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Background High Snail expression is known as a poor prognostic factor in breast cancer. However, its prognostic impact for breast cancer with different molecular subtypes is still controversial. Methods Snail expression was examined by immunohistochemistry in tissue microarray slides of 85 corresponding tumor-adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues. Multivariable Cox regression analysis was used to assess the impact of Snail expression on survival rate by different molecular subtypes of breast IDC patients. Results The level of Snail expression in IDC tumor tissues was significantly higher than that in CTAN tissues. Moreover, high Snail expression had direct impacts on poor disease specific survival (DSS) and disease-free survival (DFS) in breast IDC patients with human epidermal growth factor receptor 2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients with a combination of three prognostic factors, including high Snail expression and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a statistically significant linear trend. Conclusion High Snail expression could predict a poor prognosis for breast IDC patients with HER2/EGFR-positive subtypes.

Background/purpose Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. Methods An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. Results For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. Conclusion This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.

Objective To investigate the relationships between two single-nucleotide polymorphisms at miR-146a C > G (rs2910164) and miR-1269b G > C (rs7210937) and the risk of developing oral premalignant lesions (OPLs), oral squamous cell carcinoma (OSCC), pharyngeal SCC (PSCC), and oral and pharyngeal SCC (OPSCC). Design Genotyping of miR-146a C > G and miR-1269b G > C was performed in two case-control studies using the TaqMan assay. A total of 197 healthy control subjects, 241 OPLs patients, and 188 OPSCC patients who habitually chewed betel quid (BQ) were recruited into one case-control study. Additionally, 668 cancer-free control subjects and 658 OPSCC patients were recruited into the other case-control study. Results The G/G genotype at miR-146a C > G was associated with the decreased risk of OSCC [adjusted odds ratio (AOR) = 0.66, P = 0.040], PSCC (AOR = 0.42, P = 0.013), and OPSCC (AOR = 0.63, P = 0.020). Additionally, the C allelic type and C/C genotype at miR-1269b G > C decreased the risk of BQ-related oral leukoplakia (C vs. G: AOR = 0.68, P = 0.012; C/C vs. G/G: AOR = 0.43, P = 0.009), BQ-related OPLs (C vs. G: AOR = 0.69, P = 0.008; C/C vs. G/G: AOR = 0.44, P = 0.005), and BQ-related OPSCC (C vs. G: AOR = 0.65, P = 0.003; C/C vs. G/G: AOR = 0.47, P = 0.011). In OPSCC patients, the G/G genotype of miR-146a was correlated with well-differentiated cells (P = 0.041), and the G/C and C/C genotypes of miR-1269b were correlated with the absence of lymph node involvement (P = 0.031), especially in OSCC patients (P = 0.038 and P = 0.007, respectively). Conclusion The genetic variants of miR-146a and miR-1269b are biomarkers against the development of OPLs and OPSCC.

Interleukin (IL)-4 is a key cytokine in humoral and adaptive immunity. This study aimed to evaluate the association of IL-4 genetic variants (-590CT and VNTR in intron 3) with the risk and prognosis of oral and pharyngeal squamous cell carcinoma (OPSCC).A total of 1215 subjects, which included 623 healthy controls and 592 OPSCC cases (463 oral squamous cell carcinoma (OSCC) and 129 pharyngeal squamous cell carcinoma (PSCC) cases), were recruited. The genotypes were determined by TaqMan real-time assay and PCR-based assay.The IL-4 genotypes at locus -590CT and intron 3 VNTR were not correlated with increased risk of OSCC, PSCC, and OPSCC, with the exception of early-stage OPSCC (at -590CT: T/T vs. C/C+C/T, adjusted odds ratio (AOR)=1.42, 95% CI: 1.02-1.98; at intron 3 VNTR: RP1/RP1 vs. RP2/RP2+RP2/RP1, AOR=1.46, 95% CI: 1.05-2.04). Compared with other IL-4 diplotypes, the T,RP1/T,RP1 diplotype was associated with an increased risk of OPSCC (AOR=1.37, 95% CI: 1.03-1.81), particularly early-stage OSCC (AOR=1.43, 95% CI: 1.02-2.00), PSCC (AOR=2.35, 95% CI: 1.06-5.19), and OPSCC (AOR=1.52, 95% CI: 1.10-2.11). Interactions between the IL-4 diplotype and the alcohol drinking status were found to contribute to the risk of early-stage OPSCC (p=0.024). In addition, the T,RP1/T,RP1 diplotype was correlated with better disease-specific survival (T,RP1/T,RP1 vs. other diplotypes, adjusted hazard ratio=0.70, 95% CI: 0.50-0.97).The T, RP1/T, RP1 diplotype of IL-4 was associated with an increased risk but favourable prognosis of OPSCC.

