58 results on '"Liang TH"'
Search Results
2. Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach
- Author
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Lopez, AMH, Chen-Liang TH, Zurdo M, Carrillo-Tornel S, Panadero J, Salido EJ, Beltrán V, Muina, B, Amigo M, Navarro-Villamor N, Cifuentes R, Calabria I, Antón AI, Teruel R, Muro M, Vicente V, and Jerez A
- Subjects
azacitidine ,Cancer testis antigens ,hemic and lymphatic diseases ,t-cell response ,myelodysplastic syndromes - Abstract
Cancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) is a prerequisite for downstream immune target-discovery projects. In this study, we take advantage of the use of azacitidine to treat high-risk MDS and CMML to draw the CTAs landscape, before and after treatment, using anad hoctargeted RNA sequencing (RNA-seq) design for this group of low transcript genes. In 19 patients, 196 CTAs were detected at baseline. Azacitidine did not change the number of CTAs expressed, but it significantly increased or decreased expression in nine and five CTAs, respectively.TFDP3andDDX53, emerged as the main candidates for immunotherapeutic targeting, as they showed three main features: i) a significant derepression on day +28 of cycle one in those patients who achieved complete remission with hypomethylating treatment (FC = 6,p= .008; FC = 2.1,p= .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognizedTFDP3andDDX53reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine.
- Published
- 2020
3. Less is Enough: Outcome of Bimodality Definitive Concurrent Chemoradiation does not Differ from that of Trimodality Upfront Neck Dissection Followed by Adjuvant Treatment for >6 cm Bulky Lymph Node (N3) Head and Neck Cancer
- Author
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Huang B, Lai S, Chen T, Wang C, Chen W, and Liang Th
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Head and neck cancer ,Neck dissection ,Concurrent chemoradiation ,medicine.disease ,Concurrent chemoradiotherapy ,medicine.anatomical_structure ,Text mining ,medicine ,Radiology ,business ,Lymph node ,Adjuvant ,oncology_oncogenics - Abstract
Currently, data regarding optimal treatment modality, response, and outcome specifically for N3 head and neck cancer are lacking. This study aimed to compare the treatment outcomes between definitive concurrent chemoradiotherapy (CCRT) to the neck and upfront neck dissection followed by adjuvant CCRT. 93 N3 squamous cell carcinoma head and neck cancer patients were included. Primary tumor treatment was divided to definitive CCRT (CCRT group) or curative surgery followed by adjuvant CCRT (surgery group). Neck treatment was also classified into two treatment modalities: definitive CCRT to the neck (CCRT group) or curative neck dissection followed by adjuvant CCRT (neck dissection group). Overall, the 2-year overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 51.8%, 47.3%, 45.6%, and 43.6%, respectively. In both oropharyngeal cancer and nonoropharyngeal cancer patients, in terms of OS, LRFS, RRFS or DMFS no difference was noted regarding primary tumor treatment (CCRT vs. surgery) or neck treatment (CCRT vs. neck dissection). In summary, N3 neck patients treated with definitive CCRT can achieve similar outcomes to those treated with upfront neck dissection followed by adjuvant CCRT. Cautions should be made to avoid overtreatment for this group of patients.
- Published
- 2019
4. The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients
- Author
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Chen-Liang TH, Martin-Santos T, Jerez A, Senent L, Orero MT, Remigia MJ, Muiña B, Romera M, Fernandez-Muñoz H, Raya JM, Fernandez-Gonzalez M, Lancharro A, Villegas C, Carlos Herrera J, Frutos L, Luis Navarro J, Uña J, Igua C, Sanchez-Vaño R, Cozar Mdel P, Contreras J, Sanchez-Blanco JJ, Perez-Ceballos E, and Ortuño FJ
- Subjects
INVOLVEMENT ,PROVIDES ,Adult ,Male ,Adolescent ,Biopsy ,Multimodal Imaging ,POSITRON-EMISSION-TOMOGRAPHY ,immune system diseases ,Bone Marrow ,Fluorodeoxyglucose F18 ,hemic and lymphatic diseases ,Humans ,CLINICAL-SIGNIFICANCE ,METAANALYSIS ,Aged ,Neoplasm Staging ,Lymphoma, Non-Hodgkin ,PERFORMANCE ,Middle Aged ,Hodgkin Disease ,Positron-Emission Tomography ,Female ,Neoplasm Grading ,Tomography, X-Ray Computed ,RESPONSE ASSESSMENT ,CT - Abstract
Bone marrow infiltration (BMI), categorized as an extra-nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B-cell non-Hodgkin Lymphoma (HG B-NHL), among them 155 Diffuse Large B-Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B-NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B-NHL group, 25 patients would have been under-staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B-NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B-NHL setting and at the present moment, both techniques are complementary. Am. J. Hematol. 90:686-690, 2015. (c) 2015 Wiley Periodicals, Inc.
- Published
- 2015
5. The aggregated leapfrogging estimate: a novel approach to defining energy leapfrogging
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Hosseini-Moghaddam Sam, Gnanamoorthy Branav, Liang Thomas, Cheng Harry, and Bernier Luc
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energy leapfrogging ,renewable micro-grids ,access to electricity ,Energy conservation ,TJ163.26-163.5 ,Renewable energy sources ,TJ807-830 - Abstract
Energy leapfrogging (i.e., skipping non-renewable grid infrastructures to micro-grid renewable sources) has been promoted by researchers and politicians as a solution in fighting against climate change and for access to electricity in less developed countries. Despite research on its potential, quantitative measurement of leapfrogging is still required to determine those nations who have utilized energy leapfrogging's promise. In this study, we present a quantitative analysis using World Bank Open Database data from 2000 to 2015, creating an aggregated leapfrogging estimate (ALE) through renewable energy consumption (i.e., percentage of total energy consumption) and access to electricity (i.e., percent of total population with access). We defined the ALE by subtracting (renewable consumption % in 2000 / access to electricity % in 2015) from (renewable consumption % in 2015 / access to electricity in 2000). We included only countries whose renewable energy consumption increased during the study interval. Low-income countries collectively leapfrogged more than other income groups. Somalia (48.11), Togo (3.05), Eswatini (2.76), and Timor-Leste (1.04) all had ALE values greater than 1 (range: 1.7 × 10−5–48.11). We then conducted a policy analysis of these countries, confirming that all four had implemented renewable energy policies to create access to electricity. Our ALE accurately determined countries with energy leapfrogging, uniquely incorporating access to electricity, consistent with the fundamental purpose of leapfrogging as a strategy to increase access. Future studies are needed to understand why low-income countries with low ALEs and access to electricity failed to leapfrog in the past. Future studies are also required to design prospective quantitative statistical models predicting the outcomes of leapfrogging strategies.
- Published
- 2023
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6. Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development
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Ryo Seishima, Carly Leung, Swathi Yada, Katzrin Bte Ahmed Murad, Liang Thing Tan, Amin Hajamohideen, Si Hui Tan, Hideki Itoh, Kazuhiro Murakami, Yoshihiro Ishida, Satoshi Nakamizo, Yusuke Yoshikawa, Esther Wong, and Nick Barker
- Subjects
Science - Abstract
Uterine gland development is essential for successful embryo implantation, decidua formation and placental development. Here the authors demonstrate that neonatal Wnt-dependent Lgr5 expressing stem/progenitor cells at the tips of developing glands are indispensable for uterine gland development.
- Published
- 2019
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7. Behçet disease associated with myelodysplastic syndrome.
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Lin YC, Liang TH, Chang HN, Lin JS, and Lin HY
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- 2008
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8. Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease
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Kim, D, primary, Park, G, additional, Huuhtanen, J, additional, Lundgren, S, additional, Khajuria, RK, additional, Hurtado, AM, additional, Munoz-Calleja, C, additional, Cardenoso, L, additional, de Sora, VGG, additional, Chen-Liang, TH, additional, Eldfors, S, additional, Ellonen, P, additional, Hannula, S, additional, Kankainen, M, additional, Bruck, O, additional, Kreutzman, A, additional, Salmenniemi, U, additional, Lonnberg, T, additional, Jerez, A, additional, Itala-Remes, M, additional, Myllymaki, M, additional, Keranen, MAI, additional, and Mustjoki, S, additional
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9. Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study.
