Integration is opening the door to a new journey toward oral health value-based care.

Oral health is a key component of overall health and there is a cost to not including it in the value-based transformation conversation. Health care needs to break down the silos that exist between dentistry and medicine so we can leverage integration to achieve value-based care.

Adjuvant therapy for patients who have node-positive breast cancer.

The treatment of node-positive breast cancer has improved dramatically in the last 3 decades. Adjuvant therapies have evolved from single-agent chemotherapy to anthracycline- and taxane-based polychemotherapeutics to target-specific trastuzumab, with or without endocrine manipulation and with or without PMRT. Almost 85% of patients who have node-positive disease can now enjoy a 5-year DFS. This progress has come from incremental improvements made over the years. In spite of these advances, lingering questions remain. Is it possible to reduce treatment-associated toxicity? Can patient selection be improved based on tumor genomic profiling? Given the high cost of many of these therapies (37,000 dollars with the newer agents versus $391 for the classic six cycles of intravenous CMF), is it possible to achieve equivalent efficacy and yet reduce the economic cost per patient? Only continued clinical trials and cooperative effort among researchers, clinicians, and patients can answer these questions and improve care for breast cancer.

High eIF4E, VEGF, and microvessel density in stage I to III breast cancer.

OBJECTIVE: In a prospective trial, to determine if eIF4E overexpression in breast cancer specimens is correlated with VEGF elevation, increased tumor microvessel density (MVD) counts, and a worse clinical outcome irrespective of nodal status. SUMMARY AND BACKGROUND DATA: In vitro, the overexpression of eukaryotic initiation factor 4E (eIF4E) up-regulates the translation of mRNAs with long 5'-untranslated regions (5'-UTRs). One such gene product is the vascular endothelial growth factor (VEGF). METHODS: A total of 114 stage I to III breast cancer patients were prospectively accrued and followed with a standardized clinical surveillance protocol. Cancer specimens were quantified for eIF4E, VEGF, and MVD. Outcome endpoints were cancer recurrence and cancer-related death. RESULTS: eIF4E overexpression was found in all cancer specimens (mean +/- SD, 12.5 +/- 7.6-fold). Increasing eIF4E overexpression correlated with increasing VEGF elevation (r = 0.24, P = 0.01, Spearman's coefficient), and increasing MVD counts (r = 0.35, P < 0.0002). Patients whose tumor had high eIF4E overexpression had shorter disease-free survival (P = 0.004, log-rank test) and higher cancer-related deaths (P = 0.002) than patients whose tumors had low eIF4E overexpression. Patients with high eIF4E had a hazard ratio for cancer recurrence and cancer-related death of 1.8 and 2.1 times that of patients with low eIF4E (respectively, P = 0.009 and P = 0.002, Cox proportional hazard model). CONCLUSIONS: In breast cancer patients, increasing eIF4E overexpression in the cancer specimens correlates with higher VEGF levels and MVD counts. Patients whose tumors had high eIF4E overexpression had a worse clinical outcome, independent of nodal status. Thus, eIF4E overexpression in breast cancer appears to predict increased tumor vascularity and perhaps cancer dissemination by hematogenous means.

A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-positive breast cancer.

OBJECTIVE: A previous study of patients with stage I to III breast cancer showed that those patients whose tumors were in the highest tertile of eIF4E overexpression experienced a higher risk for recurrence. This study was designed to determine whether high eIF4E overexpression predicts cancer recurrence independent of nodal status by specifically targeting patients with node-positive disease. METHODS: The prospective trial was designed to accrue 168 patients with node-positive breast cancer to detect a 2.5-fold increase in risk for recurrence. eIF4E level was quantified by Western blots as x-fold elevated compared with breast tissues from noncancer patients. End points measured were disease recurrence and cancer-related death. Statistical analyses performed include survival analysis by the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. RESULTS: One hundred seventy-four patients with node-positive breast cancer were accrued. All patients fulfilled study inclusion and exclusion criteria, treatment protocol, and surveillance requirements, with a compliance rate >95%. The mean eIF4E elevation was 11.0 +/- 7.0-fold (range, 1.4-34.3-fold). Based on previously published data, tertile distribution was as follow: 1) lowest tertile (<7.5-fold) = 67 patients, 2) intermediate tertile (7.5-14-fold) = 54 patients, and 3) highest tertile (>14-fold) = 53 patients. At a median follow up of 32 months, patients with the highest tertile had a statistically significant higher cancer recurrence rate (log-rank test, P = 0.002) and cancer-related death rate (P = 0.036) than the lowest group. Relative risk calculations demonstrated that high eIF4E patients had a 2.4-fold increase in relative risk increase for cancer recurrence (95% confidence interval, 1.2-4.1; P = 0.01). CONCLUSIONS: In this prospective study designed to specifically address risk for recurrence in patients with node-positive breast cancer, the patients whose tumors were in the highest tertile of eIF4E overexpression had a 2.4-fold increase in relative risk for cancer recurrence. Therefore, eIF4E overexpression appears to be an independent predictor of a worse outcome in patients with breast cancer independent of nodal status.

