Chung-Ching Hua

Serial cytokine levels in patients with severe sepsis

Objective and designThe serial or dynamic changes of cytokine levels in severely septic patients, between shock and no shock, survivors and non-survivors are still unclear.MethodsSeventy-six patients with severe sepsis were enrolled to our study. Plasma levels of interferon-γ, interleukin (IL)-6, IL-10, IL-12 and transforming growth factor-β1 from day 1 to day 7 were determined.ResultsIL-6 level in non-survivors was higher than that in survivors on day 1. IL-10 level in non-survivors was higher than that in survivors on day 1, 2, and 3. IL-6 level in shock patients was higher than that in non-shock patients on day 1, 2, 6 and 7. IL-10 level in shock patients was higher than that in non-shock patients from day 1 to day 7. Plasma time-course curves of IL-6 and IL-10 were different between survivors and non-survivors. Plasma time-course curve of IL-6 was different between patients with shock and without shock. Regression analysis found that IL-6 was correlated with IL-10 and shock. IL-10 was correlated with IL-6 and mortality.ConclusionIL-6 and IL-10 were the key cytokines in the pathogenesis of severe sepsis. IL-6 was comparatively more associated with septic shock and IL-10 was comparatively more associated with mortality.

Serial increase of IL-12 response and human leukocyte antigen-DR expression in severe sepsis survivors.

IntroductionSepsis-induced immunosuppression may result in death. The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased anti-inflammatory cytokine expression and decreased expression of proinflammatory cytokines. In this study, we sought to determine the mechanisms of immune suppression in severe sepsis by repeated detection.MethodsWe designed this prospective observational study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with severe sepsis.ResultsOf the 35 enrolled patients, 23 survived for 28 days and 12 died, 6 of whom died within 7 days. Plasma levels of IL-1β, IL-6, IL-10, IL-17, transforming growth factor (TGF)-β1 and TNF-α were higher, but plasma IL-12 level was lower in septic patients than those in controls. Day 1 plasma levels of IL-1β, IL-6, IL-10 and TGF-β1 in nonsurvivors were higher than those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in survivors. IL-1β response was higher, but IL-12 and TNF-α responses were lower in septic patients than in controls. Day 1 IL-6 response was lower, but day 1 TGF-β1 response was higher in nonsurvivors than in survivors. Plasma IL-6 and IL-10 levels were decreased in survivors after 6 days. IL-6 response was decreased in survivors after 6 days, but IL-12 response was increased. Monocyte percentage was higher, but positive HLA-DR percentage in monocytes and mean fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in controls. MFI of HLA-DR was increased in survivors after 6 days.ConclusionsMonocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis.

Pneumoconiosis and liver cirrhosis are not risk factors for tuberculosis in patients with pulmonary infection

Background and objective:  It is unclear whether patients with liver cirrhosis and coal miners with pneumoconiosis are at increased risk of developing pulmonary tuberculosis (TB). Furthermore, little is known of the likelihood of pneumonia in patients with bronchiectasis, haemodialysis, diabetes mellitus or advanced lung cancer being due to TB. To answer these questions, patients with these clinical comorbidities were analysed.

Effect of interleukin-17 on in vitro cytokine production in healthy controls and patients with severe sepsis

BACKGROUND/PURPOSE Interleukin (IL)-17 family members (IL-17A to IL-17F) are appearing to play key roles in host defense and inflammatory disease. Recently, several cytokines, such as IL-6, IL-10, IL-12, and transforming growth factor (TGF)-β1, were shown to have vital roles in severe sepsis. However, the influence of IL-17 on these cytokine responses from peripheral blood mononuclear cells (PBMCs) is unclear. METHODS Fifty-two patients who were admitted to our intensive care unit (ICU) because of severe sepsis were enrolled into this study. To validate experimental findings, 25 healthy controls were enrolled. Lipopolysaccharide-stimulated PBMCs with IL-17 or anti-IL-17 treatments were cultured for 24 hours. IL-6, IL-10, IL-12, and TGF-β1 levels in supernatants were measured. RESULTS The IL-12 production from stimulated PBMCs was increased after IL-17 treatment in both control and patient groups. Additional treatment of anti-IL-17 enhanced IL-10 production but decreased IL-12 production from stimulated PBMCs of healthy controls and patients with severe sepsis. CONCLUSION IL-17 was helpful for inflammation in severe sepsis. Lack of IL-17 decreased IL-12 and enhanced IL-10 production from PBMCs, which resulted in immune imbalance.

Comparing hydrocortisone and methylprednisolone in patients with septic shock

IntroductionIntravenous hydrocortisone of 200–300 mg/day for 7 days is suggested for patients with septic shock who require vasopressors to maintain mean artery pressure ≥65 mmHg, despite adequate fluid resuscitation. No study to date has compared the effects between physiologic doses of hydrocortisone and methylprednisolone in patients with septic shock.MethodsFrom July 2007 to June 2008, patients who were admitted to the intensive care unit at Chang Gung Memorial Hospital, Keelung, Taiwan, with low-dose steroid therapy due to septic shock were enrolled in this study. The typical steroid therapy included 7 days of intravenous hydrocortisone 50 mg every 6 hours. Methylprednisolone (20 mg every 12 hours) was replaced in these patients from January 2008 because no hydrocortisone could be prescribed.ResultsA total of 21 patients were prescribed hydrocortisone and 19 patients were prescribed methylprednisolone. The survival rates for patients receiving hydrocortisone were relatively higher compared with those receiving methylprednisolone, but the difference was not significant. There were no significant differences in the Kaplan-Meier curves for the time to reverse shock between patients who received hydrocortisone, or methylprednisolone. Further regression analysis showed no significant independent factors associated with the survival rates and the time to reverse shock among age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, histories, and adverse events.ConclusionsLow-dose methylprednisolone and hydrocortisone might have a similar effect for the treatment of patients with septic shock.

