Patients In Asian Countries Research Articles

Cluster headache in Asian populations: Similarities, disparities, and a narrative review of the mechanisms of the chronic subtype.

ObjectiveHeadache disorders like migraine show geographic and ethnic differences between Asian and European/North American countries. In cluster headache, these differences are rarely mentioned and discussed. This article aimed to review the characteristics of cluster headache in Asian countries and compare the clinical features to those in European and North American populations.MethodsWe conducted a narrative literature review on the demographics, clinical presentations, and treatments of cluster headache in Asian countries.ResultsPatients with cluster headache in Asian populations showed a stronger male predominance compared to European and North American populations. Chronic cluster headache was rare in Asian countries. The clinical presentation of restlessness was not as common in Asian as it was in European and North American countries, and Asian patients with aura were extremely rare. Patients in Asian countries may have a lower circadian rhythmicity of cluster headache and a lower headache load, as demonstrated by lower attack frequencies per day, bout frequencies, and bout durations.ConclusionsRegional differences in the presentation of cluster headache exist. Greater awareness for cluster headache should be raised in Asian regions, and further studies are warranted to elucidate the mechanisms behind observed differences.

Corrigendum: Fertility Preservation for Child and Adolescent Cancer Patients in Asian Countries.

[This corrects the article DOI: 10.3389/fendo.2019.00655.].

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Low-dose statin pretreatment improves function and prognosis of recurrent ischemic stroke patients.

Background:Statins are effective in improving the prognosis of stroke patients. In clinical practice, low-dose statins are often administered to stroke patients in Asian countries but their effects on the prognosis of recurrent ischemic stroke patients are still unclear.Methods:Data of consecutive recurrent ischemic stroke patients were prospectively collected. The National Institutes of Health Stroke Scale (NIHSS) of admission and discharge and the modified Rankin scale (mRs) of 90 days after stroke onset were adopted to evaluate primary outcomes. Secondary outcomes included the subgroup analysis.Results:Among 219 patients (mean age 65.41 ± 11.58 years), 150 (68.5%) were male. The low-dose statin group had a higher percentage of milder stroke at admission (p < 0.001) and discharge (p < 0.001), and favorable functional outcome at 90 days (p < 0.001). Univariable regression analysis showed that the use of low-dose statins was inversely associated with higher discharge NIHSS [odds ratio (OR) = 0.36, p = 0.009] and higher mRs at 90 days (OR = 0.230, p < 0.001). Multivariable logistic regression analysis revealed that low-dose statins also had a significantly inverse association with higher mRs at 90 days (OR = 0.098, p = 0.049). According to subgroup analysis, a significant effect was found in the good-persistency subgroup (NIHSS score at discharge: OR = 0.051, p = 0.004; mRs score at 3 months: OR = 0.053, p = 0.005), but not in the poor-persistency subgroup.Conclusion:Low-dose statin pretreatment alleviated stroke severity and improved functional outcomes of recurrent stroke patients.

Fertility Preservation for Child and Adolescent Cancer Patients in Asian Countries.

Background: At present, fertility is one of the main concerns of young cancer patients. Following this trend, “fertility preservation (FP)” has been established and has become a new field of reproductive medicine. However, FP for child and adolescent (C-A) cancer patients is still developing, even in advanced countries. The aim of the present study was to assess the barriers to FP for C-A patients by investigating the current status of FP for C-A patients in Asian countries, which just have started FP activities.Method: A questionnaire survey of founding members of the Asian Society for Fertility Preservation (ASFP) was conducted in November 2018.Main findings: Of the 14 countries, 11 country representatives replied to this survey. FP for C-A patients is still developing in Asian countries, even in Australia, Japan, and Korea, which have organizations or academic societies specialized for FP. In all countries that replied to the present survey, the patients can receive embryo cryopreservation (EC), oocyte cryopreservation (OC), and sperm cryopreservation (SC) as FP. Compared with ovarian tissue cryopreservation (OTC), testicular tissue cryopreservation (TTC) is an uncommon FP treatment because of its still extremely experimental status (7 of 11 countries provide it). Most Asian countries can provide FP for C-A patients in terms of medical technology, but most have factors inhibiting to promote FP for C-A patients, due to lack of sufficient experience and an established system promoting FP for C-A patients. “Don't know how to provide FP treatment for C-A” is a major barrier. Also, low recognition in society and among medical staff is still a particularly major issue. There is also a problem with cooperative frameworks with pediatric departments. To achieve high-quality FP for C-A patients, a multidisciplinary approach is vital, but, according to the present study, few paramedical staff can participate in FP for C-A patients in Asia. Only Australia and Korea provide FP information by video and specific resources.Conclusion: The present study demonstrated the developing status of FP for C-A patients in Asian countries. More intensive consideration and discussion are needed to provide FP in Asian societies based on the local cultural and religious needs of patients.

