Clinical Features and Outcomes of Severe Acute Respiratory Syndrome and Predictive Factors for Acute Respiratory Distress Syndrome

BackgroundSevere acute respiratory syndrome (SARS) is an emerging infectious disease, and indeed, the SARS epidemic in Taiwan from March to July 2003 had a great impact. This study depicts the clinical characteristics and short-term outcomes of patients with SARS treated at Taipei Veterans General Hospital; potential predictive factors for acute respiratory distress syndrome (ARDS) are also analyzed.MethodsThis study retrospectively analyzed data for 67 SARS patients, who were grouped according to whether or not ARDS developed during the clinical course of SARS.ResultsThere were 32 males (mean age, 50.3 years; range, 20–75 years) and 35 females (mean age, 51.1 years; range, 23–86 years). Twenty-five patients (37.3%) were health care workers. At admission, 50 patients (74.6%) had abnormal chest radiographs, and all patients developed pulmonary infiltrates during the following week. During hospitalization, lymphopenia was found in 57 patients (85.1%); and elevated levels of lactate dehydrogenase (LDH; n = 55; 83.3%), C-reactive protein (n = 55; 83.3%), aminotransferases (n = 44; 65.7%), and creatine kinase (n = 14; 20.9%) were also noted. ARDS developed in 33 patients (49.3%), who were generally older than the patients in whom ARDS did not develop, male, non-health care workers, and who generally had dyspnea at the time of diagnosis, and a history of diabetes mellitus, hypertension or cerebrovascular accident. Patients with, versus those without, ARDS also tended to present with more severe lymphopenia and leukocytosis, and with higher levels of LDH and aspartate aminotransferase. The overall mortality rate was 31.3% (21/67), whereas the rate for patients who developed ARDS was 63.6% (21/33). Multivariate analyses showed that age greater than 65 years (odds ratio, OR, 10.6; 95% confidence interval, CI, 2.1–54.1), pre-existing diabetes mellitus (OR, 13.7; 95% CI, 1.3–146.9), and elevated levels of LDH (OR, 8.4; 95% CI, 1.9–36.9) at admission, were independent predictors of ARDS.ConclusionThe clinical manifestations of SARS showed high variability, and were related to the underlying health status of individual patients. Importantly, the development of ARDS was associated with significant mortality, despite aggressive therapy

Expression of c-Kit, Flk-1, and Flk-2 Receptors in Benign and Malignant Tumors of Follicular Epithelial Origin

BackgroundVascular endothelial growth factor (VEGF) is a key regulator of physiologic as well as pathologic angiogenesis. The response of VEGF to endothelial cell mitogenesis and survival, as well as angiogenesis and microvascular permeability, is mainly mediated through its receptor-2, VEGFR2 (kinase domain receptor or fetal liver kinase-1, KDR or Flk-1). This study aimed to detect the expression of VEGFR2 in various forms of thyroid tumors. In addition, the expression of Flk-2 (receptor for Flt-3) and c-Kit (receptor for steel locus factor), which shows strong similarity to Flk-1, was also examined in thyroid tumors.MethodsRT-PCR analyses of c-Kit and immunohistochemical staining of c-Kit, Flk-1, and Flk-2 were performed in archived samples of 18 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), 12 follicular adenoma (FA), and 7 nodular goiter (NG) samples. The data were correlated to clinicopathologic features.ResultsBy RT-PCR analyses, c-Kit expression was detected in 22% (4/18) of PTC, 22% (2/9) of FTC, 25% (3/12) of FA, and 57% (4/7) of NG samples. However, positive immunostaining signals of c-Kit were only observed in 17% (3/18) of PTC samples, and not in the others. Similarly, Flk-1 expression was only detected by immunohistochemistry in 67% (12/18) of PTC and 43% (3/7) of NG samples, and not in the others. Interestingly, the expression of Flk-2 was found in 89% (16/18) of PTC, 89% (8/9) of FTC, 75% (9/12) of FA, and 29% (2/7) of NG samples. An inverse relationship of thyroid cancer size with Flk-2 expression was found.ConclusionFlk-2 expression was detected in various forms of thyroid tumors and increased Flk-2 expression was correlated with thyroid tumors with increased transforming activity, suggesting that Flk-2 is involved in pathogenic development of thyroid malignancy. Similarly, Flk-1 expression was also found in some thyroid tumors, while the expression of c-Kit-mediated pathways may not play a major role in thyroid tumorigenesis

Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy

BRAF Mutation in Papillary Thyroid Carcinoma: Pathogenic Role and Clinical Implications

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, accounting for 85–90% of all thyroid cancers. Genetic alternations involving the mitogen-activated protein kinase (MAPK) pathway are frequently demonstrated in PTC, such as RET/PTC, RAS, and B-type Raf kinase (BRAF) mutations. Over 90% of BRAF mutations are T1799A, resulting in a BRAFV600E mutation. BRAFV600E is present in ∼50% of PTC and also found in aggressive histologic variants and PTC-derived anaplastic thyroid cancer, but is rare in follicular variants, and not found in follicular thyroid cancer. The tumorigenic role of BRAFV600E in the development of PTC was documented in thyroid-targeted BRAFV600E transgenic mice, and rat thyroid cells overexpressed with BRAFV600E suggested that BRAFV600E is an initiator of tumorigenesis and is required for tumor progression in PTC. Most clinical studies have demonstrated an association of BRAFV600E mutation with aggressive clinicopathologic characteristics and high tumor recurrence, although the results are controversial. The association is also observed in patients with papillary thyroid microcarcinomas and low-risk PTC. As a highly specific and unique mutation in PTC, testing for BRAFV600E in fine-needle aspiration specimens has been shown to refine the diagnostic accuracy of PTC in indeterminate cytology. Preoperative BRAFV600E analysis in low-risk patients may provide important value for prognostication, and these patients might benefit from receiving more intensive management and frequent follow-up. BRAF-targeted therapies have been developed to treat various human cancers including advanced thyroid cancers. Preclinical results are encouraging, but the anticancer effects of clinical trials are disappointing. Studies of multi-kinase inhibitors and/or combination with other regimens are underway in the treatment of advanced thyroid cancers. In this article, we review the pathogenesis of PTC, and the clinical implications of BRAFV600E mutation in the diagnosis, prognosis and potential targeted therapeutic strategies for thyroid cancers

