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There is an unmet need for effective biological therapies for relapsed central nervous system (CNS) lymphoma. Lenalidomide is active in activated B-cell type diffuse large B-cell lymphoma and rituximab is effective in CNS lymphoma. These observations are the basis for this first trial of an immunomodulatory drug as monotherapy in CNS lymphoma, and, in patients with inadequate responses to lenalidomide, with rituximab. In an independent cohort, we evaluated lenalidomide maintenance after salvage with high-dose methotrexate or focal irradiation in relapsed primary CNS lymphoma (PCNSL). We determined safety, efficacy, and cerebrospinal fluid (CSF) penetration of lenalidomide at 10-, 15-, and 20-mg dose levels in 14 patients with refractory CD20+ CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918.

BackgroundThe optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.MethodsTo identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).ResultsWe provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4

Intravascular large cell lymphoma (IVLCL) is a rare disease characterized by proliferation of malignant lymphocytes within the small blood vessel lumens. The association of IVLCL with autoimmune hemolytic anemia (AIHA) has been described in a single case report, but the true prevalence of this co-occurrence is not known because of declining autopsy rates. Here, we report a case of a 41-year-old woman who carried a diagnosis of AIHA for 2 years, with repeated hemolytic episodes that were initially well controlled with immunomodulatory treatment. At her last presentation, the patient developed rapidly progressive neurologic symptoms and leukoencephalopathy on MRI; she died 4 weeks later with a clinical impression of thrombotic microangiopathy, a known complication of AIHA. At autopsy, the brain showed widespread platelet thrombi and intraparenchymal hemorrhages characteristic of this disorder. In addition, there was evidence of a clinically unsuspected IVLCL, most likely of B-cell lineage. This case illustrates a potential association between IVLCL and AIHA, highlights the need for broad differential diagnosis in cases with atypical disease presentation or progression, and underlines the importance of autopsy in establishing the full cause of morbidity and mortality.

An injury to the vas deferens during inguinal herniorrhaphy from possible tethering of the vas has not, to our knowledge, previously been described in the surgical literature. We report a case of iatrogenic injury of the vas deferens that occurred during elective hernia repair in a 28-year-old man who had previously sustained blunt trauma to the abdomen and pelvis.

Hospitals are experiencing an influx of patients in active behavioral crises, leading to restraints as a behavior management strategy. Over 100 staff participated in simulation training designed to manage escalating patient behavior. The training had a direct impact on the reduction of restraint use and increased preparedness and confidence of participants managing escalating patient behavior. Results suggest simulation can be an effective strategy to train medical staff to manage challenging behavior and reduce restraint use. [ABSTRACT FROM AUTHOR]

Abstract: There is an unmet need for effective biological therapies for relapsed central nervous system (CNS) lymphoma. Lenalidomide is active in activated B-cell type diffuse large B-cell lymphoma and rituximab is effective in CNS lymphoma. These observations are the basis for this first trial of an immunomodulatory drug as monotherapy in CNS lymphoma, and, in patients with inadequate responses to lenalidomide, with rituximab. In an independent cohort, we evaluated lenalidomide maintenance after salvage with high-dose methotrexate or focal irradiation in relapsed primary CNS lymphoma (PCNSL). We determined safety, efficacy, and cerebrospinal fluid (CSF) penetration of lenalidomide at 10-, 15-, and 20-mg dose levels in 14 patients with refractory CD20+ CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918.

The effects of intercropping grapevine with aromatic plants are investigated using a multi-disciplinary approach. Selected results are presented that address the extent to which crop diversification by intercropping impacts grapevine yield and must quality, as well as soil water and mineral nutrients (NO3-N, NH4-N, plant-available K and P). The experimental field was a commercial steep-slope vineyard with shallow soils characterized by a high presence of coarse rock fragments in the Mosel area of Germany. The field experiment was set up as randomized block design. Rows were either cultivated with Riesling (Vitis vinifera L.) as a monocrop or intercropped with Origanum vulgare or Thymus vulgaris. Regarding soil moisture and nutrient levels, the topsoil (0–0.1 m) was more affected by intercropping than the subsoil (0.1–0.3 m). Gravimetric moisture was consistently lower in the intercropped topsoil. While NO3-N was almost unaffected by crop diversification, NH4-N, K, and P were uniformly reduced in topsoil. Significant differences in grapevine yield and must quality were dominantly attributable to climate variables, rather than to the treatments. Yield stabilization due to intercropping with thyme and oregano seems possible with sufficient rainfall or by irrigation. The long-term effects of intercropping on grapevine growth need further monitoring.

Discusses the advantages of using story board techniques to design a course in computer based training, and describes the use of HyperCard to create the story boards directly on the computer screen. The discussion covers HyperCard's software capabilities, programing language, and print features. (CLB)

Presents the poem "Descant of Sixth Acts," by Heather Treseler is presented. First Line: I. THEI WERE ALLE STILLE AND MEWET... Last Line: beforehand, unto himself.

Lymphoblastic lymphoma is an uncommon malignancy, with most cases showing a T-cell phenotype and presenting as a mediastinal mass. By contrast, B-cell lymphoblastic lymphoma/leukemia is a rare high-grade malignancy that comprises approximately 10% of all lymphoblastic lymphomas. Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Here we present what we believe is the first B-cell lymphoblastic lymphoma initially presenting in the oral cavity. The case involves a 46-year-old white woman who presented with a mass in the right mandible. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment, and prognosis. This case emphasizes the importance of recognizing rare entities that may present in the oral cavity and the impact of the disease and its management. [Copyright &y& Elsevier]

Background: Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist that has been shown to induce differentiation, cell cycle arrest, and apoptosis in a variety of human cancers including thyroid cancer. Methods: Ten patients with differentiated thyroid cancer were enrolled in an open-label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week, then 8 mg daily for 7 weeks). The levels of PPARγ receptor mRNA and protein expression were determined in the patient’s neoplasm. Results: Of 10 patients, 4 had positive radioiodine scans after rosiglitazone therapy with uptake in the neck in 3 patients and in the pelvis in 1 patient. After treatment, the serum thyroglobulin level decreased in 2 patients, increased in 5 patients, and was stable in 3 patients. No patient developed clinically important toxicity associated with rosiglitazone treatment. We found no relationship in the level of PPARγ mRNA and protein expression in patients who had radioiodine uptake compared with those who did not. Conclusions: Our findings suggest that rosiglitazone treatment may induce radioiodine uptake in some patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. We found no relationship between the expression level of the PPARγ mRNA and protein in the neoplasm and radioiodine uptake status after rosiglitazone therapy, questioning the potential pathway of effect. [Copyright &y& Elsevier]

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary. [ABSTRACT FROM AUTHOR]

Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node dissection (ALND) for many patients with early breast cancer and negative sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing unnecessary ALND, as no further disease is found in the axilla. The aim of our study was to determine factors associated with additional positive lymph nodes in the axilla in patients who have a positive SLN. This was a retrospective study of patients undergoing SSL with ALND as part of their treatment for breast cancer at a single institution from November 1997 to August 2003. Only patients with one or more positive SLNs were selected for this study. There were 86 patients who fit our study criteria. Of these, 38% had further positive lymph nodes upon ALND. More than one positive SLN and a ratio of positive SLNs to total SLNs of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses. The number of positive SLNs and the ratio of positive SLNs to total SLNs is an indication of total tumor burden in the sentinel nodes and may be a reflection of the propensity of the tumor for further lymphatic invasion in the axillary basin. [ABSTRACT FROM AUTHOR]