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1.
Cell ; 181(7): 1612-1625.e13, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32497499

RESUMO

Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Biomarcadores Farmacológicos/análise , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Genes MHC da Classe II , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1/genética , Receptores de Antígenos de Linfócitos T/genética , Análise de Célula Única/métodos , Linfócitos T Reguladores , Neoplasias da Bexiga Urinária/imunologia
2.
Cell ; 177(2): 414-427.e13, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30951669

RESUMO

PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches.


Assuntos
Antígeno B7-H1/metabolismo , Antígeno B7-H1/fisiologia , Microambiente Tumoral/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Linhagem Celular Tumoral , Exossomos/metabolismo , Humanos , Imunoterapia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T/imunologia , Microambiente Tumoral/fisiologia
3.
Immunity ; 50(2): 477-492.e8, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30737146

RESUMO

Resistance to checkpoint-blockade treatments is a challenge in the clinic. We found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden (LTB) state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ (IFN-γ) receptor and were more susceptible to apoptosis than naive T cells. Combination treatment induced deletion of tumor-specific T cells and altered the T cell repertoire landscape, skewing the distribution of T cells toward lower-frequency clonotypes. Additionally, combination therapy induced higher IFN-γ production in the LTB state than in the high tumor burden (HTB) state on a per-cell basis, reflecting a less exhausted immune status in the LTB state. Thus, elevated IFN-γ secretion in the LTB state contributes to the development of an immune-intrinsic mechanism of resistance to combination checkpoint blockade, highlighting the importance of achieving the optimal magnitude of immune stimulation for successful combination immunotherapy strategies.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno CTLA-4/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Interferon gama/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Antígeno CTLA-4/imunologia , Antígeno CTLA-4/metabolismo , Linhagem Celular Tumoral , Deleção Clonal/efeitos dos fármacos , Deleção Clonal/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/imunologia
4.
Environ Toxicol ; 39(8): 4120-4133, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38654489

RESUMO

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti-inflammatory properties, but whether they inhibit lipotoxicity-mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 µM palmitate (PA) in the presence or absence of 20 µM of each flavone. PA increased p-PERK, p-IRE1α, p-JNK1/2, CHOP, and TXNIP as well as p62 and LC3-II expression and induced autophagic flux damage. Caspase-1 activation and IL-1ß release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA-induced CHOP and TXNIP expression and caspase-1 activation were mitigated. Compared with PA treatment alone, Bcl-2 coupled to beclin-1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA-induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL-1ß release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA-induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress.


Assuntos
Apigenina , Autofagia , Estresse do Retículo Endoplasmático , Flavonoides , Inflamassomos , Luteolina , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Flavonoides/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apigenina/farmacologia , Animais , Luteolina/farmacologia , Autofagia/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Camundongos , Macrófagos/efeitos dos fármacos , Linhagem Celular
5.
Environ Toxicol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105397

RESUMO

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

6.
Blood ; 138(24): 2583-2588, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34424962

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Receptores de Interleucina-6/antagonistas & inibidores , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Modelos Animais de Doenças , Etanercepte/uso terapêutico , Feminino , Efeito Enxerto vs Tumor/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante Homólogo/métodos
7.
Protein Expr Purif ; 210: 106297, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37209930

RESUMO

In downstream processing of protein therapeutics, ion exchange (IEX) chromatography is a powerful tool for removing byproducts whose isoelectric point (pI) is appreciably different from that of the product. Although in theory for a given case cation exchange (CEX) and anion exchange (AEX) chromatography should be equally effective for separation, in reality they may show different effectiveness. In the current work, with a case study, we demonstrated that AEX is more effective than CEX chromatography at removing the associated byproducts. In addition, we screened AEX resins and loading conditions to achieve best separation. Finally, we demonstrated that effective separation was achieved with the selected resin/condition, and chromatography performance was comparable between runs conducted at low and high load densities, suggesting that the developed process was relatively robust. The procedure described in this work can be used as a general approach for selecting resin and loading condition that allow for effective and robust removal of byproduct that binds weaker than the product to the selected type of column.