- Author
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Hsieh M, Chan P, Sue Y, Liu J, Liang TH, Huang T, Tomlinson B, Sum MS, Kao P, and Chen Y
- Abstract
BACKGROUND: Stevioside, a natural glycoside isolated from the plant Stevia rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and Brazil for >20 years. Previous animal and human studies have indicated that stevioside has an antihypertensive effect. OBJECTIVES: This study was undertaken to investigate the long-term (2-year) efficacy and tolerability of stevioside in patients with mild essential hypertension. Secondary objectives were to determine the effects of stevioside on left ventricular mass index (LVMI) and quality of life (QOL). METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and diastolic blood pressure [DBP] 90-99 mm Hg). Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years. Blood pressure was measured at monthly clinic visits; patients were also encouraged to monitor blood pressure at home using an automated device. LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment. QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. Electrocardiographic, laboratory, and QOL parameters were assessed at the beginning of treatment, and at 6 months, 1 year, and 2 years. RESULTS: One hundred seventy-four patients (87 men, 87 women) were enrolled in the study, and 168 completed it: 82 (42 men, 40 women; mean [SD] age, 52 [7] years) in the stevioside group and 86 (44 women, 42 men; mean age, 53 [7] years) in the placebo group. After 2 years, the stevioside group had significant decreases in mean (SD) SBP and DBP compared with baseline (SBP, from 150 [7.3] to 140 [6.8] mm Hg; DBP, from 95 [4.2] to 89 [3.2] mm Hg; P < 0.05) and compared with placebo (P < 0.05). Based on patients' records of self-monitored blood pressure, these effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study. There were no significant changes in body mass index or blood biochemistry, and the results of laboratory tests were similar in the 2 groups throughout the study. No significant difference in the incidence of adverse effects was noted between groups, and QOL scores were significantly improved overall with stevioside compared with placebo (P < 0.001). Neither group had a significant change in mean LVMI. However, after 2 years, 6 of 52 patients (11.5%) in the stevioside group had left ventricular hypertrophy (LVH), compared with 17 of 50 patients (34.0%) in the placebo group (P < 0.001). Of those who did not have LVH at baseline, 3 of 46 patients (6.5%) in the stevioside group had developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in the placebo group (P < 0.001). CONCLUSIONS: In this 2-year study in Chinese patients with mild hypertension, oral stevioside significantly decreased SBP and DBP compared with placebo. QOL was improved, and no significant adverse effects were noted. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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10. AML typical mutations (CEBPA, FLT3, and NPM1) identify a high-risk CMML independent of CPSS-Mol classification.
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Castaño-Díez S, López-Guerra M, Zugasti I, Calvo X, Schulz FI, Avendaño A, Mora E, Falantes-González JF, Azaceta G, Ibañez M, Chen-Liang TH, Notario Mc Donnell C, Amer-Salas N, Palomo L, Pomares H, Vila J, Bernal Del Castillo T, Jiménez-Vicente C, Esteban D, Guijarro F, Álamo Moreno JR, Cortés-Bullich A, Torrecillas-Mayayo V, Triguero A, Mont-de Torres L, Carcelero E, Cardús A, Germing U, Betz B, Rozman M, Arenillas L, Zamora L, Díez-Campelo M, Xicoy B, Esteve J, and Díaz-Beyá M
- Abstract
Mutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2 and NPM1 are rarely found in chronic myelomonocytic leukemia (CMML) and their prognostic significance in CMML has not been clearly identified. In 127 CMML patients, we have retrospectively analyzed next-generation sequencing and PCR data from analyses of bone marrow samples performed at diagnosis of CMML. Seven patients harbored CEBPA mutations, eight FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations and 11 NPM1 mutations. CMML patients harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN)were more frequently associated with the myeloproliferative subtype (MP-CMML) , a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CPSS-Mol classification, mutCFN CMML patients had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN CMML patients closely resembled that of AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible, and consider certain targeted therapies approved for use in AML., (Copyright © 2024 American Society of Hematology.)
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- 2024
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11. Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.
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Torres-Esquius S, Beas F, Chen-Liang TH, Pomares H, Santiago M, Varela ND, Liquori A, Hernandez F, Xicoy B, Hermosín L, Arnan M, Tazón-Vega B, Blanco A, Cervera J, Diez-Campelo M, Lozano ML, Valcárcel D, Bosch F, Montoro MJ, and Jerez A
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- Humans, Middle Aged, Male, Female, Aged, Genetic Testing methods, Genetic Predisposition to Disease, Myeloproliferative Disorders genetics, Myeloproliferative Disorders diagnosis, Exome Sequencing, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Germ-Line Mutation
- Abstract
Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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12. NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.
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Hurtado-Navarro L, Cuenca-Zamora EJ, Zamora L, Bellosillo B, Such E, Soler-Espejo E, Martínez-Banaclocha H, Hernández-Rivas JM, Marco-Ayala J, Martínez-Alarcón L, Linares-Latorre L, García-Ávila S, Amat-Martínez P, González T, Arnan M, Pomares-Marín H, Carreño-Tarragona G, Chen-Liang TH, Herranz MT, García-Palenciano C, Morales ML, Jerez A, Lozano ML, Teruel-Montoya R, Pelegrín P, and Ferrer-Marín F
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- Humans, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Symptom Burden, Interleukin-1 metabolism, Inflammasomes genetics, Inflammasomes metabolism, Leukemia, Myelomonocytic, Chronic drug therapy, Leukemia, Myelomonocytic, Chronic genetics
- Abstract
Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRAS
G12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers., Competing Interests: Declaration of interests P.P. is consultant of Viva In Vitro Diagnostics SL. P.P., H.M.-B., and C.G.-P. are inventors on patent PCT/EP2020/056729. L.H.-N., L.M.-A., H.M.-B., C.G.-P., and P.P. are co-founders of Viva In Vitro Diagnostics SL but declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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13. NOTCH1 mutation in chronic lymphocytic leukaemia is associated with an enhanced cell cycle G1/S transition and specific cyclin overexpression: Preclinical ground for targeted inhibition.
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Carrillo-Tornel S, Chen-Liang TH, Zurdo M, Puiggros A, Gómez-Llonín A, García-Malo MD, Cuenca-Zamora EJ, Ortuño FJ, López AMH, Espinet B, and Jerez A
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- Humans, Cyclins genetics, Cell Cycle genetics, Cell Division, Mutation, Receptor, Notch1 genetics, Receptor, Notch1 metabolism, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell metabolism
- Abstract
Studies prior to next-generation sequencing (NGS) showed that the frequent indolent course of chronic lymphocytic leukaemia (CLL) is related to most cells remaining quiescent in the G
0 -G1 cell cycle phase, due to the expression of dysregulated cyclin genes. Of note, the activating nature of the NOTCH1 mutation in T lymphoblastic leukaemia also drives the dysregulation of cell cycle genes. Our goal was to comprehensively revisit the cell cycle in NOTCH1-mutated CLL (NOTCH1MUT ) to test for potential therapeutic targets. Among 378 NGS-annotated CLL cases, NOTCH1MUT cells displayed a unique transcriptome profile of G0 -G1 cell cycle components, with an overexpression of early-phase effectors, reaching a 38-, 27- and ninefold change increase for the complex elements CCND3, CDK4 and CDK6, respectively. This NOTCH1MUT cells' profile was related to more cells traversing through the cell cycle. In-vitro targeted inhibition of NOTCH1 gamma-secretase and CDK4/6 reversed the distribution of cells through the cycle phases and enhanced the killing of NOTCH1MUT CLL cells, suggesting new therapeutic approaches., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
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14. CD5+ follicular lymphoma rapidly transformed to high-grade B-cell lymphoma with double-hit: from BCL2 to MYC disruption.
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Soler-Espejo E, Marco-Ayala J, Chen-Liang TH, López-Poveda MJ, Teruel-Montoya R, and Ortuño FJ
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- 2023
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15. An innovative extraction strategy for herbal medicine by adopting p-sulphonatocalix[6]/[8]arenes.
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Yu X, Liang TH, Wang M, Ren XL, Zhou ZY, Jiang MM, and Zhang DQ
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- Herbal Medicine, Protons, Water, Alkaloids chemistry, Drugs, Chinese Herbal chemistry, Plants, Medicinal chemistry
- Abstract
Introduction: Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products., Objective: In this study, an innovative method of SC6A/SC8A assisted extraction of the alkaloids from herbs was established., Methods: SC6A and SC8A were designed to extract 27 alkaloids from seven herbal medicines. Based on the significant solubilisation and extraction effect, Stephaniae Tetrandrae Radix (Fangji, FJ) was selected to obtain the optimal extraction process by adopting single factor test and orthogonal experiment. Then, the alkaloids and SC6A/SC8A were separated by one-step alkalisation and SCnA were reused. The host-guest complexes between alkaloids and SCnA were determined by competitive fluorescence titration, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (
1 H-NMR) analysis., Results: The optimum condition for SC6A assisted extraction was 5:1:80 (g/g/mL) for herbs/SC6A/solution ratio, 355-250 μm particle size and ultrasonicate 0.5 h, whilst 10:1:40 (g/g/mL) for herbs/SC8A/solution ratio, 355-250 μm particle size and ultrasonicate 0.5 h for SC8A assisted extraction. The total yield of alkaloids (fangchinoline and tetrandrine) from FJ was increased by 4.87 times and 5.97 times with SC6A and SC8A. Moreover, a good reusability of SC6A/SC8A was achieved by alkalisation dissociation. Host-guest complexes were determined by competitive fluorescence titration at a molar ratio of 1:1 between most alkaloids (25/27, except evodiamine and rutaecarpine) and SC6A/SC8A. The complex structure was proved by DSC, FTIR and1 H-NMR analysis., Conclusion: The study provided an effective eco-friendly and energy-saving extraction method of alkaloids from herbal medicine., (© 2022 John Wiley & Sons Ltd.)- Published
- 2022
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16. Urolithiasis
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Thakore P and Liang TH
- Abstract
Renal stones are formed within the kidneys, and this is called nephrolithiasis. Urolithiasis is a condition that occurs when these stones exit the renal pelvis and move into the remainder of the urinary collecting system, which includes the ureters, bladder, and urethra. Many patients with urolithiasis can be managed with expectant management, analgesic, and anti-emetic medications; however, stones that are associated with obstruction, renal failure, and infection require further increasingly critical interventions.[1], (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
17. Prognosis in Myelodysplastic Syndromes: The Clinical Challenge of Genomic Integration.
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Chen-Liang TH
- Abstract
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic neoplasms characterized by ineffective hematopoiesis and myelodysplasia with a variable spectrum of clinical-biological features that can be used to build a prognostic estimation. This review summarizes the current most widely used prognostic scoring systems and gives a general view of the prognostic impact of somatic mutations in MDS patients.
