Sickle Cell Disease in Pregnancy.

Sickle cell disease (SCD) is the most common hereditary disorder and affects 30 million people worldwide. Advances in science have improved overall survival in patients with SCD and as such, more patients are reaching reproductive age and are becoming pregnant. SCD in pregnancy leads to multiple complications that put both the mother and fetus at risk, and patients with SCD have six times the mortality during pregnancy as compared with patients without SCD. This review summarizes the maternal and fetal risks of patients with SCD and makes recommendations on how best to care for these patients throughout all stages of pregnancy.

Tivozanib: status of development.

Tivozanib is a potent and highly specific orally available, tyrosine kinase inhibitor that targets vascular endothelial growth factor (VEGF) receptor-1, VEGF receptor-2, and VEGF receptor-3 at very low concentrations with a long half-life (4 days). After its promising activity in xenograft and preclinical models, tivozanib was evaluated in early phase clinical trials in various solid tumors. The phase III trial (TIVO-1) compared tivozanib with sorafenib in metastatic clear cell renal cell carcinoma (RCC). Because of detrimental overall survival (OS), Oncology Drug Advisory Committee (ODAC) voted against its approval in RCC. Tivozanib is also being evaluated in various other solid tumors like breast, gastrointestinal cancers, hepatocellular cancer, sarcomas, and gynecological cancer. In BATON-CRC trial, low-serum neuropilin-1 (NRP-1) levels were associated with better progression-free survival (PFS) in patients treated with tivozanib. The NRP-1 will be evaluated as a biomarker for tivozanib response in future clinical trials. Ongoing clinical trial will further characterize activity of tivozanib in hepatocellular carcinoma, sarcomas, and gynecologic cancers.

Emerging agents for the therapy of advanced prostate cancer.

Since 2010, multiple advances have been made in the field of metastatic castration-resistant prostate cancer including regulatory approvals for five new agents including androgen pathway inhibitors (enzalutamide, abiraterone acetate), immunotherapy (sipuleucel-T), cytotoxic chemotherapy (cabazitaxel) and radiopharmaceuticals (radium-223) that have improved overall survival in this patient population. Despite these advances, each therapy has only extended median survival by 3-5 months and data suggest substantial cross-resistance among them. Given these modest increments, there is a major role for the vigorous investigation of new drugs and predictive biomarkers to select suitable patients who will benefit from them. This review describes emerging promising agents and their ongoing clinical development.

Effect of mother's dominance rank on offspring temperament in infant rhesus monkeys (Macaca mulatta).

In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

Developmental changes of rhesus monkeys in response to separation from the mother.

The development of separation response behaviors in infant rhesus macaques across the first 6 months of life was assessed. Seventeen infants underwent a neonatal assessment at 7, 14, 21, and 30 days of age which included a brief period of social isolation. At 3 and 6 months of age these same monkeys and four additional subjects were again subjected to a period of brief social isolation and also exposed to a novel environment with their sedated mother. Results indicate a developmental increase followed by a steady decline in the frequency of separation vocalizations. A modest relationship between early-infancy locomotor profiles and separation responses was also observed at several time points suggesting a possible relationship between these measures. However, stable inter-individual measures of separation distress did not emerge until late in the infantile period. This could suggest that high levels of maternal contact-seeking behavior early in infancy are context specific and not a reliable index of enduring temperament.

Evaluating the Impact of Treatment Care Planning on Quality Measures.

PURPOSE: The Center for Medicare & Medicaid Innovation Oncology Care Model (OCM) requires documentation of a 13-point Institute of Medicine care management plan for Medicare patients. In addition, OCM includes evaluation of quality using key performance measures that align with the ASCO Quality Oncology Practice Initiative (QOPI). Both efforts are designed to improve patient-centered care and foster patients' engagement in their care plan. METHODS: A multicenter quality improvement project was conducted to develop a strategy to meet the OCM treatment planning (TP) requirement (Plan), pilot clinician education coupled with use of electronic TP in early-stage breast cancer (Do), evaluate the impact of TP on QOPI measures (Study), and develop recommendations for future implementation (Act). RESULTS: Thirty-three clinical providers and 171 women with breast cancer were included. Improved performance on several QOPI measures was observed for the intervention group compared with the historical control group. CONCLUSION: Meeting the OCM TP requirement through incorporating a technology solution provided an opportunity for quality improvement and preparation for full-scale TP within the OCM. TP delivery was associated with improved performance on select ASCO QOPI measures, which is likely to correspond with improved performance on quality measures within OCM.

Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery.

UNLABELLED: Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). All patients with metastatic melanoma treated with ipilimumab from June 2010 to September 2012 were identified and stratified by presence (A) or absence (B) of brain metastases at the time of ipilimumab administration. All patients with brain metastases received SRS. Overall survival (OS) was defined as time from the date of stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and Cox proportional hazards model was employed to compute the hazard ratios (HR). RESULTS: Five out of 10 patients in Cohort A and 10 out of 21 patients in Cohort B died as of last follow-up. In Cohort A, median number of lesions treated with SRS was 3. Median survivals from date of stage IV for Cohorts A and B were 29.3 and 33.1 months, respectively (HR = 0.93, P = 0.896). Median survival from cycle 1 ipilimumab was 16.5 and 24.5 months for Cohort A and B, respectively (HR = 1.05, P = 0.931). The 3-year survival rates from the date of cycle one of ipilimumab administration for Cohort A and B were 50% (95% CI: 27-93%) and 39% (95% CI: 19-81%), respectively. Eight of 10 patients in Cohort A maintained a good PS. Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases.

Incidental discovery of a testicular plasmacytoma at initial presentation of multiple myeloma.

Testicular plasmacytomas are a rare phenomenon reported in the literature and they can occur as a solitary plasmacytoma, as a recurrence of multiple myeloma, or concurrently in an active myeloma. We report the case of a 43-year-old man who presented with back pain and was diagnosed with multiple myeloma. A CT scan performed to determine the extent of disease revealed an incidental mass in the testicle. Immunohistochemical staining of the mass revealed monoclonal cytolpasmic IgA in the tumor cells and serum studies showed this same immunoglobulin. Following orchiectomy, radiotherapy to the vertebra, chemotherapy with bortezomib, dexamethasone, and doxorubicin, and an autologous bone marrow transplant, the patient is alive twelve months after diagnosis and is in complete remission.