Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients

Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute. Here we demonstrate that hematopoietic progenitors from GSD-1b patients are not impaired in their capacity to develop into mature neutrophils. However, optimal survival of neutrophil progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl⁻¹), suggesting that even under normoglycemic conditions these cells are more prone to apoptosis. Furthermore, analysis of cytokine levels in peripheral blood suggests an inflammatory state with an inverse correlation between the level of inflammation and the number of neutrophils. Finally, in some patients, with low numbers of peripheral blood neutrophils, high numbers of neutrophils were observed in the intestine. Together, these results suggest that the neutropenia observed in GSD-1b patients is not caused by impaired maturation, but may be caused by both increased levels of apoptosis and egress of neutrophils from the blood to the inflamed tissues.     

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Background

Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.

Design and Methods

To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade^® (EPIC) study using International Working Group 2006 criteria.

Results

Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.

Conclusions

This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.     

Incidence,Management, and Results of Hepatic Artery Stenosis After Liver Transplantation in the Era of Donor to Recipient Match

Introduction

Hepatic artery stenosis (HAS) is an important complication after liver transplantation. However, studies are not conclusive in terms of definition, incidence, best treatment, and timing of intervention. The aim of this study was to evaluate the incidence of SSHA that occurred in a single center over the past 12 years, pointing out diagnostic and therapeutic strategies.

Methods

The incidence of HAS was reviewed in 258 liver transplant recipients between January 1999 and December 2011. All patients underwent Doppler ultrasound (DUS) at fixed times. Multidetector computed tomographic angiography (MDCTA) was performed to confirm the DUS findings.

Results

HAS occurred in 23 cases (9.3%). In all cases diagnosis was performed by DUS resulting in a sensitivity of 100% and a specificity of 99.6%. Based on DUS and MDCTA data integration, in 10 cases we adopted the “wait and see” strategy, whereas 13 patients underwent interventional radiology techniques.

Conclusion

DUS monitoring is efficacious in the diagnosis of HAS after liver transplantation. Interventional radiology procedures are safe and efficacious.