The most common reason for switching a formula was concern regarding common infantile symptoms or behavior patterns perceived by parents to be related to formula intolerance. The decision to switch formula was usually made by the parents without consulting a health professional.
(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway inhibitor (TFPI)-2, which inhibit heparanase procoagulant activity, were recently demonstrated to attenuate inflammation in a sepsis mouse model. The present study was designated to explore peptides effects on tumour growth and vascularisation. Cell lines of mouse melanoma (B16), mouse breast cancer (EMT-6), and human breast cancer (MDA-231) were injected subcutaneously to mice. Inhibitory peptides 5, 6 and 7 were injected subcutaneously in the area opposite to the tumour side. In the three tumour cell lines, peptides 5, 6 and 7 inhibited tumour growth and vascularisation in a dose-dependent manner, reaching a 2/3 reduction compared to control tumours (p<0.001). Additionally, a survival advantage (p<0.05) and reduced plasma thrombin-antithrombin complex (p<0.05) were observed in the treatment groups. Peptides delayed tumour relapse by six days and inhibited relapsed tumour size (p<0.001). In vitro, peptides did not inhibit tumour cell proliferation, migration or heparanase degradation of heparan sulfate chains, but significantly decreased tube formation. In conclusion, peptides inhibiting heparanase procoagulant activity significantly reduced tumour growth, vascularisation, and relapse. The procoagulant domain in heparanase protein may play a role in tumour growth, suggesting a new mechanism of coagulation system involvement in cancer.
Metastasis most commonly occurs in the liver, lung, bone, and brain, implying its preference for specific organs. We hypothesized that organ microcirculation coagulation environment predisposes to tumor cell retention. Coagulation factors were analyzed using immunostaining, enzyme-linked immunosorbent assay, and heparanase procoagulant activity assay. In normal mice, expression levels of heparanase, tissue factor (TF), TF pathway inhibitor (TFPI), and TFPI-2 were low in the microcirculation of the liver, lung, brain cortex, and bone, and high in the microcirculation of the subcutis, skeletal muscle, brain subcortex, and bone marrow. C57BL/6 mice injected s.c. with B16 (F10) melanoma cells demonstrated lower levels of heparanase, TF, TFPI, and TFPI-2 in metastasis blood vessels compared to those in the primary tumor. In these mice with metastasis, liver and lung microcirculation turned to express high levels of coagulation proteins. Additionally, although mice with heparanase overexpression developed a larger primary tumor, they did not demonstrate a tendency for metastasis, as opposed to controls (P < 0.0001). Human umbilical vein endothelial cells, incubated with the B16 melanoma cell medium for 2 hours, expressed decreased levels of heparanase, TF, TFPI, and TFPI-2, and the effect was reversed by a peptide-inhibiting heparanase/TF complex interaction (P < 0.001). In summary, metastasis has a predilection to organs with low levels of heparanase, TF, TFPI, and TFPI-2 in the microcirculation, which enables tumor cell retention. Heparanase has a role in regulating the microcirculation milieu.
The efficacy of modafinil in comparison with methylphenidate in treatment of pediatric attention-deficit hyperactivity disorder (ADHD) has not been thoroughly investigated. This study compared the effect of modafinil versus methylphenidate on continuous attention task in children with ADHD, using the Test of Variables of Attention. Twenty-eight participants completed a baseline test followed by administration of a single dose of either methylphenidate or modafinil, after which the test was repeated. The test was performed a third time, after each subject received a dose of the medication not previously administered. Comparison of scores showed mean baseline, postmethylphenidate, and postmodafinil scores of -2.04, 0.017, and 0.09, respectively. No difference was found between improvements observed with either medication (P < .05). Adverse events for both agents were mild and self-limited, including abdominal pain, diarrhea, and hyposomnia. The authors conclude that modafinil is as effective as methylphenidate; however, a larger scale long-term study is required to confirm these results.
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