2019. The dependent variable was whether a hospital operated an IHU. The independent variables were the percentage of patients with cancer, overall severity of patients, percentage of patients 60 years and older, health care cost per patient, percentage of inpatients, and nurse staffing level. Independent hospice units were present at 21.2% of the hospitals (74/349). The odds of having an IHU were significantly associated with the following factors: the percentage of patients with cancer (odds ratio [OR], 1.228; 95% confidence interval [CI], 1.071-1.408; P = .003), disease severity (OR, 5.129; 95% CI, 2.477-10.622; P < .001), percentage of patients 60 years and older (OR, 1.053; 95% CI, 1.015-1.092; P = .006), health care cost per patient (OR, 1.018; 95% CI, 1.009-1.027; P < .001), and nurse staffing level (OR, 0.439; 95% CI, 0.292-0.661; P < .001). The organizational factors of hospitals operating IHUs were similar to those of hospice facilities.

Treatment of Polyostotic Fibrous Dysplasia of the Thoracic Spine with Intravenous Pamidronate: Result from 9 Months Follow Up.

Fibrous dysplasia of the spine is very rarely observed. We reported a case of a 57-year-old woman, who presented with neck and bilateral shoulder pain with histologically confirmed fibrous dysplasia, involving the first and second thoracic vertebrae. Clinical and radiological findings were not specific for fibrous dysplasia. The histological biopsy was required for a confirmed diagnosis. Endocrine and metabolic evaluations are required to rule out diseases such as hyperthyroidism, Cushing syndrome and osteomalacia. Fibrous dyplasia can be managed by appropriate medical and surgical treatments based on the patient's neurological status and symptoms. Our patient was given intravenous pamidronate 60mg/day for 3 days. After 9 months, her initial symptoms were improved, but computed tomography scan of the thoracic spine showed no change of the lesions.

Thoracolumbar extradural arachnoid cysts: a study of 14 consecutive cases.

BACKGROUND: To investigate characteristic clinical and radiological features of extradural arachnoid cysts (EDACs) in the thoracolumbar region, a retrospective review of medical records and imaging studies was performed. EDACs are well known but relatively rare lesions in the thoracolumbar spinal canal. The most common site is the lower thoracic spine, and it may cause neurological symptoms by compressing the spinal cord or nerve root. In this study, the pathogenesis, symptomatology, diagnostic approach, and surgical management of EDACs will be discussed. METHODS: We studied 14 consecutive patients who were surgically treated for EDACs in the thoracolumbar region at our institute between March 2000 and January 2011. The history, clinical presentations, image findings, operative findings, and surgical outcomes of these patients were retrospectively analyzed. The mean follow-up period was 28 months (range: 6-72 months). RESULTS: Progressive motor weakness was the predominant symptom in all patients. Nine patients had radicular leg pain and back pain in the thoracolumbar area. On MRI, the cyst compressed the dural sac and spinal cord posteriorly typically with bilateral foraminal extensions. On radiological study, a communication point with the subarachnoid was hardly observed. The surgical treatment of EDACs included complete resection of the walls and closing the communicating point with the subarachnoid space. All patients showed excellent outcomes according to Odom's criteria without recurrence. One CSF leakage and one postoperative hematoma were noted. CONCLUSIONS: Thoracolumbar EDAC patients presented paraparesis and leg pain. Complete excision and closing the communicating point with the subarachnoid space were the choices of treatment, and the outcomes were favorable.

The clinical features and surgical outcomes of patients with intramedullary spinal cord cavernous malformations.

BACKGROUND: Cavernous malformations (CMs) are not uncommon, but most of them are found to be located intracranially. Intramedullary CMs are rare, accounting for only 3-5% of identified total central nervous system lesions. The natural history of intramedullary CMs and their clinical features, including the risk of hemorrhage from a large series, still remains unclear and needs to be elucidated. We review our experience with surgically treated patients with intramedullary CMs and discuss the clinical features and surgical outcomes. METHODS: Between March 2004 and March 2010, a total of 21 patients with intramedullary spinal cord CMs were surgically treated in a single institution. Data from 21 patients were retrospectively analyzed. RESULTS: There were 13 females and 8 males ranging in age from 10 to 70 years (mean age 39.3 years). All patients harbored single symptomatic CM of the nervous system, and multiple lesions were not found. The annual retrospective hemorrhage rate was 2.18% per patient/year. All but one CM were completely resected, and the average follow-up period was 22.1 months (1-73 months). Ten of the 21 patients experienced an improvement in neurological state, 9 patients remained unchanged, and 2 patients experienced worsening of their conditions. CONCLUSIONS: Symptomatic intramedullary CMs should be surgically removed to avoid further neurological deterioration. Though there are some limitations due to the retrospective nature of this study and its small number of patients, the prognosis was found to be related to the preoperative neurological state and to the type of symptom presentation.

