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Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, causes severe hepatotoxicity, a severe adverse event associated with the loss of treatment opportunities. We report a case of liver injury (grade 4) during treatment with abemaciclib, in which the patient was switched to palbociclib and successfully treated with this CDK4/6 inhibitor. A 73-year-old woman with bone metastatic breast cancer (hormone-positive, HER2-negative) was treated with abemaciclib, fulvestrant, denosumab, and precipitated calcium carbonate with cholecalciferol and magnesium carbonate (pCCCM). On day 17, the patient developed skin rashes on her trunk and arms. On day 22, abemaciclib and pCCCM were discontinued due to drug eruption. Grade 3 aspartate aminotransferase (AST) and grade 4 alanine aminotransferase (ALT) levels increased on day 29. Therefore, fulvestrant and denosumab were suspended as the causes of severe hepatotoxicity, in addition to the two drugs suspected of causing the skin eruption. On day 43, AST and ALT levels did not improve, and the patient was referred to a hepatologist. The hepatologist diagnosed hepatotoxicity as a drug-induced liver injury through additional tests and interviews. Fulvestrant treatment was resumed on day 78, and palbociclib on day 92, and denosumab and pCCCM on day 134. On day 287, treatment with the CDK4/6 inhibitor was continued without evidence of liver dysfunction. This case suggests that rechallenge with palbociclib after severe liver injury with abemaciclib may allow for continued treatment with CDK4/6 inhibitors.
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Neoplasias de la Mama , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Femenino , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Fulvestrant , Denosumab/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Quinasa 4 Dependiente de la Ciclina/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Quinasa 6 Dependiente de la Ciclina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
We propose an omnidirectional measurement method without blind spots by using a convex mirror, which in principle does not cause chromatic aberration, and by using vertical disparity by installing cameras at the top and bottom of the image. In recent years, there has been significant research in the fields of autonomous cars and robots. In these fields, three-dimensional measurements of the surrounding environment have become indispensable. Depth sensing with cameras is one of the most important sensors for recognizing the surrounding environment. Previous studies have attempted to measure a wide range of areas using fisheye and full spherical panoramic cameras. However, these approaches have limitations such as blind spots and the need for multiple cameras to measure all directions. Therefore, this paper describes a stereo camera system that uses a device capable of taking an omnidirectional image with a single shot, enabling omnidirectional measurement with only two cameras. This achievement was challenging to attain with conventional stereo cameras. The results of experiments confirmed an improvement in accuracy of up to 37.4% compared to previous studies. In addition, the system succeeded in generating depth image that can recognize distances in all directions in a single frame, demonstrating the possibility of omnidirectional measurement with two cameras.
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Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 µg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 µg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores <-0.853. Thus, this score plays a supportive role in evaluating HPA axis function, particularly in patients with borderline cortisol responses to ACTH.
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Insuficiencia Suprarrenal/diagnóstico , Sulfato de Deshidroepiandrosterona/sangre , Hipopituitarismo/diagnóstico , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipopituitarismo/sangre , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: Incorporation of patient-generated health data (PGHD) into clinical research requires an investigation of the validity of outcomes and feasibility of implementation. This single-arm pilot trial investigated the feasibility of using a commercially available activity tracking wearable device in cancer patients to assess adherence to the device and real-time PGHD collection in a clinical research setting. METHODS: From July to November 2017, enrolled adult patients were asked to wear a wristband-style device. Brief Fatigue Inventory (BFI) and MD Anderson Symptom Inventory (MDASI) were assessed at baseline and on day 29. Furthermore, 29-day Pittsburgh Sleep Quality Index, global impression of the devices, and NCI CTCAE v4 were evaluated. RESULTS: Of 30 patients (mean age, 58.6 years; male, 21 [70%]), 15 (50%) and 11 (36.7%) had gastrointestinal and lung cancer, respectively, and 27 (90%, 95% CI: 0.74-0.98) were well adhered (> 70%) to the device for 28 days. The mean adherence was 84.9% (range: 41.7-95.2%). More frequent PGHD synchronization tended to show better device adherence, with moderate correlation (r = 0.62, 95% CI: 0.33-0.80, p < 000.1). CONCLUSIONS: The feasibility of using a wearable activity tracker was confirmed in cancer patients receiving chemotherapy for a month. For future implementation in clinical trials, there is a need for further comprehensive assessment of the validity and reliability of wearable activity trackers. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN: UMIN000027575.
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Actividades Cotidianas , Monitores de Ejercicio/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Cooperación del Paciente/estadística & datos numéricos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Recolección de Datos , Estudios de Factibilidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
The patient was a 56-year-old woman. A modified LSG15(VCAP-AMP-VECP)regimen was initiated as the first-line treatment for acute adult T-cell leukemia/lymphoma. On day 13 from the initiation of the second course of chemotherapy, the onset of hand-foot syndrome(HFS)(hands: Grade 2; feet: Grade 1)occurred. Therefore, the administration of a heparin analog cream and betamethasone butyrate propionate ointment was initiated. On day 20 from the start of the second course of chemotherapy, the foot symptoms improved; however, hand symptoms deteriorated to Grade 3. Frequent use of alcohol-based hand hygiene products is associated with infection prevention during neutropenia, but was likely an exacerbating factor. The symptoms gradually improved after this was taken into consideration, and the usage was discontinued. At the start of the third course, the symptoms had improved to Grade 1, and chemotherapy was continued. On day 11, symptoms worsened(Grade 2). HFS management was performed similar to that in the second course, and symptoms improved again.
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Síndrome Mano-Pie , Leucemia-Linfoma de Células T del Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino , Ciclofosfamida , Doxorrubicina , Etopósido , Femenino , Síndrome Mano-Pie/etiología , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Persona de Mediana Edad , Compuestos de Nitrosourea , Prednisolona , Vincristina , VindesinaRESUMEN
Ten-eleven translocation (TET) methylcytosine dioxygenase has potential as an active eraser to regulate the genomic DNA methylation status. We herein cloned chicken TET (cTET) family genes, and confirmed their functions. Quantitative reverse-transcription PCR showed that cTET1 was strongly expressed in erythrocytes throughout development. This cTET1 expression pattern, together with the results of methylated or hydroxymethylated DNA immunoprecipitation, suggests that cTET1 contributes to demethylation around the promoter region of the definitive-type ß-globin gene ßΑ in erythroid cells. The knockdown of cTET1 in T2ECs chicken erythroid progenitor cells suppressed the induction of ßΑ expression under differentiation conditions. These results suggest that cTET1 plays an important role in erythroid cell differentiation.
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5-Metilcitosina/metabolismo , Pollos/genética , Clonación Molecular , Dioxigenasas/genética , Eritropoyesis , 5-Metilcitosina/análogos & derivados , Animales , Línea Celular , Pollos/fisiología , Metilación de ADN , Dioxigenasas/metabolismo , Células HeLa , Humanos , Familia de Multigenes , Regiones Promotoras Genéticas , Globinas beta/genéticaRESUMEN
Introduction: Hand, foot, and mouth disease generally occurs in children. In rare cases, hand, foot, and mouth disease affects the testicles. Case presentation: A 29-year-old man presented to our emergency department with testicular pain for several days after the onset of hand, foot, and mouth disease. Ultrasonography revealed hypoechoic mass-like areas in the right testis. A mild inflammatory response was noted, tumor markers and urinary data were normal, and tests for infection were all negative. Antibiotics were initiated and ultrasonography was performed in every subsequent examination. Testicular pain disappeared 6 months later. Conclusion: We encountered a rare case of a testicular lesion related to hand, foot, and mouth disease that was successfully treated. The careful selection of treatment for testicular pain and scrotal enlargement in young adult males, such as surgery and symptomatic treatment, based on their medical history and laboratory findings, is important.
