Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and orthostatic intolerance.

OBJECTIVES: More than 10% of adolescents suffer from severe fatigue and/or orthostatic intolerance. Adult studies show correlations between iron insufficiency and fatigue as well as between hypovitaminosis D and non-specific pain. We sought to determine whether there were correlations between nutritional factors (iron status, and serum vitamin D levels) and chronic ill health. METHODS: We reviewed records of 188 adolescents with symptoms of fatigue and/or orthostatic intolerance and who underwent autonomic reflex screening. RESULTS: Of the 188 patients, 130 patients (69%) had excessive postural tachycardia (PT) with a heart rate (HR) change of ≥30 bpm. 62 patients (47%, n = 131) had iron insufficiency with low iron stores, and 29 patients (22%, n = 131) were iron deficient. HR change did not correlate to ferritin level (P = 0.15). 21 patients (22%, n = 95) had hypovitaminosis D (25-hydroxyvitamin D ≤20 ng/mL). There was a significant association with hypovitaminosis D and orthostatic intolerance (P = 0.024). CONCLUSION: In patients presenting with chronic fatigue and/or orthostatic intolerance, low ferritin levels and hypovitaminosis D are common, especially in patients with PT.

Comparison of coagulation factor XIII content and concentration in cryoprecipitate and fresh-frozen plasma.

BACKGROUND: For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh-frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study. STUDY DESIGN AND METHODS: FFP and cryoprecipitate (10 bags each from blood group O donors) were analyzed to quantify pFXIII activity and antigen. Coagulation FVIII, fibrinogen, and von Willebrand factor (VWF) were also quantitated. RESULTS: Mean (+/-SD) pFXIII activity in cryoprecipitate and FFP bags was 60 +/- 30 and 288 +/- 77 U per bag, respectively, and pFXIII antigen and activity levels were concordant. Other comparisons (mean +/- SD) between cryoprecipitate and FFP, respectively, were as follows: coagulation FVIII activity, 133 +/- 37 and 265 +/- 83 U per bag; fibrinogen content (Clauss kinetic assay), 183 +/- 44 and 725 +/- 199 mg per bag; VWF antigen content, 181 +/- 53 and 218 +/- 70 U per bag; VWF ristocetin cofactor activity, 168 +/- 34 and 221 +/- 65 U per bag; VWF collagen-binding activity, 164 +/- 40 and 208 +/- 71 U per bag; and fluid (plasma) volumes per bag, 21.3 +/- 2.7 and 245 +/- 29 mL. CONCLUSION: In contrast to other cryoprecipitable coagulation proteins, pFXIII is only mildly enriched in cryoprecipitate when compared with FFP (approx. two- to threefold). Although both products can provide effective pFXIII replacement, FFP may be preferred when infusion volume is not a major consideration and pFXIII concentrates are not available. VWF is substantially enriched in cryoprecipitate (approx. ninefold compared with its concentration in FFP), with VWF activity content exceeding that of FVIII by approximately 26 percent on average.

MPL W515 and JAK2 V617 mutation analysis in patients with refractory anemia with ringed sideroblasts and an elevated platelet count.

Discovery of a constitutively activating point mutation of the Janus kinase 2 (JAK2) receptor-associated tyrosine kinase in patients with polycythemia vera (PV) and other BCR/ABL-negative myeloproliferative disorders prompted many groups around the world to examine diverse subsets of patients with myeloid diseases for the prevalence of the JAK2 V617F mutation and its clinical and pathological associations.

A role for radiotherapy in the management of advanced medullary thyroid carcinoma: the mayo clinic experience.

Outcomes of external beam radiotherapy (EBRT) in advanced medullary thyroid carcinoma (MTC) are largely unknown. Retrospective review of data from patients with MTC, diagnosed from June 1, 1970, through December 31, 2007. Overall survival and locoregional tumor control rates were calculated. Seventeen patients had adjuvant or palliative EBRT delivered to 41 sites. Six patients initially had adjuvant EBRT (median, 60.80 Gy); none had relapse in the treated area. Five patients with locoregional recurrence after surgery were treated (median, 59.40 Gy), and durable disease control was achieved in 3. Twelve patients received palliative EBRT to 29 sites of metastatic disease (median, 30.00 Gy), which provided sustained symptom relief at 45% of sites. Five- and ten-year overall survival rates were 44% and 19%, respectively. Adjuvant EBRT may be most effective for prevention of locoregional recurrence. EBRT may provide sustained control of advanced, metastatic disease in select patients.