Minimally Invasive Muscle Sparing Transmuscular Microdiscectomy : Technique and Comparison with Conventional Subperiosteal Microdiscectomy during the Early Postoperative Period.

OBJECTIVE: The authors introduce a minimally invasive muscle sparing transmuscular microdiscectomy (MSTM) to treat herniated lumbar disc disease. Its results are compared with conventional subperiosteal microdiscectomy (CSM) to validate the effectiveness. METHODS: Muscle sparing transmuscular microdiscectomy, which involves muscle dissection approach using the natural fat cleavage plane between the multifidus to expose the interlaminar space, was performed in 23 patients to treat a single level unilateral lumbar radiculopathy. The creatine phosphokinase (CPK)-MM serum levels were measured on admission and at 1, 3, and 5 days postoperatively. Postoperative pain was evaluated using a 10-point visual analogue scale (VAS) and recorded on admission and at 1, 3, and 5 days postoperatively. The results were compared to those from the conventional subperiosteal microdiscectomy (43 patients). RESULTS: The CPK-MM levels were significantly lower in the serum of the MSTM group compared to the CSM group on postoperative days three and five (p = 0.03 and p = 0.02, respectively). The clinical scales for back pain using VAS were significantly lower in the MSTM group than in the CSM group on postoperative days three (p = 0.04). The mean VAS scores for leg pain in both groups showed no significant differences during the early postoperative period. CONCLUSION: Muscle sparing transmuscular microdiscectomy is a minimally invasive surgical option to treat lumbar radiculopathy due to herniated disc. The approach affected minimal injury to posterior lumbar supporting structures with alleviated postoperative back pain.

Full costs of dispensing and administering fluorouracil chemotherapy for outpatients: A microcosting study.

BACKGROUND: Although full costs (including direct and indirect costs) that incurred during the process of chemotherapy administration should be measured, many studies estimate only direct labor and medication costs associated with various chemotherapy delivery systems. OBJECTIVES: To estimate the total costs for dispensing and administration of fluorouracil when administered with leucovorin, by intravenous infusion or bolus, using a microcosting approach from the perspective of a provider or health system. METHODS: A time-and-motion study was used to measure the time spent by (1) pharmacy staff in the handling, admixture, and dispensing of fluorouracil and (2) patients in the clinic. The study was performed at The Cancer Institute of New Jersey for an 8-month period. Costs of dispensing and administering fluorouracil were calculated per patient visit on the basis of resources used in the processing of fluorouracil and time spent by pharmacy staff and patient. All costs were standardized to 2005 dollars. RESULTS: A total of 275 observations were made, and 74 (26.9%) of these were associated with fluorouracil-based chemotherapy. Pharmacy staff spent an average of 11 minutes for bolus fluorouracil with leucovorin infusion (fluorouracil/LCV-IV) and 8 minutes for bolus fluorouracil with bolus leucovorin (fluorouracil/LCV-B). Patients who received fluorouracil/LCV-IV spent an average of 203 minutes in the clinic, whereas patients who received fluorouracil/LCV-B spent 110 minutes. The average cost of administering fluorouracil/LCV-IV was $933, which comprised drug costs ($279), dispensing costs ($189), and administration costs ($465). The average cost of fluorouracil/LCV-B was $474, which comprised drug costs ($65), dispensing costs ($141), and administration costs ($268). CONCLUSIONS: This is the first study to formally demonstrate the high cost of administering the injectable form of fluorouracil chemotherapy with leucovorin, despite relatively low drug acquisition cost. Therefore, reimbursement rates for fluorouracil should be calculated in such a way that covers all costs, including overhead costs for the department.

