High Mortality of Pneumonia in Cirrhotic Patients with Ascites

[[abstract]]Background Cirrhotic patients with ascites are prone to develop various infectious diseases. This study aimed to evaluate the occurrence and effect of major infectious diseases on the mortality of cirrhotic patients with ascites. Methods We reviewed de-identified patient data from the National Health Insurance Database, derived from the Taiwan National Health Insurance Program, to enroll 4,576 cirrhotic patients with ascites, who were discharged from Taiwan hospitals between January 1, 2004 and June 30, 2004. We collected patients’ demographic and clinical data, and reviewed diagnostic codes to determine infectious diseases and comorbid disorders of their hospitalizations. Patients were divided into an infection group and non-infection group and hazard ratios (HR) were determined for specific infectious diseases. Results Of the total 4,576 cirrhotic patients with ascites, 1,294 (28.2%) were diagnosed with infectious diseases during hospitalization. The major infectious diseases were spontaneous bacterial peritonitis (SBP) (645, 49.8%), urinary tract infection (151, 11.7%), and pneumonia (100, 7.7%). After adjusting for patients’ age, gender, and other comorbid disorders, the HRs of infectious diseases for 30-day and 90-day mortality of cirrhotic patients with ascites were 1.81 (1.54-2.11) and 1.60 (1.43-1.80) respectively, compared to those in the non-infection group. The adjusted HRs of pneumonia, urinary tract infection (UTI), spontaneous bacterial peritonitis (SBP), and sepsis without specific focus (SWSF) were 2.95 (2.05-4.25), 1.32 (0.86-2.05), 1.77 (1.45-2.17), and 2.19 (1.62-2.96) for 30-day mortality, and 2.57 (1.93-3.42), 1.36 (1.01-1.82), 1.51 (1.29-1.75), and 2.13 (1.70-2.66) for 90-day mortality, compared to those in the non-infection group. Conclusion Infectious diseases increased 30-day and 90-day mortality of cirrhotic patients with ascites. Among all infectious diseases identified, pneumonia carried the highest risk for mortality.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

A Cost-Effectiveness Analysis of “Test” versus “Treat” Patients Hospitalized with Suspected Influenza in Hong Kong

BACKGROUND: Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong. METHODS: We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: "immunofluorescence-assay" (IFA) or "polymerase-chain-reaction" (PCR)-guided oseltamivir treatment, "empirical treatment plus PCR" and "empirical treatment alone". Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010-2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers' perspective. RESULTS: In base-case analysis, "empirical treatment alone" was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that "PCR-guided treatment" would dominate "empirical treatment alone" when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, "empirical treatment alone" and "PCR-guided treatment" were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations. CONCLUSIONS: During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong

Nationwide Surveillance of Influenza during the Pandemic (2009–10) and Post-Pandemic (2010–11) Periods in Taiwan

INTRODUCTION: Although WHO declared the world moving into the post-pandemic period on August 10, 2010, influenza A(H1N1) 2009 virus continued to circulate globally. Its impact was expected to continue during the 2010-11 influenza season. This study describes the nationwide surveillance findings of the pandemic and post-pandemic influenza periods in Taiwan and assesses the impact of influenza A(H1N1) 2009 during the post-pandemic period. METHODS: The Influenza Laboratory Surveillance Network consisted of 12 contract laboratories for collecting and testing samples with acute respiratory tract infections. Surveillance of emergency room visits and outpatient department visits for influenza-like illness (ILI) were conducted using the Real-Time Outbreak and Disease Surveillance system and the National Health Insurance program data, respectively. Hospitalized cases with severe complications and deaths were reported to the National Notifiable Disease Surveillance System. RESULTS: During the 2009-10 influenza season, pandemic A(H1N1) 2009 was the predominant circulating strain and caused 44 deaths. However, the 2010-11 influenza season began with A(H3N2) being the predominant circulating strain, changing to A(H1N1) 2009 in December 2010. Emergency room and outpatient department ILI surveillance displayed similar trends. By March 31, 2011, there were 1,751 cases of influenza with severe complications; 50.1% reported underlying diseases. Of the reported cases, 128 deaths were associated with influenza. Among these, 93 (72.6%) were influenza A(H1N1) 2009 and 30 (23.4%) A(H3N2). Compared to the pandemic period, during the immediate post-pandemic period, increased number of hospitalizations and deaths were observed, and the patients were consistently older. CONCLUSIONS: Reemergence of influenza A(H1N1) 2009 during the 2010-11 influenza season had an intense activity with age distribution shift. To further mitigate the impact of future influenza epidemics, Taiwan must continue its multifaceted influenza surveillance systems, remain flexible with antiviral use policies, and revise the vaccine policies to include the population most at risk

Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia

A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure. Confirmation of etiology by laboratory testing is warranted in such cases. Rapid antigen and immunofluorescence testing are useful screening tests, but have limited sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture. The most effective preventive measure is annual influenza vaccination in selected individuals. Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results. Neuraminidase inhibitors (NI) are the agents of choice