Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential

Aldehyde dehydrogenase (ALDH) activity is used to define normal hematopoietic stem cell (HSC), but its link to leukemic stem cells (LSC) in acute myeloid leukemia (AML) is currently unknown. We hypothesize that ALDH activity in AML might be correlated with the presence of LSC. Fifty-eight bone marrow (BM) samples were collected from AML (n=43), acute lymphoblastic leukemia (ALL) (n=8) and normal cases (n=7). In 14 AML cases, a high SSC loALDH br cell population was identified (ALDH +AML) (median: 14.89%, range: 5.65-48.01%), with the majority of the SSC loALDH br cells coexpressing CD34 +. In another 29 cases, there was undetectable (n=23) or rare (≥ 5%) (n=6) SSC lo ALDH br population (ALDH -AML). Among other clinicopathologic variables, ALDH +AML was significantly associated with adverse cytogenetic abnormalities. CD34 + BM cells from ALDH +AML engrafted significantly better in NOD/ SCID mice (ALDH +AML: injected bone 21.11±9.07%; uninjected bone 1.52±0.75% vs ALDH -AML: injected bone 1.77±1.66% (P=0.05); uninjected bone 0.23±0.23% (P=0.03)) with the engrafting cells showing molecular and cytogenetic aberrations identical to the original clones. Normal BM contained a small SSC loALDH br population (median: 2.92%, range: 0.92-5.79%), but none of the ALL cases showed this fraction. In conclusion, SSC loALDH br cells in ALDH + AML might denote primitive LSC and confer an inferior prognosis in patients.link_to_subscribed_fulltex

Lateral step up test (LSUT): reliability and associations with motor functions in people with chronic stroke

Poster Presentation: P172This Free Access journal suppl. entitled: Asia Pacific Stroke Conference 2016. Abstracts of the Annual Conference of the Asia Pacific Stroke Organization (APSO) Combined with Stroke Society of Australasia, Brisbane, Qld., Australia, July 14-17, 2016: AbstractsBACKGROUND AND RATIONALE: Muscles weakness is common after stroke, and it could impede the performance of daily motor functions including standing up from sitting, walking on level ground, and walking up and down stairs. Thus, clinicians need a reliable, valid and easy-to-administer outcome measures in order to document the changes of muscle strength during the rehabilitation process. The Lateral Step Up Test (LSUT) is one of the clinical tests which can quantify the functional muscle strength of the lower extremity. A 10 cm step was used and placed at one side of the subject. Subjects were required to extend the tested leg on the step into full extension, and then return to flexion until the non-tested leg touches the floor. Number of counts completed in 15 seconds was recorded. The objectives of this study was to investigate the reliability of LSUT and its correlation with stroke-specific impairments. METHODS: This study was a cross-sectional clinical trial with 33 people with chronic stroke. LSUT counts was administered along with Fugl-Meyer motor assessment for the lower extremities (FMA-LE), muscle strength of affected leg, Five Times Sit to stand test (FTSTS), Berg Balance Scale (BBS), timed Up and Go test (TUG) and Activities-specific Balance Confidence (ABC) scores. The LSUT was conducted in 2 sessions with 5–7 days apart by 2 independent assessors. The order of testing on motor functions was randomized by drawing lots. RESULTS: Both paretic and non-paretic LSUT counts showed excellent intra-rater, inter-rater and test-restest reliabilities (intra intraclass correlation coefficients = 0.936–0.991) Significant correlations were found between both paretic and non-paretic LSUT counts and FMA-LE scores, muscle strength of knee extensors and flexors, FTSTS times, BBS scores, TUG times and ABC scores. CONCLUSION: LSUT is a reliable, valid and easy-to-administer clinical assessment for assessing the functional muscle strength in people with chronic stroke.link_to_OA_fulltex

Successful engraftment by leukemia initiating cells in adult acute lymphoblastic leukemia after direct intrahepatic injection into unconditioned newborn NOD/SCID mice

Objective: Xenogeneic transplantation has been the gold standard for enumeration of leukemia initiating cells in acute myeloid and lymphoblastic leukemia (ALL). Most transplantation models have required conditioning in which the recipients were either irradiated or treated with chemotherapy prior to injection of human leukemia cells. In this study, we reported an undescribed model in which adult ALL cells were injected into unconditioned newborn nonobese diabetic severe combined immunodeficient mice via an intrahepatic route. Materials and Methods: Bone marrow (BM) and peripheral blood were collected from patients with ALL at diagnosis or relapse. CD34 + selected lymphoblasts or mononuclear cells were transplanted as mentioned previously. Cells were also transplanted into sublethally irradiated adult mice via intravenous route for comparison. Leukemia engraftment was enumerated from mouse BM 6 to 18 weeks after transplantation. Clonality of the engrafting cells was examined based on IGH rearrangement and fluorescent in situ hybridization. Results: Five of 13 ALL samples engrafted into the recipient BM 6 to 18 weeks after transplantation. Engrafted cells recapitulated the immunophenotype and cytogenetic characteristics of the original samples. Engraftment in BM and peripheral blood was significantly correlated. Importantly, there was significant correlation of engraftment between this and the conventional adult nonobese diabetic severe combined immunodeficient mouse model involving irradiation. Conclusion: Our results demonstrated that this unconditioned newborn mouse model could be used for enumeration of leukemia initiating cells in ALL and should be further evaluated. © 2010 ISEH - Society for Hematology and Stem Cells.link_to_subscribed_fulltex

Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study

Background Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560). Conclusions Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery

Body mass index and complications following major gastrointestinal surgery: a prospective, international cohort study and meta-analysis.

AIM: Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a meta-analysis of all available prospective data. METHODS: This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien-Dindo Grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. RESULTS: This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49-2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, P < 0.001) compared to normal weight patients. CONCLUSIONS: In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien\u2013Dindo Grades III\u2013V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49\u20132.96, P &lt; 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46\u20130.75, P &lt; 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease