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BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/metabolismo , Factores de Transcripción Forkhead , Microambiente TumoralRESUMEN
OBJECTIVE: This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea. METHOD: Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions. RESULTS: The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group. CONCLUSION: Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.
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Metaloproteinasa 9 de la Matriz , Apnea Obstructiva del Sueño , Humanos , Metaloproteinasa 9 de la Matriz/genética , Remodelación de las Vías Aéreas (Respiratorias) , Eosina Amarillenta-(YS) , Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/cirugía , Citocinas , Inflamación , ARN Mensajero , Proteínas Quinasas p38 Activadas por Mitógenos , ADN Polimerasa Dirigida por ARNRESUMEN
Single crystals of BaTiO3 exhibit small switching fields and energies, but thin-film performance is considerably worse, thus precluding their use in next-generation devices. Here, we demonstrate high-quality BaTiO3 thin films with nearly bulk-like properties. Thickness scaling provides access to the coercive voltages (<100 mV) and fields (<10 kV cm-1) required for future applications and results in a switching energy of <2 J cm-3 (corresponding to <2 aJ per bit in a 10 × 10 × 10 nm3 device). While reduction in film thickness reduces coercive voltage, it does so at the expense of remanent polarization. Depolarization fields impact polar state stability in thicker films but fortunately suppress the coercive field, thus driving a deviation from Janovec-Kay-Dunn scaling and enabling a constant coercive field for films <150 nm in thickness. Switching studies reveal fast speeds (switching times of ~2 ns for 25-nm-thick films with 5-µm-diameter capacitors) and a pathway to subnanosecond switching. Finally, integration of BaTiO3 thin films onto silicon substrates is shown. We also discuss what remains to be demonstrated to enable the use of these materials for next-generation devices.
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This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.
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Diabetes Mellitus Tipo 2 , Fracturas de Cadera , Tiazolidinedionas , Adulto , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Tiazolidinedionas/uso terapéuticoRESUMEN
We report the theoretical and experimental investigation of a self-starting mode-locked fiber laser with a nanoengineered Tm3+-doped yttrium-alumina-silica (YAS) fiber as the gain medium. The YAS fiber exhibits a higher capability of Tm3+ cluster elimination than commercial silica fibers. The Tm3+ fluorescence properties and YAS dispersion are well characterized. As a result, an efficient picosecond mode-locked fiber laser is demonstrated with a slope efficiency of 14.14% and maximum pulse energy of 1.27 nJ. To the best of our knowledge, this is the first mode-locked fiber laser based on a Tm3+-doped YAS fiber. The experimental observation is also supported by the numerical analysis.
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BACKGROUND: Previous studies suggest that increased learning satisfaction may encourage learning engagement in an online learning environment. OBJECTIVES: To evaluate the level of learning engagement and its relationship with students' perceived learning satisfaction in an online clinical nursing elective course. DESIGN: A prospective interventional study. SETTINGS: A nursing course was converted to an online format because of the coronavirus disease COVID pandemic. PARTICIPANTS: Part-time post-registration nursing undergraduates enrolled in an elective online clinical course. METHODS: Related teaching and learning strategies were deployed in the course using the Community of Inquiry framework. All students who completed the course were invited to complete an online survey that included a validated Online Student Engagement questionnaire (OSE). Pearson's correlations were used to determine the association between perceived learning satisfaction and learning engagement. A logistic regression model was used to explore the associations of gender, age, working experience and perceived learning satisfaction with higher learning engagement. RESULTS: The questionnaires were completed by 56 of 68 students (82%). The Pearson's correlation coefficient between the mean perceived learning satisfaction and OSE scores was 0.75 (p < .001). Twenty-five students (45%) were identified as highly engaged, using a cut-off of ≥3.5 for the mean OSE score. The mean perceived learning satisfaction (SD) score differed significantly between highly engaged and not highly engaged students [4.02 (0.49) vs. 3.27 (0.62), p < .001]. The logistic regression model showed that a greater perceived learning satisfaction [adjusted odds ratio (OR): 17.2, 95% C.I.: 3.46-86.0, p = .001] was associated with an increased likelihood of higher learning engagement, and >1 year of working experience (adjusted OR: 0.11, 95% C.I.: 0.01-0.89, p = .0039) was associated with a decreased likelihood of higher learning engagement. CONCLUSIONS: The study findings suggest that perceived learning satisfaction predicts learning engagement among nursing students in this online learning course.
