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A tuberculous aneurysm is an uncommon extrapulmonary tuberculosis and is usually fatal. The best way to treat it involves a combination of open surgery and medical treatment. However, it can be challenging to diagnose a tuberculous aneurysm. In this report, we describe a patient with a tuberculous aneurysm who was treated with stent-graft replacement and CT-guided biopsy for diagnosis, followed by nine months of anti-tuberculosis therapy. Despite one week of anti-tuberculous therapy, her fever persisted. A CT scan revealed new, well-defined nodules measuring 1-2mm in the lungs and hepatomegaly, indicating complications of miliary tuberculosis. After three weeks after the CT-guided biopsy, Mycobacterium tuberculosis grew from the arterial wall tissue, leading to the diagnosis of a tuberculous aneurysm complicated by miliary tuberculosis. The patient's aneurysm disappeared on follow-up CT scans, and the patient has been under observation for five years without a relapse. This rare case of tuberculous aneurysm can provide lessons for countries with a low prevalence of tuberculosis. This suggests the possibility of treatment with stent-graft replacement and anti-tuberculous medication and the usefulness of CT-guided biopsy for microbiological and pathological diagnosis.
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BACKGROUND: Older adults are more likely to experience loneliness than younger people. Moreover, greater loneliness in older adults is associated with poor mental health and increased risk of cardiovascular disease and mortality. Physical activity is an effective intervention for reducing loneliness among older adults. Among physical activities, walking is suitable for older adults, because it is easy and safe to incorporate into daily life. We hypothesized that the association between walking and loneliness depends on the presence of others and the number of people present. The aim of this study is to investigate the association between the context of walking (the number of walkers) and loneliness among community-dwelling older adults. METHODS: This cross-sectional study included 173 community-dwelling older adults aged 65 or older. Context of walking was classified as non-walking, walking alone (days of walking alone > days of walking with someone), and walking with someone (days of walking alone ≤ days of walking with someone). Loneliness was measured using the Japanese version of the University of California Los Angeles Loneliness Scale. A linear regression model was used to investigate the relationship between context of walking and loneliness, adjusted for age, sex, living situation, social participation, and physical activity excluding walking. RESULTS: Data from 171 community-dwelling older adults (mean age = 78.0 years, 59.6% women) were analyzed. After adjustment, walking with someone was associated with lower loneliness than non-walking (adjusted ß: -0.51, 95% confidence interval: -1.00, -0.01). CONCLUSIONS: The study's findings suggest that walking with a companion may effectively prevent or reduce loneliness among older adults.
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Vida Independente , Solidão , Humanos , Feminino , Idoso , Masculino , Solidão/psicologia , Estudos Transversais , Exercício Físico , Saúde MentalRESUMO
BACKGROUND: Several studies have investigated post-extraction bleeding in patients on antithrombotic therapy, but most included a small sample size. OBJECTIVE: This study aimed to analyse post-extraction bleeding in patients on antithrombotic therapy using data from a large database. MATERIALS AND METHODS: Claims data of National Health Insurance and Late-Stage Elderly Healthcare System enrollees who underwent tooth extraction between October 2014 and March 2019 (n = 107 767) in a large multiregional cohort study (Longevity Improvement and Fair Evidence study) were included. Antithrombotic therapy was determined based on the drug codes used at the time of tooth extraction (classified into six groups: no antithrombotic, single antiplatelet, dual antiplatelet, Direct Oral Anticoagulant, warfarin and combined antiplatelet and anticoagulant therapies). The outcome was defined as the presence of "post-extraction bleeding" as a receipt disease name in the same month as tooth extraction. To examine the association between antithrombotic therapy and post-extraction bleeding in detail, multiple logistic regression analysis was performed with post-extraction bleeding as the objective variable; each antithrombotic therapy as the explanatory variable; and age, sex and comorbidities as adjustment variables. RESULTS: Antithrombotic therapy was administered in 14 343 patients (13.3%), and post-extraction bleeding was observed in 419 patients (0.4%). The rate of post-extraction bleeding was significantly lower in the no antithrombotic therapy and single antiplatelet groups than that in the other groups (odds ratio: 2.00-9.02). CONCLUSION: The frequency of post-extraction bleeding is high in patients on anticoagulation or dual antithrombotic therapy. Therefore, careful preparation before extraction is necessary in these patients.
