Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases

BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies. Enrolled patients included seven patients with relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors described in this case series. MATERIALS AND METHODS: Forty patients with relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or testicular tumors were screened for CD30 expression; 14 patients had tumors that expressed CD30. Seven patients with CD30-expressing testicular cancer were enrolled in the treatment study: five patients with germ cell tumors, one patient with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every 3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles thereafter while the patient was receiving treatment. RESULTS: Two of seven patients achieved an objective response, including one durable complete response and one partial response at a single time point. Both responding patients had germ cell tumors. Treatment with brentuximab vedotin was generally well tolerated. CONCLUSION: Treatment of relapsed or refractory germ cell tumors with brentuximab vedotin can induce durable responses with a manageable toxicity profile. IMPLICATIONS FOR PRACTICE: This case series of seven patients with relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord stromal tumors demonstrates that brentuximab vedotin has activity against GCTs and is well tolerated in heavily pretreated patients with these aggressive tumor types. One patient achieved a complete response that has been durable for almost 4 years since the discontinuation of treatment with brentuximab vedotin. Therefore, brentuximab vedotin may be a valuable option for physicians who care for this difficult-to-treat patient population

Effects of Group Functional Behavior-Based Cognitive Behavioral Therapy for Obsessive-Compulsive Behavior in a Youth with Autism Spectrum Disorder

Individuals with Autism Spectrum Disorder (ASD) often present with comorbid Obsessive Compulsive Behaviors (OCBs), but little research exists on effective intervention for OCBs. Using a single-case experimental design, this study highlights the efficacy of a Group Functional Behavior-Based Cognitive-Behavior Therapy (Fb-CBT) to reduce OCBs in an 11-year-old youth. Tailored for individuals with ASD, Fb-CBT included traditional CBT components (e.g., psychoeducation, cognitive-behavioral skills training, and exposure and response prevention), functional behavior assessment and intervention, and a group parent-training component. Time-series parent report data and standardized OCB measures showed clinically significant decreases in OCBs, increase in psychosocial functioning, and high consumer satisfaction

Uric acid enhances longevity and endurance and protects the brain against ischemia

Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/− mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/− mice, but not wild-type mice, and the endurance of the UOX+/− mice is significantly greater than wild-type mice. UOX+/− mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/− mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.España, Ministerio de Educación, Cultura y Deporte EX2009–091

The effect of category variability in perceptual categorization

Exemplar and distributional accounts of categorization make differing predictions for the classification of a critical exemplar precisely halfway between the nearest exemplars of 2 categories differing in variability. Under standard conditions of sequential presentation, the critical exemplar was classified into the most similar, least variable category, consistent with an exemplar account. However, if the difference in variability is made more salient, then the same exemplar is classified into the more variable, most likely category, consistent with a distributional account. This suggests that participants may be strategic in their use of either strategy. However, when the relative variability of 2 categories was manipulated, participants showed changes in the classification of intermediate exemplars that neither approach could account for

Vertical Resolution of a Seismic Survey in Stratigraphic Sequences less than 100 m Deep in Southeastern Kansas

A 400-m long, 12-fold high-resolution common depth point (CDP) reflection seismic profile was acquired across shallow converging Pennsylvanian strata in the Independence area of southeastern Kansas. One of the principal objectives was to determine practical vertical resolution limits in an excellent shallow seismic-data area with borehole control. The dominant frequency of the CDP stacked data is in excess of 150 Hz based on peak-to-peak measurements. Interference phenomena observed on stacked seismic data incorporated with models derived from log and drill-hole information suggest a practical vertical resolution limit of about 7 m, or one-third of the dominant wavelength. The data suggest conventional rules of thumb describing resolution potential are not accurate when reflectors on shallow, narrow bandwidth data converge rapidly across horizontal distances less than the Fresnel Zone

Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa

Background: Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients. Methods: HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death. Results: Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7–90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death. Conclusions: Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge