Chien-Liang Wu

Clinical and Laboratory Features of Severe Acute Respiratory Syndrome Vis-A ` -Vis Onset of Fever*

Study objectives: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. Design: Retrospective observational study. Setting: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. Patients: Fifty-three patients with SARS seen between April 27 and June 16, 2003. Results: Fever (ie, temperature > 38°C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (± SD) time of 4.5 ± 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 ± 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 ± 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 ± 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. Conclusions: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.

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 profile 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 differ 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.

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).

Effect of a Hospital-based Case Management Approach on Treatment Outcome of Patients with Tuberculosis

Background/Purpose Tuberculosis (TB) continues to pose a heavy public health burden in Taiwan. This prospective study analyzed the factors influencing treatment outcome in patients with TB treated with and without a hospital-based case management (HBCM) approach in a referral center in Taipei. Methods A register-based cohort study design was used to enroll all new cases of pulmonary or extra-pulmonary TB from February 2003 to January 2004. The case manager served as the coordinator among patients, physicians and public health nurses, to facilitate compliance with anti-TB treatment. Treatment outcomes were assessed according to the consensus recommendations of the World Health Organization and the International Union Against Tuberculosis and Lung Disease. Results Suspected or confirmed pulmonary or extrapulmonary TB was diagnosed in 524 patients in our hospital from February 2003 to January 2004. Fifty-two of these patients were excluded due to duplicate reporting, previous treatment or death before enrollment. Out of 472 patients enrolled, 103 whose original diagnosis was revised were further excluded, leaving 369 cases eligible for analysis. Patients with case management had a significantly higher rate of successful treatment (cured plus completed treatment) compared to patients without case management, (240/277, 86.6% vs. 67/92, 72.8%; p = 0.002). The overall successful treatment rate including both case and non-case management was 83.2% (307/369), which was higher than the nationwide surveillance data of 78.3% in 2002 and 69.4% in 2003. Conclusion Treatment of TB patients by a HBCM approach provides improved treatment outcomes compared to those without case management.

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

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.

Cancer-Associated Immune Deficiency: A Form of Accelerated Immunosenescence?

Cancer (medical term: malignant tumor) is a major global health problem and a lifethreatening disease that accounts for ~13% of all deaths annually. The number of cancer deaths gradually increases year by year, and it is estimated that more than 11 million people will die from malignances in 2030. Various definitions of cancer have been proposed over the last few decades. In general, cancer displays several malignant features including the uncontrolled proliferation of abnormal cells, local invasion of normal tissue, and metastasis to a distant organ via the circulatory or lymphatic system. Environmental and genetic factors are considered to be the major causes of cancer. Cancer is believed to originate from a single normal cell through a multistage transformation that is assumed to take decades of development. Continuous exposure to some environmental factors (e.g., tobacco, unhealthy diet, radiation, chemical toxins, viruses, etc.) can potentially interact with gene changes in our bodies to enhance the formation of cancer (see http:// www.who.int/mediacentre/fac tsheets/ fs297/en/index.html). Conventional treatments include surgical resection, chemotherapy, and radiotherapy. Although these series of interventions can effectively control localized or disseminated tumors, there is still a high rate of metastatic recurrence, thus limiting a patient’s survival. Other strategies, such as immunotherapy, cytokine therapy, and adoptive cell therapy, have shown some promising results for malignances in animal models. Unfortunately, several phase I/II clinical trials have shown that most patients still fail to completely eliminate cancer (Aldrich et al., 2010). It is becoming increasingly clear that cancer cells express immunogenic antigens that can induce an effective immune response against tumor formation (Lowe et al., 2007); therefore, during the initial stages of disease, cancer cells could essentially be recognized and rejected by the immune system, which exerts hostprotective and tumor-modeling actions on developing tumors. Nonetheless, cancer cells also have numerous mechanisms to evade immunosurveillance (Burnet, 1970; Dunn et al., 2002), such as the downregulation of major histocompatibility complex (MHC) molecules or the antigen processing and presentation machineries, increasing the secretion of inhibitory cytokines, and the expression of inhibitory molecules to induce apoptosis in tumor-specific T cells (Dunn et al., 2004; Ferrara et al., 2003; Gabrilovich et al., 1996). On the basis of these phenomena, countless studies have confirmed the hypothesis that breaking self-tolerance and priming T lymphocytes are essential to treat cancer. Here, we discuss another possible

Application of Inspiratory Muscle Training in a Pregnant Guillain-Barre Syndrome Patient with Respiratory Failure: A Case Report

The annual incidence of Guillain-Barre syndrome (GBS) is from 1.1-1.8 cases/100,000 persons. Concurrent GBS during pregnancy is even rarer, and no more than 35 cases have been reported. Among them, only 10 cases of GBS with subsequent respiratory failure have been reported. It is difficult to wean these patients from ventilators because of muscle weakness and their pregnant status. We present our experience with a 21-year-old pregnant woman with GBS complicated with respiratory failure, and review what is currently known about the disease.

Experience of using activated protein C in a patient with emphysematous pyelonephritis receiving percutaneous nephrostomy drainage.

Summary Drotrecogin alfa, a type of recombinant human activated protein C, has potential to reduce the mortality in severe sepsis, but may simultaneously increase the risk of serious bleeding events. Here, we report an 81-yearold female suffering from emphysematous pyelonephritis who recovered after appropriate management, including antibiotics, percutaneous nephrostomy drainage and administration of activated protein C. This case showed that percutaneous nephrostomy drainage is not an absolute contraindication in the prescribing of activated protein C in patients with severe sepsis.

Use of a Rapid Shallow Breathing Index from a Commercially Available Respiratory Monitor in Predicting Weaning of Ventilated Patients

Objective: Frequency-to-tidal volume ratio (f/Vt) has been widely used as a weaning predictor for years. A method using a hand-held monitor with an automatic f/Vt calculation was tested in this study to verify its clinical application. Design: This was a prospective study of 102 respiratory failure patients ready for weaning in a 15-bed adult medical intensive care unit (ICU). Two f/Vt measurements were taken daily: 1 by the standard manual calculation (Yangs method) and the other by the VentCheck(superscript TM) monitor. Weaning was considered successful if the patient tolerated 2-hour trials without distress and remained free from mechanical ventilation for at least 48 hours. The patients were divided into successfully and unsuccessfully weaned groups. The sensitivity, specificity, and likelihood ratio of these predictors were calculated and the data were analyzed with an ROC curve to examine accuracy. Results: The overall weaning success rate was 67.6%. There were no significant differences in the APACHE Ⅱ score, age, gender, and diagnosis between the 2 groups. Sensitivity and accuracy were higher for Yangs method (traditional) than the 1-minute f/Vt (91.3% vs. 81.2% and 82.4% vs. 79.4%, respectively), but the areas under the ROC curve were similar for both measurements (0.86). Conclusions: The 1 minute f/Vt using the VentCheck(superscript TM) monitor is comparable to Yangs method in predicting successful weaning of ICU patients.

Effects of Age on 1-Second Forced Expiratory Volume Response to Bronchodilation

SUMMARY Background: The bronchodilation test is used to detect reversible airways obstruction, considered important for diagnosing asthma. However, little is known about the effects of age on the bronchodilation response. The aim of this study was to evaluate the effects of age on the bronchodilation response by determining changes in the 1-second forced expiratory volume (FEV1) in a Chinese population. Methods: All patients underwent pulmonary function testing to evaluate forced vital capacity, peak expiratory flow, and FEV1. We assessed bronchodilation by measuring the change in FEV1 (FEV1) before and after inhalation of 0.4 mg of fenoterol (two puffs) delivered by a metered-dose inhaler with a spacer. Results: Of the 1,616 patients tested in the clinic, the 333 (21%) who had a positive bronchodilator test, defined as FEV1 > 12% and 200 mL, were enrolled in the study. For this population, the FEV1 was +360.8 ± 138.6 mL (mean ± standard deviation) or +21.0% ± 9.1%. In a multiple linear regression model, the absolute FEV1 (expressed in milliliters) was independently and negatively predicted by age (p < 0.001), and baseline peak expiratory flow (p < 0.001), but positively predicted by height (p < 0.001). Conclusion: Age was an important determinant for response to bronchodilation as determined by the absolute change in FEV1. [International Journal of Gerontology 2009; 3(3): 149–155]