Workload of Attending Physicians at an Academic Center in Taiwan

Since the fee-for-service reimbursement mechanism has been under the global budget of the National Health Insurance program, physicians' workloads have been increasing. Attending physicians in medical centers usually have long working hours because of their clinical work as well as teaching, research, and other administrative responsibilities. Many studies regarding reasonable work hours for physicians have been undertaken globally, but few have been conducted in Taiwan. In this study, we focused on the difference in working hours among physicians in different departments. Methods: Using attending physicians from a major teaching hospital as the study population, we adopted self-administered questionnaires to investigate physicians' time allocations for 4 major categories: clinical work, teaching, research, and administrative work. We distributed 432 questionnaires and received 380 filled-out questionnaires, yielding a response rate of 88%. After eliminating questionnaires with incomplete responses, the valid sample size was 376. We used t test and 1-way ANOVA to analyze the association between physicians' characteristics and workload and used multiple linear regression to examine factors influencing physicians' work hours. Results: The average weekly work time among attending physicians was 65.6 hours; physicians under the age of 40 worked an average of 69.8 hours. Males worked an average of 66.2 hours weekly and females an average of 62.7 hours. Total work hours and hours of clinical work, teaching, research, and administrative work all reached significant differences among departments. Physicians who were under 40 years old, those with a doctoral degree, those with a teaching position as associate professor or above, and those working in anesthesiology had longer total work hours. Conclusion: This study found that work hours among departments differed significantly and that physicians in surgical departments spend the longest hours in clinical work. Those in administrative positions are most involved in clinical work. However, work hours do not definitely represent work intensity, and to define the workload by working hours may be inappropriate for some departments. This possible difference between work hours and work intensity merits further consideration

Differential Gene Expression After Hemorrhagic Shock in Rat Lung

BackgroundWe investigated the differential gene expression in rat lung after hemorrhagic shock (HS).MethodsA controlled HS model in rats was used. Male Sprague-Dawley rats were randomly segregated into 2 groups, sham and HS. Samples of lung were procured from rats 2 hours after HS and resuscitation. Commercially available gene chips for rat cDNA microarray and software packages were used for the gene expression profile study.ResultsCompared with sham-shock rats, 98 genes were upregulated in HS rat lung. Most upregulated genes were responsible for inflammation (pro-inflammatory or anti-inflammatory cytokines, cognate receptors, and signal transduction for inflammation), protein activation (kinase and phosphatase), oxidation (oxidative and antioxidative enzymes), and apoptosis (apoptosis and anti-apoptosis). Eleven genes were downregulated after HS.ConclusionHS may induce upregulation of positive and negative control genes responsible for inflammation, oxidation, protein metabolism and apoptosis, that is, a vulnerable period may develop in the host after HS. Overwhelming inflammatory response or immunosuppression may occur once a second hit, such as infection, ensues. Understanding, on a genome scale, how an organism responds to HS may facilitate the development of enhanced treatment modalities for HS

Different Clinical Presentations in Chinese People with Acute Myocardial Infarction in the Emergency Department

The purpose of this study was to investigate the clinical characteristics of younger- (≤45 years old) and older-aged (>45 years) Chinese patients presenting to the emergency department (ED) with an initial acute myocardial infarction (AMI). Methods: A retrospective review of 372 patients who had suffered an AMI (134 younger-aged, 238 older-aged), from 2,858 suspected AMI or ischemia patients during the period January 1996 to June 2003 inclusive, was conducted. Only patients who were diagnosed with AMI and who had been admitted to our institution's ED were enrolled into this study. Results: The incidence of AMI for individuals who were ≤ 45 years old was approximately 12.3% of those admitted to hospital under the impression of AMI. The percentage of males was more predominant in the younger-aged group (p<0.01). Regarding major risk factors for coronary artery disease (CAD), younger patients were more likely to have a family history of cardiac disease (p<0.01), obesity with an elevated body mass index (26.2 ±4.1 vs. 24.2 ± 3.7, p< 0.01), and hyperlipidemia (p<0.01) when compared to the older-aged patients, who were more likely to suffer from hypertension (p<0.01) and/or diabetes mellitus than their younger-aged counterparts (p<0.01). Younger patients also featured a higher incidence of single-vessel CAD (p = 0.05), an insignificant rate of CAD (p = 0.02), and a lower rate of triple-vessel CAD (p = 0.03). Conclusion: For Chinese, male gender and incidences of chest pain, positive family history of heart disease, obesity and hyperlipidemia were significantly greater in the younger-aged AMI patient group than in the older-aged AMI patient group. Younger-aged patients also had a greater rate of single-vessel CAD but a lower rate of triple-vessel CAD than older-aged patients