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Medium optimization is a crucial step during cell culture for biopharmaceutics and regenerative medicine; however, this step remains challenging, as both media and cells are highly complex systems. Here, we addressed this issue by employing active learning. Specifically, we introduced machine learning to cell culture experiments to optimize culture medium. The cell line HeLa-S3 and the gradient-boosting decision tree algorithm were used to find optimized media as pilot studies. To acquire the training data, cell culture was performed in a large variety of medium combinations. The cellular NAD(P)H abundance, represented as A450, was used to indicate the goodness of culture media. In active learning, regular and time-saving modes were developed using culture data at 168 h and 96 h, respectively. Both modes successfully fine-tuned 29 components to generate a medium for improved cell culture. Intriguingly, the two modes provided different predictions for the concentrations of vitamins and amino acids, and a significant decrease was commonly predicted for fetal bovine serum (FBS) compared to the commercial medium. In addition, active learning-assisted medium optimization significantly increased the cellular concentration of NAD(P)H, an active chemical with a constant abundance in living cells. Our study demonstrated the efficiency and practicality of active learning for medium optimization and provided valuable information for employing machine learning technology in cell biology experiments.
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Técnicas de Cultivo de Célula , NAD , Animales , Medios de Cultivo/química , Línea Celular , Algoritmos , MamíferosRESUMEN
Opioid-induced constipation (OIC), an adverse event that occurs due to opioid analgesics, reportedly causes poor quality of life and adherence to opioid analgesics in patients. Therefore, this issue must be addressed appropriately. Naldemedine (NAL), a peripherally-acting µ-opioid receptor antagonist, is currently recommended for treating OIC when other laxatives are ineffective, but there have been no clinical reports of NAL being used prophylactically for OIC. Therefore, we conducted a retrospective survey of hospitalized patients who received NAL as prophylaxis for OIC with strong opioid analgesics to clarify the reality of this situation and to consider points to be taken into account in its clinical implementation. In this study, 61.7% of the subjects had an Eastern Cooperative Oncology Group performance status score of 3 or higher. The rate of addition of new laxatives and increased laxatives during seven days of NAL prophylaxis was 46.8%, and the rate of diarrhea was 6.1%. This study suggests that patients initiated with strong opioid analgesics during hospitalization often presented with poor performance status, and it is important to pay attention to constipation even under NAL prophylaxis. However, the incidence of diarrhea was low, and the safety of NAL prophylaxis was considered to be good.
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Analgésicos Opioides , Estreñimiento Inducido por Opioides , Humanos , Analgésicos Opioides/efectos adversos , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Laxativos/uso terapéutico , Calidad de Vida , Estudios Retrospectivos , Estreñimiento/inducido químicamente , Estreñimiento/prevención & control , Estreñimiento/tratamiento farmacológico , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/uso terapéutico , Diarrea/inducido químicamenteRESUMEN
Gold nanoparticles (AuNPs) are often used for biosensing. In particular, aptamer-modified AuNPs are often used for colorimetric molecular detection, where target molecule-induced AuNP aggregates can be recognized by a color change from red to blue. However, non-specific aggregation could be induced by various compounds, leading to false-positive results. In this work we employed high-density ssDNA modification on the AuNP surface to prevent non-specific aggregation. The covalently immobilized DNA brush was used as an anchor for an aptamer specific for the target molecule. Herein, as a proof-of-concept study, we demonstrated detection of estradiol (E2), one of the endocrine-disrupting estrogen molecules as a model target, in the presence of antibiotic kanamycin (KN) as a model of co-contaminating compounds that induce non-specific aggregation of AuNPs. We also developed a smartphone dark field microscope (DFM) to visualize AuNP aggregation. Our previous study demonstrated that the observation of light scattering by AuNP aggregates with DFM can be applied for versatile molecular detection. In this work, we could successfully detect E2 with the smartphone DFM, and the results were verified by the results from a conventional benchtop DFM. This study would contribute to the future field applicability of AuNP-based sensors.
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Gold nanoparticles (AuNPs) have been commonly used in molecular sensing, in the form of observation of the color change from red to blue of the AuNP solution, caused by target-molecule-induced AuNP aggregation. In this work, the changes in absorbance and scattering spectra caused by AuNP aggregation were studied using thrombin-induced AuNP aggregation as a model. We demonstrated for the first time that scattering spectra is more sensitive to the changes owing to AuNP aggregation than absorbance spectra. Moreover, a digital color analysis of darkfield images using dark field microscopy (DFM) facilitated a simple method for detection of AuNPs aggregation without the use of spectroscopic analysis. Furthermore, we demonstrated that DFM is useful for detecting AuNPs aggregation in a colored solution, in which the color change by AuNPs aggregation is not visible.