Risk factors for heel pressure injury in cardiovascular intensive care unit patients.

This study analyzed the risk factors for heel pressure injury in cardiovascular intensive care unit patients with the aim of laying the groundwork for preventive nursing interventions. We conducted a retrospective case-control study of 92 patients who were admitted to the cardiovascular surgical or medical intensive care unit of a university hospital in South Korea between January and December 2017. Of these patients, 31 and 61 were included to the heel pressure injury group and the non-heel pressure injury group, respectively. Data on their demographic, disease-related, and intensive care unit treatment characteristics, as well as the degree of pressure injury, were collected from the hospital's electronic medical records using a standardized form. Cardiac surgery (P < .001), operation time (P = .001), use of a mechanical ventilator (P < .001), use of vasoconstrictors (P < .001), use of sedative drugs (P < .001), and extracorporeal membrane oxygenation treatment (P < .001) were identified as significant risk factors for heel pressure injury. A total of 22 patients (71%) from the heel pressure injury group developed deep tissue injury, and 16 patients (51.6%) who received extracorporeal membrane oxygenation treatment developed heel pressure injury.

Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist.

We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound. Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, we believe that 18a may represent a promising candidate for an orally available hormonal therapy.

Establishment of Age- and Gender-Specific Reference Ranges for 36 Routine and 57 Cell Population Data Items in a New Automated Blood Cell Analyzer, Sysmex XN-2000.

We established age- and gender-specific reference ranges for the 36 routine complete blood cell (CBC) and 57 cell population data (CPD) items in the Sysmex XN-2000 (Sysmex, Japan). In total, 280 peripheral blood samples were obtained from an equal number of healthy adults. Values for 36 routine items and 57 CPD items were obtained for each sample, and the results were categorized into six subgroups (N>39 in each subgroup) according to patient age (20-40, 41-60, and >60 yr) and gender (male and female), and compared with respect to age and gender differences. The majority of data items (22 of 36 routine CBC items and 44 of 57 CPD items) exhibited significant differences (P≤0.05) in their results with respect to age or gender, and several red cell-, lymphocyte-, and platelet-related data tended to decrease in women or older adults. These results provide a basis for establishing age- and gender-specific reference ranges for routine and CPD items in Sysmex XN-2000. Furthermore, these reference ranges could be used to determine clinical significance for new items of Sysmex XN-2000 in further studies.

Effect of SKI2670, a novel, orally active, non-peptide GnRH antagonist, on hypothalamic-pituitary-gonadal axis.

AIMS: Suppression of the hypothalamic-pituitary-gonadal axis has been widely utilized for the management of gonadal-hormone-dependent diseases such as endometriosis. Efforts to develop orally available gonadotropin-releasing hormone (GnRH) antagonists for the treatment of gonadal-hormone-dependent diseases led to the discovery of SKI2670, a novel non-peptide GnRH antagonist. The present study was undertaken to pharmacologically characterize SKI2670 in vitro and in vivo. MAIN METHODS: We measured binding affinity and antagonistic activity of SKI2670 for the GnRH receptors. Immediate suppression of gonadotropins by single dosing of SKI2670 was examined in castrated monkeys. Subsequently, influence on gonadal hormones by prolonged administration of SKI2670 was assessed in naive female monkeys. To investigate in vivo efficacy of SKI2670, regression of ectopic implants by repeated administration of SKI2670 was examined in a rat endometriosis model. KEY FINDINGS: SKI2670 is a potent functional antagonist for the human GnRH receptor, with subnanomolar binding affinity. In castrated monkeys, single administration of SKI2670 lowered serum luteinizing hormone (LH) levels stronger with longer duration when compared to elagolix at equivalent doses. Moreover, repeated dosing of SKI2670 suppressed serum levels of gonadotropins and gonadal hormones in intact female monkeys while elagolix suppressed serum LH levels only. Finally, it exhibited regressive effects on ectopic implants in a rat endometriosis model without bone loss. SIGNIFICANCE: Our findings demonstrate robust GnRH antagonistic efficacy of SKI2670 in animal models, suggesting that SKI2670-induced suppression of the hypothalamic-pituitary-gonadal axis may be beneficial for the treatment of gonadal-hormone-dependent diseases such as endometriosis in humans.

