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BACKGROUND: Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC. PATIENTS AND METHODS: Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. CONCLUSIONS: Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.
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Carcinoma de Células de Transição , Pirazóis , Quinoxalinas , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.
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OBJECTIVES: Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures. STUDY DESIGN: This was a nationwide population-based cohort study. METHODS: This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated. RESULTS: A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio [aHR] 1.349, 95% confidence interval [CI] 1.302-1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357-1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612-1.798, P < 0.001). CONCLUSIONS: TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.
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Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Tuberculose , Masculino , Humanos , Feminino , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Incidência , Estudos de Coortes , Osteoporose/epidemiologia , Fatores de Risco , Fraturas do Quadril/epidemiologiaRESUMO
OBJECTIVE: To investigate the prognostic significance of videofluorographic swallowing study (VFSS)-confirmed oropharyngeal dysphagia in idiopathic inflammatory myopathies (IIMs). METHOD: We reviewed the medical records of patients who were diagnosed with IIM between 2009 and 2020 at Seoul St Mary's Hospital. All oropharyngeal dysphagia cases were limited to VFSS-confirmed dysphagia found during the initial diagnostic work-up for IIM. We described the findings on VFSS and the course of the dysphagic symptoms. Logistic regression and survival analyses were performed to evaluate the risk of pneumonia and mortality, respectively. RESULTS: We found 88 patients with IIM who met the criteria. Among them, 17 patients (19%) had oropharyngeal dysphagia. Except for two cases lost to follow-up and one deceased case, all of the patients with dysphagia (14 of 14) had swallowing function restored within 6 months. The risk of pneumonia within 3 months from the diagnosis of IIM was significant [odds ratio = 4.49, 95% confidence interval (CI) 1.07-18.88]. The median follow-up duration was 34 and 27 months for the groups without and with dysphagia, respectively. The survival analysis failed to demonstrate that the presence of oropharyngeal dysphagia increased the risk of death (hazard ratio = 0.77, 95% CI: 0.085-7.00). CONCLUSIONS: Oropharyngeal dysphagia found at the initial diagnosis of IIM improved within 3-6 months in nearly all cases. Furthermore, IIM patients who had oropharyngeal dysphagia at the initial diagnosis of IIM were not likely to have shorter survival, even if the risk of pneumonia was increased in the short term.
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Transtornos de Deglutição , Miosite , Pneumonia , Humanos , Deglutição , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Miosite/complicações , PrognósticoRESUMO
We report the temperature evolution of hydrogen bond (HB) chains and rings in Mn5[(PO4)2(PO3(OH))2](HOH)4 to reveal conduction pathways based on difference Fourier maps with neutron- and synchrotron x-ray diffraction data. Localized proton dynamics for the five distinct hydrogen sites were observed and identified in this study. Their temperature evaluation over ten orders of magnitude in time was followed by means of quasielastic neutron scattering, dielectric spectroscopy, and ab initio molecular dynamics. Two out of the five hydrogen sites are geometrically isolated and are not suitable for long-range proton conduction. Nevertheless, the detected dc conductivity points to long-range charge transport at elevated temperatures, which occurs most likely (1) over H4-H4 sites between semihelical HB chains (interchain-exchanges) and (2) by rotations of O1-H1 and site-exchanging H4-O10-O5 groups along each semihelical HB chain (intrachain-exchanges). The latter dynamics freeze into a proton-glass state at low temperatures. Rotational and site-exchanging motions of HOH and OH ligands seem to be facilitated by collective motions of framework polyhedra, which we detected by inelastic neutron scattering.
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BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
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Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologiaRESUMO
AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.