Selective serotonin reuptake inhibitors, glioblastoma multiforme, and impact on toxicities and overall survival: the mayo clinic experience.

PURPOSE: The diagnoses of glioblastoma multiforme (GBM) and depression are often found to coexist. The impact of selective serotonin reuptake inhibitors (SSRI) on treatment-related toxicity and outcome in patients with GBM is unclear. METHODS AND MATERIALS: We retrospectively reviewed 160 patients with GBM who received treatment at our institution between 1999 and 2008. Those taking an SSRI during treatment for GBM were identified and toxicities were assessed. RESULTS: Median survival for the entire cohort was 1.05 years. A total of 35 patients (21.8%) took an SSRI during initial treatment for GBM. There was no statistical difference in the rate of ≥grade 3 toxicity in patients taking an SSRI when compared with those who were not (11.4% vs. 13.6%, respectively; P = 1.00). Two-year survival in the cohort of patients taking an SSRI was 32% versus 17% in those who were not (P = 0.18). After making adjustment for age, recursive partitioning analysis class, and extent of surgery, absence of an SSRI during treatment was associated with a hazard risk of 1.5 (95% confidence interval = 1.00-2.42; P = 0.05). CONCLUSIONS: This retrospective review suggests that concomitant use of an SSRI during treatment does not adversely affect survival. There was no increased toxicity with the use of SSRI concurrent with treatment of newly-diagnosed GBM.

Aberrant pre-mRNA splicing of a highly conserved cell cycle regulator, CDC25C, in myelodysplastic syndromes.

Alternative pre-mRNA splicing alters gene expression and protein function, and aberrant splicing patterns can be associated with neoplasia. The potential role of disordered RNA splicing in myelodysplastic syndrome (MDS) is unexplored. We analysed the splicing repertoire of CDC25C- a gene localised to chromosome 5q31 and encoding a cyclin/cyclin-dependent-kinase regulatory phosphatase critical for cell cycle checkpoint control - in MDS, acute myeloid leukemia, chronic lymphocytic leukemia and healthy tissues. Five novel splicing isoforms were detected, and the splicing patterns were generally distinct in neoplastic samples compared with healthy controls. One of the novel isoforms, which we have termed CDC25C-6, occurred in 58% of the samples in our cohort. The results of this study suggest the possibility of aberrant splicing contributing to the phenotype in MDS and other haematologic malignancies.

Diagnosis and management of bone malignancy in adolescence.

Approximately 6% of all childhood malignancies are malignant bone tumors, of which the 2 most frequently encountered are osteosarcoma and Ewing sarcoma. In the United States, the annual incidence in children under 20 years of age is 8.7 per million. In this article we provide an overview of the clinical manifestations, diagnosis, treatment, and prognosis of both osteosarcoma and Ewing sarcoma. Survivorship issues in children and adolescents treated for these malignancies are discussed.

C-terminal nucleophosmin mutations are uncommon in chronic myeloid disorders.

C-terminal somatic mutations in nucleophosmin (NPM), a nucleolar shuttling protein that binds p53 and p19(Arf), were recently described in karyotypically normal acute myeloid leukaemia (AML). We analysed primary marrow samples from 150 patients with various chronic myeloid disorders for mutations in the NPM1 gene encoding NPM. NPM1 mutations (tetranucleotide duplication) were detected in three patients, all of whom had chronic myelomonocytic leukaemia (CMML) and a short (<1 year) survival, with rapid progression to overt AML. All other patients were NPM1-wild type in the region analysed. In conclusion, C-terminal NPM mutations are uncommon in chronic myeloid neoplasia, but if present may represent an evolving leukaemic clone.