Predicting mortality among older adults hospitalized for community-acquired pneumonia: an enhanced confusion, urea, respiratory rate and blood pressure score compared with pneumonia severity index

Background and objective: Pneumonia Severity Index (PSI) predicts mortality better than C onfusion, U rea >7 mmol/L, R espiratory rate >30/min, low Bl ood pressure: diastolic blood pressure <60 mm Hg or systolic blood pressure <90 mm Hg, and age >65 years (CURB‐65) for community‐acquired pneumonia (CAP) but is more cumbersome. The objective was to determine whether CURB enhanced with a small number of additional variables can predict mortality with at least the same accuracy as PSI. Methods: Retrospective review of medical records and administrative data of adults aged 55 years or older hospitalized for CAP over 1 year from three hospitals. Results: For 1052 hospital admissions of unique patients, 30‐day mortality was 17.2%. PSI class and CURB‐65 predicted 30‐day mortality with area under curve (AUC) of 0.77 (95% confidence interval (CI): 0.73–0.80) and 0.70 (95% CI: 0.66–0.74) respectively. When age and three co‐morbid conditions (metastatic cancer, solid tumours without metastases and stroke) were added to CURB, the AUC improved to 0.80 (95% CI: 0.77–0.83). Bootstrap validation obtained an AUC estimate of 0.78, indicating negligible overfitting of the model. Based on this model, a clinical score (enhanced CURB score) was developed that had possible values from 5 to 25. Its AUC was 0.79 (95% CI: 0.76–0.83) and remained similar to that of PSI class. Conclusions: An enhanced CURB score predicted 30‐day mortality with at least the same accuracy as PSI class did among older adults hospitalized for CAP. External validation of this score in other populations is the next step to determine whether it can be used more widely.     

Role of 'atypical pathogens' among adult hospitalized patients with community-acquired pneumonia

Background and objective: Agents such as Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila are recognized as important causes of community‐acquired pneumonia (CAP) worldwide. This study examined the role of these ‘atypical pathogens’ (AP) among adult hospitalized patients with CAP. Methods: A prospective, observational study of consecutive adult CAP (clinico‐radiological diagnosis) patients hospitalized during 2004–2005 was conducted. Causal organisms were determined using cultures, antigen testing and paired serology. Clinical/laboratory/radiological variables and outcomes were compared between different aetiologies, and a clinical prediction rule for AP was constructed. Results: There were 1193 patients studied (mean age 70.8 ± 18.0 years, men 59.3%). Causal organisms were identified in 468 (39.2%) patients: ‘bacterial’ (48.7%), ‘viral’ (26.9%), ‘AP’ (28.6%). The AP infections comprised Mycoplasma or Chlamydophila pneumoniae (97.8%) and co‐infection with bacteria/virus (30.6%). The majority of AP infections involved elderly patients (63.4%) with comorbidities (41.8%), and more than one‐third of patients were classified as ‘intermediate’ or ‘high’ risk CAP on presentation (pneumonia severity index IV–V (35.1%); CURB‐65 2–5 (42.5%)). Patients with AP infections had disease severities and outcomes similar to patients with CAP due to other organisms (oxygen therapy 29.1% vs 29.8%; non‐invasive ventilation 3.7% vs 3.3%; admission to the intensive care unit 4.5% vs 2.7%; length of hospitalization 6 day vs 7 day; 30‐day mortality: 2.2% vs 6.0%; overall P > 0.05). Age <65 years, female gender, fever ≥38.0°C, respiratory rate <25/min, pulse rate <100/min, serum sodium >130 mmol/L, leucocyte count <11 × 10⁹/L and Hb < 11 g/dL were features associated with AP infection, but the derived prediction rule failed to reliably discriminate CAP caused by AP from bacterial CAP (area under the curve 0.75). Conclusions: M. pneumoniae and C. pneumoniae as single/co‐pathogens are important causes of severe pneumonia among older adults. No reliable clinical indicators exist, so empirical antibiotic coverage for hospitalized CAP patients may need to be considered.     

