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1.
BMC Infect Dis ; 24(1): 443, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671346

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) colitis significantly complicates the course of inflammatory bowel disease (IBD), frequently leading to severe flare-ups and poor outcomes. The role of antiviral therapy in hospitalized IBD patients with CMV colitis is currently under debate. This retrospective analysis seeks to clarify the influence of antiviral treatment on these patients. METHODS: We retrospectively reviewed IBD patients diagnosed with CMV colitis via immunohistochemistry staining from colonic biopsies at a major tertiary center from January 2000 to May 2021. The study focused on patient demographics, clinical features, risk factors, prognostic indicators, and antiviral treatment outcomes. RESULTS: Among 118 inpatients, 42 had CMV colitis. Risk factors included hypoalbuminemia and antibiotic use. IBD patients with CMV colitis receiving < 14 days of antiviral therapy had higher complication (72% vs. 43%, p = 0.028) and surgery rates (56% vs. 26%, p = 0.017) compared to those without CMV. Adequate antiviral therapy (≥ 14 days) significantly reduced complications in the CMV group (29% vs. 72%, p = 0.006), especially in Crohn's disease (20% vs. 100%, p = 0.015). Independent predictors of IBD-related complications were CMV colitis (Odds Ratio [OR] 3.532, 90% Confidence Interval [CI] 1.012-12.331, p = 0.048), biological treatment failure (OR 4.953, 95% CI 1.91-12.842, p = 0.001), and adequate antiviral therapy (OR 0.108, 95% CI 0.023-0.512, p = 0.005). CONCLUSION: CMV colitis and a history of biological treatment failure increase complication risks in IBD patients. Adequate antiviral therapy significantly mitigates these risks, highlighting its importance in managing IBD patients with CMV colitis.


Asunto(s)
Antivirales , Colitis , Infecciones por Citomegalovirus , Enfermedades Inflamatorias del Intestino , Humanos , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , Masculino , Femenino , Antivirales/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Adulto , Colitis/virología , Colitis/tratamiento farmacológico , Colitis/complicaciones , Citomegalovirus/efectos de los fármacos , Factores de Riesgo , Anciano , Pacientes Internos , Resultado del Tratamiento
2.
J Gastroenterol Hepatol ; 39(3): 544-551, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38059883

RESUMEN

BACKGROUND AND AIM: Chromoendoscopy with the use of indigo carmine (IC) dye is a crucial endoscopic technique to identify gastrointestinal neoplasms. However, its performance is limited by the endoscopist's skill, and no standards are available for lesion identification. Thus, we developed an artificial intelligence (AI) model to replace chromoendoscopy. METHODS: This pilot study assessed the feasibility of our novel AI model in the conversion of white-light images (WLI) into virtual IC-dyed images based on a generative adversarial network. The predictions of our AI model were evaluated against the assessments of five endoscopic experts who were blinded to the purpose of this study with a staining quality rating from 1 (unacceptable) to 4 (excellent). RESULTS: The AI model successfully transformed the WLI of polyps with different morphologies and different types of lesions in the gastrointestinal tract into virtual IC-dyed images. The quality ratings of the real IC-dyed and AI images did not significantly differ concerning surface structure (AI vs IC: 3.08 vs 3.00), lesion border (3.04 vs 2.98), and overall contrast (3.14 vs 3.02) from 10 sets of images (10 AI images and 10 real IC-dyed images). Although the score depended significantly on the evaluator, the staining methods (AI or real IC) and evaluators had no significant interaction (P > 0.05) with each other. CONCLUSION: Our results demonstrated the feasibility of employing AI model's virtual IC staining, increasing the possibility of being employed in daily practice. This novel technology may facilitate gastrointestinal lesion identification in the future.


