Definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma: A report from the International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH).

BACKGROUND: The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma. PROCEDURE: A comprehensive literature search was performed using PubMed and Google Scholar with the search terms "Hodgkin lymphoma," "osseous lesions," "bony involvement," and "pediatric." Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group. RESULTS: Twenty-five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0-21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications. CONCLUSIONS: The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy-proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG-PET positive correlate in a patient with biopsy-proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG-PET or magnetic resonance imaging should be confirmed by CT or Tc-99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or "E" lesions and do not represent metastatic or stage IV disease.

Staging Evaluation and Response Criteria Harmonization (SEARCH) for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (CAYAHL): Methodology statement.

International harmonization of staging evaluation and response criteria is needed for childhood, adolescence, and young adulthood Hodgkin lymphoma. Two Hodgkin lymphoma protocols from cooperative trials in Europe and North America were compared for areas in need of harmonization, and an evidence-based approach is currently underway to harmonize staging and response evaluations with a goal to enhance comparisons, expedite identification of effective therapies, and aid in the approval process for new agents by regulatory agencies.

Fatal Work-Related Injuries: Southeastern United States, 2008-2011.

In 2008, the work-related injury fatality rate was 3.8 per 100,000 workers in the United States but was 5.2 per 100,000 workers for the southeast region. Work-related fatalities in the southeast were examined for the period 2008 to 2011. Median work-related injury fatality rates are reported for the southeast region, each of the 12 states, and the United States. The percentages of employees in high fatality industries and work-related fatalities by cause were calculated. Finally, the Occupational Safety and Health Administration's database was searched for fatality reports. States with the highest rates (per 100,000 workers) included Arkansas (7.2), Louisiana (6.8), and West Virginia (6.6). Arkansas, Louisiana, Mississippi, and West Virginia each had more than 20% of their employees in high fatality industries. Forty percent of work-related injury fatalities were from transportation incidents in the southeast and the United States. Future analyses should include work-related injury fatality rates by industry and compare rates with other U.S. regions.

A review of adult asthma hospitalizations in Louisiana, 2006-2011.

This paper examines asthma inpatient hospitalizations for Louisiana residents ages 15 years and older from 2006 to 2011. There were 21,398 asthma hospitalizations, with 14,401 unique cases. Approximately 22 percent of cases had more than one asthma hospitalization. The case rate of adults hospitalized for asthma decreased significantly during the six-year period. However, the rate of all adult hospitalizations for asthma did not significantly change. Black women had the highest age-adjusted case rate, followed by white women. Days hospitalized averaged from 2.8 to 4.9 among the youngest to the oldest age groups, respectively. Differences between black and white patients were observed in type of payment and admit source. Parish rates varied significantly: Caldwell, Jefferson Davis, and LaSalle had rates that were at least twice the mean state rate. Rural parishes had a significantly higher rate than non-rural parishes. The information in this review can be used to target outreach and prevention activities.

Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction.

Sonic hedgehog (SHh) signaling is important in the pathogenesis of various human cancers, such as medulloblastomas, and it has been identified as a valid target for anticancer therapeutics. The SHh inhibitor cyclopamine induces apoptosis. The bioactive sphingolipid ceramide mediates cell death in response to various chemotherapeutic agents; however, ceramide's roles/mechanisms in cyclopamine-induced apoptosis are unknown. Here, we report that cyclopamine mediates ceramide generation selectively via induction of neutral sphingomyelin phosphodiesterase 3, SMPD3 (nSMase2) in Daoy human medulloblastoma cells. Importantly, short interfering RNA-mediated knockdown of nSMase2 prevented cyclopamine-induced ceramide generation and protected Daoy cells from drug-induced apoptosis. Accordingly, ectopic wild-type N-SMase2 caused cell death, compared with controls, which express the catalytically inactive N-SMase2 mutant. Interestingly, knockdown of smoothened (Smo), a target protein for cyclopamine, or Gli1, a downstream signaling transcription factor of Smo, did not affect nSMase2. Mechanistically, our data showed that cyclopamine induced nSMase2 and cell death selectively via increased nitric oxide (NO) generation by neuronal-nitric oxide synthase (n-NOS) induction, in Daoy medulloblastoma, and multiple other human cancer cell lines. Knockdown of n-NOS prevented nSMase2 induction and cell death in response to cyclopamine. Accordingly, N-SMase2 activity-deficient skin fibroblasts isolated from homozygous fro/fro (fragilitas ossium) mice exhibited resistance to NO-induced cell death. Thus, our data suggest a novel off-target function of cyclopamine in inducing apoptosis, at least in part, by n-NOS/NO-dependent induction of N-SMase2/ceramide axis, independent of Smo/Gli inhibition.