The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort study

BACKGROUND: It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS: We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS: We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS: Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.     

Is COPD associated with increased mortality and morbidity in hospitalized pneumonia? A systematic review and meta‐analysis

This review aimed to investigate whether chronic obstructive pulmonary disease (COPD) is associated with increased mortality and morbidity in patients hospitalized with community‐acquired pneumonia (CAP). EMBASE, PubMed and Web of Science were searched for cohort studies and case–control studies investigating the impact of COPD on CAP. The primary outcome was all‐cause mortality, and secondary outcomes included length of hospital stay, intensive care unit (ICU) admission and need for mechanical ventilation. Methodological quality was assessed using the Newcastle–Ottawa Scale. The Mantel–Haenszel method and inverse variance method were used to calculate pooled relative risks (RRs) and mean differences (MD), respectively. Eleven studies (nine cohort studies and two case–control studies), involving 257 958 patients, were included. The overall methodological quality was high. COPD was not associated with increased mortality in hospitalized CAP patients (RR, 1.20; 95% confidence interval (CI): 0.92–1.56; P = 0.19; I² = 55%) in cohort studies, and was associated with reduced mortality in case–control studies (RR, 0.82; 95% CI: 0.74–0.90; P < 0.0001; I² = 80%). COPD was not associated with longer hospital stay (MD, 0.11; 95% CI: ?0.42 to 0.64; P = 0.68; I² = 21%), more frequent ICU admission (RR, 0.97; 95% CI: 0.70–1.35; P = 0.87; I² = 65%), and more need for mechanical ventilation (RR 0.91, 95% CI: 0.71–1.16; P = 0.44; I² = 4%).The current available evidence indicates that COPD may not be associated with increased mortality and morbidity in patients hospitalized with CAP. This conclusion should be re‐evaluated by prospective population‐based cohort studies.     

Attempted validation of the NUn score and inflammatory markers as predictors of esophageal anastomotic leak and major complications

The ability to predict complications following esophagectomy/extended total gastrectomy would be of great clinical value. A recent study demonstrated significant correlations between anastomotic leak (AL) and numerical values of C‐reactive protein (CRP), white cell count (WCC) and albumin measured on postoperative day (POD) 4. A predictive model comprising all three (NUn score >10) was found to be highly sensitive and discriminant in predicting AL and complications. We attempted a retrospective validation in our center. Data were collected on all resections performed during a 5‐year period (April 2008–2013) using prospectively maintained databases. Our biochemistry laboratory uses a maximum CRP value (156 mg/L), unlike that of the original study; otherwise all variables and outcome measures were comparable. Analysis was performed for all patients with complete blood results on POD4. Three hundred twenty‐six patients underwent resection, of which 248 had POD4 bloods. There were 21 AL overall (6.44%); 16 among those with complete POD4 blood results (6.45%). There were 8 (2.45%) in‐hospital deaths; 7 (2.82%) in those with POD4 results. No parameters were associated with AL or complication severity on univariate analysis. WCC was associated with AL in multivariate binary logistic regression with albumin and CRP (OR 1.23 [95% CI 1.03–1.47]; P = 0.021). When a binary variable of CRP ≥ 156 mg/L was used rather than an absolute value, no factors were significant. Mean NUn was 8.30 for AL, compared with 8.40 for non‐AL (P = 0.710 independent t‐test). NUn > 10 predicted 0 of 16 leaks (sensitivity 0.00%, specificity 94.4%, receiver operator curve [ROC] area under the curve [AUC] 0.485; P = 0.843). NUn > 7.65 was 93% sensitive and 21.6% specific. ROC for WCC alone was comparable with NUn (AUC 0.641 [0.504–0.779]; P = 0.059; WCC > 6.89 93.8% sensitive, 20.7% specific; WCC > 15 6.3% sensitive and 97% specific). There were no associations between any parameters and other complications. In a comparable cohort with the original study, we demonstrated a similar multivariate association between WCC alone on POD4 and subsequent demonstration of AL, but not albumin or CRP (measured up to 156 mg/L). The NUn score overall (calculated with this caveat) and a threshold of 10 was not found to have clinical utility in predicting AL or complications.     