Asunto(s)
Inteligencia Artificial , Lesiones Precancerosas , Humanos , Proyectos Piloto , Endoscopía/métodos , Carmin de Índigo , Carmín , Lesiones Precancerosas/diagnóstico por imagen
3.
Dig Dis Sci ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38949750

RESUMEN

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

4.
J Formos Med Assoc ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38851916

RESUMEN

BACKGROUND/PURPOSE: The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients. METHODS: We collected baseline characteristics and dietary habits from both IBD patients and healthy controls from February and August 2022 in Chang Gung memorial hospital using a structured and validated food frequency questionnaire. The dietary habits of IBD patients in this study were focused on the six months leading up to their IBD diagnosis. RESULTS: Our study recruited 98 IBD patients and 184 healthy controls. In demographic characteristics, cigarette smoking is more common in IBD group. Besides, distinct dietary patterns were observed between groups. The healthy controls demonstrated a higher consumption of whole foods and antioxidants. By contrast, the IBD group consumed more western-style foods but the difference didn't reach statistical significance. CONCLUSION: Our study found that healthy controls in Taiwan embraced a dietary pattern rich in whole foods that may prevent IBD or reduce IBD disease activity. Nonetheless, a larger sample size is needed to further provide valuable dietary guidance for general population in Taiwan for IBD prevention or for patients with IBD for disease activity control.

5.
J Formos Med Assoc ; 122(10): 1042-1049, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37019722

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on healthcare system and patients. This study aimed to evaluate the effect of the COVID-19 pandemic on the perceptions of patients with inflammatory bowel disease (IBD). METHODS: This prospective multicenter study was conducted between July 2021 and December 2021. Patients with IBD answered a structured questionnaire, and their degree of anxiety was assessed using a visual analogue scale (VAS) before and after reading educational materials. RESULTS: A total of 225 (47.67%) patients with Crohn's disease, 244 (51.69%) with ulcerative colitis and 3 (0.64%) with indeterminate colitis were enrolled. Common concerns were adverse events from vaccination (20.34%), and higher risks of developing severe COVID-19 (19.28%) and COVID-19 infection (16.31%) than the general population. Medications deemed by the patients to increase the risk of COVID-19 were immunomodulators (16.10%), anti-tumor necrosis factor-α antagonists (9.96%), and corticosteroids (9.32%). Thirty-five (7.42%) patients self-discontinued IBD medication, of whom 12 (34.28%) had worse symptoms. Older age (>50 years) (OR 1.10, 95% CI 1.01-1.19, p = 0.03), IBD-related complications (OR 1.16, 95% CI 1.04-1.28, p = 0.01), education status below senior high school (OR 1.22, 95% CI 1.08-1.37, p = 0.001), and residing in north-central Taiwan (OR 1.21, 95% CI 1.10-1.34, p < 0.001) were associated with more anxiety. None of the enrolled patients contracted COVID-19. The anxiety VAS score (mean ± SD) improved after reading the educational materials (3.84 ± 2.33 vs. 2.81 ± 1.96, p < 0.001). CONCLUSION: The medical behavior of IBD patients was influenced by the COVID-19 pandemic, and their anxiety could be mitigated after education.


Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , COVID-19/epidemiología , Pandemias , Estudios Prospectivos , Taiwán/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología
6.
J Gastroenterol Hepatol ; 37(7): 1275-1283, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35342997

RESUMEN

BACKGROUND AND AIM: Duodenal ulcers, especially caused by increasingly drug-resistant Helicobacter pylori, are a concern in Asia. We compared oral vonoprazan versus lansoprazole for efficacy (healing duodenal ulcers) and safety in non-Japanese Asian patients. METHODS: In this phase 3, randomized (1:1), double-blind, double-dummy, parallel-group, non-inferiority study (April 5, 2017, to July 19, 2019), patients with ≥ 1 endoscopically confirmed duodenal ulcer, at 52 hospitals (China, South Korea, and Taiwan), received vonoprazan 20 mg once daily (QD) or lansoprazole 30 mg QD for 6 weeks maximum. Patients with H. pylori received bismuth-containing quadruple therapy including vonoprazan 20 mg twice daily (BID) or lansoprazole 30 mg BID, for 2 weeks, followed by vonoprazan or lansoprazole monotherapy QD (4 weeks maximum). Endpoints were endoscopically confirmed duodenal ulcer healing (Week 4/6; primary) and H. pylori eradication (4 weeks post-treatment; secondary); non-inferiority margins were -6% and -10%, using a two-sided 95% confidence interval (CI). RESULTS: Of 533 enrolled patients, one was lost to follow-up and one withdrew (full analysis set: 531 patients [vonoprazan, n = 263; lansoprazole, n = 268]; 85.4% = H. pylori positive). Vonoprazan was non-inferior to lansoprazole for duodenal ulcer healing (96.9% vs 96.5%; difference 0.4% [95% CI -3.00, 3.79]). H. pylori eradication rates were 91.5% (vonoprazan) and 86.8% (lansoprazole; difference 4.7% [95% CI -1.28, 10.69]). Vonoprazan and lansoprazole were well tolerated, with similar safety profiles, no new safety signals; no deaths occurred. CONCLUSIONS: Vonoprazan was well tolerated and non-inferior to lansoprazole for duodenal ulcer healing and achieved H. pylori eradication above the clinically meaningful threshold (90%), in non-Japanese Asian patients.


Asunto(s)
Antiulcerosos , Úlcera Duodenal , Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina , Antiulcerosos/efectos adversos , Claritromicina , Método Doble Ciego , Quimioterapia Combinada , Úlcera Duodenal/inducido químicamente , Úlcera Duodenal/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Lansoprazol/efectos adversos , Recurrencia Local de Neoplasia , Pirroles , Sulfonamidas
7.
J Formos Med Assoc ; 121(9): 1689-1695, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34924273

RESUMEN

BACKGROUND: The use of biologic agents has become the cornerstone of therapy for moderate to severe IBD. Few studies have investigated the efficacy of vedolizumab (VDZ) induction for ulcerative colitis (UC) in Asian patients in a real practice setting. AIMS: To evaluate the efficacy and safety of VDZ induction therapy for moderate to severe UC in Taiwan. METHODS: This was a retrospective and observational study. Selected moderate to severe UC patients received VZD 300 mg i.v. at weeks 0, 2, and 6 as induction therapy. Mayo scores were calculated to evaluate the efficacy. RESULTS: A total of 37 patients with UC who received VDZ and completed the induction therapy at Chang Gung Memorial Hospital (2017/10-2021/5) were included. The mean age was 46.5 year-old and the male to female ratio was 1:1 (19/18). 81.8% of the patients were biologic-naive. At weeks 8-10, a clinical response, clinical remission and endoscopic remission with VDZ induction therapy were achieved in 56.8% (21/37), 32.4% (12/37) and 58.3% (7/12) of the patients, respectively. 54.1% (20/37) were able to taper off at week 8. Overall, only 10.8% (4/37) of the patients were primary non-responders during induction therapy. No obvious VDZ-related severe adverse events were noted. Overall, 58.9% (11/19) of the patients relapsed after stopping VDZ, and the relapse rate after VDZ discontinuation was 42.1% (8/19) within first 6 months and 52.6% (10/19) within the first year. CONCLUSION: In real-world experience, induction therapy with VDZ showed promising clinical benefits and safety profile for patients with UC.


Asunto(s)
Colitis Ulcerosa , Anticuerpos Monoclonales Humanizados , Femenino , Fármacos Gastrointestinales , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento
8.
Sensors (Basel) ; 22(23)2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36501833

RESUMEN

A novel piezoelectric fiber sensor based on polyvinylidene fluoride piezoelectric (PVDF) doped with graphene is presented. The near-field electrospinning technology was used for developing the sensor. The uniform experimental design method was introduced to determine the ranges of experimental parameters, including the applied voltage, the drum speed range, the graphene doping ratios from 0% to 11 wt% in PVDF solution, and the electrode gap. By experimental results, the conductivities of PVDF solutions with different doping ratios of graphene increased from 19.6 µS/cm to 115.8 µS/cm. Tapping tests were performed to measure the voltages and currents produced by the piezoelectric fibers. The maximum output voltage was 4.56 V at 5 wt% graphene doping ratio in PVDF fibers, which was 11.54 times that of the pure PVDF sensors. Moreover, mechanical properties of the proposed sensor were measured. Motion intention and swallowing test, such as saliva-swallowing and eating, were carried out. When the subject spoke normally, the output voltage of the sensor was between 0.2 and 0.4 V, approximately. Furthermore, when the subject drank water and ate food, the output voltage of the sensor was between 0.5 and 1 V, approximately. The proposed sensor could be used to detect signals of the human body and serve as a wearable device, allowing for more diagnosis and medical treatment.