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Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Antígenos Virais , Meios de Cultura , Febre Aftosa/prevenção & controleRESUMO
AIM: To investigate the image quality and radiation dose of ultralow-dose (ULD) and low-dose (LD) lower-extremity computed tomography (CT) angiography (LE-CTA) using the advanced modelled iterative reconstruction (ADMIRE) algorithm to detect peripheral arterial disease (PAD) in comparison with standard-dose (SD) CT. MATERIALS AND METHODS: One hundred and seven consecutive patients were examined using LE-CTA at 70 kVp and a dual-source scanner to achieve three image sets using 30% (ULD), 70% (LD), and 100% (SD) tube loads. Qualitative analysis was conducted by examining the three image sets for overall quality. The image quality of arterial segments was analysed by two independent readers. In addition, the CT dose index (CTDIvol) was measured in the three image sets. RESULTS: The mean overall quality scores were 3.4±0.6 for ULD CT, 3.9±0.3 for LD CT, and 3.9±0.2 for SD CT. Both readers scored the arterial segments as 2-4 (adequate-excellent) in the three image sets. In addition, 89.4% (93/104) and 54.8% (57/104) segments of PAD with calcified plaques were scored 4 between SD and LD CT and between SD and ULD CT, respectively, and 45.2% (47/104) segments had a lower score by one point in ULD CT compared with SD CT. The mean CTDIvol was 4.1±1.1 mGy for SD CT, 2.9±0.8 mGy for LD CT, and 1.2±0.3 mGy for ULD CT. CONCLUSIONS: LD/ULD CT at 70 kVp using ADMIRE reconstruction enables a reduction in the radiation dose while enabling adequate evaluation or follow-up of PAD based on LE-CTA.
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Angiografia por Tomografia Computadorizada/métodos , Extremidade Inferior/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Doses de Radiação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: To develop a laboratory-based tooth model of simulated blood flow in teeth and evaluate it using ultrasound Doppler flowmetry (UDF). METHODOLOGY: A laboratory-based tooth model for UDF was created based on a microfluidic experimental model proposed by Kim & Park (2016 a,b). Twenty-one maxillary or mandibular anterior human teeth within 1 month of extraction were used. Four holes were made in each tooth to fit 1.6-mm diameter polytetrafluoroethylene (PTFE) tubes: at the apical foramen, palatal surface in the centre of the crown, palatal surface apical to the cementoenamel junction (CEJ) and the root centre. Fluid mimicking pulsating blood was pumped (pressure range: 0-200 mbar, flow rate range: 0-80 µL min-1 ) into the apical foramen via the PTFE tubes, which exited the tooth through the palatal surface in the centre of the crown (control group), palatal surface below the CEJ (group 1) and the palatal surface at the mid-root level (group 2). An UDF transducer of 20 MHz was placed at a 60° angle to the labial surface of tooth and was used to measure the fluid flow velocity (Vs, Vas, Vm, Vam, Vd, Vad and Vakd). The flow velocity of the different groups was compared using the Wilcoxon signed-rank test, with a 95% confidence level. RESULTS: UDF facilitated the detection of the simulated pulpal blood flow in the control group and group 1, but not in group 2. The mean and standard deviations of Vas, Vam and Vakd were 0.921 ± 0.394, 0.479 ± 0.208 and 0.396 ± 0.220 cm s-1 , respectively, in the control group, and 0.865 ± 0.368, 0.424 ± 0.215 and 0.487 ± 0.279 cm s-1 , respectively, in group 1. The pulpal blood flow values of the control group and group 1 were not significantly different (p > 0.05). CONCLUSIONS: This laboratory study revealed that ultrasound Doppler flowmetry enabled the detection of simulated blood flow below the level of the CEJ but not at the mid-root level.