Does new sensitization correlate with nasal symptoms in children with allergic rhinitis?

To evaluate the correlation between the increased number of sensitized allergens and nasal symptoms in patients with allergic rhinitis who were sensitized to house dust mites (HDMs). Among the patients who were enrolled in the Allergic Rhinitis Cohort Study for Kids, 174 children with rhinitis symptoms who were sensitized to HDMs were included in the analysis. Skin prick tests, serum total immunoglobulin E, eosinophil count, and bronchial provocation tests were carried out during the initial and 3-year follow-up visits. The patients were divided into two groups depending on the change in the number of sensitized allergens: increased number of sensitized allergens (group I) and maintained or reduced number of sensitized allergens (group II). In the analysis of allergen sensitization from baseline to the 3-year follow-up, no significant correlation was observed between the changes in the number of allergens and the total nasal visual analog scale score (R2 < 0.001, P = .813). Furthermore, the comparison of demographic data and immunological factors between groups I and II did not show any significant differences. The changes in bronchial hyper-responsiveness were not significantly different between the two groups (P = 1.000). New sensitization may not be correlated with nasal symptoms in patients in Asian countries where HDMs play a major role as a dominant allergen. Although further investigation must be conducted, the importance of new sensitization as an indicator of treatment outcome should be reconsidered in individuals in Asia. 2b Laryngoscope, 130: 1864-1871, 2020.

The effectiveness of a simplified core stabilization program (TRICCS\u2014Trivandrum Community-based Core Stabilisation) for community-based intervention in chronic non-specific low back pain

BackgroundChronic low back pain is a common public health problem all over the world. Conservative therapy is prescribed as the initial treatment strategy in chronic low back pain. The cornerstone of conservatism in back care is core muscle strengthening. However, exercises prescribed for the purpose are manifold and some are not easily done by patients in Asian countries. We developed an easy to adhere exercise protocol for core stabilization and tested its effectiveness in south Indian population.MethodsProspective study of 73 patients with chronic low back pain (CLBP) who were subjected to Trivandrum Community-based Core Stabilisation protocol of treatment. The enrolled patients underwent initial Oswestry Disability Index (ODI) evaluation and Keele Start Back (KSB) questionnaire before starting the protocol. Back education was given, and the patient started on stratified exercise protocol. ODI assessment was done weekly. The trend in ODI changes and the factors determining them were assessed using ANOVA. The correlation of quantitative variables like age, initial ODI score, and KSB score with the rate of reduction of ODI was assessed using Pearson’s correlation. Cross-tabulations were done using the chi-square test. Parametric tests were used throughout the analysis as the quantitative study variables found to be linear. Multiple linear regression (for the quantitative outcome) and binary logistic regression (for the dichotomous outcome) were performed.ResultsMean (SD) of ODI score has reduced significantly from 43.4 (16.6) to 24.6 (17.1) over the period of 6 weeks (p value < 0.001). The trend in reduction of ODI scores was significantly more in KSB score less than or equal to 3 compared to KSB more than 3 even after adjusting for the general trend of decreasing ODI score over time. The reduction in ODI scores appeared to be low for advancing age (p = 0.468) and higher KSB scores (p = 0.001).ConclusionThe TRICCS protocol is effective in a community-based approach in achieving satisfactory outcomes in CLBP in a period of 6 weeks. Patients with high KSB scores may require cognitive intervention also.

Abstract P5-18-05: Clinicopathological characteristics and prognosis of young patients with ductal carcinoma in situ