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COVID-19 , Educación a Distancia , Estudiantes de Enfermería , Humanos , Estudios Prospectivos , SARS-CoV-2RESUMEN
Chest pain complicated with electrocardiographic changes is not an uncommon scenario in emergency departments, which should be examined cautiously. We describe a 51-years-old man with a myocardial bridge of coronary artery presenting with simultaneous Mobitz type I atrioventricular block on electrocardiography. Echocardiography excluded valvular abnormality and systolic/diastolic dysfunction. Coronary angiography confirmed the diagnosis of a myocardial bridge at the middle segment of the left anterior descending artery, involving the most dominant septal perforator branch with marked systolic compression. The patient underwent coronary artery bypass grafting surgery and was followed up uneventfully at the outpatient department with medical treatment of diltiazem and clopidogrel. The present case is being reported to highlight that clinicians should be alert to such a congenital abnormality as a potential cause of repeated myocardial infarction and conduction abnormality.
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Bloqueo Atrioventricular/diagnóstico , Puente Miocárdico/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagen , Bloqueo Atrioventricular/complicaciones , Angiografía Coronaria , Ecocardiografía , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnósticoRESUMEN
OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Material Particulado/análisis , Síndrome Premenstrual/epidemiología , Adolescente , Adulto , Contaminación del Aire/estadística & datos numéricos , Atmósfera/química , Estudios de Cohortes , Femenino , Humanos , Concentración de Iones de Hidrógeno , Persona de Mediana Edad , Análisis Multivariante , Nitratos/análisis , Ozono/análisis , Modelos de Riesgos Proporcionales , Sulfatos/análisis , Taiwán/epidemiología , Adulto JovenRESUMEN
AIM: Patients with diabetes have higher rates of depression than does the general population, but diabetes management mainly aims to maintain glucose stability. For this reason, our study assessed the relationship between 1-year variations in fasting plasma glucose (FPG) and risk of depression in Chinese patients with type 2 diabetes (T2D). METHODS: This retrospective cohort study was conducted on 32,829 patients aged ≥30 years who were diagnosed with T2D and who participated in the National Diabetes Case Management Program in Taiwan. Their 1-year FPG variation as a predictor was determined by coefficient of variation (CV), whereas depressive events were analyzed by Cox's proportional hazards models. RESULTS: During a mean 8.23 years of follow-up, 1041 new cases of depression were diagnosed. When patients were grouped based on quartiles of FPG-CV, incidence rates were 3.23, 3.49, 3.96 and 4.80 per 1000 person-years in the first, second, third and fourth quartile subgroups, respectively. After adjusting for traditional risk factors, baseline fasting glucose and HbA1c levels, and diabetes complications, FPG-CV was independently linked with incident depression. Hazard ratios of depression for FPG-CV in the fourth vs first quartile subgroups was 1.33 (95% CI: 1.11-1.59), respectively. CONCLUSION: Patients whose 1-year FPG variations were>42.6% had an increased risk of depression, thus suggesting that FPG variations may be a predictor of depression in patients with T2D. Also, glucose variation during outpatient visits may be an indicator for individualized diabetes management in clinical practice.
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Glucemia/análisis , Depresión/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Comorbilidad , Depresión/sangre , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Taiwán/epidemiologíaRESUMEN
In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.
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Antibacterianos/farmacología , Dopamina/química , Grafito/química , Nanoestructuras/química , Péptidos/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Rayos InfrarrojosRESUMEN
PURPOSE: This study examined the prognostic associations of pre-treatment quality of life (QoL) with overall survival (OS) and distant metastasis-free survival (DFMS) among patients with head and neck cancer (HNC) who underwent free flap reconstruction. METHODS: A cohort of 127 HNC patients who received free flap reconstruction between November 2010 and June 2014â¯at a hospital were recruited. Pre-treatment QoL was measured by the University of Washington Quality of Life Questionnaire, which contains six physical domains, including speech, swallowing, appearance, saliva, taste and chewing, as well as the six social-emotional domains of pain, activity, recreation, shoulder, mood, and anxiety. Cox regression analyses were performed. RESULTS: Results showed that pre-treatment QoL was predictive of OS and DMFS. Of the domains, swallowing, chewing, speech, taste, saliva, pain and shoulder were demonstrated to be significant predictors of OS. Additionally, swallowing, chewing, speech, pain and activity were demonstrated making significant contributions to DMFS. CONCLUSION: Our data supported that physical domains of pre-treatment QoL were predictors for OS and DFMS in HNC patients with free-flap reconstruction. Longitudinal studies are warranted to clarify the prognostic abilities of social-emotional domains. Information on pre-treatment QoL should be taken into account to individualize care plan for these patients, and hence prolong their survival.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello/cirugía , Metástasis de la Neoplasia/prevención & control , Cuidados Preoperatorios/psicología , Calidad de Vida/psicología , Sobrevida/psicología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Procedimientos de Cirugía Plástica , Encuestas y CuestionariosRESUMEN
