Artificial intelligence for the real-time classification of intrapapillary capillary loop patterns in the endoscopic diagnosis of early oesophageal squamous cell carcinoma: A proof-of-concept study.

Background: Intrapapillary capillary loops (IPCLs) represent an endoscopically visible feature of early squamous cell neoplasia (ESCN) which correlate with invasion depth - an important factor in the success of curative endoscopic therapy. IPCLs visualised on magnification endoscopy with Narrow Band Imaging (ME-NBI) can be used to train convolutional neural networks (CNNs) to detect the presence and classify staging of ESCN lesions. Methods: A total of 7046 sequential high-definition ME-NBI images from 17 patients (10 ESCN, 7 normal) were used to train a CNN. IPCL patterns were classified by three expert endoscopists according to the Japanese Endoscopic Society classification. Normal IPCLs were defined as type A, abnormal as B1-3. Matched histology was obtained for all imaged areas. Results: This CNN differentiates abnormal from normal IPCL patterns with 93.7% accuracy (86.2% to 98.3%) and sensitivity and specificity for classifying abnormal IPCL patterns of 89.3% (78.1% to 100%) and 98% (92% to 99.7%), respectively. Our CNN operates in real time with diagnostic prediction times between 26.17 ms and 37.48 ms. Conclusion: Our novel and proof-of-concept application of computer-aided endoscopic diagnosis shows that a CNN can accurately classify IPCL patterns as normal or abnormal. This system could be used as an in vivo, real-time clinical decision support tool for endoscopists assessing and directing local therapy of ESCN.

Survival outcome of weak estrogen/progesterone receptor expression in HER2 negative breast cancer is similar to triple negative breast cancer.

BACKGROUND: Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy. METHODS: Medical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups. RESULTS: Regarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.

Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

Association of estrogen receptor, progesterone receptor and HER2 following neoadjuvant systemic treatment in breast cancer patients undergoing surgery.

AIMS: The aim of this study was to analyze the association between the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) in breast cancer with neoadjuvant therapy by using tissue biopsy and surgical specimens. METHODS: This study included 78 patients with breast cancer, who presented to our hospital between June 1999 and June 2011, and were treated with neoadjuvant therapy and subsequent mastectomy or partial mastectomy. All clinicopathological data regarding pre-neoadjuvant biopsy and definitive surgical specimens were reviewed for accuracy. The status of ER, PR, and HER2 was determined by immunohistochemistry. RESULTS: Paired samples from 78 women (mean age 51.4 ± 11.7 years) were successfully analyzed. A switch in the status of ER was identified in 16 patients (20 %); PR, in 18 (23 %); and HER2, in 27 (35 %). There were no significant differences in the status of ER, PR, and HER2 between the primary tumor and the resected tumor after neoadjuvant therapy. Neoadjuvant therapy does not significantly influence the status of the steroid hormone receptors and the HER2 level in our study. CONCLUSIONS: Initial biopsy may be reliable for determining the appropriate adjuvant therapy, but final pathology are still needed to evaluate the prognosis and provided the alternative treatment when tumor recurrence. Further prospective study is needed to optimize the care available for breast cancer patients.

Factors predictive of breast cancer in open biopsy in cases with atypical ductal hyperplasia diagnosed by ultrasound-guided core needle biopsy.

AIMS: The purpose of the study was to explore factors predictive of breast cancer as diagnosed by excision biopsy in cases with a diagnosis of atypical ductal hyperplasia (ADH) on ultrasound-guided core needle biopsy (CNB). PATIENTS AND METHODS: We carried out diagnosis of breast lesions by ultrasound-guided CNB in a single hospital in Taiwan from November 2003 to October 2009. Patients who were diagnosed with ADH and subsequently underwent excision biopsy were included in this study (n = 124). RESULTS: Fifty-six of the 124 patients who were included (45.2%) had cancer, and the remaining 68 had benign lesions. By multivariate analysis of all clinical characteristics and on the basis of the imaging features in these cases, older patient age (≥50 y/o, OR: 3.910, p = 0.005), larger tumour size (≥15 mm, OR: 3.398, p = 0.013), and the presence of architectural distortion by mammography (OR: 10.7, p = 0.036) were found likely to be associated with breast cancer. CONCLUSIONS: Open biopsy is necessary in patients who were diagnosed with ADH on CNB. Older patients (≥50 y/o), with a larger tumour size (≥15 mm) and an abnormal mammography are especially likely to have breast cancer.

