Won Jai Jung

Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis

BackgroundThe immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis.MethodsOne hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer.ResultsForty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure.ConclusionsDNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

Prediction of methicillin-resistant Staphylococcus aureus in patients with non-nosocomial pneumonia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of not only hospital acquired pneumonia, but also non-nosocomial pneumonia. However, the risk factors for non-nosocomial MRSA pneumonia are not clearly defined. Our objective was to identify risk factors at admission that were associated with non-nosocomial MRSA pneumonia.MethodsWe evaluated 943 patients admitted to a university-affiliated hospital with culture-positive bacterial pneumonia developed outside the hospital from January 2008 to December 2011. We compared the clinical characteristics between MRSA and non-MRSA pneumonia, and identified risk factors associated with MRSA pneumonia.ResultsOf 943 patients, MRSA was identified in 78 (8.2%). Higher mortality was observed in MRSA than in non-MRSA patients (33.3% vs. 21.5%; P = 0.017). In a logistic regression analysis, MRSA pneumonia was observed more frequently in patients with a previous history of MRSA infection (OR = 6.05; P < 0.001), a PSI score ≥120 (OR = 2.40; P = 0.015), intravenous antibiotic treatment within 30 days of pneumonia (OR = 2.23; P = 0.018). By contrast, non-MRSA pneumonia was observed more often in patients with a single infiltrate on chest radiography (OR = 0.55; P = 0.029).ConclusionsAnti-MRSA antibiotics could be considered in hospitalized non-nosocomial patients with several risk factors identified herein. The presence or absence of these factors would provide useful guidance in selecting initial empirical antibiotics.

Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis.

Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.

Glucagon Levels, Disease Severity, and Outcome in Severe Sepsis:

ABSTRACT Purpose: Few studies on plasma glucagon levels in patients with sepsis have been performed. We aimed to assess clinical value of glucagon levels in comparison with clinical parameters and severity scores in patients with severe sepsis or septic shock. Methods: A total of 112 patients who were admitted to intensive care unit with severe sepsis or septic shock were included. Plasma levels of glucagon on days 0, 1, 3, and 7 were serially measured in 112 patients with severe sepsis or septic shock. Results: Compared with survivors, patients who died within 28 days had significantly higher glucagon levels on every day of examination. Glucagon levels were positively correlated with and Acute Physiology and Chronic Health Evaluation II score (day 0, r = 0.288, P < 0.01) and Sequential Organ Failure Assessment (day 0, r = 0.482, P< 0.01; day 1, r = 0.588, P < 0.01; day 3, r = 0.480, P < 0.01; day 7, r = 0.454, P < 0.01). Receiver operating characteristic analysis showed that the area under the curve of glucagon levels to predict 28-day survival was 0.65 (95% confidence interval [CI], 0.55–0.75; P = 0.005), similar to the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Multivariate analysis revealed that glucagon levels of greater than 70 pg/mL (hazard ratio, 1.85; 95% CI, 1.03–3.29) and chronic liver disease (hazard ratio, 1.97; 95% CI, 1.02–3.79) were associated with mortality. Conclusions: Glucagon levels might reflect disease severity and clinical outcomes in patients with severe sepsis or septic shock.

Two Cases of Wernicke's Encephalopathy in Young Age Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Wernickes encephalopathy is an acute neurolopsychiatric syndrome caused by thiamine deficiency, and classically presents with the triad of opthalmopathy, ataxia and altered mentality. Both prolonged total parenteral nutrition and reduced oral intake can induce Wernickes encephalopathy during hematopoietic stem cell transplantation (HSCT). Although early treatment is important for recovery from Wernickes encephalopathy, the vague symptoms and characteristics hinder early diagnosis. Furthermore, Wernickes encephalopathy is not infrequent and can develop at any age during HSCT. Herein, we present two young patients developing Wernickes encephalopathy during HSCT.

Value of Serum Cystatin C Measurement in the Diagnosis of Sepsis-Induced Kidney Injury and Prediction of Renal Function Recovery

Purpose Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. Materials and Methods Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. Results Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58–144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00–2.68, p=0.048) were associated with recovery of AKI. Conclusion Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis.

Two cases of humoral hypercalcemia of malignancy in metastatic cholangiocarcinoma

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

Purpose Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Materials and Methods Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. Results A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. Conclusion Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

Risk factors for tuberculosis after gastrectomy in gastric cancer

AIMnTo examine incidence of tuberculosis (TB) in gastrectomy patients and investigate the risk factors for developing TB after gastrectomy in patients with gastric cancer.nnnMETHODSnA retrospective cohort study of gastrectomy patients with gastric cancer was performed at a university-affiliated hospital in Seoul, South Korea between January 2007 and December 2009. We reviewed patient medical records and collected data associated with the risk of TB, surgery, and gastric cancer. Standardized incidence ratios (SIRs) of TB were calculated to compare the incidence of TB in gastrectomy patients with that in the general Korean population, and risk factors for TB after gastrectomies were analyzed.nnnRESULTSnAmong the 1776 gastrectomy patients, 0.9% (16/1776) developed post-gastrectomy TB, with an incidence of 223.7 cases per 100000 patients per year. The overall incidence of TB in gastrectomy patients, adjusted by sex and age, was significantly higher than that in the general population (SIR = 2.22, 95%CI: 1.27-3.60). Previous TB infection [odds ratio (OR) = 7.1, P < 0.001], lower body mass index (BMI) (kg/m(2); OR = 1.21, P = 0.043) and gastrectomy extent (total gastrectomy vs subtotal gastrectomy) (OR = 3.48, P = 0.017) were significant risk factors for TB after gastrectomy in a multivariate analysis.nnnCONCLUSIONnTB incidence after gastrectomy is higher than that in the general population. Previous TB infection, lower BMI, and total gastrectomy are risk factors for TB after gastrectomy in patients with gastric cancer.

A 2-D compaction method using macro block for post-silicon validation

The post-silicon validation has been an important step as the complexity of system on chip (SoC) increases. Conventional trace buffer based debug methods offer consecutive observability and real time debug, but the size constraint of the trace buffer still is a challenge. The proposed method uses 2-D compaction for expanding the depth of observation window in a trace buffer. Moreover, the macro block, which is used with 2-D compaction, offers tolerance to various error patterns as a virtual window. The errors identified by the 2-D compaction using the macro block are selectively captured by using the new tag map. The experimental results show that the proposed method enables the reduction of error misidentification.