Objective: To explore the role and mechanism of 2-deoxyglucose (2-dg) in reversing osimertinib- acquired resistance of non-small cell lung cancer(NSCLC)cell line. Methods: The NSCLC line H1975 (purchased from the American Type Culture Collection) was conducted by induction method in vitro to construct the osimertinib-resistance NSCLC cell line H1975-OR. The osimertinib-resistance of H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony-formation assay, Ki67 incorporation assay and the expression of apoptosis-related protein. The glycolysis level was assayed by the lactic acid production measured in the culture medium supernatant of H1975 and H1975-OR. The expression of glycolysis key enzymes (HK2, GLUT1, P-PKM2) and apoptosis-related protein (BIM, Bcl-2) were detected by Western blot. The cells were divided into control group, 2-deoxyglucose (4 mmol/L) monotherapy group, osimertinib (3 µmol/L) monotherapy group and 2-deoxyglucose (4 mmol/L)+ osimertinib (3 µmol/L) combination therapy group, then the apoptosis rate of cells was measured by flow cytometry to evaluate the pro-apoptotic ability of drugs. Date were analyzed by Independent-Samples t-test using SPSS 16.0 statistical software. Results: The glycolysis level of osimertinib-sensitive cell line H1975 was lower than that of osimertinib-resistance cell line H1975-OR [the yield of lactic acid, respectively, was (21.0±0.9) and (26.5±2.8) mmol·L(-1)·10(4)cells(-1), P<0.05]. The osimertinib- acquired resistance of H1975-OR could be reversed by 4 mmol/L 2-deoxyglucose(the IC(50) value of osimertinib in H1975-OR cell line decreased from (7.0±1.9) µmol/L to (1.4±0.1) µmol/L, which was close to the IC(50) value of osimertinib in H1975 cell line (1.0±0.2) µmol/L. The apoptosis rate of H1975-OR was significantly higher in 2-deoxyglucose + osimertinib combination therapy group (26.7±2.4)%, compared to control group (5.1±0.7)%, 2-deoxyglucose monotherapy group (6.1±2.5)% and osimertinib monotherapy group (11.4±2.7)%(all P<0.05). The expression of pro-apoptotic protein BIM in H1975-OR was significantly higher in 2-deoxyglucose+ osimertinib combination therapy group (177.8±28.1)% and the expression of anti-apoptotic protein Bcl-2 in H1975-OR was significantly lower in 2-deoxyglucose+ osimertinib combination therapy group (24.6±5.2)%, compared to control group (100±0)%, all P<0.05. Conclusion: 2-deoxyglucose can reverse the acquired resistance of NSCLC cell line to osimertinib, which may be related to the inhibition of cell glycolysis and the induction of apoptosis.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxiglucosa/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Piperazinas/farmacología , Acrilamidas , Compuestos de Anilina , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Receptores ErbB , Humanos , Neoplasias Pulmonares/metabolismoRESUMEN
We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. INTRODUCTION: Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. METHODS: We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients' 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. RESULTS: There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00-1.40) for the third tertile compared with the first tertile. CONCLUSIONS: Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.
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Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Fracturas de Cadera/etiología , Fracturas Osteoporóticas/etiología , Anciano , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/fisiopatología , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Taiwán/epidemiologíaAsunto(s)
Angiomiolipoma/complicaciones , Embolización Terapéutica , Hemorragia/terapia , Neoplasias Renales/complicaciones , Esclerosis Tuberosa/complicaciones , Adulto , Angiomiolipoma/diagnóstico por imagen , Urgencias Médicas , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Humanos , Neoplasias Renales/diagnóstico por imagen , Masculino , Rotura Espontánea , Síndrome , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Esclerosis Tuberosa/diagnóstico por imagenRESUMEN
BACKGROUND: Hepatic steatosis (HS) can cause substantial problems for both donors and recipients in living donor liver transplantation. The controlled attenuation parameter (CAP) is a noninvasive method of measuring HS using a process based on transient elastography. AIM: To evaluate the accuracy of CAP in quantifying HS during living donor liver transplantation. METHODS: A total of 54 liver donors who received CAP and intraoperative liver biopsy (LB) were enrolled in this study. The performance of CAP compared with LB for diagnosing HS was assessed using areas under receiver operating characteristic curves. HS was defined by the presence of steatosis in >5% of hepatocytes. RESULTS: No HS was found in 47 donors, while the remaining 7 donors showed HS ranging from 10% to 30%. Using CAP, the area under receiver operating characteristic curve was 0.96 (95% CI, 0.91-1; P < .001) for HS; the optimal cutoff value for HS was 257 dB/m (sensitivity: 100%, specificity: 89.4%, positive predictive value: 58.3%, negative predictive value: 100%). Among the 42 candidates with CAP <257 dB/m, none had HS, while of the 12 candidates with CAP ≥257 dB/m, 7 had HS. In a multivariate linear regression analyses, body mass index (ß = 0.71, P < .001) was found to be independently associated with CAP in those without HS. CONCLUSIONS: CAP might be a promising tool to exclude HS in East Asian living liver donors. Body mass index was found to be independently associated with CAP values in those without HS.