Efficiency of infiltration with bupivacain after modified radical mastectomy.

BACKGROUND: Pre-incisional infiltration of anaesthetic is proven to reduce postoperative pain in breast cancer surgery. However, studies of post-incisional infiltration for modified radical mastectomy are rare. The purpose of this study was to investigate whether post-incisional infiltration with bupivacaine provides improved postoperative pain relief and a cost-effective benefit. METHODS: This is a retrospective study. Between January 2006 and May 2008, 139 patients who received modified radical mastectomy were recruited to participate in the study. Patients receiving local infiltration received bupivacaine (0.5% bupivacaine, 5 ml diluted to 10 ml with distilled water) injected into the dermis surrounding the incision after wound suture. Pain intensity was evaluated using a Visual Analogue Scale (VAS) score and measurement of the required doses of meperidine and acetaminophen. The pain score was recorded every eight hours for three days. RESULTS: All patients were female. Seventy-two patients received local infiltration with bupivacaine after wound suture and 67 patients did not. There were no significant differences between the two patient groups in age, body weight and height, length of general anaesthesia and operative time. Hospital stay was significantly shorter for patients receiving local infiltration of bupivacaine. The VAS score was higher up to 16 hours post-surgery for patients who did not receive local infiltration. Meperidine and acetaminophen consumption was less for patients who received local infiltration (P = 0.010). CONCLUSION: Post-incisional wound infiltration with bupivacaine can relieve pain during the first 16 hours after surgery and shorten hospital stay, and it provides a cost-effective benefit.

Blue angioedema of eyelip after patent blue injection for lymphatic mapping procedure.

Sentinel node biopsy using patent blue dye in breast cancer is a well-documented procedure to assess the axillary status. We presented an unusual and previously unreported complication of simple blue angioedema over bilaterally periorbital tissue after blue dye injection.

Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy.

BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.

Standardization of a broth microdilution susceptibility testing method to determine minimum inhibitory concentrations of aquatic bacteria.

A multiple laboratory study was conducted in accordance with the standards established by the Clinical and Laboratory Standards Institute (CLSI), formerly the National Committee for Clinical Laboratory Standards (NCCLS), for the development of quality control (QC) ranges using dilution antimicrobial susceptibility testing methods for bacterial isolates from aquatic animal species. QC ranges were established for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 when testing at 22, 28 and 35 degrees C (E. coli only) for 10 different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine, oxolinic acid, oxytetracycline and trimethoprim/sulfamethoxazole). Minimum inhibitory concentration (MIC) QC ranges were determined using dry- and frozen-form 96-well plates and cation-adjusted Mueller-Hinton broth. These QC ranges were accepted by the CLSI/NCCLS Subcommittee on Veterinary Antimicrobial Susceptibility Testing in January 2004. This broth microdilution testing method represents the first standardized method for determining MICs of bacterial isolates whose preferred growth temperatures are below 35 degrees C. Methods and QC ranges defined in this study will enable aquatic animal disease researchers to reliably compare quantitative susceptibility testing data between laboratories, and will be used to ensure both precision and inter-laboratory harmonization.

Clinical and molecular events in patients with Machado-Joseph disease under lamotrigine therapy.