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Polpa Dentária , Laboratórios , Polpa Dentária/diagnóstico por imagem , Humanos , Fluxometria por Laser-Doppler , Fluxo Sanguíneo Regional , Reologia , UltrassonografiaRESUMO
Objectives: To compare faecal calprotectin levels according to the type of manifestation and to investigate factors associated with increases in faecal calprotectin in patients with axial spondyloarthritis (axSpA). Method: The study enrolled 190 patients fulfilling the imaging arm of the Assessment of SpondyloArthritis international Society axSpA criteria. Faecal calprotectin levels were measured in an enzyme-linked immunosorbent assay. Systemic inflammatory markers and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were also assessed. Peripheral joint involvement was assessed using the 44-joint examination and Spondyloarthritis Research Consortium of Canada Enthesitis Index. Results: Of 190 patients, 34 (18%) had increased faecal calprotectin levels. These patients were more likely to have ongoing peripheral arthritis and enthesitis (p = 0.016 and 0.001, respectively). A history of psoriasis and uveitis, or current uveitis symptoms, had no bearing on faecal calprotectin levels. Faecal calprotectin levels increased along with ASDAS-C-reactive protein (CRP), and correlated with ASDAS-erythrocyte sedimentation rate (ESR) (r = 0.240, p = 0.001), ASDAS-CRP (r = 0.162, p = 0.025), ESR (r = 0.228, p = 0.002), and CRP levels (0.258, p < 0.001). Tender joint and swollen joint counts also correlated with faecal calprotectin levels (r = 0.252 and 0.205, p < 0.001 and p = 0.005, respectively). Faecal calprotectin levels were higher in patients with current peripheral symptoms (p = 0.003). Peripheral symptoms were independently associated with increased faecal calprotectin levels (odds ratio = 4.083; 95% confidence interval 1.580-10.556). Conclusions: Faecal calprotectin levels in axSpA patients were associated with disease activity. Subclinical gut inflammation (assessed by measuring faecal calprotectin) in axSpA is more closely related to peripheral joint inflammation than to axial joint inflammation.
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Entesopatia/metabolismo , Fezes/química , Inflamação/metabolismo , Complexo Antígeno L1 Leucocitário/análise , Sacroileíte/metabolismo , Espondilartrite/metabolismo , Adulto , Idoso , Biomarcadores , Entesopatia/diagnóstico por imagem , Feminino , Humanos , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Exame Físico , Radiografia , Sacroileíte/diagnóstico por imagem , Índice de Gravidade de Doença , Espondilartrite/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: To evaluate the association between trabecular bone score (TBS) and new bone formation in ankylosing spondylitis (AS) patients, and to investigate whether TBS is independently associated with new bone formation. METHOD: Sixty-eight patients with AS underwent spinal magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density at baseline. Lateral radiographs of the cervical and lumbar spine (baseline and 2 years) were assessed for new bone formation (syndesmophyte formation and/or growth combined), and spinal MRIs were assessed for the presence or absence of fat metaplasia (FM) at the first to fourth lumbar vertebrae. The factors associated with new bone formation were analysed at the patient level and the vertebral level. RESULTS: New bone formation had developed in 17 patients (25%) at 2 year follow-up. Patients with new bone formation had a higher prevalence of FM and lower TBS at baseline than patients without new bone formation (p = 0.013 and p = 0.041). At the patient level, FM on MRI and low TBS (< 1.23) were significantly associated with new bone formation. At the vertebral level, new bone formation had developed in 25 out of 231 vertebrae (11%) after 2 years. Vertebrae with both FM on MRI and low TBS tended to have more new bone formation (p < 0.001). Syndesmophytes and low TBS (< 1.23) independently increased the risk of new bone formation at the level of individual vertebrae. CONCLUSION: At both patient and individual vertebral levels, low TBS was associated with new bone formation independently of FM on MRI.
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Tecido Adiposo/diagnóstico por imagem , Osso Esponjoso/diagnóstico por imagem , Osteogênese , Espondilite Anquilosante/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Osso Esponjoso/patologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Metaplasia , Pessoa de Meia-Idade , Espondilite Anquilosante/patologiaRESUMO
AIMS: The objective of this study was to evaluate the antimicrobial effects of radio frequency (RF) heating and the combination treatment of RF heating with ultraviolet (UV) radiation against foodborne pathogens in roasted grain powder (RGP). METHODS AND RESULTS: Foodborne pathogens inoculated on RGP were subjected to RF heating or RF-UV combination treatments. After 120 s of RF heating, 4·68, 3·89 and 4·54 log reductions were observed for Escherichia coli, Salmonella Typhimurium and Bacillus cereus vegetative cells respectively. The combined RF-UV treatment showed synergistic effects of over 1 log unit compared to the sum of individual treatment for E. coli and S. Typhimurium, but not for B. cereus vegetative cells because of their high UV resistance. Germinated B. cereus cells were not significantly inactivated by RF heating (<1 log CFU per gram), and increased heat resistance compared to the vegetative cells was verified with mild heat treatment. The colour of RGP was not significantly affected by the RF or RF-UV treatments. CONCLUSIONS: Applying RF heating to grain-based food products has advantages for the inactivation of E. coli and S. Typhimurium in RGP. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study could be used as a basis for determining the treatment conditions for inactivating E. coli and other foodborne pathogens such as S. Typhimurium and B. cereus in RGP.