Objective The present study investigated the relationship between the expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC), and the risk of second primary tumors (SPTs). Study design Immunohistochemistry was performed to examine the expression of MnSOD, GPx, catalase, and MPO in tissue microarray slides of 173 male patients with buccal mucosal SCC who had undergone potentially curative resections. Results Forty-five (26.01%) patients developed SPTs. The prevalent subsites of SPTs were buccal mucosa (48.89%), tongue (13.33%), and lip (11.11%). High expression level of MPO was correlated with an increased risk of SPTs, even after adjustment for development of clinicopathologic parameters (high vs. low expression, adjusted hazard ratio = 3.89; 95% confidence interval, 1.33-11.41; P = .013). Conclusions SPTs are common in male buccal mucosal SCC patients. Higher MPO expression in buccal mucosal SCC is a risk factor for SPTs.

Background Interleukin-18 (IL-18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL-18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL-18 and CALs in patients with KD. Methods In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL-18 levels in the acute, subacute, and convalescent phases. Serum IL-18 levels were measured with a Bio-Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. Results Compared with febrile controls, patients with acute-stage CALs [postintravenous immunoglobulin (post-IVIG) period] had a significantly higher IL-18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute-stage CALs (post-IVIG period) lacked similarly elevated IL-18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL-18 level of patients with acute-stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL-18 level between patients with and without acute-stage CALs ( p = 0.048). Conclusion Our data show that IL-18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.

Background The effect of maternal exposure to essential minerals and heavy metals on fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy. Methods Our study recruited 145 healthy pregnant women with a mean age of 28.06 years, gathering information by collecting interviewer-administered questionnaires. Paired maternal/fetal blood samples were collected by delivery. Results There was a positive correlation of Hg ( r = 0.78, p r = 0.31, p r = 0.17, p = 0.038), and Cu ( r = 0.21, p = 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. Conclusion There was a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.

Purpose To investigate parents’ views about new vaccines, we surveyed the attitudes and awareness toward immunization program among parents of children younger than 14 years in Taiwan. Methods Parents of children were invited to complete a questionnaire in a tertiary referral medical center in Kaoshiung, southern Taiwan from 2006 to 2008. A total of 535 questionnaires were completed. We used descriptive data for the analysis of parents’ views and attitudes toward the current vaccination program in Taiwan. Results Of the 535 respondents, most parents (93%) did not think the current vaccination program was satisfactory. Few (approximately 8%) preferred self-paid vaccines. About 63% of parents believed that the new (self-paid) vaccines provided more protection, whereas 48% deemed them too expensive. The most popular reason for preferring the new vaccines was greater protection (73%). One-half of parents considered the new vaccines to be expensive. Regarding parental awareness of side effect of vaccination, fever was the most well known and of greatest concern (91%). Most parents (68%) had good awareness of conjugated pneumococcal vaccines, and only few (13%) had heard of the human papilloma virus vaccine. Most parental information of vaccines came from pamphlets at the hospital (56%). Conclusion We found the awareness of parents about new vaccines to be insufficient. They also considered the new vaccines to be expensive.