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- 2021
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18. Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach.
- Author
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Hurtado López AM, Chen-Liang TH, Zurdo M, Carrillo-Tornel S, Panadero J, Salido EJ, Beltrán V, Muiña B, Amigo M, Navarro-Villamor N, Cifuentes R, Calabria I, Antón AI, Teruel R, Muro M, Vicente V, and Jerez A
- Subjects
- Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Humans, Male, Sequence Analysis, RNA, Testis, Transcription Factor DP1, Myelodysplastic Syndromes drug therapy, Neoplasms
- Abstract
Cancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) is a prerequisite for downstream immune target-discovery projects. In this study, we take advantage of the use of azacitidine to treat high-risk MDS and CMML to draw the CTAs landscape, before and after treatment, using an ad hoc targeted RNA sequencing (RNA-seq) design for this group of low transcript genes. In 19 patients, 196 CTAs were detected at baseline. Azacitidine did not change the number of CTAs expressed, but it significantly increased or decreased expression in nine and five CTAs, respectively. TFDP3 and DDX53 , emerged as the main candidates for immunotherapeutic targeting, as they showed three main features: i) a significant derepression on day +28 of cycle one in those patients who achieved complete remission with hypomethylating treatment (FC = 6, p = .008; FC = 2.1, p = .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognized TFDP3 and DDX53 reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)
- Published
- 2020
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19. Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease.
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Kim D, Park G, Huuhtanen J, Lundgren S, Khajuria RK, Hurtado AM, Muñoz-Calleja C, Cardeñoso L, Gómez-García de Soria V, Chen-Liang TH, Eldfors S, Ellonen P, Hannula S, Kankainen M, Bruck O, Kreutzman A, Salmenniemi U, Lönnberg T, Jerez A, Itälä-Remes M, Myllymäki M, Keränen MAI, and Mustjoki S
- Subjects
- Blotting, Western, Cell Proliferation genetics, Cell Proliferation physiology, HEK293 Cells, Humans, Immunity, Cellular genetics, Immunity, Cellular physiology, Immunoprecipitation, Mutation genetics, Protein Binding genetics, Protein Binding physiology, Graft vs Host Disease genetics, T-Lymphocytes metabolism, TOR Serine-Threonine Kinases genetics
- Abstract
Graft versus host disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). Here we report studies of a patient with chronic GvHD (cGvHD) carrying persistent CD4
+ T cell clonal expansion harboring somatic mTOR, NFKB2, and TLR2 mutations. In the screening cohort (n = 134), we detect the mTOR P2229R kinase domain mutation in two additional cGvHD patients, but not in healthy or HSCT patients without cGvHD. Functional analyses of the mTOR mutation indicate a gain-of-function alteration and activation of both mTORC1 and mTORC2 signaling pathways, leading to increased cell proliferation and decreased apoptosis. Single-cell RNA sequencing and real-time impedance measurements support increased cytotoxicity of mutated CD4+ T cells. High throughput drug-sensitivity testing suggests that mutations induce resistance to mTOR inhibitors, but increase sensitivity for HSP90 inhibitors. Our findings imply that somatic mutations may contribute to aberrant T cell proliferations and persistent immune activation in cGvHD, thereby paving the way for targeted therapies.- Published
- 2020
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20. Efficacy and Safety of Opinercept Tumor Necrosis Factor Inhibitor Therapy for Drug-Refractory Rheumatoid Arthritis: A Randomized Clinical Trial.
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Liang TH, Lee CS, Lee SS, Wu CS, Chen KH, Hsu PN, and Lin HY
- Abstract
Objectives: This study aims to evaluate the efficacy and safety profile of opinercept for rheumatoid arthritis (RA) patients undergoing disease- modifying anti-rheumatic drugs (DMARDs) therapy., Patients and Methods: A total of 98 patients with active RA (17 males, 81 females; mean age 58.6±12.2 years; range, 24.3 to 85.3 years) were randomized into opinercept plus DMARDs (OD group) or placebo plus DMARDs (PD group), in a 24-week treatment period. Primary outcome was American College of Rheumatology score (ACR20) at week 24. Other exploratory endpoints included ACR50, ACR70 and disease activity score-28 (DAS28) at week 12 and 24, tender/swollen joint counts, pain, Health Assessment Questionnaire-Disability Index, erythrocyte sedimentation rate, and C-reactive protein level. Incidence of adverse events (AEs), vital signs and physical findings, and laboratory test results were also evaluated., Results: Patients in OD group showed significantly higher achievement percentage of ACR20 at week 24 than the PD group (76.6% vs. 30.3%, p<0.001). The evaluation of DAS28 was significantly improved in OD patients compared to PD patients at weeks 12 and 24. Most of the occurred AEs were mild or moderate and considered unrelated to study treatments., Conclusion: Opinercept concurrent with DMARDs was superior to DMARDs alone in slowing RA progression and ameliorating symptoms, with well- tolerated and acceptable safety profile., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2020, Turkish League Against Rheumatism.)
- Published
- 2020
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21. Outcome of bimodality definitive chemoradiation does not differ from that of trimodality upfront neck dissection followed by adjuvant treatment for >6 cm lymph node (N3) head and neck cancer.
- Author
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Chen WY, Chen TC, Lai SF, Liang TH, Huang BS, and Wang CW
- Subjects
- Adult, Aged, Chemoradiotherapy, Combined Modality Therapy, Female, Head and Neck Neoplasms mortality, Humans, Lymph Nodes pathology, Magnetic Resonance Imaging, Male, Middle Aged, Neck Dissection, Neoplasm Staging, Prognosis, Retrospective Studies, Treatment Outcome, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms therapy
- Abstract
Currently, data regarding optimal treatment modality, response, and outcome specifically for N3 head and neck cancer are limited. This study aimed to compare the treatment outcomes between definitive chemoradiotherapy (CCRT) to the neck and upfront neck dissection followed by adjuvant CCRT. Ninety-three N3 squamous cell carcinoma head and neck cancer patients were included. Primary tumor treatment was divided to definitive CCRT (CCRT group) or curative surgery followed by adjuvant CCRT (surgery group). Neck treatment was also classified into two treatment modalities: definitive CCRT to the neck (CCRT group) or curative neck dissection followed by adjuvant CCRT (neck dissection group). Overall, the 2-year overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 51.8%, 47.3%, 45.6%, and 43.6%, respectively. In both oropharyngeal cancer and nonoropharyngeal cancer patients, in terms of OS, LRFS, RRFS or DMFS no difference was noted regarding primary tumor treatment (CCRT vs. surgery) or neck treatment (CCRT vs. neck dissection). In summary, N3 neck patients treated with definitive CCRT may achieve similar outcomes to those treated with upfront neck dissection followed by adjuvant CCRT. Caution should be made to avoid overtreatment for this group of patients., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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22. Developing a Web-Based Comic for Newly Diagnosed Women With Breast Cancer: An Action Research Approach.
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Lee TI, Sheu SJ, Chang HC, Hung YT, Tseng LM, Chou SS, Liang TH, Liu HJ, Lu HL, Chen MC, Liu YC, Tsai CS, and Sun JC
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- Female, Graphic Novels as Topic, Humans, Internet, Breast Neoplasms psychology, Health Services Research methods
- Abstract
Background: Personal narratives have been seen as a useful way of communicating about cancer treatment options and providing recovery information. Many printed versions of such material are available, including comics that explore the individual memories of patients who have gone through cancer treatment. These studies have been used to orientate patients, patients' relatives, and physicians. However, only a few Web-based comics have been specifically designed for patients with breast cancer and used as aids to decision making., Objective: We aimed to describe the developmental process of creating an animated comic as a Web-based surgery decision-making tool; the comic was aimed at illustrating the feelings, thoughts, and meanings when a patient suffers from breast cancer. This was done by recounting the symptoms, diagnostic process, treatments, and treatment effects of such women from the diagnosis stage onward., Methods: Using cycles of planning, action, evaluation, and reflection, which involved collaborative work, action research was conducted to develop a Web-based animated comic. The stages of action research consisted of (1) semistructured and in-depth interviews to collect experiences of women with breast cancer; (2) construction of an animated comic by editors, graphics designers, dubbers, and information technology engineers; (3) redrawing of pictures of the comic after gathering feedback from a breast surgeon; and (4) evaluation of the Web-based animated comic using 6 patient focus groups., Results: The comic was produced and showcased on the website "The Network of Making-decision Aids for Breast Cancer Surgery"; the comic was accompanied by soft music and audio explanations. The comic functions as a personal statement that describes experiencing breast cancer. The animated comic consists of 8 chapters, based on the 8 themes deducted from the findings obtained during the analysis of relevant interviews. The 8 chapters include (1) the appearance of a lump; (2) confirmation by medical diagnosis; (3) the uncertainty of waiting (4) fear of life-threatening disease; (5) choosing life over despair; (6) being brave and deciding to undergo treatment; (7) choosing the type of surgery; and (8) being reborn., Conclusions: Using action research, this study illustrated that the comic that sheds light on issues of feelings, emotions, and thoughts that are present when a woman is diagnosed with breast cancer and provides a communication medium to explain the steps in the process. Meanwhile, it implies that hope will be able to overcome the challenges that will be faced. Within the Web-based decision aid for patients with breast cancer, the animated comic acts as an information resource and is aimed at patients' understanding of impacts of emotions arising when suffering from breast cancer. It is potentially applicable as a therapeutic tool that facilitates self-reflection and self-healing among newly diagnosed patients with breast cancer., (©Tzu-I Lee, Shuh-Jen Sheu, Hsueh-Chin Chang, Yu-Ting Hung, Ling-Ming Tseng, Shin-Shang Chou, Te-Hsin Liang, Hui-Ju Liu, Hui-Ling Lu, Mei-Chun Chen, Ying-Chun Liu, Chi-Shan Tsai, Jui-Chiung Sun. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.02.2019.)
