Xanthurenic acid and its rôle in the trytophane metabolism of pyroxidine-deficient rats

In a previous publication (1) the isolation of a green pigment from the urine of pyridoxine-deficient rats was described. The green pigment was shown to be the product of a reaction between ferric ammonium sulfate or other ferric salts and a compound whose nature was unknown. This compound has now been isolated in crystalline form. It is a yellow pigment and has been identified as xanthurenic acid

A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival

The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% CI: 6-13 %), CR rate was 17 % (N = 6943; 95% CI: 15-20 %), and median OS (mOS) was 18.6 months (N = 2820; 95% CI: 15.3-21.9). A weak correlation to mOS was detected with CR rate (207 patient cohorts, Pearson\u27s r = 0.315; P \u3c 0.0005), and a much stronger correlation with median progression-free survival (mPFS) (r=0.88, P = 3 × 1

Clinical symptoms and chemotherapy completion in elderly patients with newly diagnosed acute leukemia: a retrospective comparison study with a younger cohort

<p>Abstract</p> <p>Background</p> <p>Cancer affects older adults disproportionately. The disease is often difficult to diagnose and treat due to co-morbidities and performance status, and patients tend to discontinue chemotherapy prematurely. There are no systemic studies of the reasons and factors that create a higher withdrawal rate in older acute leukemia patients. This study tried to understand the initial characteristics, blood counts and bone marrow measurements in older acute leukemia patients by comparing them with a younger group to provide information and assistance in early clinical diagnosis, treatment and reasons for treatment withdrawal.</p> <p>Methods</p> <p>Using retrospective medical record reviews, we examined clinical characteristics and chemotherapy completion status in the patients of two groups (age ≥ 60, n = 183 and age <60, n = 183) who were diagnosed with acute leukemia for the first time and were hospitalized in Union Hospital Affiliated with Fujian Medical University from 2004 to 2008.</p> <p>Results</p> <p>There were no statistical differences in initial presenting symptoms of fatigue (67.2% vs. 57.9%, <it>P</it>>0.05) and pallor (53% vs. 59.6%, <it>P</it>>0.05) between the two groups, but older patients demonstrated more underlying diseases including lung infections (25.7%, <it>P </it>= <0.001), cardiovascular disease (4.4%, <it>P </it>= 0.007), and hypertension (20.8%, <it>P </it>=< 0.001). The complete remission rate after chemotherapy (1 to 2 courses) was 49.5% in the older group and 66.7% in the younger group (χ²= 6.202, <it>P </it>= 0.013). The percentage of patients age 60 and older who prematurely discontinued chemotherapy (50.3%), mainly due to the influences of traditional Chinese concept of critical illness, financial difficulties, and intolerance to adverse reactions to chemotherapy, was significantly higher than that of younger patients (37.7%) (χ²= 5.866, <it>P </it>= 0.015).</p> <p>Conclusions</p> <p>A comprehensive approach to diagnosis, treatment selection, and toxicity management, and implementing strategies to enhance treatment compliance may improve outcomes in older adults with acute leukemia.</p

The diagnostic role of glycosaminoglycans in pleural effusions: A pilot study

<p>Abstract</p> <p>Background</p> <p>Pleural effusions are classified into transudates and exudates. Various criteria have been used with Light's et al being the most accepted ones. Glycosaminoglycans (GAGs) have been detected during pleural fluids (PF) analysis in various causes. In this pilot study, we investigated: (a) the usefulness of GAGs in the assessment of pleural effusions, and (b) whether and in what way GAGs correlate with established criteria used to indicate an exudate.</p> <p>Methods</p> <p>LDH, total protein, cholesterol and GAG levels were measured in pleural fluid and serum from 50 patients with pleural effusion. GAG levels were defined by the photometric method of Hata. The discriminative properties of pleural GAGs (pGAG), pleural fluid/serum GAG ratio (GAGR), serum GAGs (sGAG) and serum LDH (sLDH) were explored with ROC analysis.</p> <p>Results</p> <p>According to ROC analysis, pGAG and GAGR exhibited satisfactory discriminative properties in the separation of pleural effusions. For GAGR, at a 1.1 cut off point, sensitivity and specificity reached 75.6%; 95%CI: 60.5–87.1 and 100%; 95%CI: 47.8–100, respectively. For pGAG at a cut off value of 8.4 μg/ml, these percentages changed to 86.7%; 95%CI: 73.2–94.9 and 100%; 95%CI: 47.8–100. The study also revealed the differential role of sGAG between malignancies and benign cases, scoring 68.8%; 95%CI: 50.0–83.9 for sensitivity, and 84.6%; 95%CI: 54.5–97.6 for specificity at a 7.8 μg/ml cut off.</p> <p>Conclusion</p> <p>Our results suggest that glycosaminoglycan measurement of both serum and pleural effusions could be useful for simultaneous differentiation of exudates from transudates, and of malignant from benign exudates.</p

Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson &nbsp;&gt;&nbsp;0·91, P&nbsp;&lt;&nbsp;0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (&gt;0·03% LSC) from LSClow (&lt;0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification

Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study

Abstract Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibling, haploidentical and mismatched unrelated HSCT in 56%, 24%, 16% and 4% of cases, respectively. Acute GvHD and chronic GvHD were observed in 40% and 17% of patients. While the median OS for the entire cohort of patients was 15.3 months (95% CI 9.5 – 21.7 months), OS reached 29.7 months (95% CI 7.01 – not-reached) for patients who achieved a complete remission (CR) to HMA and no intervening therapies between HMA therapy and HSCT. Our study suggests that HMA therapy can effectively bridge some patients with RR-AML to HSCT