Asunto(s)
Grafito , Seda , Humanos , Polivinilos , Electrodos
9.
J Environ Manage ; 316: 115279, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35658254

RESUMEN

Stream Channel (SC) erosion results in immense soil and nutrient losses and eutrophication of downstream lakes and rivers. Among other factors, the lack of vegetation cover within SCs and on adjacent soils can accelerate soil and nutrient losses. The combined impact of perennial sugarcane plantation and grass cover on increasing SC erosion losses have not been previously studied. Current study determined SC erosion and associated nutrient losses and clarified the effect of grass roots within SCs and the ratooned sugarcane grown on adjacent lands in Nala watershed in southern subtropics of China. Six SCs in two sub-watersheds (SW1 and SW2) surveyed after revegetation during 2019 were compared with initial survey conducted in 2017 and 2018. The SC erosion was significantly (P < 0.05) reduced by 84.2% (5.19 ± 2.16 Mg ha-1) in entire watershed in 2019 compared to 2018 (43.9 ± 15.2 Mg ha-1). It notably decreased by 99.23% and 96.50% in SC-1-3 at SW1 and SC2-3 at SW2, respectively. Total N and P losses decreased by 84.9% and 82.5%, respectively, in entire watershed. The decreases in SC erosion and nutrient losses are attributed to increasing vegetative cover (R2 = 0.7543, P < 0.001), and grass root densities of <1 mm (R2 = 0.7543, P < 0.001), 1-2 mm (R2 = 0.7051, P < 0.001) and >2 mm (R2 = 0.5746, P < 0.001). Principal component regression analysis confirmed that root densities of SC grasses, perennial sugarcane, and organic matter had positive impacts on controlling SC erosion and consequent nutrient losses.


Asunto(s)
Saccharum , China , Monitoreo del Ambiente , Ríos , Suelo
10.
Medicina (Kaunas) ; 58(12)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36557038

RESUMEN

Background and Objectives: Endoscopic variceal ligation (EVL) is the primary and secondary treatment for acute esophageal variceal bleeding. Post-banding ulcer bleeding (PBUB) may lead to bleeding episodes following EVL, increasing mortality. The aim of this study was to evaluate the risk factors for PBUB and predict the 6-week mortality risk after PBUB. Materials and Methods: We retrospectively analyzed the data collected from cirrhotic patients with EVL from 2015 to 2017. The incidence of PBUB and the 6-week mortality rate were evaluated. Risk factors for PBUB and predictive factors for mortality after PBUB were analyzed. Results: A total of 713 patients were enrolled in this study. Among the studied subjects, the incidence of PBUB was 5.8% (N = 41). The 6-week mortality rate was 63.4% (26/41). In multivariate analysis, MELD score ≥20 (OR: 3.77, 95% CI: 1.94−7.33, p < 0.001), ALBI score of 3 (OR: 2.67, 95% CI: 1.34−5.3, p = 0.005) and the presence of gastric varices (OR: 2.1, 95% CI: 1.06−4.16, p = 0.03) were associated with the development of PBUB. Patients with ALBI grade 3 (OR: 4.8, 95% CI: 1.18−19.6, p = 0.029) and Child-Pugh scores B and C (OR: 16.67, 95% CI: 1.75−158.1, p = 0.014) were associated with 6-week mortality after PBUB. Conclusions: PBUB is a complication with low incidence but increased mortality following EVL. The ALBI grade is a useful score to predict not only the development of PBUB but also the 6-week mortality after PBUB.


Asunto(s)
Várices Esofágicas y Gástricas , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Estudios Retrospectivos , Úlcera/complicaciones , Cirrosis Hepática/complicaciones , Ligadura/efectos adversos
11.
BMC Gastroenterol ; 21(1): 464, 2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34903169

RESUMEN

AIM: We aimed to compare the outcomes of different therapeutic modalities in rectal carcinoid tumors. METHOD: We retrospectively collected 145 patients with rectal carcinoid tumors which were pathologically diagnosed from 2005/01/01 to 2016/12/31. We compared tumor size, complete resection rate and recurrent rate between different therapeutic modalities. Then, prospectively compared the treatment outcomes of 28 patients treated with ligation assisted endoscopic mucosal resection (LEMR) and 25 patients treated with endoscopic mucosal resection with cap (EMRC). RESULT: The mean size of tumors was 6.5 mm (1-25 mm), and the mean follow-up duration was 26 months (6-118 months). The therapeutic modalities included ligation-assisted endoscopic mucosal resection (LEMR) (25 tumors, 17%), endoscopic mucosal resection (EMR) (31 tumors, 21%), snare polypectomy (30 tumors, 21%), biopsy forceps removal (46 tumors, 32%) and surgical resection (13 tumors, 11%), including 6 tumors treated with transanal endoscopic microsurgery (TEM) method. In view of pathologically complete resection rate, LEMR was highest (100%), followed by surgical resection (85%). However, EMR only had 42% pathologically complete resection rate. Besides, LEMR and surgical resection had no local recurrence and significantly higher clinically complete resection rate, compared to other treatments. For the further prospective study, complete resection was noted in 28 (100%) patients in LEMR group and 13 (52%) patients in EMRC group. CONCLUSION: In the treatment of rectal carcinoid tumors, LEMR is safe and effective compared with traditional endoscopic treatments.


Asunto(s)
Tumor Carcinoide , Resección Endoscópica de la Mucosa , Neoplasias del Recto , Tumor Carcinoide/cirugía , Humanos , Mucosa Intestinal/cirugía , Estudios Prospectivos , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
12.
BMC Gastroenterol ; 21(1): 206, 2021 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-33964869

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, and few cases combine with Crohn's disease. We present the first SLE patient concurrent with Crohn's disease and rectovaginal fistula. She was successfully treated with vedolizumab and surgical intervention. Besides, she also had a rare opportunistic infection, cryptococcal pneumonia, in previous adalimumab treatment course. CASE: A 57 year-old female had SLE in disease remission for 27 years. She suffered from progressive rectal ulcers with anal pain and bloody stool, and Crohn's disease was diagnosed. She received adalimumab, but the lesion still progressed to a rectovaginal fistula. Besides, she suffered from an episode of cryptococcal pneumonia under adalimumab treatment course. Therefore, we changed the biologics to vedolizumab, and arrange a transverse colostomy for stool diversion. She had clinical remission without active inflammation, but the fistula still persisted. Then, she received a restorative proctectomy with colo-anal anastomosis and vaginal repair. Follow-up endoscopy showed no more rectal ulcers or fistula tracts, and contrast enema also noted no residual rectovaginal fistula. CONCLUSION: When a SLE patient had unusual rectal ulcers, Crohn's disease should be considered. Biologics combined with surgical intervention is an optimal solution for Crohn's disease with rectovaginal fistula. Although cryptococcal pneumonia is a rare opportunistic infection in the biological treatment, we should always keep it in mind.


Asunto(s)
Enfermedad de Crohn , Lupus Eritematoso Sistémico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Persona de Mediana Edad , Fístula Rectovaginal/etiología , Fístula Rectovaginal/cirugía , Resultado del Tratamiento
13.
BMC Gastroenterol ; 21(1): 299, 2021 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-34325666

RESUMEN

BACKGROUND: Intestinal perforations and fistulas are common complications of Crohn's disease. However, chronic perforation with peritoneal space to rectal and vaginal fistulas have not been previously reported. CASE PRESENTATION: A 38-year-old female suffered from progressive lower abdominal pain, diarrhea and weight loss. Terminal ileal chronic perforation with intra-abdominal abscess, peritoneal space to rectal and vaginal fistulas were noted. The patient received surgical resection of the cecum and terminal ileum, and then vedolizumab treatment. Three months later, she had complete fistula closure, and her body mass index had increased from 13 to 22. CONCLUSION: Vedolizumab combined with stool diversion is effective at treating Crohn's disease with chronic perforation and complex peritoneal space to rectal and vaginal fistulas.


Asunto(s)
Enfermedad de Crohn , Fístula Intestinal , Fístula Vaginal , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Femenino , Humanos , Resultado del Tratamiento
14.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33478005

RESUMEN

The objective was to investigate the anti-cancer effects and underlying molecular mechanisms of cytostasis which were activated by an anti-microtubule drug, ABT-751, in two urinary bladder urothelial carcinoma (UBUC)-derived cell lines, BFTC905 and J82, with distinct genetic backgrounds. A series of in vitro assays demonstrated that ABT-751 induced G2/M cell cycle arrest, decreased cell number in the S phase of the cell cycle and suppressed colony formation/independent cell growth, accompanied with alterations of the protein levels of several cell cycle regulators. In addition, ABT-751 treatment significantly hurdled cell migration and invasion along with the regulation of epithelial-mesenchymal transition-related proteins. ABT-751 triggered autophagy and apoptosis, downregulated the mechanistic target of rapamycin kinase (MTOR) and upregulated several pro-apoptotic proteins that are involved in extrinsic and intrinsic apoptotic pathways. Inhibition of autophagosome and autolysosome enhanced apoptosis was also observed. Through the inhibition of the NFκB signaling pathway, ABT-751 suppressed S-phase kinase associated protein 2 (SKP2) transcription and subsequent translation by downregulation of active/phospho-AKT serine/threonine kinase 1 (AKT1), component of inhibitor of nuclear factor kappa B kinase complex (CHUK), NFKB inhibitor alpha (NFKBIA), nuclear RELA proto-oncogene, NFκB subunit (RELA) and maintained a strong interaction between NFKBIA and RELA to prevent RELA nuclear translocation for SKP2 transcription. ABT-751 downregulated stable/phospho-SKP2 including pSKP2(S64) and pSKP2(S72), which targeted cyclin-dependent kinase inhibitors for degradation through the inactivation of AKT. Our results suggested that ABT-751 may act as an anti-cancer drug by inhibiting cell migration, invasion yet inducing cell cycle arrest, autophagy and apoptosis in distinct UBUC-derived cells. Particularly, the upstream molecular mechanism of its anticancer effects was identified as ABT-751-induced cytostasis through the inhibition of SKP2 at both transcriptional and post-translational levels to stabilize cyclin dependent kinase inhibitor 1A (CDKN1A) and CDKN1B proteins.


Asunto(s)
Carcinoma/tratamiento farmacológico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Proteínas Quinasas Asociadas a Fase-S/genética , Transcripción Genética/efectos de los fármacos , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Carcinoma/genética , Carcinoma/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Fosfatidilinositol 3-Quinasa/genética , Inhibidores de Proteínas Quinasas/farmacología , Proto-Oncogenes Mas , Proteínas Quinasas Asociadas a Fase-S/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Sulfonamidas/farmacología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Urotelio/efectos de los fármacos , Urotelio/patología
15.
Oncologist ; 25(7): e1021-e1030, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32058649