- Published
- 2019
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23. Developing a Decision-Aid Website for Breast Cancer Surgery: An Action Research Approach.
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Hung YT, Wu CF, Liang TH, Chou SS, Chen GL, Wu PN, Su GR, Jang TH, Liu CY, Wang CY, Tseng LM, and Sheu SJ
- Subjects
- Female, Humans, Internet, Breast Neoplasms surgery, Decision Support Techniques
- Abstract
Background: Patients with early-stage breast cancer have numerous options when choosing the type of breast surgery method to be applied. Each of these options lead to a similar long-term survival rate, but result in significant differences in appearance, function, cost, recurrence rate, and various other relevant considerations. However, the time available for detailed communication with each patient is often limited in clinics, which puts these women under great psychological stress and can hinder their surgery-related decision making., Objective: The objective of this study was to develop a multipurpose surgery decision-making website providing medical information, psychological support, and decision-related simulation for women during breast cancer surgery-related decision making., Methods: Using the 4 steps of action research, which involve multigroup teamwork via regular team meetings, the following were performed: (1) Planning: searching, analyzing, and evaluating health websites to consensually decide the major infrastructure; (2) Action: work was performed simultaneously in 4 groups, which consisted of medical information collection and editing, patient interviews and data extraction, webpage content design, and programming to create or host the website; (3) Evaluation: the website was tested by clinical experts and focus groups of former breast cancer patients to assess its effectiveness and pinpoint appropriate improvements; and (4) Reflection: constant dialogue was conducted between the various participants at each step, which was used as the foundation and motivation of next plan-action-evaluation-reflection circle., Results: Using the action research approach, we completed the development of our website, which includes the following: (1) "Woman's Voice"-an animated comic depicting the story of a female breast cancer patient with interspersed questions for the users that will help them better empathize with the experience; (2) "Cancer Information Treasure House"-providing breast cancer surgery-related information through text, tables, pictures and a presentation video; (3) "Decision-making Simulator"-helping patients think through and check the pros and cons of the different surgical options via visual-based interactions including "Stairs Climbing" and "Fruit of Hope"; and (4) "Recommended Links"-providing reliable websites for further reference. Additionally, we have further improved the website based on the feedback received from postsurgery breast cancer patients and clinicians. We hope to continue improving to better meet both the patients' and health providers' needs and become a practical decision-making aid for patients undergoing breast cancer surgery., Conclusions: We have created the first breast cancer surgery decision-making assistance tool in Taiwan using a "Web-based" and multifunctional website design. This site aims to provide health care knowledge, psychological healing, and emotional support functions, as well as decision-making capability enhancement simulations. We look forward to assisting breast cancer patients in their decision-making process and expect our website to increase patient's autonomy and improve their communication with clinicians., (©Yu-Ting Hung, Ching-Fang Wu, Te-Hsin Liang, Shin-Shang Chou, Guan-Liang Chen, Pei-Ni Wu, Guan-Rong Su, Tsuey-Huah Jang, Chang-Yi Liu, Ching-Yen Wang, Ling-Ming Tseng, Shuh-Jen Sheu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.02.2019.)
- Published
- 2019
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24. Increasing therapy-related myeloid neoplasms in multiple myeloma.
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Fernández-Caballero M, Salmerón D, Dolores Chirlaque M, Chen-Liang TH, Hurtado AM, García Malo MD, Ortuño FJ, Roldán V, Vicente V, Jerez A, and De Arriba F
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Digestive System Neoplasms etiology, Female, Follow-Up Studies, Hematologic Neoplasms etiology, Humans, Kidney Neoplasms etiology, Lung Neoplasms etiology, Male, Middle Aged, Multiple Myeloma mortality, Myelodysplastic Syndromes etiology, Retrospective Studies, Stem Cell Transplantation adverse effects, Young Adult, Multiple Myeloma therapy, Neoplasms, Second Primary etiology
- Abstract
Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28-year follow-up period (1991-2018) in a tertiary single institution., Material and Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs., Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy-related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months)., Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)
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- 2019
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25. An early increase of CD56 bright natural killer subset as dominant effect and predictor of response to extracorporeal photopheresis for graft-versus-host disease.
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Iniesta P, Revilla N, Chen-Liang TH, Hurtado AM, Vicente V, Heras I, Jerez A, and Lozano ML
- Subjects
- Adult, CD56 Antigen blood, Female, Graft vs Host Disease blood, Graft vs Host Disease pathology, Humans, Killer Cells, Natural metabolism, Killer Cells, Natural pathology, Male, Middle Aged, CD56 Antigen immunology, Graft vs Host Disease immunology, Graft vs Host Disease therapy, Killer Cells, Natural immunology, Photopheresis
- Abstract
Background: CD56
bright natural killer (NK) regulatory cells were recently shown to display a differential impact on the risk of developing extensive chronic graft-versus-host disease (GVHD). To date no study has definitively established which immune populations are most responsible for the immunomodulatory effects or response to extracorporeal photopheresis (ECP) for GVHD., Study Design and Methods: To test the role of CD56bright NK cells in ECP, a prospective enhanced flow cytometry follow-up of immune subsets (CD19+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/CD56+, CD3-/CD56bright , and CD3-/CD56dim ) was performed in 32 patients with GVHD who underwent 552 procedures., Results: An early increase of CD56bright NK cells was found as a hallmark effect to ECP, particularly during the first 3 months of treatment. This was also supported by the ability to predict for complete responses when this increase was expressed as a higher CD56bright versus CD56dim NK cells ratio. Among the immune subsets tested, the only variable that had direct influence on response to ECP was a CD56bright/dim ratio more than 0.16 (hazard ratio [HR] 4.32, p = 0.014; HR 5.8, p = 0.007, at 2 and 3 months of ECP treatment, respectively)., Conclusion: These findings argue for exploring strategies for priming a CD56bright NK cell expansion during ECP and providing additional and potentially relevant data for revisiting the underpinning cellular mechanisms of ECP that could generate that expansion., (© 2018 AABB.)- Published
- 2018
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26. An increased percentage of myeloid CD34+ bone marrow cells stratifies intermediate IPSS-R myelodysplastic syndrome patients into prognostically significant groups.
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Chen-Liang TH, Casado-Prieto AM, Campos-Rodríguez V, Hurtado AM, Amigo ML, García-Malo MD, Vicente V, Ortuño FJ, and Jerez A
- Abstract
Introduction: The Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes (MDS) has established an intermediate category where a disease-modifying intervention is a matter of debate. Flow cytometry allows us to determine a fraction of immature myeloid cells in a semiautomated procedure. The aim of this study, mirroring IPSS-R study inclusion criteria, was to test whether bone marrow (BM) CD34+My percentage has independent prognostic value in the MDS setting., Methods: BM CD34+My cells were quantified, at diagnosis, selecting CD34+/CD45+/CD11b±/CD13+. Patients were excluded when receiving treatment for altering the natural course of the disease and when IPSS-R could not be calculated due to the lack of metaphases. Finally, Cox analyses were performed, on a series of 260 patients, for overall survival (OS) and time to acute myeloid leukemia (AML) transformation., Results: By analyzing ROC curves, the most accurate prognostic variable, regarding blasts by cytology and CD34+ by cytometry, was the percentage of blasts by microscopy. The percentage of CD34+My in BM showed an AUC of 0.767 and 0.576 for time to AML transformation and OS, respectively. When performing a multivariate regression including the IPSS-R and the percentage of BM CD34+My cells >1%, both factors predicted for a shorter time to AML transformation. In addition, CD34+My percentage successfully stratified the intermediate IPSS-R category into two prognostic groups with a relative risk of 5.73 (95% CI [1.2-27.8]; P = .03)., Conclusion: We found that BM CD34+My percentage has an independent value concerning the IPSS-R, especially relevant for the prediction of transformation to AML and within the intermediate group., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2018
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27. Transcriptomic rationale for synthetic lethality-targeting ERCC1 and CDKN1A in chronic myelomonocytic leukaemia.
