Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study.

Anti-thymocyte globulin (ATG) is an established approach to decrease chronic GVHD (cGVHD), yet the exact mechanism is uncertain. To better understand the mechanism of action of ATG in preventing cGVHD, we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group (CBMTG) 0801 trial, which demonstrated a significant impact of ATG on cGVHD. In a separate companion biology study, we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients. Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21low B cells, CD56bright NKreg cells, and Treg cells ST2, osteopontin, soluble B-cell activating factor (sBAFF), Interleukin-2 receptor alpha (sCD25), T-cell immunoglobulin and mucin domain-3 (TIM-3), matrix metallopeptidase 3, ICAM-1, C-X-C motif chemokine 10 (CXCL10), and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56bright NKreg cells (P < .0001). Treg cells, conventional Th cells, CD21low B cells, and all plasma markers were not affected. In the populations most affected by ATG, changes in naive Th cells were associated with the later development of cGVHD. This analysis suggests that ATG primarily impacts on cGVHD through suppression of naive Th cell expansion after transplantation. These associations need to be validated in additional studies.

Anti-N-methyl-D-aspartate receptor encephalitis in a pre-teenage girl: a case report.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune and paraneoplastic encephalitis which generally affects young adults. It is a multistage illness, with prominent extrapyramidal, neuropsychiatric and autonomic symptoms. The syndrome is frequently associated with an ovarian teratoma. Recently, it has become evident that anti-NMDAR encephalitis is more common in children and adolescents than was previously believed. Prognostic factors that determine a good outcome are presence of a tumour, prompt treatment and no need for admission to an intensive care unit. Increased awareness among paediatricians of this potentially life-threatening disease is important because early recognition and treatment will improve the patients' chances of a good clinical outcome. In this case report, we describe a 9-year-old girl with behavioural changes and severe extrapyramidal symptoms due to anti-NMDAR encephalitis associated with an ovarian teratoma. She was treated with a variety of immunomodulating therapies and made a slow, but good recovery.

Can screening for low vitamin D levels prevent bone health complications in paediatric oncology patients?

BACKGROUND: No international standards include vitamin D levels at diagnosis or during treatment. It is included in the Children's Oncology Group long-term follow-up guidelines. However, bone health complications (like osteopenia and atraumatic fractures) can occur at diagnosis or during treatment as well. CASES: In this small case series, we illustrate the complexity of bone health complications among our broad paediatric oncology population. If the vitamin D level is low we supplement the patient with one standard oral dose (150 000 units for 1-2 year olds, 300 000 units for 2-5 year olds and 600 000 units for >5 year olds). We do not adjust depending on diagnosis. CONCLUSION: Because of the potentially negative outcomes on short, medium and long term, we recommend checking vitamin D levels on diagnosis for all newly diagnosed patients. It is a simple, low cost test and one dose of oral supplementation can easily treat the deficiency.

Etoposide-based treatment of adult HLH is associated with high biochemical response but poor survival outcomes.

Etoposide-based treatment is the standard of care for adult HLH in many centers, yet there remains a paucity of data regarding treatment outcomes. We conducted a retrospective study of 23 adults treated with etoposide-based therapy compared to 10 pediatric HLH cases at a single center. At diagnosis, the median serum ferritin was 20,071 µg/L and 937 µg/L in adults and children, respectively; median sIL-2r was 14,524 U/mL and 4,478 U/mL. Biochemical response to treatment was high, with 21/23 adults achieving >75% reduction in serum ferritin, but one year survival was only 7/21 compared to 7/10 in pediatric cases.

Diagnostic accuracy of the mood module of the Patient Health Questionnaire: a systematic review.

OBJECTIVE: The nine-item mood module of the Patient Health Questionnaire (PHQ-9) was developed to screen and to diagnose patients in primary care with depressive disorders. We systematically reviewed the psychometric literature on the PHQ-9 and performed a meta-analysis to ascertain its summary sensitivity and specificity. METHODS: EMBASE, PubMed and PsycINFO were used to search literature up to July 2006. Studies were included if (1) they investigated the diagnostic accuracy of the PHQ-9 and (2) the PHQ-9 had been compared with a reference test. The quality of the studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies. We calculated sensitivity, specificity and confidence intervals for each included study. We used the random effects model to calculate the summary sensitivity and specificity. RESULTS: We found a sensitivity of 0.77 (0.71-0.84) and a specificity of 0.94 (0.90-0.97) for the PHQ-9. The positive predictive value in an unselected primary care population was 59%, which increased to 85-90% when the prior probability increased to 30-40%. CONCLUSION: In primary care, the PHQ-9 is a valid diagnostic tool if used in selected subgroups of patients with a high prevalence of depressive disorder.