Abstract Background: The peak age at diagnosis of breast cancer differs between patients in Asian countries (40 - 50 years), and those in Western countries (60 - 70 years). With the increasing use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased significantly in younger Asian women. Nevertheless, our knowledge of the clinicopathological features and prognosis in young patients with DCIS is relatively limited. We aimed to compare the clinicopathological features of younger patients with that of older patients with DCIS and to evaluate their prognostic factors.Methods: A total of 1445 women were diagnosed with DCIS between the years 2005 and 2015. Patients with the past history of breast cancer and managed without surgery were excluded. The young age group included patients &amp;lt;50 years of age, whereas the old age group included patients ≥50 years of age at diagnosis. We compared the clinicopathological characteristics [tumor size, surgery type, estrogen receptor (ER) and progesterone receptor (PgR) status, HER2 status, nuclear grade, margin status, radiotherapy, endocrine therapy, family history of breast cancer, and screening presentation or presentation with symptoms] and prognosis [disease-free survival (DFS), and overall survival (OS)] between the groups. DFS included the following events: contralateral breast cancer, loco-regional, and distant recurrences. DFS and OS were estimated using the Kaplan–Maier method. The risk factors associated with events were estimated using the log-rank test for univariate analysis. P values &amp;lt; 0.05 were considered statistically significant.Result: Among the 1445 patients diagnosed with DCIS, 1281 were included in this study. The median age at diagnosis was 47 years (range, 22-87 years). The median follow-up time was 72 months (range, 1-162 months). ER and/or PgR status was positive in 1133 patients (88%). HER2 status was positive in 289 patients (23%). Premenopausal status was noted in 867 patients (68%). The median tumor size was 3.0 cm. Of 1281, 202 (18%) patients received endocrine therapy, 846 (66%) received breast conserving surgery, and 724 (86%) received radiation therapy. There were 765 patients (60%) in the young group. Significantly more patients in the young group had low nuclear grades, were ER and/or PgR positive, were HER2 receptor negative, underwent mastectomy, presented with symptoms, and had close/positive margins. Fifty-eight (4.5%) events occurred: 41 (3.2%) contralateral breast cancers, 19 (1.5%) loco-regional recurrences, and one (0.1%) distant metastasis. No death due to breast cancer was reported. On multivariate analysis, the young group (hazard ratio: 2.24, 95% CI: 1.01 - 4.95, P = 0.04), and presentation with clinical symptoms (hazard ratio: 2.09, 95% CI: 1.07-4.10, P = 0.03) significantly correlated with worse DFS. OS was not significantly different between the groups.Conclusion: This was the largest study with young patients with DCIS in the Asian population. We found that age at diagnosis was a significant independent factor associated with DFS. While genetic background also requires consideration, women with DCIS at &amp;lt;50 year of age may require intensive surveillance. This result requires confirmation with longer follow-up. Citation Format: Seki A, Matsuda N, Kajiura Y, Kobayashi D, Hayashi N, Tsunoda H, Suzuki K, Yoshida A, Takei J, Yamauchi H. Clinicopathological characteristics and prognosis of young patients with ductal carcinoma in situ [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-05.

Health Related-Quality of Life in CKD and Dialysis Patients in Asian Countries : A Systematic Review

ABSTRACT&#x0D; Introduction: Chronic Kidney Disease (CKD) and Chronic dialysis has a great impact on patients health-related quality of life (HRQOL). The impacts are about the morbidity, mortality, and the survival rate of the dialysis therapy. We focused this systematic review in Asian countries.&#x0D; Methods: Systematic Review with PRISMA method retrieved from online database such as PubMed, Wiley and ProQuest using a keyword “Health Related-Quality Life (HRQOL)”, “Chronic Kidney Disease (CKD) patient OR ESRD (End Stage Renal Disease), CKD with Hemodialysis OR CKD dialysis at Asian Country”. The end of this search we got 10 journals.&#x0D; Results: The measurement HRQOL in CKD or dyalisis patients such EQ-5D and Kidney Disease Quality of Life (KDQOL). There are 4 country used KDQL (Korea, China, India, Singapore and Indonesia). The result show HRQOL in CKD patients has declined when the level of CKD increased especially when the amount of albumin high and the level of hemoglobin decline. HRQOL in dialysis patient has lower depressive mood in planned dialysis group than unplanned dialysis. There are no difference in KDCS, PCS, or MCS scores between patients treated by hemodialysis and CAPD. They also got 5 more years when choose dialysis (Hemodialysis). &#x0D; Conclusion: Health related quality of life (HRQOL) related with progressive of CKD level. The level that should pay attention is CKD level 3 where HRQOL can decreased. When the patients routine dialysis (CAPD or hemodialysis) used concern about the medicine (such erythropoietin, routine medicine) and the laboratory (albumin and hemoglobin). The more progressive level of CKD the lower of HRQOL.&#x0D; Keywords: Health Related Quality of Life (HQOL), CKD (Chronic Kidney Disease), Dialysis, Hemodialysis, Continuous Ambulatory Peritoneal Dialysis (CAPD).

A Prospective International Study on Safety and Efficacy of Hypofractionated Radiation Therapy for Post-Operative Breast Cancer Patients in Asian Countries

A Prospective International Study on Safety and Efficacy of Hypofractionated Radiation Therapy for Post-Operative Breast Cancer Patients in Asian Countries

Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer

BackgroundAn increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies. PurposeThe question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain. Study DesignThe present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM). MethodsThe effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated. ResultsOur results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice. ConclusionThe considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models.