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Diagnóstico por Imagen de Elasticidad/métodos , Hígado Graso/diagnóstico por imagen , Trasplante de Hígado , Donadores Vivos , Trasplantes/patología , Adulto , Área Bajo la Curva , Pueblo Asiatico , Biopsia , Índice de Masa Corporal , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Curva ROC , Índice de Severidad de la Enfermedad , Trasplantes/diagnóstico por imagenRESUMEN
We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
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Incompatibilidad de Grupos Sanguíneos/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Anticuerpos/sangre , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad/métodos , Humanos , Inmunosupresores/uso terapéutico , Donadores Vivos , Masculino , Persona de Mediana Edad , Plasmaféresis/métodos , Rituximab/uso terapéuticoRESUMEN
BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.
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Costos de la Atención en Salud/estadística & datos numéricos , Trasplante de Hígado/economía , Donadores Vivos , Complicaciones Posoperatorias/economía , Adulto , Femenino , Hepatitis B/complicaciones , Hepatitis B/economía , Virus de la Hepatitis B , Humanos , Masculino , Persona de Mediana Edad , Taiwán , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of this study is to evaluate the use of diffusion-weighted magnetic resonance imaging (DWMRI) in the assessment of graft rejection after liver transplantation (LT). METHODS: From June 2017 to January 2018, 32 patients were included in the study with a mean age of 52.3 years. All patients underwent LT. The DWMRI was performed using the apparent diffusion coefficient map and measuring the different b-values (b-400, b-600, b-800, and b-1000). These measurements were compared with the histopathology results. Statistical analysis included t test, analysis of variance, and area under the curve for receiver operating characteristic (ROC). RESULTS: There were 17 patients without rejection and 15 patients with liver graft rejection diagnosed by histopathology. The mean (SD) results between the nonrejection and rejection groups were as follows: b-400 = 1.568 (0.265) vs 1.519 (0.119) (P = .089), b-600 = 1.380 (0.181) vs 1.284 (0.106) (P = .039), b-800 = 1.262 (0.170) vs 1.170 (0.086) (P = .035), b-1000 = 1.109 (0.129) vs 1.098 (0.078) (P = .095); B-values × 10-3 mm2/s. Only b-600 (P = .04) and b-800 (P = .04) values have significant differences between the 2 groups. B-600 showed 90.48% sensitivity and 83.33% specificity (ROC area under the curve = 0.784; P < .001), and b-800 showed 90.38% sensitivity and 83.03% specificity (ROC area under the curve = 0.816; P < .001). The values obtained with the apparent diffusion coefficient in b-800 were clearly differentiated between the mild, moderate, and severe degrees of rejection (P < .001). CONCLUSION: Measurement of b-600 and b-800 values using DWMRI may be used for the diagnosis of graft rejection after LT.
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Imagen de Difusión por Resonancia Magnética/métodos , Rechazo de Injerto/diagnóstico por imagen , Trasplante de Hígado/efectos adversos , Hígado/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Bacterial Infection is the most important source of mortality and morbidity in liver transplantation recipients. Donor transmitted bacterial infection is rare but one of the most important infection sources. This kind of infection is difficult to identify, causing treatment dilemma. PATIENTS AND METHODS: In this article, we retrospectively reviewed our deceased donor liver transplants performed from January 2014 to December 2016. Forty-two recipients in Kaohsiung Chang Gung Memorial Hospital receiving liver grafts from 35 deceased liver donors were evaluated. The demography, donor transmitted infection, and outcomes were evaluated. RESULT: Two patients had probable donor transmitted bacterial infection and 1 patient died of suspected transmitted infection. CONCLUSION: Early identification of donor infection and adequate antibiotic treatment for the donor and recipient are the keys to preventing donor transmitted bacterial infection. Donor infection is not an absolute contraindication for organ donation in the area of organ shortage. Organ procurement organizations or similar authorities may establish the platform for sharing the data about donor and recipient infections.