Assuntos
Resinas de Troca Aniônica , Cromatografia por Troca Iônica/métodos , Resinas de Troca Aniônica/química , Ânions , Cátions/química
8.
BMC Infect Dis ; 23(1): 859, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057727

RESUMO

PURPOSE: To examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course. MATERIALS AND METHODS: The clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score < 8) or a rapid deterioration in consciousness level within 48 h of hospitalization. RESULTS: Among the 127 enrolled patients, 69 had a fulminant clinical course (47 men and 22 women) and 58 did not. The patients with a fulminant clinical course had a significantly higher incidence of end-stage renal disease (ESRD), severe clinical manifestations and higher mortality rate, and the survivors had significantly worse therapeutic outcomes. Klebsiella (K.) pneumoniae (50 strains) was the most important pathogen for the development of a fulminant clinical course, and all strains were susceptible to ceftriaxone and ceftazidime. With treatment, 50.7% (35/69) of the patients with a fulminant clinical course died, and the presence of K. pneumoniae infection was significant prognostic factor. CONCLUSIONS: The presence of ESRD, initial presentation of altered consciousness, septic shock, seizures and CSF total protein level and K. pneumoniae infection were significantly associated with a fulminant clinical course of adult CASBM, and patients with this specific infectious syndrome had high mortality and morbidity rates. The presence of K. pneumoniae infection is a significant prognostic factor.


Assuntos
Infecções Comunitárias Adquiridas , Falência Renal Crônica , Meningites Bacterianas , Adulto , Masculino , Humanos , Feminino , Taiwan/epidemiologia , Prognóstico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/epidemiologia , Klebsiella pneumoniae , Resultado do Tratamento , Falência Renal Crônica/complicações , Progressão da Doença , Estudos Retrospectivos
9.
Nature ; 542(7639): 75-79, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28150758

RESUMO

Perfect crystals are rare in nature. Real materials often contain crystal defects and chemical order/disorder such as grain boundaries, dislocations, interfaces, surface reconstructions and point defects. Such disruption in periodicity strongly affects material properties and functionality. Despite rapid development of quantitative material characterization methods, correlating three-dimensional (3D) atomic arrangements of chemical order/disorder and crystal defects with material properties remains a challenge. On a parallel front, quantum mechanics calculations such as density functional theory (DFT) have progressed from the modelling of ideal bulk systems to modelling 'real' materials with dopants, dislocations, grain boundaries and interfaces; but these calculations rely heavily on average atomic models extracted from crystallography. To improve the predictive power of first-principles calculations, there is a pressing need to use atomic coordinates of real systems beyond average crystallographic measurements. Here we determine the 3D coordinates of 6,569 iron and 16,627 platinum atoms in an iron-platinum nanoparticle, and correlate chemical order/disorder and crystal defects with material properties at the single-atom level. We identify rich structural variety with unprecedented 3D detail including atomic composition, grain boundaries, anti-phase boundaries, anti-site point defects and swap defects. We show that the experimentally measured coordinates and chemical species with 22 picometre precision can be used as direct input for DFT calculations of material properties such as atomic spin and orbital magnetic moments and local magnetocrystalline anisotropy. This work combines 3D atomic structure determination of crystal defects with DFT calculations, which is expected to advance our understanding of structure-property relationships at the fundamental level.

