Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: A report from the Children's Oncology Group

Background

Supratentorial PNETs (sPNET) are uncommon embryonal malignancies of the central nervous system whose prognosis has historically been poor. We evaluated the outcome and prognostic factors of children with sPNET treated prospectively on a Children's Oncology Group trial.

Procedure

Following surgery, patients received craniospinal radiotherapy with concurrent carboplatin followed by six months of maintenance chemotherapy with cyclophosphamide and vincristine.

Results

Five‐year overall survival (OS) and progression‐free survival (PFS) for all patients was 58 ± 7% and 48 ± 7%. For patients with pineoblastoma (n = 23), five‐year OS and PFS was 81 ± 9% and 62 ± 11%. Extent of resection but not M‐stage was prognostic. Five‐year OS and PFS for 37 patients with non‐pineal tumors (NPsPNET) was 44 ± 8% and 39 ± 8%, significantly worse than for PB (P = 0.055 and 0.009 respectively). Extent of resection and major radiotherapy deviations were prognostic. Five year OS was 59 +/? 11.4% for those undergoing complete resection versus 10.4 +/? 7% for those who did not (P = 0.017). Central pathologic review called 14 (38%) “classic” sPNET, 8 (22%) “undifferentiated” and 13 (35%) “malignant gliomas.” There was no significant difference between the subgroups, although survival distributions approached significance when the combined “classic” and “undifferentiated” group was compared to the “malignant gliomas.”

Conclusions

Carboplatin during RT followed by 6 months of non‐intensive chemotherapy is a feasible treatment strategy for patients with sPNET. Aggressive surgical resection should be attempted if feasible. The classification of supratentorial small cell malignancies can be difficult. Pediatr Blood Cancer 2015;62:776–783. © 2015 Wiley Periodicals, Inc.

     

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

Listening to food workers: Factors that impact proper health and hygiene practice in food service

Background

Foodborne disease is a significant problem worldwide. Research exploring sources of outbreaks indicates a pronounced role for food workers'' improper health and hygiene practice.

Objective

To investigate food workers'' perceptions of factors that impact proper food safety practice.

Method

Interviews with food service workers in Baltimore, MD, USA discussing food safety practices and factors that impact implementation in the workplace. A social ecological model organizes multiple levels of influence on health and hygiene behavior.

Results

Issues raised by interviewees include factors across the five levels of the social ecological model, and confirm findings from previous work. Interviews also reveal many factors not highlighted in prior work, including issues with food service policies and procedures, working conditions (e.g., pay and benefits), community resources, and state and federal policies.

Conclusion

Food safety interventions should adopt an ecological orientation that accounts for factors at multiple levels, including workers'' social and structural context, that impact food safety practice.     

NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity,specific activity,and radioactive concentration values by proton and tritium NMR spectroscopy

Compounds containing tritium are widely used across the drug discovery and development landscape. These materials are widely utilized because they can be efficiently synthesized and produced at high specific activity. Results from internally calibrated ³H and ¹H nuclear magnetic resonance (NMR) spectroscopy suggests that at least in some cases, this calibrated approach could supplement or potentially replace radio‐high‐performance liquid chromatography for radiochemical purity, dilution and scintillation counting for the measurement of radioactivity per volume, and liquid chromatography/mass spectrometry analysis for the determination of specific activity. In summary, the NMR‐derived values agreed with those from the standard approaches to within 1% to 9% for solution count and specific activity. Additionally, the NMR‐derived values for radiochemical purity deviated by less than 5%. A benefit of this method is that these values may be calculated at the same time that ³H NMR analysis provides the location and distribution of tritium atoms within the molecule. Presented and discussed here is the application of this method, advantages and disadvantages of the approach, and a rationale for utilizing internally calibrated ¹H and ³H NMR spectroscopy for specific activity, radioactive concentration, and radiochemical purity whenever acquiring ³H NMR for tritium location.     

Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships

Registries and cord blood banks around the world collect and store the HLA types of volunteers in order to identify matched unrelated donors for patients requiring hematopoietic stem cell transplantation. This task is complicated by the many formats in which HLA types are provided by the testing laboratories (types obtained by serology vs by DNA-based methods; high vs intermediate vs low resolution) and by the need to identify which of these diverse types are most likely to match the HLA assignments of a searching patient as closely as possible. Conversion of the assignments to 'search determinants' may be included within the algorithm used to select and prioritize a list of potentially suitable donors, either as an aid to matching or as a tool to optimize the performance of comparisons within large data files. The strategies used by registries to create search determinants are described. A set of search determinants, utilized by the National Marrow Donor Program, is provided as an example and is intended to initiate further discussion aimed at understanding the process used by each registry with the possibility of developing a standard process among registries worldwide.     

Antibody against tuberlin: the specific visualization of cytoplasmic microtubules in tissue culture cells.

Cytoplasmic microtubules in tissue culture cells can be directly visualized by immunofluorescence microscopy. Antibody against tubulin from the outer doublets of sea urchin sperm flagella decorates a network of fine cytoplasmic fibers in a variety of cell lines of human, monkey, rat, mouse, and chicken origin. These fibers are separate and of uniform thickness and are seen throughout the cytoplasm. The fibers disappear either in a medium containing colchicine or after subjection of the cells to low temperature. The same treatments do not destroy the microfilamentous structures that are visualized by means of antibody against actin. When tryspin-treated enucleated cells are replated and then stained with antibody against tubulin, the fibers can be seen to traverse the entire enucleated cytoplasm.     

Neisseria subflava endocarditis. Case report and review of the literature

Neisseria subflava is a rare cause of bacterial endocarditis. Only seven cases have been identified in the world literature if strict criteria as to organism classification and of endocarditis are applied to individual case reports. The first reported case in an intravenous drug user is described. In addition, findings on serial two-dimensional and M-mode echocardiography performed during and after the treatment period are presented. This patient's recovery with anti-microbial therapy alone despite evidence of aortic and significant mitral valve involvement is in accord with results of other antibiotic-treated cases.     

2002 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: implications for emergency department practice

The publication of comprehensive evidence-based guidelines for the management of non-ST-segment elevation acute coronary syndrome by the American College of Cardiology and the American Heart Association in September 2000 marked a sentinel event in the evolution of managing this challenging patient population. Many of the recommendations included in the guidelines have relevance to the emergency department care of patients with non-ST-segment elevation acute coronary syndrome and were summarized in Annals of Emergency Medicine in September 2001. New clinical data in this area continue to accumulate at a remarkably rapid rate, prompting the American College of Cardiology and the American Heart Association to publish an update of the 2000 guidelines in October 2002. Several of the modified and new recommendations again potentially affect ED management. These are presented and discussed here.     

Body fat content and 25-hydroxyvitamin D levels in healthy women

Obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be secondary to an alteration in tissue distribution resulting from an increase in adipose mass. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. To study the relationship between 25-OHD levels and percentage body fat content in healthy women, we studied 410 healthy women between 20 and 80 yr of age with body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between serum 25-OHD level and percentage body fat measured by dual energy x-ray absorptiometry. We also analyzed the influence of season, dietary vitamin D intake, age, and race on this relationship. The levels of serum 25-OHD inversely correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after adjusting for race, age, season, and dietary vitamin D intake. In a multiple stepwise regression, race and season were found to have a major influence on serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest (additional R2 = 0.02), also had an independent statistically significant influence on serum 25-OHD levels. We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women.