Cost effectiveness of combined spa–exercise therapy in ankylosing spondylitis: A randomized controlled trial

Objective

To evaluate the cost effectiveness and cost utility of a 3‐week course of combined spa therapy and exercise therapy in addition to standard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis (AS) patients.

Methods

A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 was treated in a spa resort in Bad Hofgastein, Austria; group 2 in a spa resort in Arcen, The Netherlands. The control group stayed at home and continued their usual activities and standard treatment during the intervention weeks. After the intervention, all patients followed weekly group physical therapy. The total study period was 40 weeks. Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index (BASFI). Utilities were measured with the EuroQoL (EQ‐5D_utility). A time‐integrated summary score defined the clinical effects (BASFI‐area under the curve [AUC]) and utilities (EQ‐5D_utility‐AUC) over time. Both direct (health care and non‐health care) and indirect costs were included. Resource utilization and absence from work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective.

Results

A total of 111 patients completed the diary. The between‐group difference for the BASFI‐AUC was 1.0 (95% confidence interval [95% CI] 0.4–1.6; P = 0.001) for group 1 versus controls, and 0.6 (95% CI 0.1–1.1; P = 0.020) for group 2 versus controls. The between‐group difference for EQ‐5D_utility‐AUC was 0.17 (95% CI 0.09–0.25; P < 0.001) for group 1 versus controls, and 0.08 (95% CI 0.00–0.15; P = 0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) in Euros (€) during the study period were €3,023 for group 1, €3,240 for group 2, and €1,754 for the control group. The incremental cost‐effectiveness ratio per unit effect gained in functional ability (0–10 scale) was €1,269 (95% CI 497–3,316) for group 1, and €2,477 (95% CI 601–12,098) for group 2. The costs per quality‐adjusted life year gained were €7,465 (95% CI 3,294–14,686) for group 1, and €18,575 (95% CI 3,678–114,257) for group 2.

Conclusion

Combined spa–exercise therapy besides standard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost‐effectiveness and cost‐utility ratios compared with standard treatment alone in patients with AS.

     

Long‐acting beta2‐agonists versus long‐acting muscarinic antagonists in patients with stable COPD: A systematic review and meta‐analysis of randomized controlled trials

Several long‐acting bronchodilators have been developed and are widely used as first‐line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long‐acting muscarinic antagonist (LAMA) and long‐acting beta2‐agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials for meta‐analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV₁), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74–0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86–0.97, P = 0.005). There were no significant differences in trough FEV₁, TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.     

Autoantibodies against apolipoprotein A-1 and phosphorylcholine for diagnosis of non-ST-segment elevation myocardial infarction