10.
Gerontology ; 69(6): 768-782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617413

RESUMO

INTRODUCTION: Regular physical exercise is believed to counteract the adverse physiological consequences of aging. However, smart fitness equipment specifically designed for older adults is quite rare. Here we designed an exergame-integrated internet of things (IoT)-based ergometer system (EIoT-ergo) that delivers personalized exercise prescriptions for older adults. First, physical fitness was evaluated using the Senior Fitness Test (SFT) application. Then, radio frequency identification (RFID) triggered the EIoT-ergo to deliver the corresponding exercise session based on the individual level of physical fitness. The exercise intensity during each workout was measured to generate the next exercise session. Further, EIoT-ergo provides an exergame to help users control and maintain their optimal cadence while engaging in exercise. METHODS: This was a randomized controlled trial with 1:1 randomization. Participants were older adults, 50+ years of age (N = 35), who are active in their community. Participants in the EIoT-ergo group received a 12-week personalized exercise program delivered by EIoT-ergo for 30 min per session, with 2 sessions per week. Participants in the control group continued with their usual activities. A senior's fitness test and a health questionnaire were assessed at baseline and at a 13-week reassessment. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) was used to evaluate the satisfaction of EIoT-ergo. RESULTS: Compared with the control group, the EIoT-ergo group showed significant improvements in muscle strength (time-by-group interaction, sit-to-stand: ß = 5.013, p < 0.001), flexibility (back stretch: ß = 4.008, p = 0.005; and sit-and-reach: ß = 4.730, p = 0.04), and aerobic endurance (2-min step: ß = 9.262, p = 0.03). The body composition was also improved in the EIoT-ergo group (body mass index: ß = -0.737, p < 0.001; and skeletal muscle index: ß = 0.268, p = 0.03). Satisfaction with EIoT-ergo was shown in QUEST, with an average score of 4.4 ± 0.32 (5 for very satisfied). The percentage maximum heart rate in each session also indicated that EIoT-ergo can gradually build up the exercise intensity of users. CONCLUSIONS: EIoT-ergo was developed to provide personal identification, exergames, intelligent exercise prescriptions, and remote monitoring, as well as to significantly enhance the physical fitness of the elderly individuals under study.


Assuntos
Jogos Eletrônicos de Movimento , Internet das Coisas , Humanos , Idoso , Projetos Piloto , Aptidão Física , Exercício Físico/fisiologia
11.
Ophthalmic Physiol Opt ; 43(2): 195-201, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36453985

RESUMO

PURPOSE: To evaluate the changes in visual function when progressive addition lenses (PAL) are added in children using topical atropine as a myopia control therapy. Daily visual complaints and the determination of their near correction were studied. METHODS: Forty children aged 7-12 years were recruited. Distance and near visual acuity, accommodative lag, heterophoria, near point of convergence and stereopsis were examined, and a questionnaire of daily visual complaints was administered. RESULTS: Significant differences in visual functions were found after the near correction was prescribed. Significant improvements in distance and near visual acuity, lag of accommodation and binocular visual function were observed, and fewer visual complaints were reported at the Harmon distance. CONCLUSION: The use of PAL is helpful for children undergoing topical atropine treatment for myopia control, particularly those receiving medium to high doses. This combination therapy could also be applied to younger children who have a low tolerance to contact lenses, with less risk of ocular adverse effects.


Assuntos
Atropina , Miopia , Humanos , Criança , Acuidade Visual , Visão Binocular , Miopia/tratamento farmacológico , Acomodação Ocular , Refração Ocular
12.
BMC Gastroenterol ; 22(1): 381, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948871

RESUMO

BACKGROUND: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach. METHODS: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches. RESULTS: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses. CONCLUSIONS: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Quimiorradioterapia , Estudos de Coortes , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Pontuação de Propensão , Estudos Retrospectivos
13.
Acta Neurol Taiwan ; 31(3): 114-120, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35437741

RESUMO

Time is the major determinant in successful reperfusion therapy of acute ischemic stroke. The evolving diagnostic tools and treatment of acute stroke has made a great progress in the past 2 decades and is remolding current management practices. It demands a timely neurologic evaluation and a neuroimaging study to determine if stroke patients are appropriate candidates for reperfusion demands. Therefore, it is critical for the setting of stroke center accreditation levels and capabilities so that timely and appropriate treatment is initiated for the eligible stroke patients. Optimal acute ischemic stroke treatment requires all levels of stroke center network operating efficiently. In the future, Taiwan should revise the criteria of stroke center accreditation and set up the efficient acute stroke treatment network as soon as possible. Keywords: stroke, reperfusion, intra-arterial thrombectomy, intravenous recombinant tissue plasminogen activator.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/terapia , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/etiologia , Taiwan , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
14.
Geriatr Nurs ; 43: 130-137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34883391

RESUMO

This study aimed to explore meaningful experiences of older Taiwanese adults who had received a Paro (social robot) companion. Semi-structured qualitative interviews elicited the perspectives of 25 older adults living in a long-term care facility after they had interacted with an individual Paro companion for 8 weeks. Thematic analysis was used in this study as it allows for rich, detailed, and complex descriptions of qualitative data. Analysis identified four themes: Bridging my social bonds; Acting as a comfort Buddy; Relieving my emotional distress; and Encountering Paro with distancing. Although Paro's functioning has some limits, such as lacking speech, most participants expressed that the experience was positive. These findings revealed that the meaningful experiences expressed by participants at the end of the intervention with Paro might provide the value of companionship and improve interpersonal relationships for older adults in geriatric nursing.


