Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study

The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17–60 years), 116 patients were suitable for analysis. MRD level ≥0·1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population ( P  < 0·0001), as well as in the standard risk (SR, P  = 0·0003) and high-risk ( P  = 0·008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0·1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects ( P  = 0·001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.     

The adverse effects of marijuana use: The present state and future directions

Marijuana is recently a subject of a global debate due to potential medical application of cannabis products and the progressive legalization of its recreational use. This situation leads to the need for access to comprehensive and reliable information about the effects of marijuana intake. Our review presents the actual state of knowledge regarding acute and chronic health effects generated by recreational marijuana use. Marijuana smoking can lead to structural and functional alterations in the central nervous system. These effects are especially significant and dangerous at the prenatal, child, and adolescence periods. In contrary to a common myth, cannabis does exhibit an addictive potency, albeit not a strong one. We discuss the “cannabis gateway hypothesis,” which suggests that marijuana use can be the first step before trying more dangerous drugs. However, drawing significant conclusions is difficult due to the strong impact of confounders and often unclear relationships among studied factors, especially in the socioeconomic context. Moreover, we point to the need for the unbiased assessment of the harm generated by marijuana in comparison with other drugs.     

Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement

Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short- and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively. Patients with different duration of RA (median 6 vs. 120 months) in the active phase of RA were enrolled in this study. We performed flow cytometric analysis of PB Th1, Th17, and Treg populations together with estimation of serum cytokine concentrations using cytometric bead array. Disease activity was calculated on the basis of clinical and biochemical indices of inflammation (DAS28, ESR, CRP). All parameters were measured and correlated with each other before and after 6 months therapy. Elevated levels of circulating Th17 cells and IL-6 were found in all active patients, of which Th17 cells were down-regulated by the treatment. Significantly reduced Th1 and functional CTLA-4+ Treg cell frequencies as well as Th1 cytokines observed only in progressive RA seemed to be irreversible. Although therapy induced clinical improvement in almost all patients, those with advanced RA remained with signs of inflammation. Our report demonstrates that both the extent of systemic immune abnormalities and their restoration are dependent on duration of the active RA.     

Multinational data on cumulative radiation exposure of patients from recurrent radiological procedures: call for action

European Radiology - To have a global picture of the recurrent use of CT imaging to a level where cumulative effective dose (CED) to individual patients may be exceeding 100 mSv at which organ...     

Hyperfibrinogenemia predicts long-term risk of death after ischemic stroke

In stroke patients higher levels of plasma fibrinogen are associated with increased risk of unfavourable functional outcome and short-term mortality. The aim of our study was to determine the relationship between plasma fibrinogen level and long-term risk of death in ischemic stroke patients. Seven hundred thirty six patients (median age 71; 47.1 % men) admitted to the stroke unit within 24 h after stroke were included. Plasma fibrinogen level was measured on day 1 of hospitalisation. Hyperfibrinogenemia was defined as plasma fibrinogen concentration >3.5 g/L. The maximal follow-up period was 84 months. Hyperfibrinogenemia was found in 25.0 % of patients. On multivariate logistic regression analysis, after adjustment for age, stroke severity, atrial fibrillation, smoking, white blood cell count, fever, in-hospital pneumonia and hyperglycemia, hyperfibrinogenemia was associated with increased case fatality (HR 1.71, 95 % CI 1.29–2.26, P < 0.01). Hyperfibrinogenemia predicts the long-term risk of death in ischemic stroke patients.     

Synthesis,structural studies and biological properties of some phosphono-perfluorophenylalanine derivatives formed by SNAr reactions

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S_NAr reactions with different types of nucleophiles such as thiols, amines and phenols. The structure of the products was confirmed using spectroscopic and spectrometric techniques. For two compounds X-ray single crystal diffraction analysis and DFT investigations were performed providing information in regard to the preferable conformation, hydrogen bonds and other interactions. The antiproliferative potency of some of the new phosphono-perfluorophenylalanine derivatives obtained as well as representatives of previously synthesized perfluorophenyl phosphonate analogues of phenylalanine was studied on selected glioma cell lines. Preliminary evaluation of the compounds drug likeness was examined with respect to Lipinski''s and Veber''s rules, and showed that they meet the criteria perfectly. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay results demonstrated that the compounds exhibit moderate activity against the glioblastoma multiforme cell lines (T98G and U-118 MG). Moreover most of the studied S_NAr reaction products displayed significantly higher inhibitory activity against both cancer cell lines than the parent diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)phosphonate.

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S_NAr reactions with thiols, amines and phenols.     

Prevalence of malnutrition in systemic sclerosis patients assessed by different diagnostic tools

Clinical Rheumatology - Gastrointestinal complaints of scleroderma (SS) patients are risk factors for impaired nutritional status, so insightful assessment is necessary. The aim was comparison of...     

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

Metabolic Brain Disease - Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of...     

Phytoremediation of Water Polluted by Thallium,Cadmium, Zinc,and Lead with the Use of Macrophyte Callitriche cophocarpa

The objective of the present work was to study the phytoremediation capacity of Callitriche cophocarpa concerning water contaminated with thallium (Tl), cadmium (Cd), zinc (Zn), and lead (Pb) derived from the natural environment. We found that after a 10-day incubation period, shoots of C. cophocarpa effectively biofiltrated the water so that it met (for Cd, Zn, and Pb) appropriate quality standards. The order of accumulation of the investigated elements by shoots (mg kg^?1 dry weight) were as follows: Zn (1120) < Tl (251) < Cd (71) < Pb (35). The order of bioconcentration factors were as follows: Cd (1177) < Tl (1043) < Zn (718) < Pb (597). According to Microtox bioassay, C. cophocarpa significantly eradicated polluted water toxicity. During the experiment, the physiological status of plants was monitored by taking measurements of photosystem II activity (maximum efficiency of PSII, photochemical fluorescence quenching, nonphotochemical fluorescence quenching, and quantum efficiency of PSII), photosynthetic pigment contents, and shoot morphology. Plants exposed to metallic pollution did not exhibit significant changes in their physiological status compared with the control. This work is potentially applicable to the future use of C. cophocarpa in the phytoremediation of polluted, natural watercourses.