Abstract. Keller P‐F, Pagano S, Roux‐Lombard P, Sigaud P, Rutschmann OT, Mach F, Hochstrasser D Vuilleumier N (Geneva University Hospitals, Geneva). Autoantibodies against apolipoprotein A‐1 and phosphorylcholine for diagnosis of non‐ST‐segment elevation myocardial infarction. J Intern Med 2012; 271 : 451–462. Objectives. To explore the diagnostic accuracies of anti‐apolipoproteinA‐1 (anti‐ApoA‐1) IgG and anti‐phosphorylcholine (anti‐PC) IgM alone, expressed as a ratio (anti‐ApoA‐1 IgG/anti‐PC IgM), and combined with the Thrombolysis In Myocardial Infarction (TIMI) score for non‐ST‐segment elevation myocardial infarction (NSTEMI) (NSTEMI‐TIMI score) to create a new diagnostic algorithm – the Clinical Autoantibody Ratio (CABR) score – for the diagnosis of NSTEMI and subsequent cardiac troponin I (cTnI) elevation in patients with acute chest pain (ACP). Methods. In this single‐centre prospective study, 138 patients presented at the emergency department with ACP without ST‐segment elevation myocardial infarction. Anti‐ApoA‐1 IgG and anti‐PC IgM were assessed by enzyme‐linked immunosorbent assay on admission. Post hoc determination of the CABR score cut‐off was performed by receiver operating characteristics analyses. Results. The adjudicated final diagnosis was NSTEMI in 17% (24/138) of patients. Both autoantibodies alone were found to be significant predictors of NSTEMI diagnosis, but the CABR score had the best diagnostic accuracy [area under the curve (AUC): 0.88; 95% confidence interval (CI): 0.82–0.95]. At the optimal cut‐off of 3.3, the CABR score negative predictive value (NPV) was 97% (95% CI: 90–99). Logistic regression analysis showed that a CABR score >3.3 increased the risk of subsequent NSTEMI diagnosis 19‐fold (odds ratio: 18.7; 95% CI: 5.2–67.3). For subsequent cTnI positivity, only anti‐ApoA‐1 IgG and CABR score displayed adequate predictive accuracies with AUCs of 0.80 (95% CI: 0.68–0.91) and 0.82 (95% CI: 0.70–0.94), respectively; the NPVs were 95% (95% CI: 90–98) and 99% (95% CI: 94–100), respectively. Conclusion. The CABR score, derived from adding the anti‐ApoA‐1 IgG/anti‐PC IgM ratio to the NSTEMI‐TIMI score, could be a useful measure to rule out NSTEMI in patients presenting with ACP at the emergency department without electrocardiographic changes.     

Evaluation of the Japanese Respiratory Society guidelines for the identification of Mycoplasma pneumoniae pneumonia

Background and objective: Community‐acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Mycoplasma pneumoniae is one of the major causative pathogens of CAP. Early diagnosis of M. pneumoniae pneumonia is crucial for initiating appropriate antibiotic therapy. The aim of this study was to determine whether the Japanese Respiratory Society (JRS) guidelines on CAP are effective for diagnosing M. pneumoniae pneumonia. Methods: Between August 2008 and July 2009, adult outpatients with CAP were consecutively enrolled. The aetiology of CAP was determined by culture and real‐time polymerase chain reaction (PCR) methods to detect M. pneumoniae, urine antigen tests to detect Streptococcus pneumoniae and Legionella pneumoniae, blood and sputum culture for bacteria and real‐time PCR for eight common respiratory viruses. The predictive value of the JRS guidelines for differentiating M. pneumoniae pneumonia from typical bacterial and viral pneumonias was determined. Results: Data from 215 adult CAP outpatients was analyzed. An aetiological diagnosis was made for 105 patients (48.8%), including 62 patients with M. pneumoniae pneumonia, 17 patients with typical bacterial pneumonia and 23 patients with viral pneumonia. According to the JRS criteria for differential diagnosis of atypical pneumonia, 55 of 62 patients were correctly diagnosed with M. pneumoniae pneumonia (sensitivity 88.7%), and 31 of 40 patients with bacterial and viral pneumonia were correctly excluded (specificity 77.5%). Conclusions: The JRS guidelines on CAP provide a useful tool for the identification of M. pneumoniae pneumonia cases and differentiating these from cases of typical bacterial or viral pneumonia.     

Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients

M. Mikulska, V. Del Bono, R. Prinapori, L. Boni, A.M. Raiola, F. Gualandi, M.T. Van Lint, A. Dominietto, T. Lamparelli, P. Cappellano, A. Bacigalupo, C. Viscoli. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.
Transpl Infect Dis 2010: 12: 505–512. All rights reserved Abstract: Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case–control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2–24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65–48.99 and OR=7.52, 95% CI, 1.56–36.31, respectively, P=0.047); severe (grades 3–4) mucositis (OR=9.04, 95% CI, 1.97–41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11–18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93–18.66 for 1–7 days of therapy, and OR=7.31, 95% CI, 1.78–30.12 for 8–23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06–0.97, P=0.045 and OR=0.11, 95% CI, 0.02–0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.     

Aetiology of community-acquired pneumonia in hospitalized adult patients in New Caledonia

Objective To describe the aetiology of community‐acquired pneumonia (CAP) in hospitalized adult patients in New Caledonia, a French archipelago in the South Pacific. Methods Confirmed CAP patients (n = 137) were enrolled prospectively. Pathogens were detected by culture, molecular methods, serology on paired sera, immunofluorescence on nasopharyngeal swabs and antigen detection in urine. Results The aetiology of CAP was determined in 82 of 137 cases (59.8%), of which 31 exhibited two or more pathogens (37.8%). Hundred and seventeen pathogens were detected: Streptococcus pneumoniae was the most common one (41.0%), followed by influenza virus A (22.1%) and Haemophilus influenzae (10.2%). The frequency of atypical bacteria was low (6.0%). The most frequent and significant coinfection was S. pneumoniae with influenza A virus (P = 0.004). Influenza virus was detected from nasopharyngeal swabs in four patients (15.4% of patients tested for influenza) and by PCR from pulmonary specimens in 15 patients (57.7%). Conclusions Streptococcus pneumoniae is the leading cause of CAP in New Caledonian adults. Viral–bacterial co‐infections involving S. pneumoniae and influenza virus are very common during the winter. Such adult patients hospitalized with CAP are a clear sentinel group for surveillance of influenza. Vaccination against influenza and S. pneumoniae should be strengthened when risk factors are identified.     

Prediction of microbial infection and mortality in medical patients with fever: plasma procalcitonin, neutrophilic elastase-alpha1-antitrypsin, and lactoferrin compared with clinical variables.

Fever suggests the likelihood of severe microbial infection. Abnormal temperature, tachycardia, tachypnea, and abnormal white blood cell counts define the systemic inflammatory response syndrome (SIRS). In 300 hospitalized medical patients with fever, we determined clinical variables and procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels in plasma. Of the patients, 71% had clinical infection (by clinical judgment) and 44% had microbial infection (by microbiological testing). SIRS occurred in 95%, and the 28-day mortality rate was 9%. The sensitivity for predicting microbial infection, bacteremia, and mortality was less but the specificity was greater for supranormal procalcitonin, elastase-alpha1-antitrypsin, and lactoferrin levels than for SIRS. The area under the receiver operating characteristic curve (AUC) for microbial infection was higher for procalcitonin and elastase-alpha1-antitrypsin levels than for clinical variables and lactoferrin level. The AUC for bacteremia was also higher for inflammatory factors (>0.70; P < .001) than for clinical variables. The AUC for mortality (P < .05) was 0.79 for the respiratory rate, 0.69 for elastase-alpha1-antitrypsin level, 0.65 for heart rate, 0.61 for procalcitonin level, and 0.60 for white blood cell count. In febrile medical patients, plasma procalcitonin and elastase-alpha1-antitrypsin levels may predict microbial infection and bacteremia better than (and mortality as well as) do clinical symptoms.     

Influence of Clinical and Procedural Predictors on Ventricular Tachycardia Ablation Outcomes: An Analysis From the Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia Trial (SMASH‐VT)

Procedural Predictors in SMASH‐VT . Background: The Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH‐VT) trial is the largest randomized trial in substrate‐based ablation. We performed a retrospective analysis of patients randomized to prophylactic ablation of ventricular tachycardia to determine the predictive value of clinical and procedural variables on outcomes. Methods: In patients treated with catheter ablation, we examined predictors of ICD‐therapy free survival using Cox proportional hazards models. Procedural variables tested included the scar location, number of VT morphologies (VTs) induced, tachycardia cycle length, catheter irrigation, catheter approach, procedural duration, and VT inducibility after ablation. Clinical variables including age, index arrhythmia, NYHA class, ejection fraction, prior revascularization, and baseline medication use were also analyzed. Results: Among 64 patients randomized to ablation, 61 received the assigned therapy and complete procedural data were available for 54 patients. Thirteen percent (7 of 54) experienced ICD therapies during 2‐year follow‐up. Patients with subsequent ICD therapies had significantly more VTs induced during the ablation procedure than those without (3.9 ± 2.1 vs 1.9 ± 1.8, P = 0.05). The hazard ratio for each additional VT induced was 1.51 (95% CI 1.07–2.13, P = 0.02). Two‐year Kaplan–Meier event‐free survival rates were 96% for 0–1 VTs induced, and 78% for two or more. The use of irrigated catheters was not predictive of ablation success. Conclusion: In this small retrospective analysis, the number of VTs induced during the procedure was predictive of 2‐year outcomes. This likely reflects a more complex arrhythmia substrate in patients who fail ablation. (J Cardiovasc Electrophysiol, Vol. pp. 799‐803, July 2010)     

Non-genetic risk factors and predicting efficacy for docetaxel--drug-induced liver injury among metastatic breast cancer patients

Background and Aim: Docetaxel has been chosen as one of the most popular anticancer drugs in the treatment of breast cancer for more than a decade. There is increasingly awareness for the occurrence of docetaxel and/or docetaxel–drug‐induced liver injury (DILI), although the underlying mechanism of occurrence and its risk factors remain unclear. Methods: We conducted a retrospective cohort study to identify non‐genetic risk factors for docetaxel–DILI among 647 metastasis breast cancer patients treated with docetaxel‐containing regimens. Results: Sixty‐seven (10.36%) patients were diagnosed as docetaxel–DILI. By logistic regression analysis, premenopausal status (odds ratio [OR][95% confidence interval {CI}] = 2.24 [1.30–3.87]), past hepatitis B virus (HBV) infections (OR [95% CI] = 4.23 [1.57–11.42]), liver metastasis (OR [95% CI] = 3.70 [2.16–6.34]). The predominant occurrence of DILI was seen in groups with docetaxel combination regimens. (OR [95% CI] = 2.66 [1.59–4.55]). The potential increasing occurrence of docetaxel–DILI was associated with multiple risk factors in an exposure–response manner (P < 0.001), and patients with more than three risk factors would be exposed to a 36.61‐fold risk of DILI (95% CI = 10.18–131.62). Further analysis by the risk score and area under the receiver–operator characteristic curve (AUC) showed that those four factors contributed to an AUC of 0.7536 (95% CI = 0.70–0.81), with a predictive sensitivity of 74.63% and specificity of 65.17%. Conclusions: Docetaxel–DILI with a relatively higher incidence should be addressed among metastatic breast cancer patients. Four predominant risk factors, including premenopausal status, past HBV infection, liver metastasis, and docetaxel combination regimens, were potential predicators for DILI.     

Analysis of HLA‐DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA‐DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Aims: Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA‐DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1–452‐month observation period. Results: Anti‐gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and anti‐centromere antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice‐ and nonjaundice‐type progression, respectively. HLA‐DRB1*0405 and *0803 predisposed patients to anti‐gp210 (OR, 1.61, 95% CI, 1.08–2.39) and anti‐centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA‐DRB1*1502 and *0901 patients were predisposed to nonjaundice‐type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA‐DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA‐DRB1 alleles revealed that anti‐gp210 antibodies was a strong risk factor, regardless of the HLA‐DRB1 alleles for jaundice‐type progression, while anti‐centromere antibodies was a significant risk factor for nonjaundice‐type progression in patients with HLA‐DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and ‐DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA‐DRB1 alleles. Conclusions: HLA‐DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.     

Clinical impact of sirolimus‐eluting stent in ST‐segment elevation myocardial infarction: A meta‐analysis of randomized clinical trials

Objectives: To evaluate outcome of patients undergoing sirolimus‐eluting stent (SES) as compared to bare‐metal stent (BMS) implantation during primary angioplasty for ST‐segment elevation myocardial infarction (STEMI). Background: The role of SES in primary percutaneous coronary intervention setting is still debated. Methods: We searched Medline, EMBASE, CENTRAL, scientific session abstracts, and relevant Websites for studies in any language, from the inception of each database until October 2008. Only randomized clinical trials with a mean follow‐up period >6 months and sample size >100 patients were included. Primary endpoint for efficacy was target‐vessel revascularization (TVR) and primary endpoint for safety was stent thrombosis. Secondary endpoints were cardiac death and recurrent myocardial infarction (MI). Results: Six trials were included in the meta‐analysis, including 2,381 patients (1,192 randomized to SES and 1,189 to BMS). Up to 12‐month follow‐up, TVR was significantly lower in patients treated with SES as compared to patients treated with BMS (4.53% vs. 12.53%, respectively; odds ratio [OR] 0.33; 95% confidence interval [CI] 0.24–0.46; P < 0.00001). There were no significant differences in the incidence of stent thrombosis (3.02% vs. 3.70%, OR = 0.81 [95% CI, 0.52–1.27], P = 0.81), cardiac death (2.77% vs. 3.28%, OR = 0.84 [95% CI, 0.52–1.35], P = 0.47), and recurrent MI (2.94% vs. 4.04%, OR = 0.71 [95% CI, 0.45–1.11], P = 0.13) between the two groups. Conclusion: SES significantly reduces TVR rates as compared to BMS in STEMI patients up to 1 year follow‐up. Further studies with larger population and longer follow‐up time are needed to confirm our findings. © 2009 Wiley‐Liss, Inc.     

Prognostic value of dynamic soluble triggering receptor expressed on myeloid cells in bronchoalveolar lavage fluid of patients with ventilator-associated pneumonia

Background and objective: The aim of this study was to investigate the time course, and correlation with prognosis, of BAL fluid concentrations of soluble triggering receptor expressed on myeloid cells (sTREM‐1) in patients with ventilator‐associated pneumonia (VAP). Methods: The study included 35 patients with clinically diagnosed VAP, eight of whom were BAL fluid culture‐negative and 27 BAL fluid culture‐positive (16 survivors, 11 non‐survivors). sTREM‐1 levels were measured in BAL fluid of these mechanically ventilated patients, at the time of diagnosis, on days 4–5 and on days 7–9. The time course of this biomarker and its prognostic value for outcome in patients with culture‐positive VAP were assessed. Results: sTREM‐1 concentrations were significantly greater in culture‐positive VAP patients than in culture‐negative VAP patients. sTREM‐1 levels decreased significantly with time in surviving patients with culture‐positive VAP, but increased significantly with time in non‐survivors. In contrast, PaO₂/fraction of inspired oxygen (FiO₂) increased significantly with time in survivors and decreased significantly with time in non‐survivors. At a cut‐off value of ?10 pg/mL 7–9 days after initial diagnosis, sTREM levels had a sensitivity of 90% and a specificity of 87.5% for predicting mortality. Conclusions: sTREM‐1 concentrations in BAL fluid are of potential prognostic value in patients with VAP.     

Usefulness of a semi-quantitative procalcitonin test and the A-DROP Japanese prognostic scale for predicting mortality among adults hospitalized with community-acquired pneumonia

Background and objective: The solid‐phase immunoassay, semi‐quantitative procalcitonin (PCT) test (B R A H M S PCT‐Q) can be used to rapidly categorize PCT levels into four grades. However, the usefulness of this kit for determining the prognosis of adult patients with community‐acquired pneumonia (CAP) is unclear. Methods: A prospective study was conducted in two Japanese hospitals to evaluate the usefulness of this PCT test in determining the prognosis of adult patients with CAP. The accuracy of the age, dehydration, respiratory failure, orientation disturbance, pressure (A‐DROP) scale proposed by the Japanese Respiratory Society for prediction of mortality due to CAP was also investigated. Hospitalized CAP patients (n = 226) were enrolled in the study. Comprehensive examinations were performed to determine PCT and CRP concentrations, disease severity based on the A‐DROP, pneumonia severity index (PSI) and confusion, urea, respiratory rate, blood pressure, age ≥65 (CURB‐65) scales and the causative pathogens. The usefulness of the biomarkers and prognostic scales for predicting each outcome were then examined. Results: Twenty of the 170 eligible patients died. PCT levels were strongly positively correlated with PSI (ρ = 0.56, P < 0.0001), A‐DROP (ρ = 0.61, P < 0.0001) and CURB‐65 scores (ρ = 0.58, P < 0.0001). The areas under the receiver operating characteristic curves (95% CI) for prediction of survival, for CRP, PCT, A‐DROP, CURB‐65, and PSI were 0.54 (0.42–0.67), 0.80 (0.70–0.90), 0.88 (0.82–0.94), 0.88 (0.82–0.94), and 0.89 (0.85–0.94), respectively. The 30‐day mortality among patients who were PCT‐positive (≥0.5 ng/mL) was significantly higher than that among PCT‐negative patients (log–rank test, P < 0.001). Conclusions: The semi‐quantitative PCT test and the A‐DROP scale were found to be useful for predicting mortality in adult patients with CAP.     

Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients

Background. Bacteremias, which are often caused by gram‐negative bacteria, are the most frequently occurring infectious complications after liver transplantation (LT). The aim of this study was to investigate bacteremic incidence, pathogenic spectrum, risk factors for bacteremia due to multidrug resistant (MDR) gram‐negative bacilli, and its impact on mortality after LT. Methods. A cohort analysis of prospectively recorded data was done in 475 LT recipients, who were divided into 3 categories: cases with gram‐negative bacteremia, cases with MDR gram‐negative bacteremia, and cases without bacteremia as controls. Results. In 475 LT recipients, there were 152 (32.0%) patients with gram‐negative bacillus bacteremia in the first 6 months after LT. Out of 152 patients, there were 225 bacteremic episodes, which accounted for 69.7% in a total 323 bacteremic episodes. A total of 190 bacteremic episodes were caused by Stenotrophomonas maltophilia, Enterobacteriaceae, Ochrobactrum anthropi, Pseudomonas, and Acinetobacter baumanii, all of which were the most frequent gram‐negative isolates in this study, and MDR bacilli constituted 56.3%. The most frequent source was intravascular catheters. There were 70 patients with MDR gram‐negative bacillus bacteremia. Independent risk factors for bacteremia due to MDR gram‐negative bacillus were as follows: post‐LT abdominal infection (P<0.0001, odds ratio [OR] 0.066, 95% confidence interval [CI] 0.019–0.226), post‐LT reoperative episodes (P<0.0001, OR 10.505, 95% CI 3.055–36.121), or one or more episodes of acute rejection (P=0.042, OR 4.457, 95% CI 0.988–20.103). In the first 6 months after LT, MDR gram‐negative bacillus bacteremia‐related mortality was significantly higher than that due to antibiotic‐susceptible bacillus (38.6% vs. 14.6%, P<0.001). Conclusion. Post‐LT bacteremias caused by MDR gram‐negative bacilli are common, and associated with allograft acute rejection, post‐LT reoperation, and abdominal infection. The increasing isolates of MDR gram‐negative bacilli pose a great challenge for clinical treatment.