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A potato fraction library was constructed to investigate functional secondary metabolites from 8 cultivars: Kitahime, Pilka, Sakurafubuki, Atlantic, Toyoshiro, Snowden, Kitamurasaki, and Northern Ruby, which were divided into flower, leaf, stem, roots, tuber peel, and tuber. Each fraction was a semi-purified extract and about 800 fractions were prepared for the library. They were analyzed by DAD-LC/MS to obtain structural information and were evaluated for various biological activities. LC/MS data showed that each part had a specific characteristic for their constituents supported by principal component analysis (PCA). Approximately 40% of fractions showed significant biological activities at 30 µg/mL, especially the flower fractions showed strong cytotoxicity. PCAs based on the activity and LC/MS data suggested that the strong cytotoxicity of flowers was derived from a complex mixture of potato glycoalkaloids. In addition, tuber peel fractions showed strong antimalarial activity, which had not been reported before. Also, some fractions showed significant antibacterial activities.
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Bibliotecas de Moléculas Pequenas , Solanum tuberosum/metabolismo , Animais , Anti-Infecciosos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular , Cromatografia Líquida/métodos , Humanos , Camundongos , Camundongos Endogâmicos C3H , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Estruturas Vegetais/metabolismo , Análise de Componente Principal , Ratos , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Information on spatiotemporal metabolic behavior is indispensable for a precise understanding of physiological changes and responses, including those of ripening processes and wounding stress, in fruit, but such information is still limited. Here, we visualized the spatial distribution of metabolites within tissue sections of tomato (Solanum lycopersicum L.) fruit using a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) technique combined with a matrix sublimation/recrystallization method. This technique elucidated the unique distribution patterns of more than 30 metabolite-derived ions, including primary and secondary metabolites, simultaneously. To investigate spatiotemporal metabolic alterations during physiological changes at the whole-tissue level, MALDI-MSI was performed using the different ripening phenotypes of mature green and mature red tomato fruits. Although apparent alterations in the localization and intensity of many detected metabolites were not observed between the two tomatoes, the amounts of glutamate and adenosine monophosphate, umami compounds, increased in both mesocarp and locule regions during the ripening process. In contrast, malate, a sour compound, decreased in both regions. MALDI-MSI was also applied to evaluate more local metabolic responses to wounding stress. Accumulations of a glycoalkaloid, tomatine, and a low level of its glycosylated metabolite, esculeoside A, were found in the wound region where cell death had been induced. Their inverse levels were observed in non-wounded regions. Furthermore, the amounts of both compounds differed in the developmental stages. Thus, our MALDI-MSI technique increased the understanding of the physiological changes and responses of tomato fruit through the determination of spatiotemporally resolved metabolic alterations. Graphical abstract á .
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Metaboloma , Metabolômica/métodos , Solanum lycopersicum/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/fisiologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/fisiologiaRESUMO
We propose a long-range three-dimensional (3D) display using a collimated optics with multi-plane configuration. By using a spherical screen and a collimating lens, users observe the collimated image on the spherical screen, which simulates an image plane located at optical infinity. By combining and modulating overlapped multi-plane images, the observed image is located at desired depth position within the volume of multiple planes. The feasibility of the system is demonstrated by an experimental system composed of a planar and a spherical screen with a collimating lens. In addition, accommodation properties of the proposed system are demonstrated according to the depth modulation method.
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Detection of platelet activation in vivo is useful to identify patients at risk of thrombotic diseases. Platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) are used for this purpose; however, they are easily released upon the minimal platelet activation that occurs during sampling. Soluble forms of several platelet membrane proteins are released upon platelet activation; however, the soluble form of C-type lectin-like receptor 2 (sCLEC-2) has not yet been fully investigated. Western blotting with an anti-CLEC-2 antibody showed that sCLEC-2 was released from washed human platelets stimulated with collagen mimetics. To detect sCLEC-2 in plasma, we established a sandwich enzyme-linked immunosorbent assay (ELISA) using F(ab')2 anti-CLEC-2 monoclonal antibodies. Although plasma mixed with citrate, adenosine, theophylline and adenosine (CTAD) is needed for the PF4 and ß-TG assays, effects of anti-coagulants (EDTA, citrate and CTAD) on the sCLEC-2 ELISA were negligible. Moreover, while special techniques are required for blood sampling and sample preparation for PF4 and ß-TG assay, the standard blood collections procedures used in daily clinical laboratory tests have shown to suffice for sCLEC-2 analysis. In this study, we found that two forms of sCLEC-2 are released after platelet activation: a shed fragment and a microparticle-bound full-length protein, both of which are detected by the sCLEC-2 ELISA. The average concentration of sCLEC-2 in the plasma of 10 healthy individuals was 97 ± 55 pg/ml, whereas that in the plasma of 25 patients with diabetes mellitus (DM) was 149 ± 260 pg/ml. A trend towards an increase in sCLEC-2 concentration in the DM patients may reflect in vivo platelet activation in the patients, suggesting that sCLEC-2 may have clinical significance as a biomarker of in vivo platelet activation.
