Chien-Ming Chu

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.

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.

Factors Associated With In Vitro Interferon-gamma Production in Tuberculosis

BACKGROUND/PURPOSE Macrophage activation assisted by interferon-gamma (IFN-γ) is a primary mechanism by which Mycobacterium tuberculosis is killed, but IFN-γ (production is inhibited in tuberculosis (TB) patients. The production of IFN-γ is influenced by many factors, such as interleukin (IL)-10, IL-12, IL-18, and clinical diseases; but the relative importance of each factor is unclear. METHODS We evaluated the effects of these factors in 46 healthy individuals, 81 patients with TB, and 88 patients with non-TB pneumonia. The responses of IFN-γ, IL-10, IL-12 and IL-18 were determined from phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs). RESULTS General linear model analysis showed that disease status and IL-12 response were the independent factors associated with the IFN-γ response. The production of IFN-γ was not affected by IL-10 and IL-18. There was a significant relationship between the IFN-γ response and the IL-12 response among patients with non-TB pneumonia, patients with TB, and healthy participants (Pearsons correlation coefficients of 0.466, 0.483, and 0.464, respectively). CONCLUSION Production of IFN-γ in PBMCs was associated with active pulmonary TB and IL-12 response.

High Interleukin-10 Expression in Type 2 T Helper Cells in Septic Patients

ABSTRACT Interleukin (IL)-10 response is associated with mortality in patients with sepsis. IL-10 is primarily produced by monocytes and type 2 T helper (Th2) cells. The aim of this study was to investigate differences in IL-10 production between monocytes and Th2 cells in patients with sepsis. Forty patients with sepsis and 35 healthy controls were enrolled. Cytokine expressions in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. The IL-10 expression in the Th2 cells of the septic patients was higher than in the healthy controls, but the expression of IL-10 in the monocytes of the septic patients was lower than in the healthy controls. After regression analysis, IL-10 expression in Th2 cells was positively associated with sepsis, but IL-10 expression in monocytes was not associated with sepsis or shock. In conclusion, the production of IL-10 in Th2 cells was higher in the patients with sepsis.

Mortality of severe septic patients between physician's high and low care volumes

Background Patients with severe sepsis frequently require intensive care unit (ICU) admission and different ICU care models may influence their outcomes. The mortality of severe septic patients between physicians high and low care volume remains unclear. Methods We analyzed the data from a three-year prospective observation study, which was performed in an adult medical ICU of Chung Gung Memorial Hospital, Keelung. The data included initial bundle therapies based on the Surviving Sepsis Campaign (SSC) guidelines for patients with severe sepsis. Results Clinical data of total 484 patients with severe sepsis were recorded. Cox regression model showed that physicians care volume was an independent factor for lowering mortality in ICU patients with severe sepsis (hazard ratio 0.708; 95% confidence interval 0.514–0.974; p = 0.034). Patients treated by high care volume physician had four out of nine bundle therapies that were significantly higher in percentage following the SSC guidelines. These four therapies were renal replacement therapy, administration of low-dose steroids for septic shock, prophylaxis of gastro-intestinal bleeding, and control of hyperglycemia. Conclusion High care volume physician may decrease mortality in ICU patients with severe sepsis through fitting bundle therapies for sepsis.

High Lymphocyte Percentage in Bronchoalveolar Lavage Fluid of Patients with H1N1-Associated Acute Respiratory Distress Syndrome

早期使用抗病毒藥物治療H1N1流感重症患者可以改善病人的存活率。然而臨床上要區分H1N1或細菌造成的急性呼吸窘迫症候群是困難的，而且流感快篩檢驗的敏感度不夠高。一般的醫院無法以即時聚合酶鏈鎖反應偵測流感病毒。我們的研究目的是以支氣管肺泡沖洗液中的淋巴球比例來早期診斷H1N1流感引起的急性呼吸窘迫症候群。我們回朔性分析2014年到2016年3月基隆長庚醫院內科加護病房因為肺炎引起急性呼吸窘迫症候群並且有接受支氣管肺泡沖洗的病人，有9位是H1N1流感而18位是細菌引起的。H1N1-急性呼吸窘迫症候群的病人的病人有較低的APACHE II分數，支氣管肺泡沖洗液中的淋巴球比例比起細菌-急性呼吸窘迫症候群的病人還要高(15.6 ± 7.5% vs. 7.6 ± 8.0%, p=0.009)。以支氣管肺泡沖洗液中的淋巴球比例11%來區分是H1N1流感或是細菌造成的急性呼吸窘迫症候群，ROC曲線下面積為0.829，敏感度85.5%，特異度77.8%，陽性預測值79.4%，陰性預測值84.3%。這個結果可以幫助我們對於急性呼吸窘迫症候群的病人早期區分是H1N1流感所致，早期給予抗病毒藥以改善病人的存活率。

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.