Role of TMPRSS4 during cancer progression.

Proteases play important roles in the development and homeostasis of an organism. These versatile proteins participate in a variety of biological processes. In addition to these functions, the importance of proteases as a key player in cancer progression has been increasingly recognized. Proteolysis by dysregulated proteases is one of the hallmarks of cancer progression. In many cancers, a variety of functions have been uncovered for the type II transmembrane serine proteases (TTSPs), which are recently discovered members of the family of cell-surface associated proteases. In this review, we describe the characteristics of TTSPs and their role in many human cancers. Among the many TTSPs, we discuss TMPRSS4/MT-SP2 in the greatest detail. TMPRSS4 is upregulated in prostate, colon and gastric cancers, and was recently shown to promote tumor growth, invasion, metastasis and the epithelial-mesenchymal transition (EMT). Currently, efforts are being made to understand the pathways through which TMPRSS4 activates the EMT. Recent studies indicate that the EMT induced by TMPRSS4 involves activation of extracellular signal regulated kinase (ERK) 1/2 and mitogen-activated protein kinase (MAPK). The target molecule for TMPRSS4 that initiates the EMT stimulatory pathway is still not defined. Regulation of the EMT by proteases such as TMPRSS4 may provide novel therapeutic targets for a cancer metastasis inhibitor.

Transduction of artificial transcriptional regulatory proteins into human cells.

Protein transduction (PT) is a method for delivering proteins into mammalian cells. PT is accomplished by linking a small peptide tag--called a PT domain (PTD)--to a protein of interest, which generates a functional fusion protein that can penetrate efficiently into mammalian cells. In order to study the functions of a transcription factor (TF) of interest, expression plasmids that encode the TF often are transfected into mammalian cells. However, the efficiency of DNA transfection is highly variable among different cell types and is usually very low in primary cells, stem cells and tumor cells. Zinc-finger transcription factors (ZF-TFs) can be tailor-made to target almost any gene in the human genome. However, the extremely low efficiency of DNA transfection into cancer cells, both in vivo and in vitro, limits the utility of ZF-TFs. Here, we report on an artificial ZF-TF that has been fused to a well-characterized PTD from the human immunodeficiency virus-1 (HIV-1) transcriptional activator protein, Tat. This ZF-TF targeted the endogenous promoter of the human VEGF-A gene. The PTD-attached ZF-TF was delivered efficiently into human cells in vitro. In addition, the VEGF-A-specific transcriptional repressor retarded the growth rate of tumor cells in a mouse xenograft experiment.

Novel cancer antiangiotherapy using the VEGF promoter-targeted artificial zinc-finger protein and oncolytic adenovirus.

Inhibition of tumor angiogenesis through modulation of vascular endothelial growth factor (VEGF) and its signaling pathway has been clinically validated as a viable therapeutic modality in the treatment of cancer. The use of artificial transcription factors based on Cys2-His2 zinc-finger proteins (ZFPs) targeting the VEGF promoter offers a novel strategy for modulating VEGF levels in tumors. In order to demonstrate the utility of VEGF-targeted ZFPs as therapeutic agents, we generated adenoviruses (Ads) expressing VEGF promoter-targeted transcriptional repressor ZFP, F435-KOX. A replication-incompetent Ad expressing F435-KO X, namely, Ad-DeltaE1-KOX, significantly reduced VEGF expression and functionally led to inhibition of angiogenesis. In vivo, an oncolytic Ad expressing F435-KOX, namely, Ad-DeltaB7-KOX, elicited a pronounced antitumor effect against a human glioblastoma xenograft model, U87MG. Further, consistent with its expected mechanism of action, Ad-DeltaB7-KOX was shown to greatly reduce the level of VEGF and vessel density in tumor tissue and increase terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells in tumors. Survival rates were also significantly increased in Ad-DeltaB7-KOX-treated mice. Taken together, the findings from this study identify F435-KOX as a novel and potent ZFP transcription factor that can inhibit VEGF-A-mediated angiogenesis and offer a novel therapeutic modality in the treatment of cancer.

Occipitocervical fusion after resection of craniovertebral junction tumors.