The organ center of the United Network for Organ Sharing and twenty years of organ sharing in the United States.

The increasing size of the transplant waiting list and the increasing use of expanded criteria donors places a premium on efficient use of recovered organs. Maximal organ utilization often necessitates organ sharing between transplant organizations. Optimal organ sharing requires rapid, integrated communication of donor information combined with expedited organ transportation. For more than 20 years, the United Network for Organ Sharing's Organ Center has fulfilled this task for the United States transplant community. This overview details a brief history of United States organ sharing and the role played by the Organ Center. The current scope and modes of Organ Center operations are detailed.

Soluble HLA in saliva of patients with autoimmune rheumatic diseases.

OBJECTIVES: The limited number of studies addressing the presence of soluble human leukocyte antigen (HLA) in body fluids such as tears, urine, sweat, and saliva are restricted to healthy subjects. In this study, we applied solid-phase enzyme-linked immunoassay to quantify soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in saliva and in selected serum samples obtained from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS). RESULTS: While saliva from normal subjects (n=35) contained levels of sHLA-I that were undetectable (n=7) or ranged from 9 ng/ml to 70 ng/ml (30+/-3.7 ng/ml, n=28), sHLA-I among 38 patients with moderately active RA ( n=24) or SLE (n=14) were significantly elevated (222+/-81.4 ng/ml and 120+/-27.3 ng/ml, respectively, P<0.0001). Intriguingly, sHLA-I levels were even higher in patients whose disease was regarded as active. Specifically, sHLA-I averaged 683+/-189 ng/ml in patients with active RA (n=13) and 230+/-24.5 ng/ml in patients with active SLE (n=7). This was significantly higher than in patients with milder forms of these diseases (P<0.0001). All five subjects with SS had severe disease with high levels of sHLA-I (mean 486+/-86 ng/ml). The concentrations of saliva sHLA-II in the disease groups studied were comparable with levels found in normal controls. The sHLA-I in severe and mild states was investigated in purified serum and saliva from a patient with SS. While 44-kDa fragments of serum HLA-I were detectable in severe SS, they were undetectable in saliva HLA at any time; 35-37-kDa fragments of serum or saliva HLA-I were detected during both mild and severe disease. Interestingly, the 39-kDa fragment was detected in both body fluids during severe but not mild forms of SS. Similarly, the isoforms with the molecular masses 39 kDa and 44 kDa were mainly identified in the purified material obtained from serum of SLE patients. CONCLUSIONS: Collectively, our data suggest that the measurement of soluble HLA in body fluids can be of both diagnostic and prognostic value in the assessment of patients with autoimmune rheumatic disorders. The mechanism by which sHLA enters saliva is unclear, but they probably are not acquired from serum.

Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome.

OBJECTIVE: To validate the authors' initial hypothesis-generating observation that eukaryotic initiation factor 4E (eIF4E) protein elevation predicts a higher cancer recurrence rate in patients with stage 1 to 3 breast cancer. SUMMARY BACKGROUND DATA: Tumor size and nodal status continue to be the two most important independent prognostic markers in breast cancer, despite well-documented limitations. In a previous smaller retrospective study, eIF4E, important in the regulation of protein synthesis of mRNAs with long or complex 5' untranslated regions, appeared promising as an independent predictor of breast cancer recurrence. METHODS: Specimens and clinical data from 191 patients with stage 1 to 3 breast cancer were accrued prospectively. Data collected include stage of disease, tumor grade, age at diagnosis, and menopausal status. Endpoints measured were disease recurrence and cancer-related death. eIF4E protein level was quantified using Western blot analysis. Immunohistochemical staining was used to determine estrogen receptor, progesterone receptor, and HER-2/neu receptor status. Statistical analysis include Cox proportional hazards model, log-rank test, Kaplan-Meier survival curve, Fisher exact test, and t test. RESULTS: Patients were divided into three groups based on tertile distribution of eIF4E: low, defined as less than 7.5-fold elevation (n = 64); intermediate, defined as 7.5- to 14-fold elevation (n = 61); and high, defined as more than 14-fold elevation (n = 66). The relative risk for cancer recurrence with intermediate elevation was 4.1 times that of patients with low elevation. For patients with high elevation, the relative risk for recurrence was higher, at 7.2 times that of the low group. The relative risk for cancer-related death for high elevation was 7.3 times that of patients with low eIF4E. Using multivariate analysis, high eIF4E remained an independent predictor of cancer recurrence after adjusting for tumor size, tumor grade, nodal disease, estrogen receptor status, progesterone receptor status, and menopausal status. CONCLUSIONS: High eIF4E is an independent predictor of cancer recurrence in patients with stage 1 to 3 breast cancer. The relative risk for cancer recurrence increases with eIF4E protein elevation. High eIF4E elevation is also associated with an increased relative risk for cancer-related death.