Disseminated neuroendocrine carcinoma in a pediatric patient: a rare case and diagnostic challenge.

A previously healthy 16-year-old female presented with 1-month history of fever, cough, extremity pain, left upper quadrant pain, and night sweats. Imaging studies revealed mediastinal lymphadenopathy, lung and liver masses, and bony lesions. Liver and bone marrow biopsies revealed small tumor cells with a high nuclear cytoplasmic ratio, stippled chromatin, and inconspicuous nucleoli surrounded by bands of collagen. Immunohistochemically, the tumor cells were positive for epithelial (epithelial membrane antigen and cytokeratin AE1/AE3) and neuroendocrine markers (chromogranin and synaptophysin), and negative for other antigens tested, including vimentin, desmin, CD99, and WT-1. The morphologic features and immunohistochemical profile was consistent with neuroendocrine carcinoma. Despite several chemotherapeutic regimens, the patient had progressive disease and enrolled in a phase 1 trial. Thorough histopathologic evaluation, including immunohistochemical stains is a crucial component for diagnosing this rare, aggressive tumor in children and adolescents.

Exposure matrices of endotoxin, (1→3)-ß-d-glucan, fungi, and dust mite allergens in flood-affected homes of New Orleans.

This study examined: (i) biocontaminant levels in flooded homes of New Orleans two years after the flooding; (ii) seasonal changes in biocontaminant levels, and (iii) correlations between biocontaminant levels obtained by different environmental monitoring methods. Endotoxin, (1→3)-ß-d-glucan, fungal spores, and dust mite allergens were measured in 35 homes during summer and winter. A combination of dust sampling, aerosolization-based microbial source assessment, and long-term inhalable bioaerosol sampling aided in understanding exposure matrices. On average, endotoxin found in the aerosolized fraction accounted for <2% of that measured in the floor dust, suggesting that vacuuming could overestimate inhalation exposures. In contrast, the (1→3)-ß-d-glucan levels in the floor dust and aerosolized fractions were mostly comparable, and 25% of the homes showed aerosolizable levels even higher than the dust-borne levels. The seasonal patterns for endotoxin in dust and the aerosolizable fraction were different from those found for (1→3)-ß-d-glucan, reflecting the temperature and humidity effects on bacterial and fungal contamination. While the concentration of airborne endotoxin followed the same seasonal trend as endotoxin aerosolized from surfaces, no significant seasonal difference was identified for the concentrations of airborne (1→3)-ß-d-glucan and fungal spores. This was attributed to the difference in the particle size; smaller endotoxin-containing particles can remain airborne for longer time than larger fungal spores or (1→3)-ß-d-glucan-containing particles. It is also possible that fungal aerosolization in home environments did not reach its full potential. Detectable dust mite allergens were found only in dust samples, and more commonly in occupied homes. Levels of endotoxin, (1→3)-ß-d-glucan, and fungi in air had decreased during the two-year period following the flooding as compared to immediate measurements; however, the dust-borne endotoxin and (1→3)-ß-d-glucan levels remained elevated. No conclusive correlations were found between the three environmental monitoring methods. The findings support the use of multiple methods when assessing exposure to microbial contaminants.

Post-hematopoietic stem cell transplant immunization practices in the Pediatric Blood and Marrow Transplant Consortium.

BACKGROUND: A survey of National Marrow Donor Program transplant centers in 1995 demonstrated a wide range of immunization practices in post-hematopoietic stem cell transplant (HSCT) recipients, which led to the 2000 Centers for Disease Control and Prevention (CDC) recommendations for vaccination after HSCT. We surveyed the principal investigators of the Pediatric Blood and Marrow Transplant Consortium (PBMTC) to identify immunization practice patterns after HSCT and assess compliance with the 2000 CDC guidelines. PROCEDURE: Approval was obtained from the Medical University of South Carolina Institutional Review Board. A 33 question survey using surveymonkey.com was distributed by email to principal investigators in the PBMTC. RESULTS: Forty-one (40%) of the 102 pediatric HSCT centers participating in the PBMTC responded. Thirty of the responding centers completed the entire survey. For individual vaccines, compliance with the CDC guidelines ranged from 22% to 93%. Less than 20% of the centers reported schedules consistent with the 2000 CDC recommendations for both allogeneic and autologous HSCT recipients. CONCLUSION: Despite the 2000 CDC guidelines, wide variation in post-HSCT immunization practices still exists. Updated guidelines have been needed, particularly to address the use of the pneumococcal conjugate vaccine. In conjunction with multiple other groups, the CDC recently released new immunization guidelines in October 2009. Additional data are still needed to adequately address the utility of incorporating immunologic parameters with the timing of vaccination after HSCT.

