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Objectives: To assess clinically relevant difference in hepatic iron quantification using R2* relaxometry with (FS) and without (non-FS) fat saturation for the evaluation of patients with suspected hepatic iron overload. Methods: We prospectively enrolled 134 patients who underwent 1.5-T MRI R2* relaxometry with FS and non-FS gradient echo sequences (12 echoes, initial TE = 0.99 ms). Proton density fat fraction for the quantification of steatosis was assessed. Linear regression analyses and Bland-Altman plots including Lin's concordance correlation coefficient were performed for correlation of FS R2* with non-FS R2*. Patients were grouped into 4 severity classes of iron overload (EASL based), and agreement was evaluated by contingency tables and the proportion of overall agreement. Results: A total of 41.8% of patients showed hepatic iron overload; 67.9% had concomitant steatosis; and 58.2% revealed no iron overload of whom 60.3% had steatosis. The mean R2* value for all FS data was 102.86 1/s, for non-FS 108.16 1/s. Linear regression resulted in an R-squared value of 0.99 (p < 0.001); Bland-Altman plot showed a mean R2* difference of 5.26 1/s (SD 17.82). The concordance correlation coefficient was only slightly lower for patients with steatosis compared with non-steatosis (0.988 vs. 0.993). The overall agreement between FS and non-FS R2* measurements was 94.8% using either method to classify patients according to severity of iron storage. No correlation between R2* and proton density fat fraction was found for both methods. Conclusion: R2* relaxometry showed an excellent overall agreement between FS and non-FS acquisition. Both variants can therefore be used in daily routine. However, clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. We therefore recommend choosing a method and keeping it straight in the context of follow-up examinations. Key Points: • Both variants of R2* relaxometry (FS and non-FS) may be used in daily routine. • Clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. • It seems advisable choosing one method and keeping it straight in the context of follow-up examinations. [ABSTRACT FROM AUTHOR]

Objectives: To assess if the administration of gadoxetate disodium (Gd-EOB-DTPA) significantly affects hepatic magnetic resonance elastography (MRE) measurements in the delayed hepatobiliary phase (DHBP).Methods: A total of 47 patients (15 females, 32 males; age range 23-78 years, mean 54.28 years) were assigned to standard hepatic magnetic resonance imaging (MRI) with application of Gd-EOB-DTPA and hepatic MRE. MRE was performed before injection of Gd-EOB-DTPA and after 40-50 min in the DHBP. Liver stiffness values were obtained before and after contrast media application and differences between pre- and post-Gd-EOB-DTPA values were evaluated using a Bland-Altman plot and the Mann-Whitney-Wilcoxon test. In addition, the data were compared with regard to the resulting fibrosis classification.Results: Mean hepatic stiffness for pre-Gd-EOB-DTPA measurements was 4.01 kPa and post-Gd-EOB-DTPA measurements yielded 3.95 kPa. We found a highly significant individual correlation between pre- and post-Gd-EOB-DTPA stiffness values (Pearson correlation coefficient of r = 0.95 (p < 0.001) with no significant difference between the two measurements (p =0.49)). Bland-Altman plot did not show a systematic effect for the difference between pre- and post-stiffness measurements (mean difference: 0.06 kPa, SD 0.81). Regarding the classification of fibrosis stages, the overall agreement was 87.23% and the intraclass correlation coefficient was 96.4%, indicating excellent agreement.Conclusions: Administration of Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver in the DHBP. Therefore, MRE can be performed in the DHBP.Key Points: • MRE of the liver can reliably be performed in the delayed hepatobiliary phase. • Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver. • MRE performed in the delayed hepatobiliary-phase is reasonable in patients with reduced liver function. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (B-PLL) to definitely describe the impact of this antibody in clinical routine use. Data were collected from 208 consecutive, mainly pretreated, patients with CLL ( n = 202), and B-PLL ( n = 6) who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) in various settings were assessed, and toxicities were documented. In these routine patients, a comparably low cumulative dose of alemtuzumab (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various pre-therapeutic parameters were predictive for inferior response, among them, the prior administration of ≥3 therapy lines ( P < 0.001), refractoriness to fludarabine ( P = 0.002), and bulky lymphadenopathy ( P = 0.003). PFS and OS after start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky lymphadenopathy was the prominent risk factor for both inferior PFS ( P < 0.001) and OS ( P = 0.002). In B-PLL, four patients experienced a fatal outcome, whereas two patients had some benefit with alemtuzumab. The main adverse effects were CMV reactivation (20 %) and a broad spectrum of infections, which together were the main reasons for treatment interruption and/or premature termination. In conclusion, alemtuzumab administered even at low dose levels was effective but overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab remains an important therapeutic option in subsets of CLL patients. [ABSTRACT FROM AUTHOR]

A main effector mechanism of rituximab (RTX) is the induction of complement-dependent cytotoxicity (CDC). However, this effector function is limited, because CLL cells are protected from complement-induced damage by regulators of complement activation (RCAs). A prominent RCA in fluid phase is factor H (fH), which has not been investigated in this context yet. Here, we show that fH binds to CLL cells and that human recombinant fH-derived short-consensus repeat 18-20 (hSCR18-20) interferes with this binding. In complement-based lysis assays, CLL cells from therapy-naive patients were differently susceptible to RTX-induced CDC and were defined as CDC responder or CDC non-responder, respectively. In CDC responders, but notably also in non-responders, hSCR18-20 significantly boosted RTX-induced CDC. Killing of the cells was specific for CD20+ cells, whereas CD20− cells were poorly affected. CDC resistance was independent of expression of the membrane-anchored RCAs CD55 and CD59, although blocking of these RCAs further boosted CDC. Thus, inhibition of fH binding by hSCR18-20 sensitizes CLL cells to CDC and may provide a novel strategy for improving RTX-containing immunochemotherapy of CLL patients. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is the most prevalent lymphoid malignancy in the elderly of the Western world. Although treatment options have improved over the past two decades, 10-15% of patients still have a poor prognosis and are often resistant to therapy. Aberrations in the p53 pathway, such as a deleted (del17p13) or mutated p53 gene, are highly enriched in this class of patients. In an extensive screen for p53-independent apoptosis inducers, actinomycin D was identified from 1496 substances and shown to induce apoptosis in primary CLL cells derived from high-risk patients including those with aberrant p53, revealing a novel p53-independent mechanism of action. Both pro-survival genes BCL2 and MCL1 are targeted by actinomycin D, in contrast to fludarabine the backbone of current treatment schedules. In the well-established TCL1 transgenic mouse model for high-risk CLL, actinomycin D treatment was more effective in reducing tumor load than fludarabine, with no evidence of resistance after three treatment cycles and an overall survival increase of over 300%. Tumor load reduction was coupled to BCL2 downregulation. Our results identify the clinically approved compound actinomycin D as a potentially valuable treatment option for CLL high-risk patients. [ABSTRACT FROM AUTHOR]

Intravenous administration of fluids, electrolytes and glucose are the most common interventions in hospitalized pediatric patients. Parenteral fluid administration can be life-saving, however, if used incorrectly it also carries substantial risks. Perioperatively, adequate hydration, prevention of electrolyte imbalances and maintenance of normoglycemia are the main goals of parenteral fluid therapy. Conceptionally, the distinction between maintenance requirements, deficits and ongoing loss is helpful. Although the pathophysiological basis for parenteral fluid therapy was clarified in the first half of the 20th century, some aspects still remain controversial. In newborn infants, rational parenteral fluid therapy must take into account large insensible fluid losses, adaptive changes of renal function in the first days of life and the fact that neonates do not tolerate prolonged periods of fasting. In older infants the occurrence of iatrogenic hyponatremia with the use of hypotonic solutions has led to a critical reappraisal of the validity of the Holliday-Segar method for calculating maintenance fluid requirements in the postoperative period. Pragmatically, only isotonic solutions should be used in clinical situations which are known to be associated with increases in antidiuretic hormone (ADH) secretion. In this context, it is important to realize that in contrast to lactated Ringer's solution, the use of normal saline can lead to hyperchloremic acidosis in a dose-dependent fashion. Although there is no convincing evidence that colloids are better than crystalloids, there are clinical situations where the use of the more expensive colloids seems justified. It may be reasonable to choose a solution for fluid replacement which has a composition comparable to the composition of the fluid which must be replaced. Although hypertonic saline can reduce an elevated intracranial pressure, this therapy cannot be recommended as a routine procedure because there is currently no evidence that this intervention improves long-term outcome in pediatric patients with traumatic brain injury. [ABSTRACT FROM AUTHOR]

This report dwells on selected abstracts presented at the 49th Annual Meeting of the American Society of Hematology (ASH), which was held at the Georgia World Congress Center in Atlanta, Georgia in December 2007. The aim of this report is not to discuss the very details of distinct scientific questions or clinical problems but rather to inform the practising haematologist about relevant clinical and scientific advances in the broad field of haematology. This selection of studies is of course a subjective one as the abstracts presented herein were judged upon their significance solely by the reflection of authors' personal interests. The presentation of the first pilot studies exploring the efficacy and safety of JAK-2 inhibitors in Philadelphia-chromosome negative chronic myeloproliferative disorders was certainly one of the most notable topics of the meeting. Concerning other haematologic malignancies, we felt that there were no groundbreaking developments as in recent years when novel forms of treatment such as proteasome inhibitors, tyrosine kinase inhibitors or thalidomide and its analogues were presented. But with large and often randomized trials with sufficient follow-up periods, the progress suggested by smaller phase II trials was further consolidated allowing the physician to recognize not only the true benefit but also the potential harm of these novel therapies in broad clinical practice. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing the prognostic value of the adhesion molecules CD44 and E-cadherin in myelodysplastic syndromes, is presented.

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer. [ABSTRACT FROM AUTHOR]

Cefdinir is a new, extended-spectrum, orally active, third-generation cephalosporin that is resistant to bacterial β-lactamase production. To evaluate efficacy and safety of the antibiotic in maxillary sinusitis, its use was compared with amoxicillin/clavulanate (amox/clav), which is a well-accepted β-lactamase-resistant antibiotic. In this investigator-blinded multicenter phase III clinical study, 569 patients were randomly assigned to one of three treatment regimens: one daily dose of cefdinir ¶600 mg (OD), cefdinir 300 mg every 12 h (BD), and amox/clav 500/125 mg every 8 h. All antibiotics were administered orally for 10 days. Maxillary sinusitis was documented by typical clinical signs and symptoms and was confirmed by X-ray imaging. Before treatment, the genus and species of any pathogens were determined from sinus aspirates. Cultures were tested for β-lactmase production and in vitro resistance to cefdinir and amox/clav. The ¶effectiveness of antibiotic treatment was evaluated 7–¶14 days after therapy and whether or not recurrent clinical symptoms or persistent infection was determined 21–¶35 days post-therapy. The appearance of any adverse events was classified as associated or not associated with the medication of the study. Present findings showed that the in vitro susceptibility of pathogens to cefdinir and amox/clav was similar. Cefdinir OD or BD was therapeutically as effective as or better than amox/clav, although cefdinir BD was not as useful as amox/clav clinically. Cefdinir OD and BD and amox/clav were well tolerated. The statistical incidence of adverse events was the same among the three treatment groups, although cefdinir OD treatment had significantly fewer treatment discontinuations due to adverse events than BD and amox/clav. [ABSTRACT FROM AUTHOR]

The annual meeting of the American Society of Hematology 2010 offered a wealth of interesting pilot studies in CLL rather than large practice changing trials. Although these new compounds are mostly in a very early phase of drug development, the results are impressive. Concerning clinical practice, new or updated results of trials exploring alemtuzumab in CLL underscore the clinical value of this drug, in particular for high-risk CLL patients. And finally, preliminary data indicate that rituximab maintenance strategies as applied for the treatment of indolent lymphoma may also have a role in CLL. [ABSTRACT FROM AUTHOR]

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