OBJECTIVE: Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 is an autosomal dominant spinocerebellar degeneration, for which there is no effective treatment. PATIENTS AND METHODS: This study involved the clinical response of lamotrigine (LTG) on six MJD patients with early truncal ataxia and the effect of LTG on the alteration of ataxin-3 expression in the transformed MJD lymphoblastoid cells. RESULT: LTG medication was found, on the basis of single leg standing test tandem gait index, to effectively improve gait balance, but did not prove to be effective in the withdrawal period. In Western blot analysis of ataxin-3 in MJD lymphoblastoid cells, extracellular application of LTG, while leaving the normal level of ataxin-3 intact, decreased the expression of mutant ataxin-3 in a dose-related manner. CONCLUSION: Our results indicated that LTG may have significant benefits in relief of gait disturbance in MJD patients with early ataxia, and may be related to the decreased expression of mutant ataxin-3.

Re-emergence of meningococcal disease in Taiwan: circulation of domestic clones of Neisseria meningitidis in the 2001 outbreak.

The annual incidence of meningococcal disease (meningitis and septicaemia) in Taiwan was 0.94/10(5) population in 1953. It then declined to below 0.001 from 1980 to 1987, and re-emerged in 2000 with a rate of 0.07/10(5) population. In 2001 there was a further increase in incidence (43 cases, 0.19/10(5)). Of 43 isolates of Neisseria meningitidis available for this study, including 41 from patients treated in 2001, three (7.0%) were penicillin insensitive (MIC > or = 0.12 microg/ml), though all were beta-lactamase negative: 16 (37.2%) were resistant to trimethoprim-sulphamethoxazole (MIC > or = 4/76 microg/ml). Serogrouping and genotype analysis revealed nine domestic clones. None of the 43 patients had any relationship (travel or contact history) with the 2000 or 2001 Hajj pilgrimage. Epidemiological information and typing results suggested wide dissemination of a limited number of domestic clones of N. meningitidis, manifesting as serogroups W-135, B and Y. Two clones of serogroup W-135 involved in the outbreak were genetically distinct from the 2000 or 2001 Hajj-related W-135 clone.

Antimicrobial susceptibility testing of aquatic bacteria: quality control disk diffusion ranges for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 at 22 and 28 degrees C.

Quality control (QC) ranges for disk diffusion susceptibility testing of aquatic bacterial isolates were proposed as a result of a multilaboratory study conducted according to procedures established by the National Committee for Clinical Laboratory Standards (NCCLS). Ranges were proposed for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 at 22 and 28 degrees C for nine different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, gentamicin, oxolinic acid, oxytetracycline, ormetoprim-sulfadimethoxine, and trimethoprim-sulfamethoxazole). All tests were conducted on standard Mueller-Hinton agar. With >/=95% of all data points fitting within the proposed QC ranges, the results from this study comply with NCCLS guidelines and have been accepted by the NCCLS Subcommittee for Veterinary Antimicrobial Susceptibility Testing. These QC guidelines will permit greater accuracy in interpreting results and, for the first time, the ability to reliably compare susceptibility test data between aquatic animal disease diagnostic laboratories.

Job satisfaction of hospital nurses: an empirical test of a causal model in Taiwan.

AIM: The purpose of this research was to empirically test a model of job satisfaction in Taiwan. METHODS: The model represents a revision of the Price-Mueller model, which is based on empirical research conducted since 1972 at the University of Iowa. This empirical test contributes to the generalization, on cross-national settings, of results from American-based research on job satisfaction. FINDINGS: The results, based on a sample of 308 non-supervisory hospital nurses in Taiwan, indicate that 45% of the variance in job satisfaction was accounted for by the revised model. The work characteristic variable "routinization" had the greatest impact on job satisfaction, followed by the personality traits "positive affectivity" and "job involvement". Although it is difficult to change the routine nature of nursing, the manager should make efforts to diversify the job description and empower his/her subordinates. CONCLUSIONS: It is suggested that having information on a nurse's personality will help to predict her/his future job satisfaction and may lead to improved selection of personnel. In addition, different management styles or reward systems that are sensitive to different personalities should be carefully studied and implemented, as appropriate.

Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in infants in Taiwan.

