Phase III Trial of Carboplatin and Paclitaxel Compared With Cisplatin and Paclitaxel in Patients With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study.

In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population.

Phase I study of the anti-FcRH5 antibody-drug conjugate DFRF4539A in relapsed or refractory multiple myeloma.

FcRH5 is a cell surface marker enriched on malignant plasma cells when compared to other hematologic malignancies and normal tissues. DFRF4539A is an anti-FcRH5 antibody-drug conjugated to monomethyl auristatin E (MMAE), a potent anti-mitotic agent. This phase I study assessed safety, tolerability, maximum tolerated dose (MTD), anti-tumor activity, and pharmacokinetics of DFRF4539A in patients with relapsed/refractory multiple myeloma.

Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay.

While proteasome inhibition is a validated therapeutic approach for multiple myeloma (MM), inhibition of individual constitutive proteasome (c20S) and immunoproteasome (i20S) subunits has not been fully explored owing to a lack of effective tools. We utilized the novel proteasome constitutive/immunoproteasome subunit enzyme-linked immunosorbent (ProCISE) assay to quantify proteasome subunit occupancy in samples from five phase I/II and II trials before and after treatment with the proteasome inhibitor carfilzomib. Following the first carfilzomib dose (15-56 mg/m(2) ), dose-dependent inhibition of c20S and i20S chymotrypsin-like active sites was observed [whole blood: ≥67%; peripheral blood mononuclear cells (PBMCs): ≥75%].

Pulmonary hypertension complicating multiple myeloma.

Pulmonary hypertension (PH) is an infrequently reported complication of multiple myeloma (MM). PH has been more commonly associated with amyloidosis, myeloproliferative diseases, and the POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome. PH in MM is typically mild to moderate and may be secondary to a variety of conditions, which include left ventricular dysfunction, high-output cardiac failure, chronic kidney disease, treatment-related toxicities, and precapillary involvement.

Minimal Residual Disease Detection by Droplet Digital PCR in Multiple Myeloma, Mantle Cell Lymphoma, and Follicular Lymphoma: A Comparison with Real-Time PCR.

Real-time quantitative PCR (qPCR) is a well-established tool for minimal residual disease (MRD) detection in mature lymphoid malignancies. Despite remarkable sensitivity and specificity, qPCR has some limitations, particularly in the need for a reference standard curve, based on target serial dilutions. In this study, we established droplet digital PCR (ddPCR) for MRD monitoring in multiple myeloma, mantle cell lymphoma, and follicular lymphoma and compared it head-to-head with qPCR.

Novel Induction Regimens in Multiple Myeloma.

Multiple myeloma is the second most common hematologic malignancy and predominantly affects the elderly. The introduction of novel agents such as thalidomide, lenalidomide, and bortezomib has improved progression-free survival, overall survival, and quality of life in myeloma patients. Next generation agents such as carfilzomib hold further promise for increased depth and length of remission.

Potential role of daratumumab in the treatment of multiple myeloma.

Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options.

Preclinical and clinical results with pomalidomide in the treatment of relapsed/refractory multiple myeloma.

Despite the evolution of effective frontline treatment strategies, many patients with myeloma inevitably relapse. Treatment can be complicated by the interplay of disease-, treatment-, and patient-related factors. Unfortunately, many patients eventually develop disease that is refractory to lenalidomide and bortezomib and have few treatment options.

Pomalidomide in the treatment of relapsed multiple myeloma.

The novel agents bortezomib and lenalidomide improve outcomes in multiple myeloma, yet most patients will relapse after exhausting treatment. Management of relapsed and refractory multiple myeloma (RRMM) is challenging owing to disease-, patient- and treatment-related factors, and new therapies for these patients are required. Pomalidomide (POM) is an immunomodulatory compound that has been recently approved in the USA for the treatment of RRMM after two prior therapies, including lenalidomide and bortezomib.

Do DSM-5 personality disorder proposals meet criteria for clinical utility?

The Work Group for the DSM-5 personality disorders has submitted their proposal to the professional community. In this paper, we consider the proposal in light of its ability to meet criteria for clinical utility as proposed by First and colleagues (2004). While the Work Group's proposal has addressed some of these concerns, we conclude that there remain several unanswered problems with how the proposal will improve the clinical utility of personality disorders section of the DSM-5.

Thrombophilia and the risk of thromboembolic events in women on oral contraceptives and hormone replacement therapy.

Thrombophilia contributes to the risk of thrombosis in women using female hormones. The objective of the present study was to evaluate the prevalence of thrombophilia in women with thromboembolic events (TEEs) using oral contraceptives or hormone replacement therapy (HRT) and assess the contribution of a family history and the duration of hormone use in predicting thrombosis. A retrospective analysis was performed of the case records of women who developed a TEE while on oral contraceptives or HRT and were referred for thrombophilia evaluation over a 4-year period.

Sleep disturbances in pregnancy.

Objective: To estimate the prevalence and patterns of sleep disturbances during pregnancy among healthy nulliparous women.

Methods: This was a prospective, cohort study of healthy nulliparous women, recruited between 6 and 20 weeks of gestation, who completed a baseline sleep survey at enrollment with follow-up in the third trimester. The survey was composed of the following validated sleep questionnaires: Berlin Questionnaire for Sleep Disordered Breathing, Epworth Sleepiness Scale, National Institutes of Health/International Restless Legs Syndrome Question Set, Women's Health Initiative Insomnia Rating Scale, and the Pittsburgh Sleep Quality Index.

Aortic distensibility and dilation in Turner's syndrome.

Background: Aortic dilation and dissection is reported in patients with Turner's syndrome, both with and without cardiovascular risk factors. The bicuspid aortic valve is closely associated with dilated aortic root, although expression of aortic dilation is variable. The determinants for variable expression of aortic dilation in individuals with Turner's syndrome, however, are unknown.

Milatuzumab: a promising new agent for the treatment of lymphoid malignancies.

Background: Non-Hodgkin's lymphoma and multiple myeloma are often incurable and respond to a limited set of treatment options. The selective expression of CD74, the invariant chain of the MHC class II molecule, in these malignancies provides an attractive target for antibody-based therapy.

Objective: This review evaluates the preclinical data for milatuzumab, a humanized antibody targeting CD74, as a treatment for non-Hodgkin's lymphomas and multiple myeloma.

Intraoperative assessment of endoscopic third ventriculostomy success.

Object: The authors' aim in this study was to determine if standardizing the evaluation of intraoperative findings during endoscopic third ventriculostomy (ETV) could predict patients with hydrocephalus in whom endoscopic treatment will fail and require ventriculoperitoneal shunt treatment. The creation of a uniform scale with predictive outcomes may reduce returns to the operating room for shunt treatment and reliance on postoperative externalized ventricular monitoring and MR imaging.

Methods: The authors evaluated the preoperative history, intraoperative findings, and postoperative monitoring and imaging findings in 109 consecutive patients undergoing 112 consecutive attempted ETVs for obstructive hydrocephalus.

Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma.

The M-protein is the major reference measure for response in multiple myeloma (MM) and its correct interpretation is key to clinical management. The emergence of oligoclonal banding is recognized as a benign finding in the postautologous stem cell transplantation setting (ASCT) for MM but its significance during non-myeloablative therapy is unknown. In a study of the immunomodulatory combination BiRD, (lenalidomide and dexamethasone with clarithromycin), we frequently detected the emergence of mono- and oligo-clonal immunoglobulins unrelated to the baseline diagnostic M-protein.

Use of an accelerated immunization schedule for combined hepatitis A and B protection in the corporate traveler.

Increased international business travel to moderate or high endemic areas of hepatitis A and B may leave many business travelers at risk for infection if not vaccinated. Many international business travelers depart for hepatitis A and B endemic areas within 2 months of the decision to travel. Many of these travelers do not seek pretravel medical advice and are unaware of the risks and modes of acquiring hepatitis A and B.

Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma.

A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P < .

BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21.

Neurological complications following percutaneous coronary interventions (a report from the 2000-2001 New York State Angioplasty Registry).

Stroke is 1 of the most devastating complications associated with percutaneous coronary intervention. The present study used the combined 2000 to 2001 New York State Angioplasty Registry to compare the clinical characteristics and in-hospital outcomes of patients with and without stroke after percutaneous coronary intervention. Of the 76,903 patients who underwent angioplasty, 140 (0.

c-kit and ureteral peristalsis.

Purpose: c-kit encodes a tyrosine kinase receptor that is required for the differentiation of a wide variety of cells during embryogenesis, including pacemaker cells of the gut. Functional expression of this tyrosine kinase receptor is required for gut peristalsis and c-kit expression has recently been documented in the adult murine urinary tract. In this study we analyzed the temporal onset of c-kit expression during ureter morphogenesis in vivo and determined if c-kit activity is essential for ureteral peristalsis in vitro.

Differential diagnosis and management of thrombocytopenia in childhood.

The purpose of this article is to provide the reader with a firm knowledge of the major causes of thrombocytopenia and their treatments, and to form a broad differential diagnosis, so that it will be clearer when to consider a rare etiology. The various etiologies are presented by known disease entities, grouped by age,and described as they would occur and be considered in a realistic clinical setting. A brief categorization of causes of thrombocytopenia by mechanism, notably abnormal platelet production, platelet destruction, or sequestration, is included.