Liver Cirrhosis and Diabetes Mellitus Are Risk Factors for Staphylococcus aureus Infection in Patients with Healthcare-Associated or Hospital-Acquired Pneumonia

Background. The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy. Methods. From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign. Results. The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis. Conclusion. Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP.

Comparison of interferon-γ response between tuberculosis and non-tubercular Pneumonia

Abstract.Objective and design:Macrophages aided by interferon-gamma (IFN-γ) are vital to controlling Mycobacterium tuberculosis (M. tuberculosis) infection. Although numerous studies have compared IFN-γ response between tubercular patients and healthy controls, no studies have investigated IFN-γ response in patients with pulmonary tuberculosis and non-tubercular pneumonia. The aim of this work was to examine the difference in IFN-γ response between patients with tuberculosis and non-tubercular pneumonia.Methods:IFN-γ production was detected based on the difference in supernatants between non-stimulated and stimulated peripheral blood mononuclear cells by phytohemagglutinin in 83 tubercular patients and 47 patients with pneumonia. Presence of a cavity on chest radiography and co-morbidities of pneumoconiosis, bronchiectasis, liver cirrhosis, renal failure on hemodialysis, diabetes mellitus (DM) and lung cancer were recorded for analysis.Results:Interferon-gamma response, DM and a cavity on chest radiography were independent factors for predicting active pulmonary tuberculosis. Interferon-gamma response was decreased in patients with pulmonary tuberculosis compared with that in patients with non-tubercular pneumonia. Notably, M. tuberculosis infection was the principal factor correlated with IFN-γ response.Conclusion:The IFN-γ response was principally affected by M. tuberculosis infection and not by other co-morbidities. Further study is required to identify the mechanism of decreased IFN-γ production.

Combination Antibiotics for Gram-negative Bacteria in Patients with Healthcare-associated or Hospital-acquired Pneumonia with Severe Sepsis or Septic Shock

Guidelines suggest that patients with multiple drug resistance pathogen-related hospital-acquired pneumonia (HAP) or healthcare-associated pneumonia (HCAP) should initially be prescribed with two empiric antibiotics for gram-negative pathogens. Traditional antibiograms cannot provide information about which combination therapy is the best choice. We therefore conducted this observational study to determine which combination of antibiotics is optimal. From July 2007 to June 2010, patients who were admitted to the medical intensive care unit at Chang Gung Memorial Hospital, Keelung due to HCAP or HAP with severe sepsis or septic shock were screened in this study. The clinical characteristics and antimicrobial resistance profiles were analyzed. A total of 117 patients who met the inclusion and exclusion criteria were enrolled for analysis. The most frequently isolated pathogens were Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. In monotherapy, the highest susceptibility to gram-negative bacteria was 76.1% with imipenem/cilastatin. In combination therapy, the highest susceptibility was 82.9% with a 6.8% additional advantage with a base of imipenem/cilastatin with amikacin, gentamicin, ciprofloxacin, or levofloxacin. The secondary highest susceptibility in combination therapy was 76.9% with piperacillin/tazobactam and amikacin. Thus, the first choice of combination therapy in this study was imipenem/cilastatin combined with ciprofloxacin or levofloxacin, which covered the most pathogens.

RIFLE Classification Did Not Have Satisfactory Predictive Value for Septic Patients with High Severity Scores

Background: Predicting the outcome of patients with severe sepsis is important. The RIFLE classification has been evaluated for its ability to predict mortality. The aim of this study was to compare the predictive value of 3 scoring systems: the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Multiple Organ Dysfunction Score (MODS), and the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification. Patients and methods: Seventy-one severe septic patients admitted to intensive care units (ICU) directly from the emergency department were enrolled into this study. The APACHE II score, MODS, and RIFLE classification were calculated within 24 hours after admission. Areas under the receiver operating characteristic (ROC) curves were computed in order to analyze the discriminatory power of these 3 scoring systems. Results: The value of the APACHE II score and the MODS in the non-survivors was statistically significantly higher than that in the survivors. The RIFLE classification showed no significant difference between survivors and non-survivors. Areas under the ROC curves were 0.801, 0.715, and 0.602, respectively, for the APACHE II score, the MODS, and the RIFLE classification. The APACHE II score and the MODS were better tools for outcome prediction, compared with the RIFLE classification. The discriminatory power of the RIFLE classification did not have significance (p=0.226) for outcome prediction in severe septic patients. Conclusions: The APACHE II score and the MODS were useful tools in patients with severe sepsis. The RIFLE classification did not show satisfactory power in predicting 28-day mortality in more severe septic patients.