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Lectinas Tipo C/sangue , Glicoproteínas de Membrana/sangue , Biomarcadores , Estudos de Casos e Controles , Diabetes Mellitus/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Humanos , Ativação Plaquetária , Sensibilidade e EspecificidadeRESUMO
The generation of full-parallax and 360-degree three-dimensional (3D) images on a table screen is proposed. The proposed system comprises a small array of high-speed projectors and a rotating screen. Because the screen has a lens function, a large number of viewpoints are generated on a circle when the screen rotates. Thus, 360-degree 3D images having horizontal parallax are generated. Because all projectors are located at different heights from the screen, they generate the viewpoints on a circle at different heights. Therefore, plural viewpoints are aligned in the vertical direction to provide vertical parallax. A prototype display system that employs three high-speed color projectors is constructed.
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Human locomotion is most naturally achieved through walking, which is good for both mental and physical health. To provide a virtual walking experience to seated users, a system utilizing foot vibrations and simulated optical flow was developed. The current study sought to augment this system and examine the effect of an avatar's cast shadow and foot vibrations on the virtual walking experience and cybersickness. The omnidirectional movie and the avatar's walking animation were synchronized, with the cast shadow reflecting the avatar's movement on the ground. Twenty participants were exposed to the virtual walking in six conditions (with/without foot vibrations and no/short/long shadow) and were asked to rate their sense of telepresence, walking experience, and occurrences of cybersickness. Our findings indicate that the synchronized foot vibrations enhanced telepresence as well as self-motion, walking, and leg-action sensations, while also reducing instances of nausea and disorientation sickness. The avatar's cast shadow was found to improve telepresence and leg-action sensation, but had no impact on self-motion and walking sensation. These results suggest that observation of the self-body cast shadow does not directly improve walking sensation, but is effective in enhancing telepresence and leg-action sensation, while foot vibrations are effective in improving telepresence and walking experience and reducing instances of cybersickness.
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AIM: To investigate the association between locomotive syndrome and anemia among community-dwelling older adults. METHODS: This cross-sectional study was conducted at specific health checkup centers in Japan between 2019 and 2020. We sent a questionnaire to older adults aged ≥65 years who participated in health checkups. A total of 2507 community-dwelling older adults were included in this study (mean age = 72.3 years, 51.4% women). Locomotive syndrome was measured using a 25-question Geriatric Locomotive Function Scale with a score range of 0-100, and was defined as ≥16 points. Anemia was defined using World Health Organization criteria, as a hemoglobin concentration of <13.0 g/dL in men and <12.0 g/dL in women. Logistic regression analyses were performed to investigate the association between locomotive syndrome and anemia, adjusted for age, sex, body mass index, depression symptoms, self-reported comorbidities (cancer, rheumatoid arthritis, knee osteoarthritis, fractures, and spinal disease), hypertension, and renal function. RESULTS: Of all the participants, 11.6% had locomotive syndrome and 12.8% had anemia. Even after adjustment, a relationship between locomotive syndrome and anemia was observed (adjusted odds ratio = 1.9, 95% confidence interval = 1.3-2.7). CONCLUSIONS: Community-dwelling older adults with anemia had a significantly higher prevalence of locomotive syndrome than those without. This finding suggests that older adults with anemia are at risk of locomotive syndrome, and appropriate measures should be taken for prevention. Geriatr Gerontol Int 2023; 23: 426-429.
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Anemia , Vida Independente , Masculino , Humanos , Feminino , Idoso , Estudos Transversais , Síndrome , Anemia/epidemiologia , Inquéritos e Questionários , Japão/epidemiologiaRESUMO
An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.
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Neoplasias Brônquicas , Tumor Carcinoide , Feminino , Humanos , Idoso de 80 Anos ou mais , Neoplasias Brônquicas/diagnóstico por imagem , Broncoscopia , Brônquios/patologia , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/cirurgia , BiópsiaRESUMO
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction caused by the fungus Aspergillus, and it is often treated with steroids or antifungal agents. However, long-term use of these medications can lead to infections and drug interactions. We present the case of a 71-year-old woman with ABPA who was diagnosed with hepatitis B and active hepatitis C, and sputum analysis revealed the presence of bacteria. Oral steroids were initially administered, but the patient was switched to mepolizumab because of numerous infectious complications. The early introduction of mepolizumab is effective in patients with ABPA complicated by infectious diseases.
