Correlation between capillary oxygen saturation and small intestinal wall thickness in the equine colic patient

The surgical evaluation of haemorrhagic infarcted intestine and the decision for or against bowel resection require a lot of experience and are subjective. The aim of this prospective, clinical study was to examine the correlation between oxygen saturation and small intestinal wall (IW) thickness, using two objective methods. In 22 colicky horses, the blood flow, oxygen saturation and relative amount of haemoglobin were measured intraoperatively via laser Doppler and white light spectroscopy (O2C, oxygen to see, LEA Medizintechnik) at six measuring points (MPs) in small and large intestines. Furthermore, the IW thickness was measured ultrasonographically. Nine of 22 horses had an increased small IW thickness greater than 4?mm (Freeman 2002, Scharner and others 2002, le Jeune and Whitcomb 2014) at measuring point 1 (MP1) (strangulated segment), four horses had a thickened bowel wall at measuring point 3 (MP3) (poststenotic) and one at measuring point 2 (MP2). The oxygen saturation was 0 at MP1 in six horses, at MP3 in two horses and at MP2 (prestenotic) in one. Oxygen saturation and small IW thickness were independent of each other at MP1 and MP2. At MP3, the two parameters were negatively correlated. In summary, it is not possible to draw conclusions about oxygen saturation based on IW thickness

Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells

Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease relapse and/or malignant progression. TKI-naive and TKI-treated leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) accumulate high levels of reactive oxygen species (ROS) and oxidative DNA damage. To determine the role of TKI-refractory LSCs in genomic instability, we used a murine model of CML-CP where ROS-induced oxidative DNA damage was elevated in LSCs, including quiescent LSCs, but not in LPCs. ROS-induced oxidative DNA damage in LSCs caused clinically relevant genomic instability in CML-CP–like mice, such as TKI-resistant BCR-ABL1 mutations (E255K, T315I, H396P), deletions in Ikzf1 and Trp53, and additions in Zfp423 and Idh1. Despite inhibition of BCR-ABL1 kinase, imatinib did not downregulate ROS and oxidative DNA damage in TKI-refractory LSCs to the levels detected in normal cells, and CML-CP–like mice treated with imatinib continued to accumulate clinically relevant genetic aberrations. Inhibition of class I p21-activated protein kinases by IPA3 downregulated ROS in TKI-naive and TKI-treated LSCs. Altogether, we postulate that genomic instability may originate in the most primitive TKI-refractory LSCs in TKI-naive and TKI-treated patients