RESUMEN

PURPOSE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for fluorouracil-based adjuvant chemotherapy in colorectal cancer has been a paradigm shift. However, whether this applies to gastric cancer is questionable. Furthermore, we herein investigated whether and how autophagy plays a role in MSI-relevant chemoresistance. MATERIALS AND METHODS: A total of 929 patients with deficient MMR (dMMR) and proficient MMR (pMMR) gastric cancers who underwent curative-intent gastrectomy were enrolled. We compared clinicopathological variables and survival among dMMR and pMMR cohorts and tested the responses of MSI-high and microsatellite stable (MSS) gastric cancer cell lines to 5-fluorouracil (5-FU) with or without chloroquine, an autophagy inhibitor. RESULTS: We identified an 8.9% prevalence of dMMR cases (83 out of 929) in our cohort. This was associated with old age, tumor site at the distal stomach, an intestinal phenotype, fewer nodal metastasis, and early pathological stages. MMR was an independent prognostic factor after multivariate adjustment. Overall survival (OS) of dMMR patients was better than that of the pMMR patients but was only applicable to stage III patients. There was no difference in OS between dMMR patients treated with or without adjuvant chemotherapy, although the latter showed more medical morbidities. The MSI-high gastric cancer cell lines, versus the MSS counterparts, displayed increased resistance to 5-FU and increased autophagy. Interestingly, autophagy inhibition abrogated the chemoresistance. CONCLUSION: Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. IMPLICATIONS FOR PRACTICE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor for gastric cancer. Standard fluorouracil-based adjuvant chemotherapy did not work for deficient MMR cases, and was likely worse. Instead, strategies like autophagy inhibition and/or immune checkpoint inhibition should be taken into consideration in the future.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Gástricas , Autofagia , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Humanos , Inestabilidad de Microsatélites , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética
16.
BMC Gastroenterol ; 20(1): 309, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32962643

RESUMEN

BACKGROUND: Delayed post-polypectomy bleeding (PPB) is a major complication of polypectomy. The effect of prophylactic hemoclipping on delayed PPB is uncertain. The aim of this study was to evaluate the effectiveness of prophylactic hemoclipping and identify the risk factors of delayed PPB. METHODS: Patients with polyps sized 6 to 20 mm underwent snare polypectomy from 2015 to 2017 were retrospectively reviewed. The patients with prophylactic hemoclipping for delayed PPB prevention were included in the clipping group, and those without prophylactic hemoclipping were included in the non-clipping group. The incidence of delayed PPB and time to bleeding were compared between the groups. Multivariate analysis was used to identify the risk factors of delayed PPB. Propensity score matching was used to minimize potential bias. RESULTS: After propensity score matching, 612 patients with 806 polyps were in the clipping group, and 576 patients with 806 polyps were in the non-clipping group. There were no significant differences in the incidence of delayed PPB and days to bleeding between two groups (0.8% vs 1.3%, p = 0.4; 3.4 ± 1.94 days vs 4.13 ± 3.39 days, p = 0.94). In the multivariate analysis, the polyp size [Odds ratio (OR):1.16, 95% confidence interval (CI):1.01-1.16, p = 0.03), multiple polypectomies (OR: 4.64, 95% CI:1.24-17.44, p = 0.02) and a history of anticoagulant use (OR:37.52, 95% CI:6.49-216.8, p < 0.001) were associated with delayed PPB. CONCLUSIONS: In polyps sized 6 to 20 mm, prophylactic hemoclip placement did not decrease the risk of delayed PPB. Patients without risk factors including multiple polypectomies and anticoagulant use are no need to performing prophylactic hemoclipping.


Asunto(s)
Pólipos del Colon , Pólipos del Colon/cirugía , Colonoscopía , Humanos , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo
17.
BMC Gastroenterol ; 20(1): 218, 2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32650737

RESUMEN

BACKGROUND: There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin. METHODS: After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion. RESULTS: A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. CONCLUSIONS: Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Preparaciones Farmacéuticas , Amoxicilina/uso terapéutico , Antibacterianos/efectos adversos , Claritromicina/uso terapéutico , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Rifabutina/uso terapéutico , Resultado del Tratamiento
18.
Digestion ; 101(3): 339-346, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30982036

RESUMEN

BACKGROUND: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. METHODS: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. RESULTS: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). CONCLUSIONS: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.