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Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results. Design: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year. Methods: The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study. Results: In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation. Conclusion: This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
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Background: The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure. Methods: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate. Results: Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3-38)], including 27.5% (14/51) in <14 days. Common reasons for failure to proceed to durvalumab were disease progression (2/59, 3.4%) and adverse events (6/59, 10.2%). Among the latter cases, four resumed treatment and proceeded to durvalumab within 42 days on off-protocol. The objective response rate and the disease control rate were 62.7% and 93.2%, respectively. The incidences of ⩾grade 3 pneumonitis, febrile neutropenia, and esophagitis were 0%, 8.5%, and 3.4%, respectively. Conclusion: Regarding durvalumab after CRT, this interim analysis of the SAMURAI study clarified the high transition rate, early introduction, and reasons for failure to proceed to consolidation therapy, which were not determined in the PACIFIC trial. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
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The resolution redistribution (RR) technique can increase the horizontal viewing-zone angle and screen size of electronic holographic display. The present study developed a zone plate method that would reduce hologram calculation time for the RR technique. This method enables calculation of an image displayed on a spatial light modulator by performing additions of the zone plates, while the previous calculation method required performing the Fourier transform twice. The derivation and modeling of the zone plate are shown. In addition, the look-up table approach was introduced for further reduction in computation time. Experimental verification using a holographic display module based on the RR technique is presented.
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A lenticular-type super multi-view (SMV) display normally requires an ultra high-resolution flat-panel display. To reduce this resolution requirement, two or more views are generated around each eye with an interval smaller than the pupil diameter. Cylindrical lenses constituting a lenticular lens project a group of pixels of the flat-panel display to generate a group of viewing zones. Pixel groups generating left and right viewing zones through the same cylindrical lens are partitioned to separate the two zones. The left and right pixel groups for different cylindrical lenses are interlaced horizontally. A prototype SMV display is demonstrated.
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Gráficos por Computador , Terminais de Computador , Apresentação de Dados , Lentes , Iluminação/instrumentação , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
Visual perspective taking is inferring how the world looks to another person. To clarify this process, we investigated whether employing a humanoid avatar as the viewpoint would facilitate an imagined perspective shift in a virtual environment, and which factor of the avatar is effective for the facilitation effect. We used a task that involved reporting how an object looks by a simple direction judgment, either from the avatar's position or from the position of an empty chair. We found that the humanoid avatar's presence improved task performance. Furthermore, the avatar's facilitation effect was observed only when the avatar was facing the visual stimulus to be judged; performance was worse when it faced backwards than when there was only an empty chair facing forwards. This suggests that the avatar does not simply attract spatial attention, but the posture of the avatar is crucial for the facilitation effect. In addition, when the directions of the head and the torso were opposite (i.e., an impossible posture), the avatar's facilitation effect disappeared. Thus, visual perspective taking might not be facilitated by the avatar when its posture is biomechanically impossible because we cannot embody it. Finally, even when the avatar's head of the possible posture was covered with a bucket, the facilitation effect was found with the forward-facing avatar rather than the backward-facing avatar. That is, the head/gaze direction cue, or presumably the belief that the visual stimulus to be judged can be seen by the avatar, was not required. These results suggest that explicit perspective taking is facilitated by embodiment towards humanoid avatars.
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Julgamento , Postura , Desempenho Psicomotor , Tempo de Reação , Processamento Espacial/fisiologia , Realidade Virtual , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Imaginação , Masculino , Adulto JovemRESUMO
AIM: The oral health status of elderly adults has implications for general health problems. Polypharmacy for elderly adults is associated with an increased risk of potentially inappropriate medicines and many adverse drug events; however, no report has shown that polypharmacy itself is associated with complex oral problems. This study aimed to determine the association between polypharmacy and oral health status in patients admitted to the recovery and rehabilitation ward. METHODS: This cross-sectional study included 471 patients (age: 81.9 ± 7.7 years, women: n = 346). Oral health status was measured using the Oral Health Assessment Tool and poor oral health status was defined as a score of ≥3. Cases of patients taking six or more medications were defined as polypharmacy. Logistic regression analysis was performed to examine the relationship between polypharmacy and oral health status. Age, sex, body mass index, number of comorbidities, cognitive and motor functions, and potentially inappropriate medicines were set as confounding factors. RESULTS: Using the Oral Health Assessment Tool, 51.0% (n = 240) of patients scored ≥3. The prevalence of patients with polypharmacy was 56.9% (n = 268). Polypharmacy was significantly associated with poor oral health status (odds ratio = 1.65, 95% confidence interval = 1.14-2.39, P = 0.007; adjusted odds ratio = 1.65, 95% confidence interval = 1.12-2.43, P = 0.011). CONCLUSIONS: This study showed that polypharmacy was associated with poor oral health status. Focusing on the number of medications may be helpful in detecting oral problems. Geriatr Gerontol Int 2021; 21: 66-70.
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Saúde Bucal , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hospitalização , Humanos , Prescrição Inadequada , Lista de Medicamentos Potencialmente InapropriadosRESUMO
BACKGROUND: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study. METHODS: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m2, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate. DISCUSSION: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
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There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC.