Soluble TREM-like Transcript-1 Acts as a Damage-Associated Molecular Pattern through the TLR4/MD2 Pathway Contributing to Immune Dysregulation during Sepsis.

Studies have shown that elevated plasma levels of platelet-derived soluble TREM-like transcript-1 (sTLT-1) are associated with an unfavorable outcome in patients with septic shock. However, the underlying molecular mechanisms are not well defined. This research aimed to study the role of sTLT-1 in mediating immune dysfunction during the development of sepsis. Our study demonstrated that patients with septic shock have significantly higher plasma concentrations of sTLT-1, whereas sTLT-1 is not detectable in healthy subjects. Plasma concentrations of sTLT-1 were correlated with the degree of immunosuppressive parameters in monocytes from patients with septic shock. sTLT-1 can first activate monocytes by binding to the TLR4/MD2 complex but subsequently induce immunosuppressive phenotypes in monocytes. Blocking Abs against TLR4 and MD2 led to a significant decrease in sTLT-1-induced activation. Treatment with an anti-TLT-1 Ab also significantly reduces sTLT-1 binding to monocytes and proinflammatory cytokine secretion in a mouse model of endotoxemia. sTLT-1 acts as an endogenous damage-associated molecular pattern molecule, triggering the activation of monocytes through the TLR4/MD2 complex followed by sustained immune suppression. This process plays a crucial role in the development of sepsis-associated pathophysiology. Our findings outline, to our knowledge, a novel pathway whereby platelets counteract immune dynamics against infection through sTLT-1.

Author response to "lack of benefit from low dose computed tomography in screening for lung cancer".

We explain to Dr. Benjamin (corresponding author) about why low-dose computed tomography reduce lung cancer mortality without significantly reducing all-cause mortality. We also conduct an up-to-date meta-analysis to evaluate low-dose computed tomography clinical effectiveness compared with usual care of lung cancer screening.

Effects of low-dose computed tomography on lung cancer screening: a systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: The Nelson mortality results were presented in September 2018. Four other randomized control trials (RCTs) were also reported the latest mortality outcomes in 2018 and 2019. We therefore conducted a meta-analysis to update the evidence and investigate the benefits and harms of low-dose computed tomography (LDCT) in lung cancer screening. METHODS: Detailed electronic database searches were performed to identify reports of RCTs that comparing LDCT to any other type of lung cancer screening. Pooled risk ratios (RRs) were calculated using random effects models. RESULTS: We identified nine RCTs (n = 97,244 participants). In pooled analyses LDCT reduced lung cancer mortality (RR 0.83, 95% CI 0.76-0.90, I2 = 1%) but had no effect on all-cause mortality (RR 0.95, 95% CI 0.90-1.00). Trial sequential analysis (TSA) confirmed the results of our meta-analysis. Subgroup defined by high quality trials benefitted from LDCT screening in reducing lung cancer mortality (RR 0.82, 95% CI 0.73-0.91, I2 = 7%), whereas no benefit observed in other low quality RCTs. LDCT was associated with detection of a significantly higher number of early stage lung cancers than the control. No significant difference (RR 0.64, 95% CI 0.30-1.33) was found in mortality after invasive procedures between two groups. CONCLUSIONS: In meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival. The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, Asian) being screened.

Synthesis of novel C4-benzazole naphthalimide derivatives with potent anti-tumor properties against murine melanoma.

Novel C4-benzazole naphthalimide derivatives were synthesized and tested in vitro and in vivo as anti-cancer drugs. Among these synthetic molecules, compounds 9 and 10 exhibited cytotoxicity against murine B16F10 melanoma cells. In addition, the above-mentioned compounds significantly suppressed lung tumor metastasis with no visible sign of toxicity.

Potential effect of ezetimibe against Mycobacterium tuberculosis infection in type II diabetes.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy. METHODS: Intracellular mycobacteria survival was determined by measurements of ATP activity and colony-formation units (CFUs). Gene expression profiles of hypoxia-induced dormant Mycobacterium tuberculosis (Mtb) were analysed by real-time PCR. Flow cytometry and microscopy analysis were used to measure the lipid loads of human macrophages with or without ezetimibe treatment. QuantiFERON-TB Gold In-Tube (QFT-G-IT) assays were performed to diagnose latent TB infection. The levels of intracellular cholesterol/ triglyceride were measured by an enzymatic fluorometric method. RESULTS: Ezetimibe was capable of effectively lowering intracellular growth of Mtb and hypoxia-induced dormant Mtb. There was a significant decrease in Mtb growth in leucocytes from ezetimibe-treated patients with diabetes in terms of ATP levels of intracellular mycobacteria and CFU formation. Also, patients receiving ezetimibe therapy had a lower prevalence of latent TB and had lower intracellular lipid contents. CONCLUSION: Ezetimibe, which is a currently marketed drug, could hold promise as an adjunctive, host-directed therapy for TB.

Analysis of the immune response of human dendritic cells to Mycobacterium tuberculosis by quantitative proteomics.

BACKGROUND: The cellular immune response for Mycobacterium tuberculosis (M. tuberculosis) infection remained incompletely understood. To uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed M. tuberculosis (HKTB) treatment. RESULTS: Organic solvent-assisted trypsin digestion coupled with stable-isotope labeling and LC-MS/MS analysis was applied to quantitatively analyze the membrane protein expression of THP-1 derived dendritic cells. We evaluated proteins that were upregulated in response to HKTB treatment, and applied STRING website database to analyze the correlations between these proteins. Of the investigated proteins, aminopeptidase N (CD13) was found to be largely expressed after HKTB treatment. By using confocal microscopy and flow cytometry, we found that membranous CD13 expression was upregulated and was capable of binding to live mycobacteria. Treatment dendritic cell with anti-CD13 antibody during M. tuberculosis infection enhanced the ability of T cell activation. CONCLUSIONS: Via proteomics data and STRING analysis, we demonstrated that the highly-expressed CD13 is also associated with proteins involved in the antigen presenting process, especially with CD1 proteins. Increasing expression of CD13 on dendritic cells while M. tuberculosis infection and enhancement of T cell activation after CD13 treated with anti-CD13 antibody indicates CD13 positively involved in the pathogenesis of M. tuberculosis.

Aminopeptidase N facilitates entry and intracellular survival of Mycobacterium tuberculosis in monocytes.

BACKGROUND AND OBJECTIVE: Aminopeptidase N (CD13) is an ectoenzyme located in the outer membrane of a variety of cells. Proteomic profiling indicates an increased expression of CD13 in phagocytes during Mycobacterium tuberculosis infection. The purpose of this study was to investigate the role of CD13 on the internalization and intracellular survival of M. tuberculosis in monocytes. METHODS: Magnetic nanoparticles and confocal microscopy were used to observe interactions between CD13 and M. tuberculosis. Mycobacterial entry and intracellular survival in monocytes were assessed with and without anti-CD13 antibody (WM15 and WM47) using flow cytometry and colony formation assay. RESULTS: By using magnetic nanoparticles and confocal microscopy, M. tuberculosis was found to be capable of binding to either soluble CD13 or membranous CD13 on monocytes. Flow cytometry showed that pretreatment of monocytes with WM15 or WM47 reduced the number of intracellular M. tuberculosis. Collectively, the data suggest that CD13 is a binding and entry receptor for M. tuberculosis on monocytes. Treatment of infected monocytes showed a greater effect of WM47 than WM15 in reducing the intracellular colonization of M. tuberculosis, suggesting that specific epitopes of CD13 may play an important role modulating intracellular M. tuberculosis survival. CONCLUSIONS: CD13 acts as a receptor for M. tuberculosis on human monocytes. The molecule facilitates internalization, and interaction of CD13 with an anti-CD13 antibody reduces intracellular M. tuberculosis survival.

Mycobacterium tuberculosis DNA detection using surface plasmon resonance modulated by telecommunication wavelength.

A surface plasmon resonance sensor for Mycobacterium tuberculosis (MTB) deoxyribonucleic acid (DNA) is developed using repeatable telecommunication wavelength modulation based on optical fiber communications laser wavelength and stability. MTB DNA concentrations of 1 µg/mL and 10 µg/mL were successfully demonstrated to have the same spectral half-width in the dip for optimum coupling. The sensitivity was shown to be -0.087 dB/(µg/mL) at all applied telecommunication wavelengths and the highest sensitivity achieved was 115 ng/mL without thiolated DNA immobilization onto a gold plate, which is better than the sensor limit of 400 ng/mL possible with commercial biosensor equipment.

Detecting small lung tumors in mouse models by refractive-index microradiology.

Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm(3) with accuracy better than 1 × 10(-3) mm(3). This level of performance is currently suitable for animal studies, while further developments are required for clinical application.

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, PaO(2)/fraction of inspired oxygen (FiO(2)) 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.

A Microfluidic Flip-Chip Combining Hydrodynamic Trapping and Gravitational Sedimentation for Cell Pairing and Fusion.

Cancer cell-immune cell hybrids and cancer immunotherapy have attracted much attention in recent years. The design of efficient cell pairing and fusion chips for hybridoma generation has been, subsequently, a subject of great interest. Here, we report a three-layered integrated Microfluidic Flip-Chip (MFC) consisting of a thin through-hole membrane sandwiched between a mirrored array of microfluidic channels and saw-tooth shaped titanium electrodes on the glass. We discuss the design and operation of MFC and show its applicability for cell fusion. The proposed device combines passive hydrodynamic phenomenon and gravitational sedimentation, which allows the transportation and trapping of homotypic and heterotypic cells in large numbers with pairing efficiencies of 75~78% and fusion efficiencies of 73%. Additionally, we also report properties of fused cells from cell biology perspectives, including combined fluorescence-labeled intracellular materials from THP1 and A549, mixed cell morphology, and cell viability. The MFC can be tuned for pairing and fusion of cells with a similar protocol for different cell types. The MFC can be easily disconnected from the test setup for further analysis.

Immune impairment in patients with terminal cancers: influence of cancer treatments and cytomegalovirus infection.

Although immunodeficiency is usually considered a prerequisite of oncogenesis, a detailed immune pro- file in cancer has not yet been described. Without such profiling, it is not surprising that there is a vast discrepancy in the responses of cancer patients to immunotherapy. Our results show that the integrity of the immune system deteriorates with cancer progression by displaying a trend toward decreasing levels of functional T cells, including CD4, naïve, and central memory T cells, and an expansion of hyporesponsive populations such as CD28⁻ and CMV-specific T cells. One hundred and one patients constitute the study group for the observational study reported in this paper. Forty-eight patients with newly diagnosed stages III and IV and 53 patients with extensively treated stage IV disease. The costimulatory molecules CD27 and CD28 were downregulated in all patients. Among the proinflammatory cytokines (IL-6, TNF-α, IFN-γ), only IL-6 differed significantly among the groups, increasing as the cancer stage progressed. Plasma IL-7 did not diVer among the participants. The relative deficits of naïve T cells in cancer patients may be associated with the downregulation of IL-7Rα expression rather than changes in the circulating levels of IL-7. The downregulation of IL-7Rα expression was shown to be associated with increased levels of intracellular CMV. The present study suggests that the immune impairment in patients with cancer is associated with multiple factors, such as the stage of cancer, consequence of CMV infection and impact of treatment.

Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability of Mtb in human macrophages. METHODS: Epidemiological data from the National Health Insurance Research Database of Taiwan were used to present outcomes of TB patients treated with fenofibrate. In the laboratory, we assessed Mtb infection in macrophages treated with or without fenofibrate. Mtb growth, lipid accumulation in macrophages, and expression of transcriptional genes were examined. RESULTS: During 11 years of follow-up, TB patients treated with fenofibrate presented a higher risk of mortality. Longer duration of fenofibrate use was associated with a significantly higher risk of mortality. Treatment with fenofibrate significantly increased the number of bacilli in human macrophages in vitro. Fenofibrate did not reduce, but induced an increasing trend in the intracellular lipid content of macrophages. In addition, dormant genes of Mtb, icl1, tgs1, and devR, were markedly upregulated in response to fenofibrate treatment. Our results suggest that fenofibrate may facilitate intracellular Mtb persistence. CONCLUSIONS: Our data shows that long-term treatment with fenofibrate in TB patients is associated with a higher mortality. The underlying mechanisms may partly be explained by the upregulation of Mtb genes involved in lipid metabolism, enhanced intracellular growth of Mtb, and the ability of Mtb to sustain a nutrient-rich reservoir in human macrophages, observed during treatment with fenofibrate.

Involvement of p29 in DNA damage responses and Fanconi anemia pathway.

Human p29 is a chromatin-associated protein and the silencing of p29 expression increases cell population in G(1) phase and decreases phosphorylation levels of Chk1 and Chk2 in response to UV treatment. To further characterize the function of p29, U2OS and Fanconi anemia complementation group G (FA-G) cells with constitutive p29 expression have been established. Analyses of these cells identified increased phosphorylation levels of Chk1 and Chk2, which were accompanied by elevated amounts of chromatin-associated Mre11-Rad50-Nbs1 complex and ATR-IP. Monoubiquitination of the FA ID complex was restored in p29 stably expressing FA-G cells. Moreover, lower tumor incidence was observed in mp29 transgenic mice after UV irradiation. These results suggest the involvement of p29 in the DNA damage responses and Fanconi anemia pathway.

Bronchodilatation effects of a small volume spacer used with a metered-dose inhaler.

BACKGROUND AND OBJECTIVE: In an effort to improve the delivery of drugs to the lungs, various spacer devices have been developed to attach to metered-dose inhalers (MDIs). The aim of the study was to determine whether use of a small volume tube spacer with MDI is associated with better bronchodilatation. METHODS: We assessed bronchodilatation by measuring forced expiratory volume in 1 second (FEV(1)) before and after inhalation of fenoterol 0.4 mg (2 puffs) delivered by using a MDI in four different ways: with or without a spacer alone or with a mouth rinse of 100 mL of water immediately after inhalation with or without a spacer. Results. A total of 303 patients who had a positive bronchodilator test were studied. There was no significant difference in the Delta FEV(1) (mL or %) with or without a spacer (MDI + spacer vs. MDI, mean +/- SD, 365.1 +/- 146.5 mL vs. 356.3 +/- 131.1 mL, p = 0.696; and 21.4 +/- 9.4% vs. 21.4 +/- 9.5%, p = 0.968, respectively). When patients rinsed their mouth after inhalation, bronchodilatation was significantly less in those using an MDI alone compared with MDI + spacer (302.6 +/- 116.5 mL vs. 367.6 +/- 128.3 mL, p = 0.002; and 18.0% +/- 7.9% vs. 21.7% +/- 9.5%, p = 0.013, respectively). CONCLUSIONS: When patients correctly use an MDI, addition of a spacer does not significantly improve bronchodilatation. However, if the mouth is rinsed after inhalation, a spacer does yield better bronchodilatation. Our results suggest that systemic effects from bronchodilator inhalation may not be negligible.

Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease.

BACKGROUND: Triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses. The aim of this study was to investigate the expression of TREM-1 in pleural effusions of various causes. METHODS: For this cross-sectional, observational study conducted between February and August 2005 in Taiwan, 74 patients with pleural effusions of varying etiology were investigated. Soluble TREM-1 (sTREM-1) was measured in pleural fluid samples, and cells in the fluid were assessed for surface expression of TREM-1. RESULTS: Concentrations of sTREM-1 were significantly higher in infectious and neoplastic pleural effusions (189.1+/-36.7 and 69.9+/-22.8ng/ml, mean+/-sem) than in transudates (10.1+/-5.3ng/ml; P<0.001). Among infectious effusions, the sTREM-1 levels were significantly higher in parapneumonic than in tuberculous effusions (301.8+/-49.8 vs. 38.9+/-17.3ng/ml; P<0.001). TREM-1 was expressed on a portion of the myeloid (CD11b positive) cells in each type of effusion, without significant differences among them (transudative, 34.7%; neoplastic, 36.0%; parapneumonic, 27.7%; tuberculous, 21.2%; P=0.861). Non-myeloid cells expressed very little TREM-1 (transudative, 6.3%; neoplastic, 0.5%; parapneumonic, 1.0%; tuberculous, 0.7%; P=0.192). CONCLUSIONS: sTREM-1 expression in pleural fluids is highest in parapneumonic and neoplastic effusions but low in transudates. In infectious effusions, a high concentration of sTREM-1 may exclude tuberculous pleurisy.

Colonization of severe acute respiratory syndrome-associated coronavirus among health-care workers screened by nasopharyngeal swab.

STUDY OBJECTIVES: To report the efficacy and findings of a large-scale preventive screening program for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using amplification of the virus from a nasopharyngeal swab (NPS) obtained from the health-care workers (HCWs). DESIGN: A prospective observational study. SETTING: A medical center in Taiwan. PARTICIPANTS: Two hundred thirty HCWs. INTERVENTION: NPS examination for the presence of SARS-CoV by two nested reverse transcription-polymerase chain reaction (RT-PCR) assays. MEASUREMENTS AND RESULTS: During the outbreak of severe acute respiratory syndrome (SARS), NPS polymerase chain reaction screening of HCWs for SARS-CoV was performed. SARS-CoV was examined by two nested RT-PCRs and a quantitative RT-PCR. Serum-specific antibodies were assessed by enzyme immunoassay and indirect immunofluorescence. We monitored 230 HCWs, including 217 first-line HCWs and 13 non-first-line HCWs. One hundred ninety first-line HCWs and 13 non-first-line HCWs had negative results in both nested RT-PCR assays. Two first-line HCWs who were positive on both nested RT-PCR assays had SARS. They had 16,900 +/- 7,920 copies (mean +/- SD) of RNA per milliliter in the NPS and had detectable anti-SARS antibodies. The remaining 25 first-line HCWs were negative for the first nested RT-PCR but positive for the second nested RT-PCR. Their corresponding titers were 338 +/- 227 copies of RNA per milliliter; antibodies developed in none of these 25 HCWs. The expression and function of angiotensin-converting enzyme-2 were not different among these HCWs. This study shows that colonization of SARS-CoV occurred in 25 of 217 well-protected first-line HCWs on a SARS-associated service, but they remained seronegative. CONCLUSION: With the second RT-PCR assay more sensitive than the first RT-PCR assay, we are able to show that approximately 11.5% of well-protected HCWs exposed to SARS patients or specimens may have colonization without seroconversion. Only those with significant clinical symptoms or disease would have active immunity. Thus, regular NPS screening for nested RT-PCR assays in conjunction with a daily recording of body temperature in all first-line HCWs may provide an effective way of early detection.

Viral load and outcome in SARS infection: the role of personal protective equipment in the emergency department.

This study was conducted to evaluate the effectiveness of personal protective equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non-HCWs were studied. We compared the initial viral load by nasopharyngeal swabs, clinical progression, and outcome of this cluster. The HCWs had a lower viral load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation, and a higher incidence of intubation and death. Secondary household transmission developed in three of the non-HCWs' families. One month after discharge, non-HCWs had more signs of fibrosis on high resolution computed tomography (HRCT) scan and an impaired pulmonary function test. Although most of the PPE do not confer absolute protection against SARS, it seems that they may lower exposure to the virus, leading to a lower risk of secondary transmission, and be associated with relatively mild disease and a better early outcome.

Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers.

STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS). DESIGN: A retrospective observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Comparative study of patients with and without SARS who fulfilled the WHO SARS case definition.

To differentiate severe acute respiratory syndrome (SARS) from non-SARS illness, we retrospectively compared 53 patients with probable SARS and 31 patients with non-SARS who were admitted to Mackay Memorial Hospital from April 27 to June 16, 2003. Fever (> 38 degrees C) was the earliest symptom (50/53 SARS vs. 5/31 non-SARS, p < 0.0001), preceding cough by a mean of 4.5 days. The initial chest X-ray study was normal in 22/53 SARS cases versus 5/31 non-SARS cases. SARS patients with an initially normal chest X-ray study developed infiltrates at a mean of 5 +/- 3.44 days after onset of fever (21/22 SARS vs. 0/5 non-SARS). Rapid radiographic progression of unifocal involvement to multifocal infiltrates was seen in 22 of 24 SARS vs. 0 of 26 non-SARS patients (p < 0.0001). Pleural effusion was not present in any SARS patients but was seen in 6 of 26 non-SARS cases (p < 0.0001). Initial lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase were all more common in SARS than non-SARS (p < 0.0001). They may help differentiate SARS from non-SARS if a reliable and rapid diagnostic test is not available.