Cognitive function in Japanese women with posttraumatic stress disorder: Association with exercise habits

BackgroundPosttraumatic stress disorder (PTSD) has been associated with cognitive impairments, yet little is documented on the cognitive function of PTSD patients in Asian countries. It is shown that regular exercise can reduce PTSD symptoms, while no study has investigated the association between exercise and cognition in PTSD patients. This study aimed to examine cognitive functions of Japanese women with PTSD, and to explore the association between regular exercise and cognitive functions. MethodsForty-two women with DSM-IV PTSD and 66 demographically matched healthy control women participated in this study. Most of the patients developed PTSD after experiencing interpersonal violence. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regular exercise habit was assessed by a self-reported questionnaire. ResultsCompared to controls, PTSD patients performed significantly more poorly in all cognitive domains examined, including immediate memory, visuospatial construction, language, attention, delayed memory, as well as the total score of RBANS (all p < 0.001). Compared to PTSD patients without the habit of exercise, those who habitually exercised showed significantly better performance on delayed memory (p = 0.006), which survived after controlling for potentially confounding variables in a multiple regression model. LimitationsThe cross-sectional design and relatively small sample size limited our findings. ConclusionsPTSD in Japanese women is associated with pervasively impaired cognitive functions, including notable impairments in verbal memory. Such memory deficits might be improved by regular exercise, although further studies are needed to investigate the causal relationship between exercise and cognition in PTSD.

Evaluating clinical risk factors for suicide attempts in patients with epilepsy

ObjectiveWe would like to exam whether epilepsy patients in Taiwan have a high risk of attempted and completed suicide. MethodsIn this study, we used a subset of the National Health Insurance Research Database (NHIRD) of Taiwan. Inpatients (≥ 18 years) who received a new diagnosis of epilepsy between 2000 and 2011 were enrolled in the epilepsy cohort. The epilepsy and comparison cohorts included 68,543 patients and 2-fold controls respectively. We calculated the adjusted hazard ratio (aHR) for suicide attempts after adjustment for age, sex, monthly income, the urbanization level, occupation, and comorbidity. ResultsThe epilepsy cohort had a 2.06-fold risk of suicide attempts (95% CI = 1.65–2.56) compared with the control cohort. The suicide attempt risk did not significantly differ between men and women and between patients with and without psychiatric comorbidity. The mortality risk after a suicide attempt was higher in the epilepsy cohort than in the comparison cohort (aHR = 1.66, 95% CI = 1.02–2.69). ConclusionEpilepsy is an independent and predisposing factor for suicide attempt. These results provide important information for clinicians and governments to prevent suicide in epilepsy patients in Asian countries.

Status of essential elements in autism spectrum disorder: systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that imposes heavy financial burden on governments and families of affected children. It is considered a multifactorial condition, where trace elements are among environmental factors that may contribute to ASD. Meanwhile, the between-study variance is high. The present systematic review was designed to investigate the difference in trace element measures between patients with ASD and control subjects. Meta-analyses showed that the hair concentrations of chromium (p=0.024), cobalt (p=0.012), iodine (p=0.000), iron (p=0.017), and magnesium (p=0.007) in ASD patients were significantly lower than those of control subjects, while there were higher magnesium levels in the hair of ASD patients compared to that of controls (p=0.010). Patients with ASD had higher blood levels of copper (p=0.000) and lower levels of zinc compared to controls (p=0.021). Further urinary iodine levels in patients with ASD were decreased in comparison with controls (p=0.026). Sensitivity analyses showed that ASD patients in non-Asian but not in Asian countries had lower hair concentrations of chromium compared to controls. Also, such analyses indicated that ASD patients in Asian countries had lower hair zinc concentrations, whereas ASD patients in non-Asian countries had higher hair zinc concentrations in comparison with control subjects. This study found significant differences in the content of trace elements between patients with ASD compared to controls. The findings help highlighting the role of trace elements as environmental factors in the etiology of ASD.

Decrease in regulatory T-cell function in chronic hepatitis C patients receiving pegylated-interferon plus ribavirin

Regulatory T-cells (Tregs) play an important role in the pathogenesis of chronic hepatitis C (CHC) infection. Pegylated interferon is the standard therapy for CHC patients in Asian countries. This study aimed to evaluate the frequency and function of Tregs in CHC patients receiving combination therapy. CHC patients (n=30) who had elevated alanine aminotransferase and underwent combination therapy were included. Clinical data and Treg function were checked at baseline, 12 weeks after treatment, at the end of treatment, and at the end of 24 weeks of follow-up. Treg immunosuppressive activity was measured as the inhibition ratio of conventional T-cell proliferation. Treg-mediated immunosuppression was significantly lower during therapy than at baseline (baseline 44.45%; 12 weeks 18.41% (p=0.042); end of treatment 22.62% (p=0.036); end of follow-up 17.46% (p=0.003)). Treg-mediated immunosuppression was higher in patients with a sustained virological response (SVR) than in those without SVR at the end of follow-up (SVR 24.20%, non-SVR 6.87%; p=0.030). Treg-mediated immunosuppression was lower during and after combination therapy, regardless of the treatment response, and higher in patients with SVR than in those without SVR at the end of follow-up.

