Clinical Demographics and Outcomes in Mechanically Ventilated Patients in Korean Intensive Care Units

Knowledge of clinical demographics and outcomes of mechanically ventilated patients is important but there are few prospectively collected data in Korea. The objective of the present study was to describe the current status of mechanically ventilated patients in Korea as of 2010. We analyzed the data of Korean patients (275 patients in 12 Korean intensive care units [ICU]) participating in a multinational prospective cohort study on mechanical ventilation. The most common indication for mechanical ventilation was pneumonia (23%). Pressure-limited ventilation modes were preferred over volume-cycled ventilation modes. Non-invasive positive pressure ventilation was used in only seven (2%) patients as the initial ventilatory support. Median duration of mechanical ventilation was 7 days and ICU mortality was 36%. The multiple logistic regression model revealed that the Simplified Acute Physiology Score II (SAPS II) score at ICU admission (odds ratio [OR], 1.034; 95% confidence interval [CI], 1.001-1.036; P=0.033), peak pressure (OR, 1.054; 95% CI, 1.016-1.095; P=0.006), and the number of failed organs (OR, 2.132; 95% CI, 1.634-2.781; P<0.001) were independently associated with ICU mortality. This study provides a snapshot of current practice of mechanical ventilation in Korea.

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Autosomal-dominant nystagmus,foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.     

The Effect of Body Mass Index on Survival in Advanced Epithelial Ovarian Cancer

Controversy remains regarding the effect of obesity on the survival of patients with ovarian cancer in Asia. This study examined the impact of obesity on the survival outcomes in advanced epithelial ovarian cancer (EOC) using Asian body mass index (BMI) criteria. The medical records of patients undergoing surgery for advanced (stage III and IV) EOC were reviewed. Statistical analyses included ANOVA, chi-square test, Kaplan-Meier survival and Cox regression analysis. Among all 236 patients, there were no differences in overall survival according to BMI except in underweight patients. In a multivariate Cox analysis, surgical optimality and underweight status were independent and significant prognostic factors for survival (HR, 2.302; 95% CI, 1.326-3.995; P=0.003 and HR, 8.622; 95% CI, 1.871-39.737; P = 0.006, respectively). In the subgroup of serous histology and optimal surgery, overweight and obese I patients showed better survival than normal weight patients (P = 0.012). We found that underweight BMI and surgical optimality are independent risk factors for the survival of patients with advanced ovarian cancer. High BMI groups (overweight, obese I and II) are not associated with the survival of advanced EOC patient. However, in the subgroup of EOC patients with serous histology and after optimal operation, overweight and obese I group patients show better survival than the normal weight group patients.

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Production of certified reference materials for the sports doping control of the REV‐ERB agonist SR9009

Two human metabolites of the REV‐ERB agonist SR9009, identified by researchers with an interest in sports doping control, have been synthesized and assessed for purity. The synthesis employed was a modification of published procedures for the parent SR9009, careful attention to the purification of intermediates and the final product ensuring materials of the highest purity were available for certification. For each candidate material impurities of related structure were identified and quantified as a relative mass fraction using high performance liquid chromatography–ultraviolet (HPLC–UV) detection and proton nuclear magnetic resonance (¹H NMR) spectroscopy. The quantification of water, occluded solvent, and inorganic residue was assessed using Karl Fischer, ¹H NMR, and thermogravimetric analysis, thereby completing the assessment of all impurities typically characterized by the mass balance approach. Summation and subtraction from 1000 mg/g afforded the mass fraction of the main component, the associated uncertainty ensuring certified reference material status can be applied to the resulting pure substance calibration standards. The availability of these standards to the sports doping control community will facilitate delivery of metrological traceability to the SI unit for mass (kg) to routine testing results and aid method development for the detection and quantification of SR9009 abuse.     

N10‐carbonyl‐substituted phenothiazines inhibiting lipid peroxidation and associated nitric oxide consumption powerfully protect brain tissue against oxidative stress

During some investigations into the mechanism of nitric oxide consumption by brain preparations, several potent inhibitors of this process were identified. Subsequent tests revealed the compounds act by inhibiting lipid peroxidation, a trigger for a form of regulated cell death known as ferroptosis. A quantitative structure–activity study together with XED (eXtended Electron Distributions) field analysis allowed a qualitative understanding of the structure–activity relationships. A representative compound N‐(3,5‐dimethyl‐4H‐1,2,4‐triazol‐4‐yl)‐10H‐phenothiazine‐10‐carboxamide (DT‐PTZ‐C) was able to inhibit completely oxidative damage brought about by two different procedures in organotypic hippocampal slice cultures, displaying a 30‐ to 100‐fold higher potency than the standard vitamin E analogue, Trolox or edaravone. The compounds are novel, small, drug‐like molecules of potential therapeutic use in neurodegenerative disorders and other conditions associated with oxidative stress.     

阻塞性睡眠呼吸暂停患者肺动脉僵硬度的评价及其与低氧的关系

目的:旨在研究阻塞性睡眠呼吸暂停患者(OSA)夜间间歇性缺氧程度对肺动脉僵硬度(PAS)和右心室功能的影响。方法:对可疑OSA的患者进行多导睡眠图(PSG)和经胸超声心动图检查(n=376)。按夜间最低脉搏血氧饱和度(SpO2)分为三组(对照组:Sp O2≥90%,轻中度低氧组:80%≤SpO2<90%,重度低氧组:SpO2<80%)。比较三组患者的PAS和右心室功能,并进一步分析其相关影响因素。结果:最终本研究对278例患者进行分析。重度低氧组PAS显著升高(P=0.003),与平均肺动脉压(mPAP)有良好的相关性(r=0.780,P<0.001),而mPAP在不同组间差异无统计学意义(P>0.05)。各组间右心室功能相关参数,差异无统计学意义(P>0.05)。单因素和多因素Logistic分析表明,只有夜间最低SpO2(OR=1.807,P=0.001)是PAS升高的相关因素。结论:在重度低氧血症的OSA患者中PAS增加,仅夜间最低SpO2是其相关因素。     

Is the AIMS65 score useful in predicting outcomes in peptic ulcer bleeding?

AIM:To evaluate the applicability of AIMS65 scores in predicting outcomes of peptic ulcer bleeding.METHODS:This was a retrospective study in a single center between January 2006 and December 2011.We enrolled 522 patients with upper gastrointestinal haemorrhage who visited the emergency room.Highrisk patients were regarded as those who had rebleeding within 30 d from the first endoscopy as well as those who died within 30 d of visiting the Emergency room.A total of 149 patients with peptic ulcer bleeding were analysed,and the AIMS65 score was used to retrospectively predict the high-risk patients.RESULTS:A total of 149 patients with peptic ulcer bleeding were analysed.The poor outcome group comprised 28 patients[male:23(82.1%)vs female:5(10.7%)]while the good outcome group included 121patients[male:93(76.9%)vs female:28(23.1%)].The mean age in each group was not significantly different.The mean serum albumin levels in the poor outcome group were slightly lower than those in the good outcome group(P=0.072).For the prediction of poor outcome,the AIMS65 score had a sensitivity of35.5%(95%CI:27.0-44.8)and a specificity of 82.1%(95%CI:63.1-93.9)at a score of 0.The AIMS65 score was insufficient for predicting outcomes in peptic ulcer bleeding(area under curve=0.571;95%CI:0.49-0.65).CONCLUSION:The AIMS65 score may therefore not be suitable for predicting clinical outcomes in peptic ulcer bleeding.Low albumin levels may be a risk factor associated with high mortality in peptic ulcer bleeding.