Hou-Tai Chang

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study

IntroductionSystemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU).MethodsFrom January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis.ResultsA total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death.ConclusionThe mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

Nationwide surveillance of antimicrobial resistance among Enterobacteriaceae in intensive care units in Taiwan

To determine the antimicrobial resistance profiles among clinical isolates of Enterobacteriaceae in Taiwanese intensive care units (ICUs), a national surveillance of antibiotic resistance among important Enterobacteriaceae was conducted from September 2005 through November 2005 at the ICUs of ten major teaching hospitals in Taiwan. A total of 574 Enterobacteriaceae isolates recovered from various clinical samples of our ICU patients were submitted for in vitro test. Minimum inhibitory concentrations (MICs) of these isolates to 18 antimicrobial agents were determined by the broth microdilution method. The prevalences of Enterobacteriaceae isolates with phenotypic extended-spectrum β-lactamase (ESBL) production were 26% in Klebsiella pneumoniae, 16% in Serratia marcescens, 14% in Escherichia coli, and 13% in Proteus mirabilis, in which a significantly rising prevalence of ESBL production among K. pneumoniae was noted (p = 0.002) when compared with a previous Taiwanese survey in 2000. Heterogeneous resistance to various fluoroquinolones was found among our Enterobacteriaceae isolates, except for Entetrobacter cloacae. Emergence of ertapenem-resistant isolates of E. coli, K. pneumoniae, E. cloacae, and S. marcescens was noted. Gradually increasing rates of drug-resistant Enterobacteriaceae were noted in Taiwanese ICUs. Periodic surveillance of the evolutionary trend of antimicrobial resistance among ICU isolates is crucial for starting appropriately empirical antimicrobial therapy in the future.

High levels of serum macrophage migration inhibitory factor and interleukin 10 are associated with a rapidly fatal outcome in patients with severe sepsis

OBJECTIVES The aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome. METHODS One hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48 h), late fatal outcome (LFO, death between 48 h and 28 days), and survival at 28 days. RESULTS Among the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094-1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis. CONCLUSIONS Patients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO.

Clinical characteristics and outcomes of patients with Burkholderia cepacia bacteremia in an intensive care unit

The purpose of this study was to investigate a cohort of patients with Burkholderia cepacia bacteremia in the intensive care unit (ICU) at our institution. A large outbreak of B. cepacia bacteremia involving 95 patients lasted for 4 years in an ICU in northern Taiwan. The clinical characteristics and antimicrobial treatment responses of these patients were analyzed. Minimal inhibitory concentrations were determined and pulse-field gel electrophoresis was performed for the 73 available isolates. Overall, the in-hospital mortality rate was 53.8% and the 14-day mortality rate was 16.8%. Most patients (95.6%) had several underlying diseases and all but 1 patient had tracheal intubation. Malignancy (37.5% versus 13.9%, P = 0.02) and higher Sequential Organ Failure Assessment (SOFA) scores at the onset of bacteremia (11.9 ± 4.7 versus 7.9 ± 3.6, P < 0.001) were significant risk factors for 14-day mortality. In contrast, treatment with ceftazidime (76.0% versus 43.7%, P = 0.02) and diabetes (51.9% versus 13.8%, P = 0.01) were associated with decreased mortality. In the multivariate analysis, malignancy and higher SOFA score were significant risk factors for mortality [odds ratio (OR) 12.45, 95% confidence interval (CI) 2.35-65.94; OR 1.20, 95% CI 1.00-1.45, respectively]. Meropenem, ceftazidime, and piperacillin-tazobactam were the most active agents (susceptible rate 100%, 97.3%, and 97.3%, respectively). Pulsed-field gel electrophoresis results indicated 49 of the 73 isolates could be classified as outbreak-related strains. There was no significant difference in the clinical characteristics and outcomes of patients with bacteremia due to outbreak-related and non-outbreak-related strains. In conclusion, malignancy and a higher SOFA score at onset of bacteremia predicted increased mortality, but the clinical presentation and outcome of patients with outbreak and non-outbreak strains were similar.

Pulmonary changes induced by trans,trans-2,4-decadienal, a component of cooking oil fumes

Cooking oil fumes (COF) are known to be associated with respiratory diseases and risk of lung cancer. Involvement of trans,trans-2,4-decadienal (tt-DDE), a major component in COF, is suspected. Male CD-1® (ICR) mice were intratracheally instilled with either 8 or 24 mg·kg−1 tt-DDE weekly for 8 weeks. Total numbers and types of cells in bronchoalveolar lavage fluid (BALF), as well as pathological changes, and inflammatory gene modulations in the lung tissues were assessed. We demonstrated that the number of alveolar macrophages in the BALF was significantly increased in tt-DDE-exposed animals. Histologically, there was a dose-correlated increase in epithelial hyperplasia and granulomatous nodules at the bronchioloalveolar junctions (BAJ). Although both Clara and alveolar type II cells were present in the BAJ lesion, only Clara cells were actively proliferative. However, only alveolar type II cells were found in the BAJ granulomatous nodules. Enhanced accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a known pro-carcinogenic factor, was also detected in many alveolar type II cells at the BAJ lesions. As both BAJ hyperplasia and enhanced pSTAT3 accumulation are known risk factors associated with increased lung adenocarcinoma development, these findings suggest that tt-DDE may pose a risk in lung carcinogenesis.

Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis.

ABSTRACT Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 103/&mgr;L. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor &agr;, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482−8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.

CENTRAL VENOUS OXYGEN SATURATION UNDER NON-PROTOCOLIZED RESUSCITATION IS NOT RELATED TO SURVIVAL IN SEVERE SEPSIS OR SEPTIC SHOCK

ABSTRACT Protocolized hemodynamic resuscitation in severe sepsis or septic shock is not universally applied in all emergency departments and general hospital wards around the world. It is unknown whether ScvO2 levels are associated with the clinical outcome of severe sepsis or septic shock under nonprotocolized resuscitation. In this prospective study, we enrolled 124 noncirrhotic patients who were admitted to intensive care units for severe sepsis or septic shock. The average Acute Physiology and Chronic Health Evaluation II score was 25.3 (SD, 7.6). According to ScvO2 levels after initial resuscitation before intensive care unit admission, patients were divided into high (ScvO2 ≥ 70%, n = 63) and low (ScvO2 < 70%, n = 61) ScvO2 groups. Compared with high ScvO2 groups, low ScvO2 groups showed no significant differences in 28-day mortality (25.4% vs. 24.6%; P = 0.943) or hospital mortality (30.2% vs. 31.1%; P = 0.794). Multivariate logistic regression models showed that low mean arterial pressure (hazard ratio, 0.967; 95% confidence interval, 0.940–0.994; P = 0.019) and high central venous pressure (hazard ratio, 1.150; 95% confidence interval, 1.057–1.251; P = 0.001) after initial resuscitation were associated with higher 28-day mortality. On the contrary, ScvO2 levels after resuscitation were not related to 28-day or hospital mortality. In conclusion, our results showed that mean arterial pressure and central venous pressure were still the most important hemodynamic variables in initial hemodynamic resuscitation. Low postresuscitation ScvO2 was not associated with a worse outcome. It is possible that ScvO2 less than 70% might not necessarily be associated with tissue hypoxia, and critical ScvO2 levels require to be determined by further studies.

Effect of Tracheostomy on Weaning Parameters in Difficult-to-Wean Mechanically Ventilated Patients: A Prospective Observational Study

Background and Objective Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients. Methods In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning. Weaning parameters were measured before and after the conversion to tracheostomy and compared, and the post-tracheostomy data were tested for associations with weaning outcomes. Results A total of 86 patients were included. After tracheostomy, maximum inspiratory pressure (mean difference (Δ) = 4.4, 95% CI, 2.7 to 6.1, P<0.001), maximum expiratory pressure (Δ = 5.4, 95% CI, 2.9 to 8.0, P<0.001) and tidal volume (Δ = 33.7, 95% CI, 9.0 to 58.5, P<0.008) significantly increased, and rapid shallow breathing index (Δ = -14.6, 95% CI, -25.4 to -3.7, P<0.009) and airway resistance (Δ = -4.9, 95% CI, -5.8 to -4.0, P<0.001) significantly decreased. The patients who were successfully weaned within 90 days of the initiation of mechanical ventilation had greater increments in maximum inspiratory pressure (5.9 vs. 2.4, P = 0.04) and maximum expiratory pressure (8.0 vs. 2.0, P = 0.02) after tracheostomy than those who were unsuccessfully weaned. Conclusions In conclusion, the conversion from endotracheal tube to tracheostomy significantly improved the measured values of weaning parameters in difficult-to-wean patients who subsequently weaned successfully from the mechanical ventilator. The change was significant only for airway resistance in patients who failed weaning. Trial Registration ClinicalTrials.gov NCT01312142

Staphylococcus lugdunensis endocarditis with isolated tricuspid valve involvement

Staphylococcus lugdunensis is often misidentified as S aureus and as a rare cause of infective endocarditis. The clinical course of S lugdunensis endocarditis is aggressive and the mortality rate is high in contrast to S epidermidis endocarditis. Most reported cases of S lugdunensis endocarditis have involved mitral or aortic valves. Herein, we present a case with isolated tricuspid endocarditis due to S lugdunensis.

Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas

HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one‐step reverse transcription‐polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation‐positive lung ADC patients were analyzed and compared to those with HER2 mutation‐negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients. HER2 mutations tended to occur in male patients with advanced‐stage disease and never‐smokers. A775_G776insYVMA (n = 22, 55%) was the most prevalent HER2 mutation, followed by P780_Y781insGSP (n = 4, 10%). For patients diagnosed with stage‐IIIB/IV disease, HER2‐mutant patients showed clinical outcomes comparable to EGFR‐mutant patients (P = 0.721, log‐rank test) and a better overall survival (OS) compared to patients lacking driver mutations in the investigated genes (P = 0.033, Breslow test). Specifically, lung ADC patients with stage‐IV HER2‐mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti‐HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P = 0.870). In addition, multivariate analysis indicated that HER2 mutation status was not a major risk factor for diminished OS in stage‐IV lung cancer. In conclusion, lung ADC harboring HER2 mutations showed distinct characteristics from other driver mutations, including increased chemosensitivity with in advanced stage disease.