Spectrophotometric Evaluation of Colour Stability of Nano Hybrid Composite Resin in Commonly Used Food Colourants in Asian Countries.

There is growing interest in colour stability of aesthetic restorations. So far few studies have been reported. This study was designed to investigate the effects of different common food colourants i.e., Turmeric and Carmoisine (orange red dye) consumed by patients in Asian countries on a recent nano hybrid composite resin. A total of sixty disk shaped specimens measuring 10 mm in diameter and 2 mm in thickness were prepared. The samples were divided into two groups {Z 100 (Dental restorative composite) Filtek Z 250 XT (Nano hybrid universal restorative)}. Baseline colour measurement of all specimens were made using reflectance spectrophotometer with CIE L*a*b* system. Specimens were immersed in artificial saliva and different experimental solutions containing food colourants (carmoisine solution and turmeric solution) for three hours per day at 37°C. Colour measurements were made after 15 days. Colour difference (ΔE*) was calculated. Mean values were compared by one-way analysis of variance (ANOVA). Multiple range test by Tukey Post-hoc test procedure was employed to identify the significant groups at 5% level. Z 100 showed minimum staining capacity when compared to Z 250 XT in both the colourant solutions. The nanohybrid composite resin containing TEGDMA showed significant colour change when compared to that of microhybrid composite resin as a result of staining in turmeric and carmoisine solution.

Distraction-Based Interventions for Children Undergoing Venipuncture Procedures: A Randomized Controlled Study.

Little is known about the effects of distraction techniques when undertaking medical procedures with hospitalized pediatric patients in Asian countries. This study examined the effects of distraction interventions on behavioral distress related to venipuncture procedures in Taiwanese children aged 3 to 7 years. Using concealed randomization, eligible children were allocated to receive a picture book ( n = 92), or animated cartoon ( n = 92) compared with routine oral instructions ( n = 92), when being injected with an intravenous cannula. Two trained observers independently scored the responses of each child using the Observational Scale of Behavioral Distress-Revised before, during, and after the procedure. All children experienced distress during needle insertion, but distress was less in the distraction-based intervention groups. Moreover, distraction interventions were more effective for children aged 4 to 5 years. Our culturally tailored intervention engaged child participants, was age-appropriate, and could be adapted for use in other Chinese cultures.

CRP-Cyclic AMP Regulates the Expression of Type 3 Fimbriae via Cyclic di-GMP in Klebsiella pneumoniae.

Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP) signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of PmrkA were increased in Δcrp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP)-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of PmrkHI and PmrkJ were decreased in ΔlacZΔcrp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Δcrp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of PmrkHI in the ΔlacZΔcrp strain was diminished in ΔlacZΔcrpΔmrkHI, but increased in the ΔlacZΔcrpΔmrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Δcrp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP-cAMP and c-di-GMP signaling pathways in K. pneumoniae.

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

Pediatric sialendoscopy in Asians: A preliminary report

Background/purposeThe sialendoscopic approach in treating pediatric salivary gland disorders has been reported with great success through the years. Whereas this success has been widely reported in Caucasian populations, relatively little has been reported regarding the use of this procedure in pediatric patients in Asian countries. The purpose of this study is to report our preliminary experience in pediatric sialendoscopy. MethodsThe data from 20 patients (<18years old), who underwent sialendoscopy for obstructive sialoadenitis in the Department of Otorhinolaryngology of Mackay Memorial Hospital between October 2013 and November 2015, were reviewed. ResultsTwelve of our 20 patients (60%) were diagnosed with sialolithiasis and 8 of our 20 patients (40%) presented with non-lithiasis obstructive sialoadenitis. Ductal stenosis was found in 13 patients, and 18 patients had debris/mucous plug formation. The overall success rate was 95% (19/20) in our series, and 85% (17/20) of the patients had achieved a complete remission after a single sialendoscopy procedure. ConclusionsSialendoscopy is an ideal treatment in the management of obstructive sialoadenitis in Asian pediatric patients. If necessary, Holmium:YAG laser lithotripsy and sialostent placement could be applied, and both procedures are well tolerated in pediatric patients.