Asunto(s)
Pólipos del Colon/diagnóstico , Colonoscopía/instrumentación , Neoplasias Colorrectales/diagnóstico , Rayos Láser , Imagen de Banda Estrecha/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Colon/diagnóstico por imagen , Colon/patología , Pólipos del Colon/patología , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Femenino , Humanos , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Japón , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha/métodos , Clasificación del Tumor , Valor Predictivo de las Pruebas , Recto/diagnóstico por imagen , Recto/patología , Taiwán , Adulto Joven
19.
Sensors (Basel) ; 20(17)2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32872202

RESUMEN

This research aimed to develop a direct-write near-field electrospinning system (DW-NFES) with three-axis positioning of controllable speed, torque and position to produce sizable and high-quality piezoelectric fibers for sensing purposes. Sensor devices with high electrical response signals were developed and tested. To achieve DW-NFES purpose, a servo motor controller was designed to develop a high response rate, accurate positioning, and stable mobile device through the calculation of bandwidth and system time delay. With this retooled system of DW-NFES, controllable and uniform size fibers in terms of diameters, stretching force, and interspaces can be obtained. Sensor devices can be made selectively without a complicated lithography process. The characteristics of this DW-NFES platform were featured by high response rate, accurate positioning, and stable movement to make fibers with high piezoelectric property. In this study, polyvinylidene fluoride (PVDF) was used to explore and enhance their sensing quality through the platform. The parametric study of the process factors on piezoelectric sensing signals mainly included the concentration of electrospinning PVDF solution, high voltage electric field, and collection speed. Finally, the surface morphology and piezoelectric properties of the as-electrospun PVDF fibers were examined by scanning electron microscopy (SEM) and characterized by electrical response measurement techniques. The results showed that the fiber spinning speed of the DW-NFES system could be increased to ~125 from ~20 mm/s and the accuracy precision was improved to ~1 from ~50 µm, compared to conventional step motor system. The fiber diameter reached ~10 µm, and the electrospinning pitch reached to as small as ~10 µm. The piezoelectric output voltage of the electrospun fibers was increased ~28.6% from ~97.2 to ~125 mV; the current was increased ~27.6% from ~163 to ~208 nA, suggesting that the piezoelectric signals can be enhanced significantly by using this retooled system. Finally, an external control module (Arduino-MAGE) was introduced to control the PVDF piezoelectric fiber sensors integrated as a sensing array. The behavior of long-term sedentary patients can be successfully detected by this module system to prevent the patients from the bedsores.


Asunto(s)
Electricidad , Polivinilos , Úlcera por Presión , Humanos , Microscopía Electrónica de Rastreo , Movimiento , Úlcera por Presión/diagnóstico
20.
Sensors (Basel) ; 20(11)2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32503274

RESUMEN

This paper presents an improved control system for a small flux-switching permanent magnet motor (FSPM) to enhance its performance and torque sensing. The analytical magnetic circuit design was used to determine the related motor parameters, such as the air gap flux density, permeance coefficient (Pc), torque, winding turns, pole number, width, length, magnet geometry, and the current density of FSPM. The electromagnetic analysis of this motor was performed by software (ANSYS Maxwell) to optimize the motor performance. In this study, the performance of FSPM was investigated by the uniform design experimentation (UDE). For the control system, the model predictive current control (MPCC) is currently recognized as a high-performance control strategy, due to its quick response and simple principle. This model contained the nonlinear part of the system, to improve the torque ripple of FSPM. A modified MPCC strategy was proposed to improve the distortion of the current waveform and decrease the computational burden. The new modified control architecture was mainly composed of three parts, such as the estimation of electromotive force (EMF), current prediction, and optimal vector selection/vector duration. When the reference voltage vector was obtained, the three-phase duties were easily determined by the principle of space vector modulation (SVM). The results show the different strategy methods between the newly proposed modified MPCC and traditional proportional integral (PI) controller. In the control of FSPM, a modified MPCC strategy was able to achieve a better performance response and decrease the computational burden. At a low speed of 350 rpm, the proposed modified MPCC can achieve a better dynamic response. The nonlinear problem of the startup speed was also effectively resolved. The torque sensing performance of the simulation and the experimental test value were compared. The torque sensing performance of the simulation and the actual test value were also examined. In this study, the optimization focused not only on the motor design and fabrication, but also on an improved motor control strategy and torque sensing, in order to achieve the integrity of the FSPM system.

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