Background/Purpose Infective endocarditis caused by Staphylococcus lugdunensis is a rare disease. Since its first description in 1988, there have only been a few reports of this disease and the causative organism. These publications were primarily case reports and brief case series. We conducted a literature review to identify the nature of the disease and its risk factors. Methods We retrospectively reviewed the cases reported between 1988 and 2008 by searching the relevant literature using the keywords "endocarditis" and " Staphylococcus lugdunensis " in the Medline database. All cases included met the definition of the modified Duke criteria. Results For the period 1988-2008, 67 cases from 27 articles were reviewed. The mean age of individuals was 53.9 years. Left-sided valvular endocarditis represented 52 (82.5%) of cases and native-valve endocarditis was evident in 48 (78.7%) of cases. A large proportion (82%) of 50 S. lugdunensis strains were susceptible to penicillin. Valve replacement operations were performed in 42 (66.7%) patients and the mortality rate was 38.8%. Univariate analysis showed a higher mortality rate in patients aged more than 50 years, those treated before 1995, those treated with antibiotics alone, and those with growth not detected by echocar-diography. Medical treatment alone was the independent risk factor for mortality by multivariate analysis. Conclusion S. lugdunensis endocarditis led to substantial morbidity and mortality. Detailed microbiological identification, echocardiography evaluation, and valve replacement may improve the clinical outcome of individuals with S. lugdunensis endocarditis.

Background There has been concern over the effect of vigorous bubbling on the delivery pressure during the operation of the bubble nasal continuous positive airway pressure (CPAP) system. We investigated the relationship between intra-tubing pressure changes and flow rates in a closed bubble CPAP system in vitro . Methods Using an experimental ( in vitro ) model, the distal connecting tube of the CPAP system was immersed under the water seal to a depth of 5 cm. Sixteen different flow rates, ranging from 2 L/min to 20 L/min, were tested. The procedure was repeated 10 times at each flow rate, and the intra-tubing pressure was recorded. Results The intra-tubing pressure within the model increased as the air flow rates were adjusted from 2 L/min to 20 L/min. The relationship was represented by the following equation, pressure (cmH 2 O) = 5.37 + 0.15 × flow rate (L/min) ( R 2 = 0.826, p Conclusion These results demonstrated that the intra-tubing pressure in a bubble CPAP system was highly correlated with flow rate in vitro .

A hospital-based quasi-experimental (pretest and post-test) study was conducted in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a continuing education program (CEP) on nurses' practices of cancer pain assessment and their acceptance of patients' pain reports with respect to four types of misconceptions. A questionnaire was sent to on-duty nurses or head nurses with patient care responsibilities before the implementation of CEP (n=645) and six months after the program (n=630). The response rates were 92.6% and 91.3% for pretest and post-test surveys, respectively. The CEP was implemented in 8 weeks with four-repeated sessions of 4-hour lectures. A one-day workshop focused on cancer pain assessment and treatment was held 3 months after the four-repeated sessions. Several educational strategies and teaching materials were used in the CEP. The results showed that CEP made statistically significant yet moderate improvement in nurses' practices of pain assessment using pain rating scales (pretest 3.29+/-0.76 vs. post-test 3.48+/-0.75, P

