Insulin‐like growth factor‐1 receptor is associated with better prognosis in classical Hodgkin's lymphoma: Correlation with MET expression

The purpose of this study was to examine the prognostic significance of insulin‐like growth factor‐1 receptor (IGF‐1R) expression alone and in relation to the expression of the MET‐ receptor and the MET‐homologous receptor RON, in classical Hodgkin's lymphoma (cHL). Tumour samples from patients with cHL (n = 202; median age 37.5 years) were analysed retrospectively for IGF‐R1, MET or RON expression by immunohistochemistry using tissue microarrays. The median follow‐up time was 3.7 years (range, 0.1–20 years). Twenty‐nine patients (14.3%) expressed IGF‐1R protein in Hodgkin/Reed–Sternberg (HRS) cells, which was associated with a better overall survival (OS) (P = 0.036). IGF‐1R expression was closely associated with MET receptor expression and low level of lactate dehydrogenase. In patients with cHL receiving doxorubicin, bleomycin, vinblastine and dacarbazine, those expressing IGF‐1R showed a trend towards better OS and event‐free survival than IGF‐1R‐negative patients (P = 0.129 and P = 0.115 respectively), but statistical significance was not reached. This study suggests that IGF‐1R expression could be associated with better clinical outcome in cHL but is significantly associated with the expression of MET receptor.     

Modafinil in the treatment of idiopathic hypersomnia without long sleep time—a randomized,double‐blind,placebo‐controlled study

In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo‐controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug‐free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep–wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non‐significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.     

Percutaneous Papillary Large Balloon Dilation during Percutaneous Cholangioscopic Lithotripsy for the Treatment of Large Bile-Duct Stones: A Feasibility Study

When access to a major duodenal papilla or endoscopic retrograde cholangiopancreatography has failed, percutaneous transhepatic cholangioscopic lithotripsy (PTCS-L) may be useful for removing common bile duct (CBD) stones. However, the feasibility and usefulness of percutaneous transhepatic papillary large-balloon dilation (PPLBD) during PTCS-L for the removal of large CBD stones has not been established. We aimed to determine the safety and efficacy of PPLBD for the treatment of large CBD stones. Eleven patients with large CBD stones in whom the access to the major papilla or bile duct had failed were enrolled prospectively. Papillary dilation was performed using a large (12-20 mm) dilation balloon catheter via the percutaneous transhepatic route. Post-procedure adverse events and efficacy of the stone retrieval were measured. The initial success rate of PPLBD was 100%. No patient required a basket to remove a stone after PPLBD. Electrohydraulic lithotripsy was required in 2 (18.2%) patients. The median time to complete stone removal after PPLBD was 17.8 min and no adverse events occurred after PPLBD. Asymptomatic hyperamylasemia was not encountered in any patients. This study indicates that PPLBD is safe and effective for removal of large CBD stones.

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Epidemiological and Survival Trends of Pediatric Cardiac Arrests in Emergency Departments in Korea: A Cross-sectional,Nationwide Report

Cardiac arrest (CA) in children is associated with high mortality rates. In Korea, cohort studies regarding the outcomes of pediatric CAs are lacking, especially in emergency departments (EDs) or in-hospital settings. This study was conducted to examine the trends in epidemiology and survival outcomes in children with resuscitation-attempted CAs using data from a cross-sectional, national, ED-based clinical registry. We extracted cases in which cardiopulmonary resuscitation and/or manual defibrillation were performed according to treatment codes using the National Emergency Department Information System (NEDIS) from 2008 to 2012. The total number of ED visits registered in the NEDIS during the 5-yr evaluation period was 20,424,530; among these, there were 2,970 resuscitation-attempted CAs in children. The annual rates of pediatric CAs per 1,000 ED visits showed an upward trend from 2.81 in 2009 to 3.62 in 2012 (P for trend = 0.045). The median number of estimated pediatric CAs at each ED was 7.8 (25th to 75th percentile, 4 to 13) per year. The overall rates for admission survival and discharge survival were 35.2% and 12.8%, respectively. The survival outcome of adults increased substantially over the past 5 yr (11.8% in 2008, 11.7% in 2010, and 13.6% in 2012; P for trend = 0.001); however, the results for children did not improve (13.6% in 2008, 11.4% in 2010, and 13.7% in 2012; P for trend = 0.870). Conclusively, we found that the overall incidence of pediatric CAs in EDs increased substantially over the past 5 yr, but without significantly higher survival outcomes.

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Ethical Issues Recognized by Critical Care Nurses in the Intensive Care Units of a Tertiary Hospital during Two Separate Periods

This research aimed to investigate the changes in ethical issues in everyday clinical practice recognized by critical care nurses during two observation periods. We conducted a retrospective analysis of data obtained by prospective questionnaire surveys of nurses in the intensive care units (ICU) of a tertiary university-affiliated hospital in Seoul, Korea. Data were collected prospectively during two different periods, February 2002-January 2003 (Period 1) and August 2011-July 2012 (Period 2). Significantly fewer cases with ethical issues were reported in Period 2 than in Period 1 (89 cases [2.1%] of 4,291 ICU admissions vs. 51 [0.5%] of 9,302 ICU admissions, respectively; P < 0.001). The highest incidence of cases with identified ethical issues in both Periods occurred in MICU. The major source of ethical issues in Periods 1 and 2 was behavior-related. Among behaviorrelated issues, inappropriate healthcare professional behavior was predominant in both periods and mainly involved resident physicians. Ethical issue numbers regarding end-oflife (EOL) care significantly decreased in the proportion with respect to ethical issues during Period 2 (P = 0.044). In conclusion, the decreased incidence of cases with identified ethical issues in Period 2 might be associated with ethical enhancement related with EOL and improvements in the ICU care environment of the studied hospital. However, behaviorrelated issues involving resident physicians represent a considerable proportion of ethical issues encountered by critical care nurses. A systemic approach to solve behavior-related issues of resident physicians seems to be required to enhance an ethical environment in the studied ICU.

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Epigenetic Role of Histone 3 Lysine Methyltransferase and Demethylase in Regulating Apoptosis Predicting the Recurrence of Atypical Meningioma

Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.

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Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1α, 25-dihydroxyvitamin D₃ (VitD₃) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD₃. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD₃ increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD₃-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

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Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report

Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient''s renal function was markedly improved after short-term treatment with high-dose steroid.

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