Clinical benefit of trabectedin in uterine adenosarcoma.

Uterine adenosarcoma is an extremely rare uterine malignancy, and the utility of chemotherapy in this disease is not well defined. This study assessed the safety and efficacy of trabectedin in patients with recurrent/metastatic uterine adenosarcoma with sarcomatous overgrowth. A retrospective search of a prospectively maintained database was performed to identify patients with adenosarcoma treated with trabectedin between 2010 and 2012, within a compassionate use trial.

Management of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) comprise <1% of all gastrointestinal tumors, but are the most common mesenchymal tumors of the GI tract. This review highlights the dramatic changes in clinical practice with regards to GIST in the last decade, with a focus on overall management and recent developments. For localized primary GISTs, surgical resection is the mainstay of therapy with the 5-year survival rate after complete resection averaging approximately 50-65%.

The evolution of systemic therapy in sarcoma.

Approximately 50% of patients with localized soft tissue sarcomas will develop recurrent disease after complete surgical resection, requiring alternative means of treatment. Conventional chemotherapy comprising of doxorubicin and ifosfamide has shown benefit in advanced disease, however, there remains a clear need for more effective, less toxic, therapies for the treatment of this heterogeneous group of mesenchymal malignancies. Recently, greater emphasis has been placed on the underlying biology of individual sarcoma subtypes, with the development and evaluation of novel therapies both in common and in rare subtypes.

Systemic therapy in primary angiosarcoma of the spleen.

Primary splenic angiosarcoma is a very rare neoplasm with a high propensity for metastatic disease and poor prognosis. There is a paucity of literature concerning this specific sarcoma subtype and the role of systemic therapy is not well defined. A retrospective review of the prospectively maintained University of Washington/Seattle Cancer Care Alliance Sarcoma Unit database was performed to identify patients with splenic angiosarcoma treated between 2007 and 2012.

[Outcome of treatment with peg-interferon and ribavirin in HIV-HCV co-infected patients: "real life" single center experience].

Background And Aim: Recently, with the emergence of highly effective antiretroviral treatment (ART), chronic liver disease has become the leading cause of morbidity and mortality in co-infected HIV-HCV (Human immunodeficiency virus-Hepatitis C virus) patients. The overall SVR rate in this population remains unsatisfactory. The aim of this study was to evaluate the response to therapy in HIV-HCV co-infected patients in a single center.

Informed conditioning on clinical covariates increases power in case-control association studies.

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low-BMI cases are larger than those estimated from high-BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment).

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

Objective: To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure.

Design: Case report and literature review.

Setting: Large university-affiliated infertility practice.

Vitamin D status in young HIV infected women of various ethnic origins: incidence of vitamin D deficiency and possible impact on bone density.

Background: Decreased bone mineral density (BMD) was reported in HIV infected patients. Mechanisms leading to this decrease are poorly understood.

Aims: To assess factors relating to BMD in young HIV infected Israeli women of Ethiopian and Caucasian origin.

Human factors-focused reporting system for improving care quality and safety in hospital wards.

Objective: The aim was to develop a reporting system for collecting human factors problem reports to establish a database to guide activities for improving health care quality and patient safety.

Background: The current error and incident report systems do not provide sufficient and adequate coverage of the factors contributing to impaired safety and care quality. They fail to examine the range of difficulties that clinical staff encounters in the conduct of daily work.

Analysis of case-control association studies with known risk variants.

Motivation: The question of how to best use information from known associated variants when conducting disease association studies has yet to be answered. Some studies compute a marginal P-value for each Several Nucleotide Polymorphisms independently, ignoring previously discovered variants. Other studies include known variants as covariates in logistic regression, but a weakness of this standard conditioning strategy is that it does not account for disease prevalence and non-random ascertainment, which can induce a correlation structure between candidate variants and known associated variants even if the variants lie on different chromosomes.

Prevalence of Adenomas Found on Colonoscopy in Patients With HIV.

Background: The life expectancy of patients with HIV has increased significantly since the introduction of highly active antiretroviral therapy in 1995. Although this population of patients now carries less risk for the development of AIDS defining illnesses and malignancies, they are still at risk for non-AIDS defining cancers, such as colon, prostate, and breast. Several studies have shown that HIV infected patients have a higher prevalence of advanced colonic neoplasia which occur at a younger age.

NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine.

Background: Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy.

NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma.

Background: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors.

Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer.

Development of specific immunotherapy for colorectal cancer (CRC) will require identification of antigens selectively or exclusively expressed on CRC cells and strategies to induce and enhance immune responses against these antigenic targets. Cancer-testis (C-T) antigens are proving to be excellent targets for immunotherapy of solid tumors such as melanoma, but their clinical utility for treatment of CRC has to date been limited by their infrequent expression in CRC cells. Here we report that the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) induces expression of NY-ESO-1 and other C-T genes in CRC cells both in vitro and in vivo in a dose-dependent manner but has negligible effects on the expression of C-T genes in normal nontransformed cells such as fibroblasts.

BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors.

Cancers with specific genetic mutations are susceptible to selective kinase inhibitors. However, there is a wide spectrum of benefit among cancers harboring the same sensitizing genetic mutations. Herein, we measured apoptotic rates among cell lines sharing the same driver oncogene following treatment with the corresponding kinase inhibitor.

Integrative rehabilitation of elderly stroke survivors: the design and evaluation of the BrightArm™.

Purpose: To describe the development of the BrightArm upper extremity rehabilitation system, and to determine its clinical feasibility with older hemiplegic patients.

Method: The BrightArm adjusted arm gravity loading through table tilting. Patients wore an arm support that sensed grasp strength and communicated wirelessly with a personal computer.

Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population.

Background: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected Americans of African ancestral heritage has been attributed to APOL1 genetic variation. We determined the frequency of the APOL1 G1 and G2 risk variants together with the prevalence of HIV-associated nephropathy (HIVAN) among individuals of Ethiopian ancestry to determine whether the kidney disease genetic risk is PanAfrican or restricted to West Africa, and can explain the previously reported low risk of HIVAN among Ethiopians.

Methods: We studied a cohort of 338 HIV-infected individuals of Ethiopian ancestry treated in one Israeli and one Ethiopian center.

Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease.

Left ventricular torsional mechanics in uncomplicated pregnancy.

Background: Alterations in left ventricular (LV) twist (torsion) and untwist have been described for a variety of physiologic and pathologic conditions. Little information is available regarding changes in these parameters during normal pregnancy.

Hypothesis: Pregnancy is associated with significant changes in LV torsional mechanics.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients.

Objective: To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients.

Design: Case report.

Setting: Academic IVF program.

A comparative study of fragment screening methods on the p38α kinase: new methods, new insights.

The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore(™) T100 against p38α and two selectivity targets. A sub-set of our library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor.

Men who have sex with men, risk behavior, and HIV infection: integrative analysis of clinical, epidemiological, and laboratory databases.

Background: Centralized data collection and analytic tools facilitate tracing HIV transmission trends at the patient-population level with increasing resolution, complementing behavioral studies while avoiding sampling biases. By several measures, the rate of HIV infection among men who have sex with men (MSM) in Israel increased in the past several years more rapidly than was expected. We describe features of the data that connect this increase to behavioral changes.