Assuntos
Enfermagem Geriátrica , Robótica , Idoso , Humanos , Relações Interpessoais , Casas de Saúde , Interação Social
15.
BMC Gastroenterol ; 21(1): 153, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827451

RESUMO

BACKGROUND: The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. METHODS: Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. RESULTS: Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24-0.53, P < 0.001). Similar results were found for IECM. Statistical significance was only observed in the standard RT dose but not in the low dose in subgroup analyses. CONCLUSIONS: In this population-based nonrandomized study of cT4bNanyM0 ESqCC patients from Asia (Taiwan), we found that the use of radiotherapy with chemotherapy was associated with better overall survival than chemotherapy alone. Further studies (especially RCTs) are needed to confirm our findings.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Pontuação de Propensão , Taiwan/epidemiologia
16.
J Comput Assist Tomogr ; 45(6): 919-925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34347702

RESUMO

OBJECTIVE: The aim of the study was to evaluate cerebral hemorrhage (CH) and contrast media leakage (CML or commonly synonymous with "contrast staining") differentiation on flat-panel volume computed tomography (FPVCT) after intra-arterial mechanical thrombectomy. METHODS: We evaluated patients with hyperattenuation on FPVCT after intra-arterial mechanical thrombectomy between 2018 and 2021 by multiple parameters on CT angiography, FPVCT, CT, and/or magnetic resonance imaging. RESULTS: The CH (n = 43) versus CML (n = 24) groups revealed: (1) regional anatomical characteristics (preserved and distorted): 7 of 43 (9.6%) and 36 of 43 (83.7%) versus 22 of 24 (91.7%) and 2 of 24 (8.3%, P < 0.001); (2) thrombus in proximal two-thirds versus distal one-thirds M1 segment of middle cerebral artery (preserved and distorted): 17 of 21 (81.0%) and 4 of 21 (19.0%) versus 5 of 11 (45.5%) and 6 of 11 (54.5%, P = 0.040); and (3) average density ratio: 1.83 ± 0.65 versus 1.35 ± 0.13 (P = 0.004). CONCLUSIONS: Contrast media leakage can be differentiated from CH by preserved regional anatomical characteristics and relatively low average density ratio on FPVCT. Patients with CML who have embolism in proximal two thirds of M1 segment are more likely to develop hyperattenuation with preserved regional anatomy.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , AVC Embólico/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Idoso , Encéfalo/diagnóstico por imagem , AVC Embólico/complicações , Extravasamento de Materiais Terapêuticos e Diagnósticos/fisiopatologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações
17.
J Formos Med Assoc ; 120(12): 2176-2185, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33451864

RESUMO

BACKGROUND/PURPOSE: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. METHODS: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan-Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. RESULTS: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p < 0.001) was the most important independent prognostic factor predicting real-world progression. EGFR mutation status had no impact on the outcomes. CONCLUSION: SABR provides excellent local control in ES-NSCLC, although disseminated failures remains a major concern. ACCI is the best indicator for OS, while tumor sizes ≥4 cm predicts poor disease control.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Estudos Retrospectivos , Resultado do Tratamento
18.
Sensors (Basel) ; 21(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578684

RESUMO

Smart toothbrushes equipped with inertial sensors are emerging as high-tech oral health products in personalized health care. The real-time signal processing of nine-axis inertial sensing and toothbrush posture recognition requires high computational resources. This paper proposes a recurrent probabilistic neural network (RPNN) for toothbrush posture recognition that demonstrates the advantages of low computational resources as a requirement, along with high recognition accuracy and efficiency. The RPNN model is trained for toothbrush posture recognition and brushing position and then monitors the correctness and integrity of the Bass Brushing Technique. Compared to conventional deep learning models, the recognition accuracy of RPNN is 99.08% in our experiments, which is 16.2% higher than that of the Convolutional Neural Network (CNN) and 21.21% higher than the Long Short-Term Memory (LSTM) model. The model we used can greatly reduce the computing power of hardware devices, and thus, our system can be used directly on smartphones.


