<b><i>Introduction:</i></b> This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). <b><i>Patents and Methods:</i></b> Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (<i>n</i> = 7) or unrelated (<i>n</i> = 13) donors. GVHD prophylaxis included only PTCy and ruxolitinib (45 mg) from day–7 to day–2, and 15 mg from day+5 to day+100. This trial was registered at www.clinicaltrials.gov as #NCT02806375. <b><i>Results:</i></b> Primary engraftment was documented in 17 patients. One patient experienced primary graft failure and 2 died before engraftment. Eleven patients demonstrated severe poor graft function (SPGF), which required ruxolitinib dose reduction. The regimen was well tolerated, with grade 3–4 non-haematological toxicity in 30%, viral reactivation in 45%, and severe sepsis in 15% of patients. The incidence of acute GVHD grade II–IV was 25%, grade III-IV GVHD was 15%, and moderate chronic GVHD was 20%, with no severe cases. Only 2 patients required systemic steroids. Haematological relapse was documented in 1 patient. Two-year non-relapse mortality was 15%, 2-year overall survival was 85%, and 2-year event-free survival was 72%. <b><i>Conclusion:</i></b> GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence. However, the relatively high rate of SPGF should be taken into account. SPGF could possibly be mitigated by ruxolitinib dose reduction.
The presented study is devoted to one of the urgent problems of the conservative treatment of chronic pancreatitis — relief of painful abdominal and dyspeptic syndromes. Polymorphism of the etiopathogenetic variants of the formation of pancreatic diseases naturally justifies the need for complex therapy, including secretolytics, antispasmodics medications and polyenzyme drugs. The use of Meteospasmyl in complex therapy effectively relieves abdominal pain and dyspepsia, modifies the composition of the intestinal microbiota and improves the quality of life in patients with chronic pancreatitis.
Background: The standard approach to an occlusive vascular injury is open arterial reconstruction, although endovascular stenting is becoming more common, despite limited evidence. The aim of this study is to examine the performance of bare-metal stents in an ovine model of occlusive arterial trauma.
Methods: Through a groin incision, a 2 cm segment of the left superficial femoral artery (SFA) was bluntly injured using a hemostat and injection of air to achieve thrombosis. Animals then underwent a stent deployment (Stent group, n=5) or no-treatment (Control group, n=5). In the Stent group, recanalization of the thrombotic lesion, thromboaspiration and bare-metal stent deployment were performed. Enoxaparin 1.5 mg/kg was given to all animals. The stent group animals were fed Clopidogrel 75 mg and Aspirin 125 mg daily. Angiography and doppler ultrasound were used to evaluate arterial patency during the 7-day observation period.
Results: A thrombosis was obtained in all cases. After the fall in the systolic velocity (SV, cm/sec) in both the Control (43 (36–56) to 6 (0–16); p<0.001) and Stent Groups (45 (32–53) to 8 (0–12); p<0.001), stent implantation resulted in a significant permanent increase of the SV. Day 7 angiography confirmed SFA patency in all (5/5) stented animals, with persisting occlusions in the Control group (p=0.008). There was no evidence of distal emboli in the run-off arteries.
Conclusions: Bare-metal stent implantation restores arterial patency of a traumatic occlusive lesion in a standardized ovine model with a short follow-up period.
Paraoxonase-1 (PON1) and butyrylcholinesterase (BCHE) are natural bioscavengers of organophosphate acetylcholinesterase inhibitors in the human body, which can determine individual sensitivity to organophosphate toxicity. Interindividual differences in activity of PON1 (catalytic bioscavenger) and substrate specificity are strongly associated with the substitution of two amino acids: Leu/Met (L/M) at position 55 (rs854560) and Gln/Arg (Q/R) at position 192 (rs662). In the case of BCHE (stoichiometric bioscavenger) substitution, Ala/Thr (A/T) at position 539 produces the so-called "K-variant" of the enzyme (rs1803274). Threonine allele is often co-inherited with an atypical BCHE allele (rs1799807). The atypical variant of BCHE displays a lower affinity for cholinesterase inhibitors. Genotyping rs662 and rs1803274 single-nucleotide polymorphisms (SNP) by high-resolution melting (HRM) is facilitated by the nucleotide substitution A>G (G>A), which resulted in a changed number of hydrogen bonds in the PCR product and, consequently, shifted T m. In the case of rs854560, genotyping is complicated by the nucleotide substitution T>A, which has no significant effect on the T m of the PCR product. An addition of a small quantity of LL homozygote DNA into the reaction mixture before PCR discriminates the three genotypes by the melt curves due to different amounts of heteroduplexes formed in the LM and MM samples. HRM analysis can be applied for genotyping human rs854560, rs662, and rs1803274 SNPs.
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