OBJECTIVES: To assess the annual mortality rate associated with fulminant hepatitis in infants before and after the mass immunization program that was launched in Taiwan in July 1984. STUDY DESIGN: From the National Mortality Registry System, the data on the mortality from fulminant hepatitis in infants from 1975 to 1998 were retrieved. Poisson regression analysis was used to assess the difference in average mortality from fulminant hepatitis in infants before (1975-1984) and after (1985-1998) the implementation of the mass hepatitis B vaccination program. RESULTS: The ratio of yearly mortality from 1975 to 1998 was 1.10 (P <.001), representing a progressive decrease in the number of the cases. The average mortality associated with fulminant hepatitis in infants from 1975 to 1984 and from 1985 to 1998 was 5.36 and 1.71 per 100,000 infants, respectively. The ratio of the average mortality in the period from 1985 to 1998 to that in the period from 1975 to 1984 was 0.32 (P <.001). CONCLUSIONS: These data indicate that since the institution of a program of mass hepatitis B vaccination in Taiwan, the mortality associated with fulminant hepatitis in infants has declined significantly.

Efficacy of a mass hepatitis B immunization program after switching to recombinant hepatitis B vaccine: a population-based study in Taiwan.

To study the efficacy of immunization against hepatitis B after plasma-derived vaccine was replaced by recombinant vaccine, 2-year-old Taiwanese children were recruited by stratification random sampling and tested for hepatitis B markers. They were grouped according to maternal infectivity and children's immunization status. Of 2010 children, 2.5% had hepatitis B surface antigen (HBsAg), 94.1% had its antibody (anti-HBs), 6.8% had core antibody, and 3.3% were seronegative. Children of highly infectious mothers immunized with hepatitis B immunoglobulin and vaccine on schedule had a lower HBsAg-positive rate and a higher anti-HBs-positive rate than those with vaccine only and off-schedule. The efficacy of the Taiwanese mass hepatitis B immunization was maintained after switching to recombinant hepatitis B vaccine.

Carcinoid tumor of the spleen: report of a case.

Carcinoid tumors are uncommon tumors of the neuroendocrine system. They grow slowly and may remain silent for years before presenting with carcinoid syndrome. A diagnosis of asymptomatic carcinoid tumor is difficult. Wide resection of the primary tumor and metastatic lesions is the first choice of treatment. Primary carcinoid is sometimes distributed throughout the entire body, but it is rare in the spleen. We herein present a rare case of a symptomless carcinoid tumor that predominantly invaded the spleen with liver metastasis.

Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls.

CONTEXT: Hepatocellular carcinoma (HCC) has a male predominance and is closely related to hepatitis B virus (HBV) infection. Hepatitis B virus vaccination was launched in 1984 in Taiwan for neonates of mothers carrying hepatitis B e antigen, resulting in a decreased incidence of HCC in children. The effect on boys vs girls is not known. OBJECTIVE: To evaluate the association between a HBV vaccination program with incidence of childhood HCC by sex. DESIGN AND SETTING: Analysis of data collected from Taiwan's National Cancer Registry System and the Taiwan Childhood Hepatoma Study Group between 1981 and 1996. PARTICIPANTS: Children aged 6 to 14 years who were diagnosed as having HCC (201 boys and 70 girls). MAIN OUTCOME MEASURE: Incidence of HCC in boys and girls before and after implementation of the vaccination program. RESULTS: The boy-girl incidence ratio decreased steadily from 4.5 in 1981-1984 (before the program's introduction) to 1.9 in 1990-1996 (6-12 years after the vaccination program was launched). The incidence of HCC in boys born after 1984 was significantly reduced in comparison with those born before 1978 (relative risk [RR], 0.72; P =.002). No significant decrease in HCC incidence was observed in girls born in the same periods (RR, 0.77; P =.20). The incidence of HCC in boys remained stable with increasing age, while an increase of HCC incidence with age in girls was observed. These age and sex effects remained the same regardless of birth before or after the vaccination program. CONCLUSION: Our results suggest that boys may benefit more from HBV vaccination than girls in the prevention of HCC.

Protective titres of measles neutralising antibody.