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Hurtado AM, Luengo-Gil G, Chen-Liang TH, Amaral F, Batta K, Palomo L, Lumbreras E, Przychodzen B, Caparros E, Amigo ML, Dıez-Campelo M, Zamora L, Salido Fierrez EJ, Maciejewski JP, Ortuño FJ, Vicente V, Del Canizo M, Sole F, Ferrer-Marin F, Wiseman DH, and Jerez A
- Subjects
- Aged, Bone Marrow pathology, Case-Control Studies, DNA Mutational Analysis, Female, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myeloid, Acute genetics, Male, Middle Aged, Myelodysplastic Syndromes genetics, Poly (ADP-Ribose) Polymerase-1 genetics, Serine-Arginine Splicing Factors genetics, Transcription, Genetic, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA Repair genetics, DNA-Binding Proteins metabolism, Endonucleases metabolism, Leukemia, Myelomonocytic, Chronic genetics
- Abstract
Despite the absence of mutations in the DNA repair machinery in myeloid malignancies, the advent of high-throughput sequencing and discovery of splicing and epigenetics defects in chronic myelomonocytic leukaemia (CMML) prompted us to revisit a pathogenic role for genes involved in DNA damage response. We screened for misregulated DNA repair genes by enhanced RNA-sequencing on bone marrow from a discovery cohort of 27 CMML patients and 9 controls. We validated 4 differentially expressed candidates in CMML CD34
+ bone marrow selected cells and in an independent cohort of 74 CMML patients, mutationally contextualized by targeted sequencing, and assessed their transcriptional behavior in 70 myelodysplastic syndrome, 66 acute myeloid leukaemia and 25 chronic myeloid leukaemia cases. We found BAP1 and PARP1 down-regulation to be specific to CMML compared with other related disorders. Chromatin-regulator mutated cases showed decreased BAP1 dosage. We validated a significant over-expression of the double strand break-fidelity genes CDKN1A and ERCC1, independent of promoter methylation and associated with chemorefractoriness. In addition, patients bearing mutations in the splicing component SRSF2 displayed numerous aberrant splicing events in DNA repair genes, with a quantitative predominance in the single strand break pathway. Our results highlight potential targets in this disease, which currently has few therapeutic options., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2018
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28. The breast graded prognostic assessment is associated with the survival outcomes in breast cancer patients receiving whole brain re-irradiation.
- Author
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Lai SF, Chen YH, Liang TH, Hsu CY, Lien HC, Lu YS, Huang CS, and Kuo SH
- Subjects
- Adult, Biomarkers, Tumor metabolism, Brain Neoplasms mortality, Breast Neoplasms mortality, Breast Neoplasms radiotherapy, Disease Progression, Humans, Middle Aged, Prognosis, Receptor, ErbB-2 metabolism, Retrospective Studies, Survival Analysis, Transcription Factors metabolism, Brain Neoplasms diagnosis, Brain Neoplasms radiotherapy, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Cranial Irradiation adverse effects, Re-Irradiation adverse effects
- Abstract
Introduction: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation., Methods: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed. Patients were divided according to the 4 molecular subtypes of luminal A/B (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-), luminal HER2 (HR+/HER2+), HER2 (HR-/HER2+), and triple negative (HR-/HER2-). The clinical and radiological responses and survival rates after WB re-irradiation were analyzed., Results: At 1 month after WB re-irradiation, 13 of 23 patients (56.5%) exhibited disappearance or alleviation of neurological symptoms. The median survival time after WB re-irradiation was 2.93 months (95% confidence interval [CI], 1.79-4.08). After WB re-irradiation, patients with HER2-negative tumors had poorer median survival times than those with HER2-positive tumors (2.23 vs. 3.0 months, respectively; p = 0.022). Furthermore, patients with high breast GPA scores (2.5-4.0, n = 11) had longer median survivals than those with low-scores (0-2.0, n = 12) after WB re-irradiation (4.37 vs. 1.57 months, respectively; p < 0.005)., Conclusions: WB re-irradiation may be a feasible treatment option for certain breast cancer patients who develop brain metastatic lesions after first-course WBRT when these lesions are ineligible for radiosurgery or surgery.
- Published
- 2018
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29. Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan.
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Yu KH, Chen DY, Chen JH, Chen SY, Chen SM, Cheng TT, Hsieh SC, Hsieh TY, Hsu PF, Kuo CF, Kuo MC, Lam HC, Lee IT, Liang TH, Lin HY, Lin SC, Tsai WP, Tsay GJ, Wei JC, Yang CH, and Tsai WC
- Subjects
- Biomarkers blood, Comorbidity, Consensus, Down-Regulation, Gout blood, Gout diagnosis, Gout epidemiology, Gout Suppressants adverse effects, Humans, Hyperuricemia blood, Hyperuricemia diagnosis, Hyperuricemia epidemiology, Interdisciplinary Communication, Risk Factors, Taiwan epidemiology, Treatment Outcome, Uricosuric Agents therapeutic use, Gout drug therapy, Gout Suppressants therapeutic use, Hyperuricemia drug therapy, Uric Acid blood
- Abstract
Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)
- Published
- 2018
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30. Bone marrow biopsy superiority over PET/CT in predicting progression-free survival in a homogeneously-treated cohort of diffuse large B-cell lymphoma.
- Author
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Chen-Liang TH, Martín-Santos T, Jerez A, Rodríguez-García G, Senent L, Martínez-Millán C, Muiña B, Orero M, Teruel A, Martín A, Gómez-Espuch J, Kennedy K, Benet C, Raya JM, Fernández-González M, de la Cruz F, Guinot M, Villegas C, Ballester I, Baile M, Moya M, López-Jiménez J, Frutos L, Navarro JL, Uña J, Fernández-López R, Igua C, Contreras J, Sánchez-Vañó R, Cozar MDP, Tamayo P, Mucientes J, Sánchez-Blanco JJ, Pérez-Ceballos E, and Ortuño FJ
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biopsy, Cyclophosphamide therapeutic use, Disease-Free Survival, Doxorubicin therapeutic use, Female, Follow-Up Studies, Health Status, Humans, Lymphoma, Large B-Cell, Diffuse drug therapy, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prednisone therapeutic use, Retrospective Studies, Rituximab administration & dosage, Survival Rate, Vincristine therapeutic use, Young Adult, beta 2-Microglobulin blood, Bone Marrow diagnostic imaging, Bone Marrow pathology, Lymphoma, Large B-Cell, Diffuse diagnostic imaging, Lymphoma, Large B-Cell, Diffuse pathology, Positron Emission Tomography Computed Tomography
- Abstract
Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B-cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R-CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow-up of 25 months the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB-BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2-microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first-line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2017
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31. Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT3 mutations.
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Muñoz-Ballester J, Chen-Liang TH, Hurtado AM, Heras I, de Arriba F, García-Malo MD, Iniesta P, Lozano ML, Nieto JB, Ortuño FJ, Osma Mdel M, Padilla J, Teruel-Montoya R, Vicente V, Castilla-Llorente C, and Jerez A
- Subjects
- Adult, Female, Gene Rearrangement, T-Lymphocyte genetics, Graft vs Host Disease immunology, Graft vs Host Disease prevention & control, Humans, Immunophenotyping, Leukemia, Large Granular Lymphocytic genetics, Leukemia, Large Granular Lymphocytic immunology, Longitudinal Studies, Male, Middle Aged, Neoplasm Proteins genetics, Survival Analysis, Young Adult, Hematopoietic Stem Cell Transplantation, Leukemia, Large Granular Lymphocytic therapy, Mutation, STAT3 Transcription Factor genetics, T-Lymphocytes, Cytotoxic immunology
- Abstract
Peripheral expansion of cytotoxic T lymphocytes (CTL) derived from the graft in the initial stages of allogeneic haematopoietic stem cell transplantation (alloHSCT) immune recovery is a well-known physiological event. The description of symptomatic large granular lymphocyte leukaemia in this setting may generate uncertainty, mostly in those cases in which the CTL expansion (CTLe) persists beyond the early transplantation period. We aimed to assess the nature of CTLe during the post-alloHSCT period in 154 adult patients with a long-term surveillance. We studied the longitudinal kinetics of those expansions, their relationship to clinical events, and their phenotypic and molecular features, including recently reported CTL leukaemia-STAT3 mutations. Persistent relative CTLe cases are frequent (49%), related with thymoglobulin prophylaxis (P ≤ 0·001), acute graft-versus-host disease (GVHD, P = 0·02), and reduced intensity conditioning (P = 0·04). Absolute CTLe are scarce (9%) and related to chronic GVHD. T cell receptor rearrangement was reported as clonal and oligoclonal in the majority of patients with CTLe. The absence of STAT3 mutations and the CD8/CD4 declining longitudinal kinetics in the late period supports its benign nature, expressed clinically by the null detrimental impact of these expansions on post-transplant outcome and/or serious infectious events., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
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32. Adverse prognosis and distinct progression patterns after concurrent chemoradiotherapy for glioblastoma with synchronous subventricular zone and corpus callosum invasion.
- Author
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Liang TH, Kuo SH, Wang CW, Chen WY, Hsu CY, Lai SF, Tseng HM, You SL, Chen CM, and Tseng WY
- Subjects
- Adult, Aged, Aged, 80 and over, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Cerebral Ventriculography, Corpus Callosum diagnostic imaging, Female, Glioblastoma diagnostic imaging, Glioblastoma pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Invasiveness, Prognosis, Proportional Hazards Models, Retrospective Studies, Tomography, X-Ray Computed, Young Adult, Brain Neoplasms therapy, Cerebral Ventricles pathology, Chemoradiotherapy, Corpus Callosum pathology, Disease Progression, Glioblastoma therapy
- Abstract
Background and Purpose: The subventricular zone (SVZ) and the corpus callosum (CC) invasion status are separately associated with adverse prognosis for glioblastoma. We investigated the prognosis and progression patterns of glioblastoma with and without synchronous SVZ and CC (sSVZCC) invasion., Material and Methods: Glioblastoma patients completing concurrent chemoradiotherapy with temozolomide were retrospectively categorized by the preoperative sSVZCC invasion status. The associations between sSVZCC invasion and the survival and progression patterns were analyzed., Results: In total, 108 patients, including 36 with sSVZCC invasion, were followed for a median period of 60.2 (range 34.2-86.3) months. The median overall survival (OS) of patients with and without sSVZCC were 18.6 and 26.4 months, respectively (p=0.005). Using multivariate analyses with the factors of age, performance, surgery extent, and tumor size, sSVZCC invasion remained significant for a poor OS (hazard ratio, 1.96; 95% confidence interval, 1.19-3.21). The rates of progression at tumor bed, preoperative edematous areas, bilateral hemispheres, and ventricles for tumors with and without sSVZCC invasion were 75% and 63.9% (p=0.282), 41.7% and 9.7% (p<0.001), 47.2% and 13.9% (p<0.001), and 38.9% and 13.9% (p=0.006), respectively., Conclusions: The sSVZCC invasion status determined the distinct prognosis and progression areas of glioblastoma, which suggests individualized radiotherapy and drug administration strategies., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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33. Reply to Adams and Kwee.