The purposes of this study were to examine the attitudes of physicians regarding the optimal use of analgesics for cancer pain management (CPM), to evaluate their knowledge and attitudes toward opioid prescribing, and to comprehend their perceptions of the barriers to optimal CPM. A survey was conducted on 356 physicians with cancer patient care responsibilities practicing in two medical centers in Taiwan. A total of 204 (57%) physicians responded, including internists (28%), surgeons (27%), oncologists (11%), anesthesiologists (10%), and other specialties (24%). The majority of physicians displayed significantly inadequate knowledge and negative attitudes toward the optimal use of analgesics and opioid prescribing. Multivariate analyses showed that the following six categories of physicians would be inclined to have inadequate knowledge of opioid prescribing: 1) those with perception of good medical school training in CPM, 2) those with perception of poor residency or fellowship training in CPM, 3) those with a medical specialty in surgery, medicine, or oncology (vs. anesthesiology), 4) those with limited clinical experience in cancer patient care (number of patients less than 30), 5) those with a limited aim of pain relief, and 6) those with an underestimation of analgesic effect. Additionally, physicians with inadequate knowledge of opioid prescribing and with hesitation to intervene earlier with maximal dose of analgesia would be inclined to have reluctant attitudes toward opioid prescribing. The most important barriers to optimal CPM identified by physicians themselves were physician-related problems, such as inadequate guidance from a pain specialist, inadequate knowledge of CPM, and inadequate pain assessment. The results of this study suggest that active analgesic education programs are urgently needed in Taiwan.

Assessment of pain in cancer patients is very important to all health care professionals. This paper describes the development of a Taiwanese version of the Brief Pain Inventory (BPI-T) and discusses its psychometric properties in Taiwan. The BPI-T was developed from the original BPI using back-translation and committee review. A total of 534 cytologically or pathologically diagnosed cancer patients in three medical centers in Taiwan were interviewed between July 1992 and October 1997. The intraclass correlation coefficient for the test–retest reliability was 0.79 for the pain severity scale and 0.81 for the pain interference scale. The explained variance for the within-scale factor analyses was larger than 60% in both scales. The coefficient alpha for the internal reliability was 0.81 for the severity scale and 0.89 for the interference scale. Confirmatory factor analysis of the BPI-T clearly identified the same two scales (severity and interference scales) in the 299 adult patients (age between 20–64) with high education (education years > 9) or patients at an early stage of disease. However, in the 235 nonadult patients with distant metastasis or low education patients with distant metastasis, the "most severe pain" item loaded more to the interference scale than the severity scale. Convergent validity of the pain severity was demonstrated by significant correlations with stage of disease (National Cancer Institute's Surveillance, Epidemiology, and End Results Program [SEER]), performance status (Eastern Cooperative Oncology Group [ECOG]), and pain interference. In conclusion, interviewer-administered BPI-T was a reliable instrument for cancer pain severity and its interference in Taiwan. Additionally, it was a valid instrument on adult cancer patients with high education or patients at an early stage of disease.

Cancer pain is a relatively neglected public health issue in Taiwan. To characterize the nature of this problem, interviews were conducted on newly diagnosed cancer patients admitted to the Tri-Service General Hospital during a period of 18 months. Data were collected on the prevalence and severity of cancer pain, its treatment, and impact on patients in the week before the interview. Correlates of prevalence and severity of cancer pain were also examined. The final analysis included 296 patients who had no history of recent surgery. Most of the patients (69%) were interviewed within 14 days of their definitive diagnosis of cancer. Thirty-eight percent (N = 113) of the patients had cancer-related pain. Of these 113 patients, 65% had "significant worst pain" (worst pain level at or above five on a ten-point scale) and 31% had "significant average pain" (average pain level at or above five most of the time); 69% received no pain medication at all or inadequate medication (not "by the ladder"), and 23% had pain medication that was not administered at a fixed interval (not "by the clock"). Multivariate analyses showed that cancer pain was more prevalent in non-Mainlanders, those with a lower level of insurance, those with a history of excellent pain tolerance, those with poor Eastern Cooperative Oncology Group (ECOG) performance status, and those with distant metastases. Patients who were at greater risk of "significant worst pain" were those with regional or distant metastases, those in whom an inadequate analgesic medication had been prescribed (not "by the ladder"), and those who had received an appropriate analgesic medication but no fixed schedule dosing ("by the ladder" but not "by the clock"). Patients who were at greater risk of "significant average pain" were those not undergoing any resection of the tumor lesion and those who received an appropriate drug but no fixed schedule dosing ("by the ladder" but not "by the clock").