A nation-wide measles outbreak occurred in 1988 in Taiwan. A retrospective cohort study was conducted to define the protective titre of measles neutralising (NT) antibody. Paired sera collected in 1987 and 1988 were available from 190 individuals born in 1984 who had participated in an annual hepatitis B immunisation follow-up from 1986 to 1991. Measles NT titres were quantified using a standardised neutralisation enzyme immunoassay. Measles infection was defined as a >/=4-fold rise in NT titre or seroconversion between paired sera. Symptomatic measles infection was ascribed to individuals who had measles infection and who reported measles-like symptoms between 1987 and 1988. Results demonstrated a dose-response relationship between pre-exposure NT titres and protection against measles infection. 47 of 48 individuals with measles infection in 1988 had pre-exposure NT titres 1, 000 mIU/ml may prevent measles infection and NT titres >500 mIU/ml may prevent symptomatic infection but vaccinees with undetectable or low NT titres may not necessarily be susceptible to symptomatic infection.

Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization.

A hepatitis B mass immunization program was launched in Taiwan in July 1984, beginning with newborns of hepatitis B carrier mothers for the first 2 years of the program, which was then extended to all newborns. Seroepidemiology was studied in 3 cohorts at age 6 years. Each cohort consisted of 1500 children proportionally and randomly sampled from those entering elementary school in 1989, 1991, and 1993, representing those born 1 year before the program began and years 1 and 3 of the program, respectively. By RIA, the hepatitis B surface antigen positivity rates in the groups were 10.5%, 6.3%, and 1.7%, respectively; hepatitis B surface antibody positivity rates were 36.9%, 62.0%, 65.4%; and hepatitis B infection rates were 25.0%, 15.9%, 4.3%. Thus, universal immunization was more effective in reducing hepatitis B carriage than selective immunization of newborns of carrier mothers only. The program has proved effective in controlling chronic hepatitis B infection in Taiwan.

[Seroepidemiology of Japanese encephalitis viral infection among 3-6 years old children from mountainous and plains townships located in the northern, central, southern and eastern Taiwan].

In order to evaluate the Japanese encephalitis virus (JEV) vaccination program in rural Taiwan, we conducted a seroepidemiological survey of JEV among rural children 3 to 6 years of age in Taiwan. The children were selected through a systemic sampling following stratification by age of children in 4 selected aboriginal villages and 4 adjacent nonaboriginal villages. The overall vaccine coverage rate for the primary (2 doses) dose was 81.2% (1853/2281) with higher rates (87.7%-87.9%) found among the more recent birth cohort of 3 to 4 years of age. The neutralizing antibody (NT) against JEV was measured with plaque reduction neutralization test (PRNT) using Nakayama strain as the virus. With a positive NT antibody defined as > or = 1:10 dilution of serum yielding more than 50% plaque reduction, the overall JEV NT antibody positive rate among children receiving 3 doses of vaccine was 67%. However, the age-specific positive rates varied significantly with varying ages; the lowest of 47% being among children 4 years of age which was lower than the rates of 68%, 76% and 87% among children of 3, 5 and 6 years of age, respectively. This trend of rising seropositive rates of JEV antibody with increasing age among 4 and 6 years of age was also noted among children who had received no vaccine, suggesting the importance of natural infection among rural Taiwanese children. Despite the high frequency of natural infection, the seropositive rates of JEV antibody still correlated well with the dose of vaccine received, i.e., 67% (1122/1664), 66% (65/97), 33% (4/12) and 40% (19/47) for children receiving 3, 2, 1, and 0 dose of JE vaccines, respectively (P < 0.0001 Chi-square for trend test). When stratified analysis by dose and by type of vaccines was conducted, a significantly higher seropositive rate of JEV NT antibody was noted among children receiving JE vaccine of Beijing type (87%) than children receiving Nakayama type (39%) (p < 0.0001, Chi-square test). Our data indicated that the JEV vaccination, in conjunction with JEV natural infection, has maintained high JEV NT antibody level among rural children of Taiwan.