Aerosolization of fungi, (1-->3)-beta-D glucan, and endotoxin from flood-affected materials collected in New Orleans homes.

Standing water and sediments remaining on flood-affected materials were the breeding ground for many microorganisms in flooded homes following Hurricane Katrina. The purpose of this laboratory study was to examine the aerosolization of culturable and total fungi, (1-->3)-beta-D glucan, and endotoxin from eight flood-affected floor and bedding materials collected in New Orleans homes, following Hurricane Katrina. Aerosolization was examined using the Fungal Spore Source Strength Tester (FSSST) connected to a BioSampler. Dust samples were collected by vacuuming. A two-stage cyclone sampler was used for size-selective analysis of aerosolized glucan and endotoxin. On average, levels of culturable fungi ranged from undetectable (lower limit=8.3 x 10(4)) to 2.6 x 10(5) CFU/m(2); total fungi ranged from 2.07 x 10(5) to 1.6 x 10(6) spores/m(2); (1-->3)-beta-D glucan and endotoxin were 2.0 x 10(3) - 2.9 x 10(4) ng/m(2) and 7.0 x 10(2) - 9.3 x 10(4) EU/m(2), respectively. The results showed that 5-15 min sampling is sufficient for detecting aerosolizable biocontaminants with the FSSST. Smaller particle size fractions (<1.0 and <1.8 microm) have levels of glucan and endotoxin comparable to larger (>1.8 microm) fractions, which raises additional exposure concerns. Vacuuming was found to overestimate inhalation exposure risks by a factor of approximately 10(2) for (1-->3)-beta-D glucan and by 10(3)-10(4) for endotoxin as detected by the FSSST. The information generated from this study is important with respect to restoration and rejuvenation of the flood-affected areas in New Orleans. We believe the findings will be significant during similar disasters in other regions of the world including major coastal floods from tsunamis.

Pancytopenia with myelodysplasia due to copper deficiency.

We present a case of pancytopenia in a 9-month-old infant with total parenteral nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination revealed left-shifted myeloid maturation, erythroid and myeloid dysplasia with normal iron stores. Serum copper level was 2 microm/dl (normal range 90-190 mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency should be considered in the differential diagnosis of cytopenias and myelodsyplasia, particularly in the growing number of pediatric patients with TPN dependency or malabsorption.

Time-dependent toxicity of dichlorodiphenyldichloroethylene to Hyalella azteca.

Temporal effects on body residues of dichlorodiphenyldichloroethylene (DDE) associated with mortality in the freshwater amphipod Hyalella azteca were evaluated. Toxicokinetics and body residues were determined from water-only exposures that varied from 4 to 28 d, and DDE concentrations ranging from 0.0013 to 0.045 micromol L(-1). Uptake and elimination parameters were not affected significantly by the various temporal and concentration treatments. Uptake rate coefficients ranged from 134.3 to 586.7 ml g(-1) h(-1), and elimination rate coefficients ranged from 0.0011 to 0.0249 h(-1). Toxicity metric values included body residue for 50% mortality at a fixed sample time (LR50) and mean lethal residue to produce 50% mortality from individual exposure concentrations (MLR50) for live organisms and dead organisms. A twofold increase occurred in the MLR50 values calculated using live organisms compared to MLR50 values using dead organisms. Toxicity and kinetic data were fit to a damage assessment model that allows for the time course for toxicokinetics and damage repair, demonstrating the time-dependence of body residues to toxicity. The DDE appeared to act through a nonpolar narcosis mode of action for both acute and chronic mortality in H. azteca. Furthermore, the temporal trend in the toxic response using body residue as the dose metric is steep and found to be similar to another chlorinated hydrocarbon, pentachlorobenzene, but was more potent than that found for polycyclic aromatic hydrocarbons (PAHs).