Background The CYFRA 21–1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21–1 is a sensitive and specific tumor marker for non-small cell lung cancer. Methods CYFRA 21–1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21–1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. Results The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21–1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21–1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21–1 assay has the highest sensitivity. The median level of CYFRA 21–1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p 0.1). Conclusion For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21–1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.

Summary Background In August, 1995, there was an outbreak in Taiwan of rapidly progressive respiratory distress associated with consumption of uncooked Sauropus androgynus , a vegetable with a claimed yet unconfirmed effect on weight control. We report on 23 patients with strikingly similar clinical presentations. Methods A structured questionnaire for clinical manifestations was completed. Radiographic findings, pulmonary physiological changes, immunological and microbiological studies, and pathological examination were evaluated. Findings All patients were young and middle-aged women (mean age 39 years [range 21–52]). They took uncooked S androgynus juice, generally mixed with guava or pineapple juice, for a mean duration of 10 weeks. Progressive dyspnoea and persistent cough were the main symptoms on presentation. Pulmonary function testing uniformly revealed moderate to severe airflow obstruction with mean forced expiratory volume in 1 s (FEV 1 ) of 0·66 L (26% of predicted). No bronchodilator response was observed. Room-air arterial blood gas analysis showed hypoxaemia (mean PaO 2 9·6 [SD 1·6] kPa). Chest radiographs were essentially normal. High-resolution computed tomography showed bilateral bronchiectasis and patchy low attenuation of lung parenchyma with mosaic perfusion. Ventilation-perfusion scintigraphic findings were compatible with obstructive lung disease. Histopathology of open lung biopsy specimens in four patients confirmed the presence of bronchiolitis obliterans. Immunohistochemical stains of the open lung biopsy specimens showed predominance of T cells over B cells. Immunofluorescent stains for IgG, IgM, IgA, C1q, C3, and C4 were negative. Serum concentrations of tumour necrosis factor a were higher than those of normal controls. Clinical response to prednisolone was limited. Interpretation We describe an unusual association between bronchiolitis obliterans and ingestion of the vegetable S androgynus. T-cell mediated immunity may be involved in the pathogenesis.

To investigate the role of sex in modifying risk factors for retinal detachment (RD) after cataract surgery.Prospective cohort study based on medical records and insurance claims from Taiwan's Bureau of National Health Insurance (BNHI).Nine thousand three hundred eighty-eight patients who underwent extracapsular cataract extraction (CE), including phacoemulsification procedures, between August 1999 and December 2001.Medical charts and claims submitted by insurance beneficiaries who underwent CE and intraocular lens implantation were collected from the sixth branch of the BNHI. Data recorded for analysis included each patient's demographic characteristics, medical history, refractive status, axial length (AL), type of CE, and intraoperative complications. Posterior capsulotomy, diagnostic procedures, and treatments for retinal complications and other ocular diseases were identified on the basis of codes from physicians' billing records at the end of 2005.Incidence of RD in the full study group and in subgroups defined by sex, age, AL, type of CE procedure, concurrent systemic diseases, presence of intraoperative complications, and subsequent posterior capsulotomy.The mean follow-up time of patients at the time of analysis was 54.99+/-15.53 months. The rate of lost follow-up was 11.55%. Cumulative 6-year RD rates were 1.16% in the full study group, 1.90% in the male subgroup, and 0.56% in the female subgroup at the end of the follow-up period. Gender distribution had a significant influence on the occurrence of RD after CE (P0.001). Factors that were found to have a significant effect on the risk of pseudophakic RD included age under 50 years (P = 0.002), AL (P0.001), and history of RD (P = 0.003). Surgical types (extracapsular vs. phacoemulsification) were not correlated significantly with RD, and neither were such systemic diseases as diabetes and hypertension. Subgroup analysis indicated that the significance of age, AL, and history of RD as risk factors persisted in the male subgroup but not in the female subgroup.The impact of axial myopia, age, and RD history as risk factors for pseudophakic RD was seen predominantly in males.