- Author
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Chen-Liang TH, Jerez A, and Ortuño FJ
- Subjects
- Female, Humans, Male, Bone Marrow pathology, Hodgkin Disease diagnosis, Lymphoma, Non-Hodgkin diagnosis
- Published
- 2015
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34. Prognostic signature and clonality pattern of recurrently mutated genes in inactive chronic lymphocytic leukemia.
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Hurtado AM, Chen-Liang TH, Przychodzen B, Hamedi C, Muñoz-Ballester J, Dienes B, García-Malo MD, Antón AI, de Arriba F, Teruel-Montoya R, Ortuño FJ, Vicente V, Maciejewski JP, and Jerez A
- Subjects
- Aged, DNA Mutational Analysis, Female, Gene Frequency, Genes, Neoplasm, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Prognosis, Proportional Hazards Models, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation
- Abstract
An increasing numbers of patients are being diagnosed with asymptomatic early-stage chronic lymphocytic leukemia (CLL), with no treatment indication at baseline. We applied a high-throughput deep-targeted analysis, especially designed for covering widely TP53 and ATM genes, in 180 patients with inactive disease at diagnosis, to test the independent prognostic value of CLL somatic recurrent mutations. We found that 40/180 patients harbored at least one acquired variant with ATM (n=17, 9.4%), NOTCH1 (n=14, 7.7%), TP53 (n=14, 7.7%) and SF3B1 (n=10, 5.5%) as most prevalent mutated genes. Harboring one 'sub-Sanger' TP53 mutation granted an independent 3.5-fold increase of probability of needing treatment. Those patients with a double-hit ATM lesion (mutation+11q deletion) had the shorter median time to first treatment (17 months). We found that a genomic variable: TP53 mutations, most of them under the sensitivity of conventional techniques; a cell phenotypic factor: CD38-positive expression; and a classical marker as β2-microglobulin, remained as the unique independent predictors of outcome. The high-throughput determination of TP53 status, particularly in this set of patients frequently lacking high-risk chromosomal aberrations, emerges as a key step, not only for prediction modeling, but also for exploring mutation-specific therapeutic approaches and minimal residual disease monitoring.
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- 2015
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35. [Neoplastic mastocytosis evolving from a poor prognosis acute myeloid leukemia].
- Author
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Chen-Liang TH, Jerez A, Florensa L, and Ortuño FJ
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine administration & dosage, Disease Progression, Drug Resistance, Neoplasm, Fatal Outcome, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoietic Stem Cell Transplantation, Humans, Idarubicin administration & dosage, Immunophenotyping, Leukemia, Mast-Cell diagnosis, Leukemia, Mast-Cell drug therapy, Leukemia, Mast-Cell pathology, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Mast Cells pathology, Mutation, Neoplasm Proteins analysis, Neoplastic Stem Cells pathology, Prognosis, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Leukemia, Mast-Cell etiology, Leukemia, Myeloid, Acute pathology
- Published
- 2015
- Full Text
- View/download PDF
36. Effectiveness of a multidisciplinary itch clinic in the management of chronic pruritus.
- Author
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Michelle LW, Yan L, Soon-Leong AT, and Liang TH
- Published
- 2015
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- View/download PDF
37. Variant acute promyelocytic leukemia presenting with loss of visual acuity and extreme pancytopenia.
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Chen-Liang TH, Lajara J, and Ortuño FJ
- Subjects
- Adult, Bone Marrow pathology, Female, Humans, In Situ Hybridization, Tomography, Optical Coherence, Vision, Low diagnosis, Vision, Low etiology, Leukemia, Promyelocytic, Acute diagnosis, Pancytopenia pathology
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- 2014
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38. Truth-telling to patients' terminal illness: what makes oncology nurses act individually?
- Author
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Huang SH, Tang FI, Liu CY, Chen MB, Liang TH, and Sheu SJ
- Subjects
- Adult, Communication, Female, Humans, Nurse's Role, Pilot Projects, Professional Autonomy, Socioeconomic Factors, Surveys and Questionnaires, Taiwan, Attitude of Health Personnel, Neoplasms psychology, Nurse-Patient Relations, Oncology Nursing methods, Terminal Care methods, Terminally Ill psychology, Truth Disclosure
- Abstract
Purpose: Nurses encounter the challenge of truth-telling to patients' terminal illness (TTPTI) in their daily care activities, particularly for nurses working in the pervasive culture of family protectiveness and medical paternalism. This study aims to investigate oncology nurses' major responses to handling this issue and to explore what factors might explain oncology nurses' various actions., Methods: A pilot quantitative study was designed to describe full-time nurses' (n = 70) truth-telling experiences at an oncology centre in Taipei. The potential influencing factors of nurses' demographic data, clinical characteristics, and truth-telling attitudes were also explored., Results: Most nurses expressed that truth-telling was a physician's responsibility. Nevertheless, 70.6% of nurses responded that they had performed truth-telling, and 20 nurses (29.4%) reported no experience. The reasons for inaction were "Truth-telling is not my duty", "Families required me to conceal the truth", and "Truth-telling is difficult for me". Based on a stepwise regression analysis, nurses' truth-telling acts can be predicted based on less perceived difficulty of talking about "Do not resuscitate" with patients, a higher perceived authorisation from the unit, and more oncology work experience (adjusted R² = 24.1%)., Conclusions: Oncology care experience, perceived comfort in communication with terminal patients, and unit authorisation are important factors for cultivating nurses' professional accountability in truth-telling. Nursing leaders and educators should consider reducing nursing barriers for truth-telling, improving oncology nurses' professional accountability, and facilitating better quality care environments for terminal patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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39. Pathologic finding of increased expression of interleukin-17 in the synovial tissue of rheumatoid arthritis patients.
- Author
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Li N, Wang JC, Liang TH, Zhu MH, Wang JY, Fu XL, Zhou JR, Zheng SG, Chan P, and Han J
- Subjects
- Adult, Aged, Arthritis, Rheumatoid pathology, Biomarkers analysis, Case-Control Studies, Female, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, Severity of Illness Index, Synovial Membrane pathology, Arthritis, Rheumatoid immunology, Interleukin-17 analysis, Synovial Membrane immunology
- Abstract
Rheumatoid arthritis (RA) is a common autoimmune disease of chronic systemic inflammatory disorder that will affect multiple tissues and organs such as skin, heart or lungs; but it principally attacks the joints, producing a nonsuppurative inflammatory and proliferative synovitis that often progresses to major damaging of articular cartilage and joint ankylosis. Although the definite etiology is still unknown, recent studies suggest that T-helper cells (Th17) may play a pivotal role in the pathogenesis of RA. And interleukin-17 (IL-17), which is a cytokine of Th17 cells, may be a key factor in the occurrence of RA. The binding of IL-17 to specific receptor results in the expression of fibroblasts, endothelial and epithelial cells and also synthesis of several major factors such as tumor necrosis factor alpha (TNF-α), IL-1β that result in the structural damage of RA joints. Though some previous studies have shown that IL-17 exists in the synovium of RA, few has definite proof quantitatively by pathology about its existence in synovial membrane. This study comprised of 30 RA patients and 10 healthy control, pathologic study of the synovial membrane showed increased expression of IL-17 in the synovial tissue of RA patients, the intensity is compatible with clinical severity of disease as validated by DAS28 score and disease duration. Northern blot study also confirmed the increased expression of IL-17 in the synovial tissues. This study sheds further light that IL-17 may be a key factor in the pathogenesis of RA and a determinant of disease severity.