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Bactérias/efeitos da radiação , Grão Comestível/microbiologia , Irradiação de Alimentos/métodos , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/microbiologia , Viabilidade Microbiana/efeitos da radiação , Ondas de Rádio , Esporos Bacterianos/fisiologia , Esporos Bacterianos/efeitos da radiação , Raios UltravioletaRESUMO
AIM: The main aim of this study was to compare the long-term outcome of a conventional colorectal endoscopic submucosal dissection (ESD) in which submucosal dissection was continued throughout until the completion of resection (ESD-T) to hybrid endoscopic submucosal dissection (ESD-H) in the colorectum. METHOD: Medical records of 836 colorectal neoplasia patients treated by ESD-T or ESD-H were reviewed. ESD-H was defined as colorectal ESD with additional snaring in the final stage of the procedure. Primary outcomes were the overall and metastatic recurrence rates. Secondary outcomes were short-term outcomes such as the en bloc resection rate, procedure time and adverse events. RESULTS: The overall recurrence rate was higher in the ESD-H than in the ESD-T group (5.7% vs 0.7%, P = 0.001). The metastatic recurrence rate showed no significant difference between these groups (1.4% vs 1.4%, P = 1.000). Multivariate analysis revealed that a failed en bloc resection (hazard ratio 24.097; 95% CI 5.446-106.237; P < 0.001) and larger tumour size (hazard ratio 1.042; 95% CI 1.014-1.070; P = 0.003) were independently associated with overall recurrence. The ESD-H group showed a lower en bloc resection rate (56.8% vs 96.5%, P < 0.001), shorter procedure time (45.6 vs 54.3 min, P < 0.001) and higher perforation rate (10.3% vs 6.0%, P = 0.029). CONCLUSION: Although long-term outcomes in terms of overall recurrence are inferior following ESD-H, a failed en bloc resection and large tumour size are the only independent risk factors for recurrence. Further investigations are warranted to improve the long-term outcomes of ESD-H.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/cirurgia , Dissecação , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: The possibility of an association between early menopause and the risk of non-alcoholic fatty liver disease (NAFLD) is as yet unclear.Methods: The subjects consisted of 4354 postmenopausal women who participated in the 2010-2012 Korea National Health and Nutrition Examination Survey. Early, normal, and late menopause were defined as age at menopause <45 years, 45-54 years, and ≥55 years, respectively. NAFLD was defined by a hepatic steatosis index of >36.Results: When compared with normal menopausal women, early or late menopausal women had no significant differences in the odds ratios (ORs) of NAFLD: OR = 1.05, 95% confidence interval (CI), 0.83-1.32 and OR = 1.02, 95% CI, 0.75-1.39, respectively. These results remained similar after adjustment for known risk factors for NAFLD, reproductive factors, and comorbidities. The OR for NAFLD per 1-year increase in age at menopause was 1.01 (95% CI, 0.99-1.03; p = 0.329). The prevalence of advanced fibrosis was 2.1% (95% CI, 0.7-6.4%), 2.2% (95% CI, 1.3-3.8%), and 3.9% (95% CI, 1.2-12.2%) in early, normal, and late menopausal women, respectively.Conclusions: This study provides no evidence for an association of early menopause with NAFLD risk. However, NAFLD-related advanced fibrosis is highly prevalent in postmenopausal women.
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Menopausa Precoce , Hepatopatia Gordurosa não Alcoólica/etiologia , Pós-Menopausa , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.
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Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Metástase Linfática , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Carga TumoralRESUMO
Femtosecond laser-induced spatial redistribution of silver species (ions, clusters, and hole centers) in a silver-containing phosphate glass is investigated by correlative means of near-field scanning optical microscopy (NSOM) images, numerical simulations, chemical micro-probe analysis, and nanoscale spatial profiles after soft etching. In particular, we found that the chemical etching selectivity for nanoscale patterning is strongly dependent upon the irradiation of femtosecond laser due to the spatial redistribution of silver species within the affected area. These results strongly indicate that controlling the distribution of silver species by femtosecond laser irradiation may open new routes for surface nanoscale chemical and/or spatial patterning for the fabrication of 2D surface photonic crystals.
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OBJECTIVE: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS). METHOD: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period. RESULTS: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of ß2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.
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Ceratoconjuntivite Seca , Síndrome de Sjogren/complicações , Xerostomia , Adulto , Fatores Etários , Anticorpos Antinucleares/sangue , Estudos de Coortes , Feminino , Humanos , Ceratoconjuntivite Seca/diagnóstico , Ceratoconjuntivite Seca/etiologia , Ceratoconjuntivite Seca/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Fator Reumatoide/sangue , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Avaliação de Sintomas , Xerostomia/diagnóstico , Xerostomia/etiologia , Xerostomia/imunologiaRESUMO
AIM: To assess whether multimodal magnetic resonance imaging (MRI) could detect neuroanatomical substrates that are distinctive to hyposmic Parkinson's disease (PD). MATERIALS AND METHODS: Among 102 PD patients, 62 were hyposmic and 40 were normosmic. For each patient, a sagittal structural three-dimensional (3D) T1-weighted image was obtained with the magnetisation-prepared rapid acquisition of the gradient-echo sequence to generate subcortical grey matter masking templates and to perform a voxel-based morphometry analysis of the subcortical grey matter volumes. A 3D multi-echo gradient sequence was run to obtain axial magnitude and phase images to produce a quantitative susceptibility map (QSM), and a diffusion-weighted image was acquired to generate an apparent diffusion coefficient (ADC) map. The volumes and average QSM and ADC values of the 15 subcortical grey matter structures were calculated, and the group differences were evaluated using a one-way analysis of covariance with age and gender as covariates. RESULTS: The QSM of the left thalamus significantly increased, while that of the right thalamus significantly decreased in hyposmia. No effects on the cortical volume changes were found other than aging. CONCLUSION: The present results suggest that accumulation of disease-related substances in the left and right thalamus and the increasing asymmetry between the two sides are associated with hyposmia in PD.
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Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Avaliação Geriátrica/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/diagnóstico por imagem , Idoso , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Childhood obesity is a complex and multifaceted problem involving interactions among child, family and community environment. AIM: The purpose of this study was to examine the contributing factors to early childhood obesity within a multilevel context, including child and family, childcare setting and community. METHODS: A cross-sectional, quantitative research design was employed. A total of 129 preschoolers and their parents in northwest Florida participated in this study. Child height and weight were measured, and body mass index (BMI) was calculated. Parents and directors of preschools completed survey questionnaires to assess child/family, childcare setting and community factors, respectively. Hierarchical multiple regression was used to evaluate the association of each level of factors with child BMI z-score. RESULTS: Twenty-one per cent of children were overweight or obese (≥85th BMI percentile). In hierarchical multiple regression, household income, parent beliefs, attitudes and practices for child feeding, family obesogenic environment, child routines (screen time on weekends, sleep hours, bedtime) and physical activity environment were significantly related to child BMI z-score. CONCLUSIONS: The findings of this study provide a broader understanding of factors that influence child BMI z-score. Shaping a non-obesogenic environment by establishing healthy routines for children in the home, childcare setting and community is essential in childhood obesity prevention. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: Paediatric nurses should routinely assess accurate parental perception of child weight, feeding style and child routines in well-child care visits. Healthcare professionals and health policymakers should enact policies that build a healthy environment for preschoolers in their childcare setting and community.
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Relações Familiares/psicologia , Comportamento Alimentar/psicologia , Poder Familiar/psicologia , Obesidade Infantil/prevenção & controle , Índice de Massa Corporal , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pais/psicologia , Obesidade Infantil/psicologiaRESUMO
Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy. Trial registration: ClinicalTrials.gov: NCT02625623.