OBJECT: Surgical access to tumors at the craniovertebral junction (CVJ) requires extensive bone removal. Guidelines for the use of occipitocervical fusion (OCF) after resection of CVJ tumors have been based on anecdotal evidence. The authors performed a retrospective study of factors associated with the use of OCF in 46 patients with CVJ tumors. The findings were used to develop recommendations for use of OCF in such patients. METHODS: The authors retrospectively reviewed the cases of 51 patients with CVJ tumors treated by their group between March 1991 and February 2004. Forty-six patients were available for follow up. Charts were reviewed to obtain data on demographic characteristics, presenting symptoms, and perioperative complications. Preoperative computerized tomography scans and magnetic resonance imaging studies were obtained in all patients. Occipitocervical fusion was performed in patients who had undergone a unilateral condyle resection in which 70% or more of the condyle was removed, a bilateral condyle resection with 50% removal, or C1-2 vertebral body destruction. Of the 46 patients, 16 had foramen magnum meningiomas, 17 had chordomas, one had a chondrosarcoma, two had Schwann cell tumors, two had glomus tumors, and eight had other types of tumors. Twenty-three (50%) of the 46 patients underwent OCF, including 15 of the 17 patients with chordomas (88%). None of the patients with meningiomas required fusion. Seventeen (71%) of the 24 patients presenting with neck pain preoperatively underwent OCF. CONCLUSIONS: Patients presenting with neck pain had a 71% chance of undergoing OCF. Patients with chordomas and metastatic tumors were most likely to require OCF. One patient with a 50% unilateral condylar resection returned with OC instability for which OCF was required. Based on their clinical experience and published biomechanical studies, the authors recommend that OCF be performed when 50% or more of one condyle is resected.

Suppression of vascular endothelial growth factor expression at the transcriptional and post-transcriptional levels.

Gene expression is regulated at the transcriptional and post-transcriptional levels. Therefore, in order to achieve a high level of silencing, which includes minimizing any residual expression of a target gene, suppression at both the transcriptional and post-transcriptional levels is required. In this study, we describe a new method for highly efficient gene silencing that combines zinc finger protein-mediated transcriptional repression and small interfering RNA (siRNA)-mediated inhibition of post-transcriptional events. To measure the amount of gene expression under various conditions, we used a luciferase reporter gene that was driven by a variety of promoters, including that of the human vascular endothelial growth factor-A (VEGF-A) gene. We also measured expression of the endogenous VEGF-A gene. Inhibition of gene expression by each of the two individual technologies was effective, but in-depth analyses revealed residual expression of the target gene. The combination of specific zinc finger transcription factors and siRNAs greatly enhanced the silencing of the human VEGF-A gene, not only when cells were grown in the presence of normal amounts of oxygen but also under conditions of hypoxic stimulation. These results suggest that a bi-level approach to the silencing of VEGF-A expression may be clinically beneficial as part of a cancer treatment protocol.

Artificial zinc finger fusions targeting Sp1-binding sites and the trans-activator-responsive element potently repress transcription and replication of HIV-1.

Tat activates transcription by interacting with Sp1, NF-kappaB, positive transcription elongation factor b, and trans-activator-responsive element (TAR). Tat and Sp1 play major roles in transcription by protein-protein interactions at human immunodeficiency virus, type 1 (HIV-1) long terminal repeat. Sp1 activates transcription by interacting with cyclin T1 in the absence of Tat. To disrupt the transcription activation by Tat and Sp1, we fused Sp1-inhibiting polypeptides, zinc finger polypeptide, and the TAR-binding mutant Tat (TatdMt) together. A designed or natural zinc finger and Tat mutant fusion was used to target the fusion to the key regulatory sites (GC box and TAR) on the long terminal repeat and nascent short transcripts to disrupt the molecular interaction that normally result in robust transcription. The designed zinc finger and TatdMt fusions were targeted to the TAR, and they potently repressed both transcription and replication of HIV-1. The Sp1-inhibiting POZ domain, TatdMt, and zinc fingers are key functional domains important in repression of transcription and replication. The designed artificial zinc fingers were targeted to the high affinity Sp1-binding site, and by being fused with TatdMt and POZ domain, they strongly block both Sp1-cyclin T1-dependent transcription and Tat-dependent transcription, even in the presence of excess expressed Tat.