- Published
- 2013
40. Matrix analysis of the digital divide in eHealth services using awareness, want, and adoption gap.
- Author
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Liang TH
- Subjects
- Adolescent, Adult, Humans, Taiwan, Awareness, Diffusion of Innovation, Telemedicine
- Abstract
Background: The digital divide usually refers to access or usage, but some studies have identified two other divides: awareness and demand (want). Given that the hierarchical stages of the innovation adoption process of a customer are interrelated, it is necessary and meaningful to analyze the digital divide in eHealth services through three main stages, namely, awareness, want, and adoption., Objective: By following the three main integrated stages of the innovation diffusion theory, from the customer segment viewpoint, this study aimed to propose a new matrix analysis of the digital divide using the awareness, want, and adoption gap ratio (AWAG). I compared the digital divide among different groups. Furthermore, I conducted an empirical study on eHealth services to present the practicability of the proposed methodology., Methods: Through a review and discussion of the literature, I proposed hypotheses and a new matrix analysis. To test the proposed method, 3074 Taiwanese respondents, aged 15 years and older, were surveyed by telephone. I used the stratified simple random sampling method, with sample size allocation proportioned by the population distribution of 23 cities and counties (strata)., Results: This study proposed the AWAG segment matrix to analyze the digital divide in eHealth services. First, awareness and want rates were divided into two levels at the middle point of 50%, and then the 2-dimensional cross of the awareness and want segment matrix was divided into four categories: opened group, desire-deficiency group, perception-deficiency group, and closed group. Second, according to the degrees of awareness and want, each category was further divided into four subcategories. I also defined four possible strategies, namely, hold, improve, evaluate, and leave, for different regions in the proposed matrix. An empirical test on two recently promoted eHealth services, the digital medical service (DMS) and the digital home care service (DHCS), was conducted. Results showed that for both eHealth services, the digital divides of awareness, want, and adoption existed across demographic variables, as well as between computer owners and nonowners, and between Internet users and nonusers. With respect to the analysis of the AWAG segment matrix for DMS, most of the segments, except for people with marriage status of Other or without computers, were positioned in the opened group. With respect to DHCS, segments were separately positioned in the opened, perception-deficiency, and closed groups., Conclusions: Adoption does not closely follow people's awareness or want, and a huge digital divide in adoption exists in DHS and DHCS. Thus, a strategy to promote adoption should be used for most demographic segments.
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- 2012
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41. The awareness and want matrix with adoption gap ratio analysis for e-service diffusion effect.
- Author
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Liang TH
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Taiwan, Attitude to Computers, Awareness, Decision Making, Diffusion of Innovation, Internet
- Abstract
Since the hierarchical stages of a customer purchasing decision or innovation adoption process are interrelated, an analysis of all their stages, including awareness, want, and adoption, in relation to product or service diffusion, is urgently needed. Therefore, this study proposes the use of an awareness and want matrix, together with an adoption gap ratio analysis, to assess the effectiveness of innovation and technology diffusion for e-services. This study also conducts an empirical test on the promotion performance evaluation of 12 e-services promoted by the Taiwanese government.
- Published
- 2011
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42. Better short-term clinical response to etanercept in Chinese than Caucasian patients with active ankylosing spondylitis.
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Chou CT, Tsai CY, Liang TH, Chang TM, Lai CH, Wei CC, Chen KH, Lin SC, Yu CL, Liou LB, Luo SF, Lee CS, Hsue YT, Huang CM, Chen JH, Lai NS, Cheng HH, Cheng TT, Lai HM, Tsai WC, Yen JH, Lu LY, and Chang CP
- Subjects
- Adult, Etanercept, Female, Health Status, Humans, Male, Middle Aged, Prospective Studies, Recovery of Function, Remission Induction, Severity of Illness Index, Spondylitis, Ankylosing physiopathology, Treatment Outcome, Young Adult, Antirheumatic Agents therapeutic use, Asian People, Immunoglobulin G therapeutic use, Receptors, Tumor Necrosis Factor therapeutic use, Spondylitis, Ankylosing drug therapy, Spondylitis, Ankylosing ethnology, White People
- Abstract
Tumor necrosis factor-alpha (TNF-α) inhibitors including etanercept have been demonstrated to be very effective in severe ankylosing spondylitis (AS) in Caucasian patients. However, clinical efficacy of etanercept to treat active AS in Chinese patients has not been reported. In this study, a prospective, open-label trial of etanercept (25 mg BIW), involving 46 AS patients from 16 medical centers of Taiwan, was conducted. Questionnaire was utilized to record demographic data and clinical parameters, including Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Assessment in Ankylosing Spondylitis (ASAS) 20, 50, and 70, and others, before and at different time intervals after etanercept treatment. Laboratory tests including blood chemistry, hematology, urine analysis, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were done at baseline and at weeks 4, 8, and 12. In this 12-week study, etanercept demonstrated rapid and significant improvement in the ASAS20 response criteria (91.3%), at as early as 2 weeks of therapy (71.3%). Partial remission of AS was achieved in 49.3% of patients after 12 weeks of treatment. Disease activity (BASDAI) and function (BASFI) were also significantly improved after 12 weeks etanercept treatment (p < 0.0001 and p < 0.0001, respectively). In addition, significant increase of chest expansion (2.77 ± 1.69 cm versus 3.56 ± 1.82 cm, p = 0.0004) and lumbar flexion (2.11 ± 2.76 cm versus 2.58 ± 3.42 cm, p = 0.0075) and significant reduction of occiput-to-wall distance (6.59 ± 7.14 cm versus 5.32 ± 6.65 cm, p = 0.0006) were also demonstrated. Both ESR and CRP declined significantly after patients were treated with etanercept. There were no severe adverse effects during the treatment period. Etanercept is generally safe, well tolerated, and effective in Chinese patients with severe AS. Clinical efficacy, including partial remission and BASDAI, is even better in Chinese than in Caucasian patients. Further study is required to assess long-term efficacy and safety in Chinese patients with AS.
- Published
- 2010
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43. Human leukocyte antigen-G in ankylosing spondylitis and the response after tumour necrosis factor-alpha blocker therapy.
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Chen CH, Liao HT, Chen HA, Liu CH, Liang TH, Wang CT, Tsai CY, and Chou CT
- Subjects
- Adalimumab, Adult, Antibodies, Monoclonal, Humanized, Biomarkers blood, C-Reactive Protein metabolism, Female, Follow-Up Studies, HLA-G Antigens, Humans, Leukocytes, Mononuclear immunology, Male, Middle Aged, Severity of Illness Index, Spondylitis, Ankylosing drug therapy, Spondylitis, Ankylosing physiopathology, Antibodies, Monoclonal therapeutic use, Antirheumatic Agents therapeutic use, HLA Antigens blood, Histocompatibility Antigens Class I blood, Spondylitis, Ankylosing immunology, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Objective: To investigate the role of HLA-G in AS., Methods: Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-alpha blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels., Results: Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (s.d.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P = 0.028], and correlated significantly with modified Schober index (r = 0.326; P = 0.009), chest expansion (r = 0.319; P = 0.011), lateral lumbar flexion (r = 0.377; P = 0.002), cervical rotation (r = 0.396; P = 0.004), whereas inversely correlated with fingertip-to-floor distance (r = -0.282; P = 0.026) and tragus-to-wall distance (r = -0.270; P = 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (s.d.) 18.5 (6.10)% vs 15.41 (4.84)%; P = 0.012], and correlated significantly with ESR (r = 0.421; P < 0.001) and CRP (r = 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P = 0.016]., Conclusions: Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-alpha blocker therapy, suggesting an index of disease activity.
- Published
- 2010
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44. Differences between juvenile-onset ankylosing spondylitis and adult-onset ankylosing spondylitis.
- Author
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Lin YC, Liang TH, Chen WS, and Lin HY
- Subjects
- Adolescent, Adult, Age Factors, Age of Onset, Aged, Child, Child, Preschool, Female, Glomerulonephritis, IGA etiology, Humans, Male, Middle Aged, Risk Factors, Spondylitis, Ankylosing diagnosis, Spondylitis, Ankylosing therapy, Spondylitis, Ankylosing complications
- Abstract
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease, which involves the spine, peripheral joints and entheses. Juvenile-onset ankylosing spondylitis (JAS) affects children under the age of 16 years. JAS has been noted to present as clinical courses different from those of adult-onset ankylosing spondylitis (AAS). Therefore, the purpose of the present study was to compare the possible risk factors, clinical manifestations, laboratory markers, radiological changes, and functional outcome between these 2 patient groups., Methods: AS patients were enrolled from the rheumatologic clinic of a tertiary medical center from January 1 to June 30 in 2006. The demographic data, clinical symptoms/signs, Bath AS indices, HLA-B27, inflammatory markers, radiological findings, and treatment history were acquired with questionnaires, clinical evaluation, and chart review. The differences between JAS and AAS patients were evaluated and analyzed., Results: A total of 169 patients (142 males, 27 females) were included, comprising 47 JAS and 122 AAS patients. The ages of onset were 12.8 +/- 2.7 years and 25.0 +/- 7.4 years for JAS and AAS, respectively. They had similar gender distribution, years of delay to diagnosis and disease duration. A substantial proportion of our patients (40.4% of JAS and 34.4% of AAS) had physical trauma in the 1 month before disease onset. Also, 22.7% of JAS patients had intense physical training, while 25.2% of AAS patients did heavy work during the period. The first manifestation of JAS was mainly peripheral enthesopathy or arthritis, but axial symptoms in most AAS. More JAS patients had peripheral enthesopathies and arthritis on any occasion. Although there was a trend of higher score in Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index (BASMI) and Physician's Global Assessment (PGA) score, JAS patients had a comparable Bath AS Functional Index (BASFI) and Bath AS Patient's Global Assessment (BAS-G) as AAS patients. As to the laboratory and radiological tests, JAS patients had higher levels of C-reactive protein and erythrocyte sedimentation rate, and more radiographic changes of hip joints., Conclusion: JAS and AAS patients had distinct presentations. JAS presented more peripheral enthesopathies and arthritis at disease onset and at any time of the course. If treated effectively, JAS will not lead to a worse functional outcome than AAS. Therefore, it is mandatory to diagnose and treat JAS as early as possible.
- Published
- 2009
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45. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a new mediator involved in early ankylosing spondylitis.
