Long-term assessment of Swanson implant arthroplasty in the proximal interphalangeal joint of the hand

PURPOSE: The purpose of this study was to evaluate the clinical results of Swanson silicone implant arthroplasty of the proximal interphalangeal (PIP) joint, specifically evaluating clinical results with long-term assessment. METHODS: A retrospective review of 70 silicone implants of the PIP joint in 48 patients was performed with an average follow-up period of 6.5 years (range, 3-20 y). Clinical assessment included motion, stability, and alignment. Radiographic assessment included implant fracture, deformity, and cystic bone resorption. The pathology consisted of degenerative joint disease in 14, posttraumatic arthritis (TA) in 11, rheumatoid arthritis (RA) in 13, and idiopathic arthritis (IA) associated with collagen disease in 12 patients. Swan neck and boutonniere deformities were assessed separately. Statistical analysis of preoperative risk factors was compared with the postoperative assessment of pain, motion, and function (return to work). RESULTS: There was no significant change in the active range of motion (ROM) before and after PIP arthroplasty (26 degrees vs 30 degrees ). Correction of swan neck and boutonniere deformities was difficult, usually leading to poor results. There was improvement in maximum active extension before surgery lacking 32 degrees to after surgery lacking 18 degrees . From a statistical standpoint rheumatoid joint involvement with PIP arthroplasty had poorer results than degenerative or posttraumatic arthritis with respect to pain relief and ROM. Pain relief was present in 70% of replaced PIP joints with residual pain and loss of strength in 30%. Radiographic analysis showed abnormal bone formation (cystic changes) in 45%. There were 11 implant fractures and 9 joints that required revision surgery. CONCLUSIONS: Silicone replacement of the PIP joint is effective in providing relief of pain from arthritis but does not provide improvement in motion or correction of deformity. It provided a poorer outcome in rheumatoid disease in comparison with degenerative, posttraumatic, or idiopathic arthritis.     

A phase II study of tandutinib (MLN518), a selective inhibitor of type III tyrosine receptor kinases, in patients with metastatic renal cell carcinoma

Therapies which target VEGF and mTOR are now available for patients with metastatic renal cell carcinoma, but there is a continued need to develop agents for patients who become refractory to these initial agents. Tandutinib is a relatively selective inhibitor of type III tyrosine kinase receptor kinases with promising activity in some tumors. In this trial, 10 patients with metastatic renal cell carcinoma refractory to previous therapy with sunitinib or sorafenib (median age 61 years, 80% performance status 0, 60% intermediate MSKCC risk classification) received tandutinib 500 mg bid daily with RECIST-defined response as the primary endpoint and progression-free survival (PFS) and overall survival (OS) as secondary endpoints. No patient had more than 2 cycles of therapy and 50% of patients only received 1 cycle with 70% of patients discontinuing for progressive disease and 30% for toxicity. Tandutinib was not well tolerated with dose reduction in 60% of patients due to adverse events. The most common grade 3 toxicity was fatigue (30%). Tandutinib had no clinical activity and due to the excessive toxicity should not be developed further in patients with sunitinib or sorafenib-refractory metastatic renal cell carcinoma.     

Hereditary prostate cancer as a feature of Lynch Syndrome

Lynch Syndrome is an autosomal dominant condition characterized by early onset colorectal cancer (CRC) and is associated with cancers of the gastrointestinal and reproductive tracts. Germline mutations in DNA mismatch repair (MMR) genes have been causally associated with cancers of Lynch Syndrome. We investigated the occurrence of prostate cancer (PCa) in families with a history of colorectal cancer to assess prostate cancer as a feature of the Lynch Syndrome spectrum. Family pedigrees containing at least one CRC case as well as those meeting guidelines for Lynch Syndrome were identified and tumors were requested from participants who underwent radical prostatectomy (RP). Selected families were analyzed for association with type of PCa and clinical characteristics of aggressive disease. Microsatellite Instability (MSI) analysis was preformed on available tumors and correlated to loss of expression in MMR genes by immunohistochemical (IHC) staining. 95 individuals were identified as members of potential Lynch Syndrome families who underwent RP and 35 tumors from 31 families were received for MSI analysis. Two tumors from two unrelated families with known MMR mutations were MSI-high and one additional case from a third family was MSI-low. The remainder of the prostate cancer cases demonstrated no evidence of MSI. PCa incidence in families enriched for hereditary PCa with a history of Lynch Syndrome cancers is not strongly suggestive of the presence of an MMR mutation. However prostate tumors in known MMR mutation carriers did display MSI and loss of gene expression suggesting that PCa may arise in Lynch Syndrome due to defective DNA mismatch repair.     

Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells

Introduction

We have previously demonstrated that chondroitin sulfate glycosaminoglycans (CS-GAGs) on breast cancer cells function as P-selectin ligands. This study was performed to identify the carrier proteoglycan (PG) and the sulfotransferase gene involved in synthesis of the surface P-selectin-reactive CS-GAGs in human breast cancer cells with high metastatic capacity, as well as to determine a direct role for CS-GAGs in metastatic spread.