Development and validation of effective real-time and periodic interinstrument comparison method for automatic hematology analyzers.

OBJECTIVES: We developed and validated an interinstrument comparison method for automatic hematology analyzers based on the 99th percentile coefficient of variation (CV) cutoff of daily means and validated in both patient samples and quality control (QC) materials. METHODS: A total of 120 patient samples were obtained over 6 months. Data from the first 3 months were used to determine 99th percentile CV cutoff values, and data obtained in the last 3 months were used to calculate acceptable ranges and rejection rates. Identical analyses were also performed using QC materials. Two instrument comparisons were also performed, and the most appropriate allowable total error (ATE) values were determined. RESULTS: The rejection rates based on the 99th percentile cutoff values were within 10.00% and 9.30% for the patient samples and QC materials, respectively. The acceptable ranges of QC materials based on the currently used method were wider than those calculated from the 99th percentile CV cutoff values in most items. In two-instrument comparisons, 34.8% of all comparisons failed, and 87.0% of failed comparisons were successful when 4 SD was applied as an ATE value instead of 3 SD. CONCLUSIONS: The 99th percentile CV cutoff value-derived daily acceptable ranges can be used as a real-time interinstrument comparison method in both patient samples and QC materials. Applying 4 SD as an ATE value can significantly reduce unnecessarily followed recalibration in the leukocyte differential counts, reticulocytes, and mean corpuscular volume.

Estimation of Stellate Ganglion Block Injection Point Using the Cricoid Cartilage as Landmark Through X-ray Review.

BACKGROUND: Stellate ganglion block is usually performed at the transverse process of C6, because the vertebral artery is located anterior to the transverse process of C7. The purpose of this study is to estimate the location of the transverse process of C6 using the cricoid cartilage in the performance of stellate ganglion block. METHODS: We reviewed cervical lateral neutral-flexion-extension views of 48 patients who visited our pain clinic between January and June of 2010. We drew a horizontal line at the surface of the cricoid cartilage in the neutral and extension views of cervical lateral x-rays. We then measured the change in the shortest distance from this horizontal line to the lowest point of the transverse process of C6 between the neutral and extension views. RESULTS: There was a statistically significant difference in the shortest distance from the horizontal line at the surface of the cricoid cartilage to the lowest point of transverse process of C6 between neutral position and neck extension position in both males and females, and between males and females in both neutral position and neck extension position. The cricoid cartilage level was 4.8 mm lower in males and 14.4 mm higher in females than the lowest point of transverse process of C6 in neck extension position. CONCLUSIONS: Practitioners should recognize that the cricoid cartilage has cephalad movement in neck extension. In this way, the cricoid cartilage can be still useful as a landmark for stellate ganglion block.

Asymmetric transformations of acyloxyphenyl ketones by enzyme-metal multicatalysis.

A multipathway process comprising several enzyme- and metal-catalyzed reactions has been explored for the asymmetric transformations of acyloxyphenyl ketones to optically active hydroxyphenyl alcohols in the ester forms. The process comprises nine component reactions in three pathways, all of which take place by the catalytic actions of only two catalysts, a lipase and a ruthenium complex. The synthetic reactions were carried out on 0.2-0.6 mmol scales for eight different substrates under an atmosphere of hydrogen (1 atm) in toluene at 70 degrees C for 3 days. In most cases, the yields were high (92-96%) and the optical purities were excellent (96-98% ee), This work thus has demonstrated that enzyme-metal multicatalysis has great potential as a new methodology for asymmetric transformations.