[Concept for Planning the Nurse-Patient Ratio and Nursing Fee Payment Linkage System].

This article describes the current situation in Taiwan with regard to the nurse-patient ratio and nursing fee payments, reviews the related policies and results in developed countries, and then proposes a plan for improving the domestic situation. Direct relationships exist between patient nursing quality and patient safety and the nurse-patient ratio as well as between nursing fee payments and the nurse-patient ratio. Therefore, in order to enhance the quality and safety of nursing care, it will be necessary to develop and institute a payment linkage system that links nursing fee payments to the nurse-patient ratio. This process requires public consensus and planning in order to institute an equitable and effective payment linkage system in the future.

Matrix metalloproteinase-8 is overexpressed in Waldenström's macroglobulinemia cells, and specific inhibition of this metalloproteinase blocks release of soluble CD27.

Soluble CD27 (sCD27) is produced by Waldenström's macroglobulinemia (WM) cells, with high levels found in WM patients which may facilitate disease expansion. Matrix metalloproteinases (MMP) may facilitate sCD27 release by cleavage of CD27. By gene expression analysis, we observed significantly higher transcription levels of MMP-8 and MMP-9, with 58.5 and 16.7 fold increase in mean transcription levels in WM cells relative to healthy donor peripheral blood B cells (P = .04, and .05, respectively). We developed a model for study of sCD27 release by transfecting BCWM.1 WM cells and BL2126 lymphoblastic B cells, both of which express MMP-8 and MMP-9 with a vector expressing FLAG-tagged CD27 (pFLAG-CD27) which in the presence of phorbol myristate acetate resulted in ≥ 10-fold increase in sCD27 release. MMP inhibitors against MMP-8, but not MMP 2, 3, or 9 blocked release of sCD27. The results suggest that MMP-8 may play a role in the pathogenesis of WM, and that its inhibition may be of therapeutic value in WM.

Vorinostat induced cellular stress disrupts the p38 mitogen activated protein kinase and extracellular signal regulated kinase pathways leading to apoptosis in Waldenström macroglobulinemia cells.

Histone deacetylases (HDACs) are aberrantly expressed, and inhibitors of HDACs induce apoptosis in lymphoplasmacytic cells (LPCs) in Waldenström macroglobulinemia (WM). The molecular profile by which these agents induce apoptosis in WM LPCs remains to be delineated. We examined the activity of the histone deacetylase inhibitor, vorinostat, and dissected its pro-apoptotic pathways in WM LPCs. Vorinostat induced apoptosis in WM cells through activating specific caspases at varying times. Inhibitors of apoptosis (IAPs) were down-regulated after vorinostat treatment. Cellular stress induced in vorinostat-treated WM cells was reflected by changes in the mitogen activated protein kinase (MAPK) pathways. Activated phospho-p38 MAPK was up-regulated at 12 h, while phospho-extracellular signal-regulated kinase (Erk) abruptly decreased at 24 h. Bortezomib did not augment vorinostat induced primary WM cell killing as reported in other B-cell disorders. These studies support that stress induced apoptosis in vorinostat-treated WM LPCs is mediated through disrupting the activity of the Erk and p38 MAPK pathways.

Attainment of complete/very good partial response following rituximab-based therapy is an important determinant to progression-free survival, and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia.

The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression-free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. The median follow-up was 33·5 months, and categorical responses were as follows: complete response (CR, 8·8%); very good partial response (VGPR, 13·2%); partial response (50%); minor response (18·9%); Non-Responders (8·8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0·0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time-to-progression. Neither age, serum IgM, haematocrit, platelet count, serum ß(2) microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A-48 and -158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P ≤ 0·03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab-naïve WM patients undergoing rituximab-based therapy, and was predicted by polymorphisms in FCGR3A.

Hepcidin is produced by lymphoplasmacytic cells and is associated with anemia in Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) patients often present with anemia as their primary disease manifestation that may be related to hepcidin, an important regulator of iron homeostasis. We therefore determined hepcidin levels in 53 WM patients, and 20 age-matched healthy patient donors by hepcidin-25 ELISA. Serum hepcidin levels were elevated in WM patients versus healthy patients (P=.04), and correlated with BM disease involvement (P=.004), beta-2-microglobulin levels (P=.029), and inversely with hemoglobin (P=.05). No correlation with serum iron indices was observed, though in patients with high hepcidin levels, increased iron deposition in bone marrow macrophages was observed. Importantly, hepcidin transcripts and protein were produced by primary WM cells. Hepcidin levels correlated with serum IL-6 (P<.001) and C-Reactive Protein (P=.033) levels. The results of this study implicate hepcidin as a contributor to anemia in WM, and suggest that an iron re-utilization defect accompanies hepcidin overproduction leading to its sequestration in WM patients.

AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.

Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA mutant cancer cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations.

Soluble CD27 is a faithful marker of disease burden and is unaffected by the rituximab-induced IgM flare, as well as by plasmapheresis, in patients with Waldenström's macroglobulinemia.

BACKGROUND: The assessment of disease burden is often difficult in patients with Waldenström's macroglobulinemia (WM) who receive rituximab due to the induction of an IgM flare, and following the removal of serum IgM by plasmapheresis. Soluble CD27 (sCD27) is a tumor necrosis factor family member secreted by WM cells which is strongly correlated with serum IgM levels and clinical responses in patients with WM. As such, we attempted to delineate its potential role in WM patients experiencing a rituximab-induced IgM flare and following plasmapheresis. PATIENTS AND METHODS: sCD27 levels were serially measured by serum-based ELISA in 8 patients who ultimately demonstrated a response to therapy, and in whom a rituximab-mediated IgM flare was observed, as well as in 3 WM patients undergoing plasmapheresis. RESULTS: Among the 8 patients who experienced a rituximab-mediated IgM flare, IgM levels rose from 3515 to a peak of 5270 mg/dL (P = .008), while sCD27 levels decreased from 174.1 to 155.9 U/mL (P = .012), with a decline observed in all patients. Among 3 patients undergoing plasmapheresis, IgM levels declined from a median of 6940 to 4770 mg/dL (P = .031), while median sCD27 levels remained without significant change (P = .317). CONCLUSION: sCD27 is a faithful marker of disease burden and is unaffected by the rituximab-induced IgM flare, as well as plasmapheresis in WM. The use of this marker may aid in correctly predicting clinical outcome in patients undergoing treatment with rituximab and/or plasmapheresis in WM.

Modeling genomic diversity and tumor dependency in malignant melanoma.

The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors.

Fall risk factors assessment tool: enhancing effectiveness in falls screening.

A quasi-experimental study was conducted to explore the effectiveness of fall prevention among hospital patients based on the modified fall risk factors assessment tool. We investigated the frequency of falls among hospital patients at a medical center in Taiwan. The experimental group of falls victims was selected from patients (n = 39) hospitalized in 2002 after falls. The control group of patients falls was selected by means of a retrospective incident report review which identified patients (n = 43) hospitalized one year earlier. The results showed that there was no significant difference in the incidence of falls between the two groups. Nevertheless, there were significant differences in age, indications of falls, use of sedatives, walking ability and evaluated grade of fall risk factors. In addition, the average level of satisfaction under recently modified fall risk factors evaluation guideline was 2.68 points (upper limit = 4 points) based upon investigation derived from nursing staff ' s opinions. Moreover, nursing staff from GYN/OBS and orthopedics departments acknowledged the enhanced effectiveness of these new guidelines. The screening rate for high-risk orthopedic patients was increased from 20.7 % to 41.9 %. Furthermore, the screening rate among the experimental group (74.4 % ) was also higher than that among the control group (60.5 % ) ( p <.01). In line with our effective tool to screen high-risk patients, we also added the concept of continuous quality improvement in nursing care to implement a fall prevention program to reduce unnecessary injury. This strategy may assist nursing personnel in providing immediate and individualized care as well as health education for high-risk patients. It may also cause the incidence of patient falls in hospitals to continue to decline.

Effect of a clinical pathway on selected clinical outcomes of pulmonary lobectomy.

BACKGROUND: North American hospitals use clinical care pathways to reduce length of stay, readmissions, and resource utilization and also to increase patient satisfaction. This study examined the effects of clinical pathways after pulmonary lobectomy in Taiwanese patients. METHODS: During 1997, a multidisciplinary team developed a lobectomy clinical pathway. The Program Evaluation Review Technique was used to analyze variances from the clinical pathway. Based on these findings, a standardized clinical pathway was implemented in late 1997. Forty patients participated. The variables of the study are length of hospital stay, readmission rates, spirometry usage, patient education and costs benefited from clinical care pathway use. RESULTS: Fourteen lobectomy patients following the clinical pathway had a mean length of stay of 17.9+/-4.18 days (p < 0.001) and 0% readmission (p < 0.001). Without a pathway, 26 lobectomy patients had a mean length of stay of 37.5+/-6.18 days and 18% were readmitted. Factors affecting clinical pathway success were preoperative days(p < 0.001), postoperative days (p = 0.033), spirometry usage (p = 0.043) and patient education (p = 0.02). Clinical pathway use reduced mean hospital costs by 16% for lobectomy. CONCLUSIONS: Length of hospital stay, readmission rates, spirometry usage, patient education and costs benefitted from clinical care pathway use. Factors critical to success appear to be multidisciplinary teamwork and communication.