Methods

Quantitative real-time PCR (qRT-PCR) and flow cytometry assays were used to detect the expression of genes involved in the sulfation and presentation of chondroitin in several human breast cancer cell lines. Transient transfection of the human breast cancer cell line MDA-MB-231 with the siRNAs for carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) and chondroitin sulfate proteoglycan 4 (CSPG4 ) was used to investigate the involvement of these genes in expression of surface P-selectin ligands. The expression of CSPG4 and CHST11 in 15 primary invasive breast cancer clinical specimens was assessed by qRT-PCR. The role of CS-GAGs in metastasis was tested using the 4T1 murine mammary cell line (10 mice per group).

Results

The CHST11 gene was highly expressed in aggressive breast cancer cells but significantly less so in less aggressive breast cancer cell lines. A positive correlation was observed between the expression levels of CHST11 and P-selectin binding to cells (P < 0.0001). Blocking the expression of CHST11 with siRNA inhibited CS-A expression and P-selectin binding to MDA-MB-231 cells. The carrier proteoglycan CSPG4 was highly expressed on the aggressive breast cancer cell lines and contributed to the P-selectin binding and CS-A expression. In addition, CSPG4 and CHST11 were over-expressed in tumor-containing clinical tissue specimens compared with normal tissues. Enzymatic removal of tumor-cell surface CS-GAGs significantly inhibited lung colonization of the 4T1 murine mammary cell line (P = 0.0002).

Conclusions

Cell surface P-selectin binding depends on CHST11 gene expression. CSPG4 serves as a P-selectin ligand through its CS chain and participates in P-selectin binding to the highly metastatic breast cancer cells. Removal of CS-GAGs greatly reduces metastatic lung colonization by 4T1 cells. The data strongly indicate that CS-GAGs and their biosynthetic pathways are promising targets for the development of anti-metastatic therapies.     

A plastic, disposable microfluidic flow cell for coupled on-chip PCR and microarray detection of infectious agents

Clinical laboratories are recognizing the importance of implementing sensitive and specific molecular diagnostic tests. However, widespread adoption of these tests requires simplified workflows without requiring expensive supporting instrumentation. To enable microarray-based analysis to meet these requirements, we describe a valveless flow cell for disposable use that supports PCR coupled with microarray hybridization in the same chamber. The flow cell assembly consists simply of double-faced tape, a plastic microarray substrate, an absorbent, and a commercially-available hydrophilic thin film. The simple construction lends itself to low-cost and ease of manufacturing, yet several features reduce the complexity of the standard microarray workflow. First, there is no requirement for custom instrumentation. Second, the hydrophilic thin film allows uniform filling of a microfluidic chamber. Third, a geometric capillary stop design confines liquid to the microarray chamber during PCR, and thus eliminates the need for a valve or hydrophobic surface treatment. And fourth, imbibition drives the uniform removal of liquid reagents from the array chamber. Three hundred genomic copies of methicillin-resistant Staphylococcus aureus (MRSA) are detected in a flow cell with gel drop microarrays printed on an unmodified plastic substrate. This sensitivity is shown to be comparable to conventional methods (i.e., PCR in a tube, with separate hybridization in a microarray chamber, where amplicon is exposed to the workspace before and after hybridization). However, the flow cell combines these multiple steps into a simple, compact workflow without the need for complex valves or custom instrumentation and is less susceptible to contamination of the workspace than conventional methods because the amplicon is confined to the device.     

The Importance of a High‐Performance Work Environment in Hospitals

Objective

To examine the benefits of a high-performance work environment (HPWE) for employees, patients, and hospitals.

Study Setting

Forty-five adult, medical-surgical units in nine hospitals in upstate New York.

Study Design

Cross-sectional study.

Data Collection

Surveys were collected from 1,527 unit-based hospital providers (68.5 percent response rate). Hospitals provided unit turnover and patient data (16,459 discharge records and 2,920 patient surveys).

Principal Findings

HPWE, as perceived by multiple occupational groups on a unit, is significantly associated with desirable work processes, retention indicators, and care quality.

Conclusion

Our findings underscore the potential benefits for providers, patients, and health care organizations of designing work environments that value and support a broad range of employees as having essential contributions to make to the care process and their organizations.     

American Society for Pain Management Nursing Position Statement with Clinical Practice Guidelines: Authorized Agent Controlled Analgesia

The American Society for Pain Management Nursing (ASPMN) has updated its 2007 position statement on the use of authorized agent controlled analgesia (AACA) for patients who are unable to independently utilize patient-controlled analgesia (PCA). ASPMN continues to support the use of AACA to provide timely and effective pain management while promoting equitable care for vulnerable patient populations who are unable to utilize PCA. ASPMN does not support the use of “PCA by Proxy” in which unauthorized individuals activate PCA for a patient. The background of the development of the position statement, definitions related to AACA, and application of ethical principles to the use of AACA are presented in the document. This position statement includes an updated review of the evidence related to AACA and a call for further research. Clinical practice recommendations for authorized agents, nurses, prescribers, and organizations are provided with an emphasis on the importance of appropriate authorized agent selection, education, diligent patient assessment and medication management.