Elderly do benefit from induction chemotherapy: High dose mitoxantrone-based (“5 + 1”) induction chemotherapy regimen in newly diagnosed acute myeloid leukemia

An intensive “5 + 1” regimen, which included bolus high dose cytarabine (HiDAC) at 3 g/m² once daily over 3 hours on days 1-5 and high dose mitoxantrone (HDM) 80 mg/m² on day 2, was evaluated in 101 consecutively treated newly diagnosed acute myeloid leukemia (AML) patients at a single center since 2009. The median age was 65 (range 18-90) years. The 4 and 8-week mortality in our cohort was 3/101 (2.9%) and 7/99 (7%), respectively. The overall response (complete remission [CR] + CRi) was 76.2% (77/101). The median overall survival (OS) stratified by age group <60, 60-69 and ≥70 years were 56, 31 and 9 months respectively (log-rank, P = 0.02). 51.7% (45/84) of patients with intermediate/adverse risk category proceeded to allogeneic stem cell transplants. Among these 84 patients, the percentage of patients able to proceed to transplant in age groups <60, 60-69, and ≥ 70 years were 75% (18/24), 60.7% (17/28), and 31.2% (10/32), respectively. In conclusion, HDM-based chemotherapy regimen produces high CR rates, is well tolerated and more patients can undergo curative postremission therapy including stem cell transplant.     

Novel exon 2 α spectrin mutation and intragenic crossover: three morphological phenotypes associated with four distinct α spectrin defects

Hereditary pyropoikilocytosis is a severe hemolytic anemia caused by spectrin deficiency and defective spectrin dimer self-association, typically found in African populations. We describe two Utah families of northern European ancestry including 2 propositi with atypical non-microcytic hereditary pyropoikilocytosis, 7 hereditary elliptocytosis members and one asymptomatic carrier. The underlying molecular defect is a novel mutation in the alpha(α) spectrin gene, SPTA^R34P that impairs spectrin tetramer formation. It is inherited in trans to the hypomorphic SPTA^αLELY in the 2 propositi and 5 of 7 hereditary elliptocytosis individuals indicating that SPTA^αLELY is not the sole determinant of the variable clinical expression. α Spectrin mRNA was mildly decreased in all hereditary elliptocytosis subjects, whereas both hereditary pyropoikilocytosis propositi had a severe decrease to ~10% of normal. Genotyping identified a unique SPTA intragenic crossover and uniparental disomy in one hereditary elliptocytosis individual. Two additional crossover events demonstrated the susceptibility of SPTA gene to rearrangement and revealed a novel segregation of the two SPTA^αLELY mutations. We conclude that the profound phenotypic heterogeneity in these families can be attributed to the SPTA^R34P mutation in combination with: 1) inheritance in trans of either SPTA^αLELY; or 2) the wild-type SPTA; 3) a decrease of α spectrin mRNA; and 4) SPTA intragenic crossover.     

Regenerative endodontics as a tissue engineering approach: Past,current and future

With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)₂ in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence‐based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth).     

Complete mesocolic excision and central vascular ligation for right colon cancer: an introduction for abdominal radiologists

Abdominal Radiology - To provide an overview of complete mesocolic excision, along with a review of the relevant vascular anatomy and locoregional staging concepts, for abdominal radiologists....