Assuntos
Redes Neurais de Computação , Escovação Dentária , Monitorização Fisiológica
19.
Acta Neurol Taiwan ; 30(4): 141-150, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34841499

RESUMO

BACKGROUND: To examine the clinical characteristics and therapeutic outcome of Escherichia (E.) coli adult bacterial meningitis (ABM). METHODS: The demographic data, clinical and laboratory features and therapeutic outcome of 25 E. coli ABM patients were examined retrospectively. The clinical features of the reported E. coli ABM cases were also included for analysis. RESULTS: The 25 E. coli ABM patients included 12 women and 13 men, aged 33-78 years (mean= 59.9). Of these 25 patients, 13 had a postneurosurgical state as the underlying condition. As to the underlying medical conditions, diabetes mellitus was the most common, found in 9 of the 25 cases. Of the clinical manifestation, severe neurologic manifestations including altered consciousness (19), hydrocephalus (10), seizure (7) acute/subacute cerebral infarct (5), brain abscess (2), subdural empyema (1) and spinal abscess (1) were found, and the other clinical features included fever (21), septic shock (8), bacteremia (6) and hyponatremia (3). With treatment, the mortality rate was more than 44.0% and the presence of septic shock was a significant prognostic factor. With literature review, 29 community-acquired and 12 postneurosurgical E. coli ABM cases were enrolled, and severe neurologic manifestation and high mortality rate were also found. CONCLUSIONS: This preliminary overview of E. coli ABM revealed the underlying conditions, severe neurologic manifestation and high mortality rate. Further large-scale, prospective study is needed for a better delineation of this specific infectious syndrome of adult E. coli meningitis.


Assuntos
Meningites Bacterianas , Meningite devida a Escherichia coli , Adulto , Escherichia coli , Feminino , Humanos , Masculino , Meningites Bacterianas/terapia , Meningite devida a Escherichia coli/terapia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Gastroenterol Hepatol ; 35(2): 233-240, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31408909

RESUMO

BACKGROUND AND AIM: The reported prevalence of Helicobacter pylori infection in Taiwan was 54.4% in 1992. An updated prevalence of H. pylori infection in asymptomatic adults is lacking in Taiwan. We aimed to assess the updated age-standardized prevalence of H. pylori infection in asymptomatic subjects and in patients with dyspepsia and to assess the accuracy of H. pylori stool antigen (HpSA) test for screening of H. pylori in Chinese population. METHODS: Asymptomatic adult subjects (N = 189) were screened for H. pylori infection using HpSA, serology, and 13 C-urea breath test (13 C-UBT) in 2016-2017. Adult patients with dyspepsia (N = 145) were screened for H. pylori using 13 C-UBT, HpSA, serology, rapid urease test, and histology during 2016-2018. Two types of HpSA, including the Diagnostec HpSA ELISA Kit (HpSA ELISA) and Rapid Test Kit (HpSA Rapid), were used in this study. Sensitivity, specificity, and accuracy of the HpSA tests were calculated using the 13 C-UBT as golden standard test. RESULTS: The unadjusted prevalence of H. pylori was 21.2% in asymptomatic adults and 37.9% in patients with dyspepsia (P < 0.001). The age-standardized prevalence of H. pylori was 28.9% in asymptomatic adults in Taiwan. Of the 334 patients included for analysis, the area under the curve of HpSA ELISA test was 0.978, and the optimal cutoff value of optical density was 0.03. The sensitivity, specificity, and accuracy of the HpSA ELISA were 0.929, 0.983, and 0.967, respectively. The sensitivity, specificity, and accuracy of the HpSA Rapid were 0.929, 0.958, and 0.949, respectively. CONCLUSIONS: The prevalence of H. pylori infection has decreased in Taiwan. HpSA test is an accurate tool for screening of H. pylori in Chinese population.


Assuntos
Antígenos de Bactérias , Gastrite/diagnóstico , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Testes Imunológicos/métodos , Gastrite/epidemiologia , Helicobacter pylori/imunologia , Humanos , Prevalência , Taiwan/epidemiologia
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