- Author
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Chen CH, Liao HT, Chen HA, Liang TH, Wang CT, and Chou CT
- Subjects
- Adult, Biomarkers blood, Female, Health Status, Humans, Male, Severity of Illness Index, Spondylitis, Ankylosing diagnosis, Spondylitis, Ankylosing physiopathology, Triggering Receptor Expressed on Myeloid Cells-1, Inflammation Mediators blood, Membrane Glycoproteins blood, Receptors, Immunologic blood, Spondylitis, Ankylosing blood, Synovial Fluid metabolism
- Abstract
Objective: To investigate the possible role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in ankylosing spondylitis (AS)., Methods: Serum sTREM-1 levels were measured in 80 patients with AS and 30 healthy controls, and synovial fluid (SF) sTREM-1 levels were tested in 6 AS patients using ELISA. Demographic data were collected, and patient's disease activity (BASDAI), functional ability (BASFI), and global assessment (BAS-G) were evaluated. We also tested erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IgA in these patients., Results: Serum sTREM-1 levels were detectable (definition, > or = 15 pg/ml) in 31.3% (25/80) of the AS patients, as compared to only 10% (3/30) of healthy controls (p = 0.027). SF sTREM-1 levels were detectable (> or = 15 pg/ml) in 83% (5/6) of the AS patients. The detectable rate of sTREM-1 in SF was significantly higher than in serum (p = 0.018). Disease duration was shorter in AS patients with "higher" serum sTREM-1 levels (> or = 30 pg/ml) versus those with "lower" levels (< 30 pg/ml) [mean (SD), 4.3 (3.7) vs 8.6 (7.8) yrs, p = 0.036], but the differences between these 2 groups of patients were not evident based on results of BASDAI, BASFI, BAS-G, ESR, CRP, or IgA levels. Of note, serum sTREM-1 levels inversely correlated with disease duration (r = -0.433, p = 0.03) in the 25 AS patients with detectable sTREM-1 levels., Conclusion: sTREM-1 seems to be a new mediator involved in patients with AS, particularly in the early stages of disease.
- Published
- 2008
46. Human leukocyte antigen and clinical and demographic characteristics in psoriatic arthritis and psoriasis in Chinese patients.
- Author
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Liao HT, Lin KC, Chang YT, Chen CH, Liang TH, Chen WS, Su KY, Tsai CY, and Chou CT
- Subjects
- Adolescent, Adult, Alleles, Arthritis, Psoriatic ethnology, Arthritis, Psoriatic immunology, Case-Control Studies, China, Female, Genotype, HLA-A Antigens genetics, HLA-B27 Antigen genetics, HLA-C Antigens genetics, Humans, Male, Middle Aged, Psoriasis ethnology, Psoriasis immunology, Retrospective Studies, Arthritis, Psoriatic genetics, Asian People genetics, HLA Antigens genetics, Psoriasis genetics
- Abstract
Objective: Psoriasis and psoriatic arthritis (PsA) are interrelated disorders. To date, no study has compared the differences of genes between patients with PsA and psoriasis and healthy controls in a Chinese population. We conducted a retrospective study to determine the human leukocyte antigen (HLA) -A, -B, -Cw, -DR, and -DQ alleles in Chinese patients with PsA and psoriasis., Methods: HLA studies were performed using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) genotyping methods in 91 patients with PsA and 80 with psoriasis and 75 controls. Age at disease onset, sex, disease duration, enthesitis, and uveitis were also analyzed., Results: Among the patients with PsA and psoriasis, the frequency of HLA-B27 was significantly higher in PsA and HLA-A*30, -Cw*06, -DR*07 in psoriasis compared with controls. In contrast, HLA-B*58 was more common in controls than in PsA and psoriasis groups, and the prevalence of HLA-DR*17 was significantly higher in controls than in those with psoriasis. Comparing PsA and psoriasis, the prevalence of HLA-B*27 and HLA-Cw*12 were more common in PsA patients, while the prevalence of HLA-DR*07 was higher in those with psoriasis (p < 0.05). Among PsA patients, the association between HLA-B*27 and axial joint involvement and uveitis was significant (p < 0.05)., Conclusion: Certain HLA alleles are found in Chinese patients with psoriasis (HLA-A*30, -Cw*06, -DR*07) and PsA (HLA-B*27). Psoriasis patients with the HLA-B*27 and/or -Cw*12 may have higher risk of developing PsA. Ours is the first study to assess the genetic role of HLA in patients with psoriasis and PsA in a Chinese population.
- Published
- 2008
47. Spontaneous Bier's spots.
- Author
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Tey HL
- Subjects
- Adult, Humans, Male, Skin Diseases, Vascular physiopathology, Hypopigmentation diagnosis, Skin blood supply, Skin Diseases, Vascular diagnosis
- Published
- 2008
- Full Text
- View/download PDF
48. Human leukocyte antigens in undifferentiated spondyloarthritis.
- Author
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Liao HT, Lin KC, Chen CH, Liang TH, Lin MW, Tsai CY, Tak Yan Yu D, and Chou CT
- Subjects
- Adolescent, Adult, Female, HLA-B Antigens genetics, HLA-B27 Antigen genetics, HLA-C Antigens genetics, HLA-DR Antigens genetics, HLA-DR Serological Subtypes, Humans, Male, Pilot Projects, Retrospective Studies, Spondylarthritis immunology, Genetic Linkage, HLA Antigens genetics, Spondylarthritis genetics
- Abstract
Objectives: Undifferentiated spondyloarthritis (USpA) is a major member of the spondyloarthritis family. Ankylosing spondylitis (AS), the prototype of the family, is a largely genetic disease, with human leukocyte antigens (HLA)-B27 being the essential gene. Other genes in the HLA region have also been implicated. The purpose of this study was to identify the alleles of the HLA-A, -B, -C, -DR, and -DQ, which are present at higher frequencies in USpA patients compared with an ethnically matched control population., Methods: Sixty-three Taiwanese patients with USpA were compared with 75 matched healthy controls. HLA typing was performed by polymerase chain reaction-sequence specific oligo-nucleotide genotyping., Results: The frequencies of HLA-B27, -B60, -C3, and -DR12 were strikingly higher in USpA patients compared with healthy subjects, with odds ratios of 75.4, 14.0, 9.6, and 7.0, respectively. When USpA patients with axial involvement were compared with those with peripheral arthritis, the following were more marginally frequent in those with axial involvement: HLA-B27 and -DR12 (odds ratios, 4.0 and 4.0, respectively). There was no association of HLA typing with other variables, including enthesitis, uveitis, erythrocyte sedimentation rate, and serum C-reactive protein. Interestingly, in 12 HLA-B27-negative USpA patients, HLA-B60, -C3, and -DR12 were more frequent compared with controls (odds ratios, 35, 16.2, and 8.1, respectively)., Conclusions: Similar to AS, USpA is also linked to HLA-B27. A linkage to other HLA alleles observed here, even in our HLA-B27-negative USpA patients, strongly suggests that USpA in general is a genetic disease.
- Published
- 2007
- Full Text
- View/download PDF
49. Temporomandibular joint disorders in patients with rheumatoid arthritis.
- Author
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Lin YC, Hsu ML, Yang JS, Liang TH, Chou SL, and Lin HY
- Subjects
- Adult, Aged, C-Reactive Protein analysis, Female, Humans, Male, Middle Aged, Arthritis, Rheumatoid complications, Temporomandibular Joint Disorders etiology
- Abstract
Background: Temporomandibular joint disorders (TMD) are not uncommon in patients with rheumatoid arthritis (RA). However, the extent of involvement and its clinical relevance have not been well characterized. This study evaluated the correlation between the severity of RA-related TMD and RA, as well as determined the potential predictors for early identification and management of TMD in RA patients., Methods: We sequentially recruited 56 adult RA patients from our Arthritis Clinic. TMD and RA were surveyed, clinically by questionnaires and physical examinations, and radiologically by tomography in TMD and conventional radiography in RA. The patients were stratified into no, mild and severe TMD groups according to the physical and tomographic examinations. The correlation of the severity of TMD and RA were evaluated. The relative importance of relevant predictors of severe TMD was analyzed by a logistic regression model., Results: Physical and radiologic temporomandibular joint abnormalities were found to be highly prevalent (85.7% and 74.5%) in these patients, and the occurrence increased to as much as 92.9% when the 2 data sets were combined. More than half of the patients had severe TMD presenting with debilitating symptoms or with a significant degree of bony destruction. The severity of TMD was variably correlated with RA severity. The score of hand-joint space narrowing was found to be the most influential predictor of severe TMD by logistic regression analysis., Conclusion: There was a high prevalence of TMD in RA patients. The severity of TMD variably correlated with RA severity. Clinically, a high score of hand-joint space narrowing may serve as an early indicator of RA patients at risk of severe TMD. This may facilitate early management and prevent the functional impairment of the temporomandibular joint.
- Published
- 2007
- Full Text
- View/download PDF
50. Serum levels of matrix metalloproteinase-3 in undifferentiated spondyloarthropathy.
- Author
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Chen CH, Liao HT, Chen HA, Liang TH, Wang HP, and Chou CT
- Subjects
- Adult, Female, Humans, Male, ROC Curve, Reproducibility of Results, Spondylarthritis enzymology, Spondylitis, Ankylosing enzymology, Matrix Metalloproteinase 3 blood, Spondylarthritis blood, Spondylitis, Ankylosing blood
- Published
- 2007
- Full Text
- View/download PDF
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