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Alkylamide-substituted [1]benzothieno[3,2-b][1]benzothiophene (BTBT) derivative of BTBT-NHCOC14H29 (1), which has ferroelectric N-H···O= hydrogen-bonding network of alkylamide group and two-dimensional (2D) electric structure of BTBT π-cores, was prepared to design the external electric field-responsive organic semiconductors. The short-chain derivative of BTBT-NHCOC3H7 (1') revealed the coexistence of a 2D electronic band structure based on the herringbone BTBT arrangement and the one-dimensional (1D) hydrogen-bonding chain. 1 formed a smectic E (SmE) liquid crystal phase above 412 K and showed ferroelectric hysteresis in the electric field-polarization (P-E) curves at 403-433 K. The remanent polarization (Pr) and coercive electric field (Ec) of 1 at 408 K, 0.1 Hz were 24.0 µC cm-2 and 5.54 V µm-1, respectively. By thermal annealing of thin-film 1 at 443 K, the molecular assembly structure of 1 changed from a monolayer to a bilayer structure with high crystallinity, resulting in conducting layers of BTBT parallel to the substrate surface. The organic field-effect transistor (OFET) device with thermally annealed thin-film 1 showed p-type semiconducting behavior with the hole mobility of 1.0 × 10-3 cm2 V-1 s-1. Furthermore, device 1 showed switching behavior of semiconducting properties by electric field poling and thermal annealing cycle. The electric field response of ferroelectrics modulated the molecular orientation and conduction properties of organic semiconductors, resulting in external electric field control of carrier transport properties.
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Cultured epidermal autograft, JACE®, was introduced into the Japanese national health insurance system in 2009 and has been used in more than 1000 cases of extensive burns. The aim of this study was to investigate whether the use of JACE® contributes to survival rate in extensive burns. In this study, 119 cases were selected from 3990 cases in Tokyo Burn Unit Association registry data from 2009 to 2023, excluding cases with less than 40% total body surface area, cases of deaths within 4 weeks and cases with unknown length of hospital stay. In total, 25 patients treated with JACE® were selected and matched with another 25 patients who did not receive JACE® using propensity score matching. The results showed that patients treated with JACE® had a significantly higher survival rate than did those who were not treated with JACE® at all time points between 6 and 9 weeks post-injury. In addition, there was no significant difference in length of hospital stay between the groups. These results suggest that the use of JACE® in patients with extensive burns contributes to patient survival and does not prolong hospital stay.
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Queimaduras , Pontuação de Propensão , Sistema de Registros , Transplante de Pele , Humanos , Queimaduras/mortalidade , Queimaduras/terapia , Masculino , Feminino , Sistema de Registros/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Transplante de Pele/métodos , Idoso , Tóquio , Taxa de Sobrevida , Adulto Jovem , Tempo de Internação/estatística & dados numéricos , Autoenxertos , Estudos Retrospectivos , Transplante Autólogo/métodos , Adolescente , Resultado do TratamentoRESUMO
Incisional scarring is a factor of cosmetic appearance evaluated after breast reconstruction, along with the shape, position, and size of the breast. This study aimed to examine the effect of the incision scar location on patient satisfaction after breast reconstruction. Using the Japanese version of the SCAR-Q, we assessed the scar appearance, symptoms and psychosocial effects. Plastic surgeons performed assessments using the Manchester Scar Scale. The patients were divided into two groups: those with scars on the margins of the breast (MB group) and those with scars in the breast area (IB group). The results revealed that patients in the MB group reported significantly higher satisfaction with the scar appearance and psychological impact than those in the IB group. However, assessments using the Manchester Scar Scale did not reveal any significant differences between the two groups. In conclusion, this study underscores the importance of patient-reported outcomes in the evaluation of scar satisfaction after breast reconstruction. Patients tend to prefer and have higher satisfaction with scars along the breast margin, which offers valuable insights into surgical decisions. Further studies with larger and more diverse sample sizes are required for validation.
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Implante Mamário , Neoplasias da Mama , Mamoplastia , Ferida Cirúrgica , Humanos , Feminino , Cicatriz/etiologia , Cicatriz/cirurgia , Neoplasias da Mama/cirurgia , Implante Mamário/métodos , Mama , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Ferida Cirúrgica/cirurgiaRESUMO
BACKGROUND: In oculoplastic surgery, reconstruction of a large defect after the removal of a massive malignant lower lid tumor still represents a unique challenge. We will report on this case, including a presentation of the case using step ladder V-Y advancement flap. METHODS: During November 2018 to March 2023, five patients of lower eyelid malignant tumor had wide resection with safety margin and reconstructed using step ladder V-Y advancement flap. The flap was used step ladder V-Y advancement flap. RESULTS: No complications, including ectropion deformity, occurred. This flap does not sacrifice healthy skin as seen with the cheek rotation flap, and the area of dissection is very small and can be performed in a short time. CONCLUSIONS: Step ladder V-Y advancement flap is highly useful in cases that require a reconstruction of a large defect after the removal of a massive malignant lower lid tumor from viewpoints of operating time, ease of procedure, aesthetics, and complications.
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Blefaroplastia , Neoplasias Palpebrais , Pálpebras , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Humanos , Neoplasias Palpebrais/cirurgia , Masculino , Idoso , Blefaroplastia/métodos , Feminino , Pálpebras/cirurgia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Idoso de 80 Anos ou mais , Carcinoma Basocelular/cirurgiaRESUMO
Despite improvements in treatment methods and outcomes, burns remain one of the principal causes of mortality and morbidity worldwide. Burns involving the hands are estimated to occur in >80% of people with burns. Hand burns have also been associated with long-term social, psychological and physical consequences that can impede a patient's full reintegration to the community and decrease their overall quality of life. Clinically, when the trajectory towards complete re-epithelialisation stalls in deep burn wounds of the hand, skin grafting is indicated, but cosmetic problems often remain. A recent publication highlighted common complications for burns involving the hand such as scar disturbances (26%) and scar contractures (14%). Innovative approaches with the potential to reduce the occurrence of complicating scar disturbances and contractures are sought by healthcare providers specialising in burns. This case report describes a novel approach to wound closure using a topical concentrate of proteolytic enzymes followed by the application of an autologous skin cell suspension. This combination was effective in achieving early and complete re-epithelialisation of a deep burn of the palm of a 28-year-old male patient, while potentially affording a favourable impact on hypertrophic scarring or scar contracture.
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Queimaduras , Cicatriz Hipertrófica , Contratura , Masculino , Humanos , Adulto , Cicatrização , Desbridamento/métodos , Qualidade de Vida , Queimaduras/cirurgia , Transplante de Pele/métodos , Cicatriz Hipertrófica/terapia , Contratura/terapiaRESUMO
Tracheocutaneous fistula and tracheostomy scar are complications associated with the prolonged use of tracheostomy tubes. They have functional and cosmetic problems owing to tracheal tugging during swallowing and easily visible scars. Although many procedures exist to correct this issue, there is no consensus on the optimal surgical technique. Therefore, an ideal surgical procedure was devised. The study was performed on 12 patients between September 2016 and May 2021. All patients had persistent tracheocutaneous fistulas or hypertrophic scars on the neck after tracheostomy. All procedures were performed using a hinged flap and two myocutaneous local flaps. All patients had no complications, and their aesthetics were excellent in postoperative photographs. The scar was better on the straight scar when the flap's skin is denuded than on the VY advancement flap. It should be noted, however, that this procedure can cause the flap to become congested in a short period after head and neck surgery. This procedure is safe, reliable and simple for surgical closure. This was found to produce excellent cosmetic results with no major complications.
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Cicatriz Hipertrófica , Fístula Cutânea , Retalho Miocutâneo , Doenças da Traqueia , Humanos , Traqueostomia/efeitos adversos , Traqueostomia/métodos , Fístula Cutânea/complicações , Doenças da Traqueia/etiologia , Doenças da Traqueia/cirurgiaRESUMO
The grief experienced by bereaved families can lead to positive changes, and its relevance to the emerging concept of posttraumatic growth has been explored. However, studies on survivors bereaved of a spouse by cancer are scarce; consequently, the nature of growth remains poorly understood. This study aimed to explore the growth experiences of survivors bereaved of a spouse by cancer. Based on Merleau-Ponty's theory of the body, we phenomenologically analyzed narratives/qualitative data collected through interviews of 21 survivors bereaved of a spouse by cancer. The assessment of the growth of survivors bereaved of a spouse by cancer began before the bereavement, with the questioning of habits with the living spouse because of illness and prognosis announcement and/or bereavement, reaffirming the connection with the spouse, realizing that it provides emotional support, and becoming accustomed to who they are now in the new environment.
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Negative-pressure wound therapy (NPWT) is often used for skin graft site dressing, and several studies have reported that its use improves skin graft failure in the forearm flap donor site. The present systematic review aimed to evaluate the efficacy of NPWT with skin graft for donor-site closure in radial forearm free flap (RFFF) reconstruction. A systematic search in PubMed, Web of Science, and Cochrane Library databases was conducted. The search terms used for PubMed were ([radial forearm]) AND ([donor]) AND ([negative pressure or vacuum]). This review was registered in the International Prospective Register of Systematic Reviews and performed in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. Three prospective randomised controlled trials and three retrospective comparative studies were included. Compared with conventional bolster dressing, the use of NPWT dressing did not lead to significant improvements in partial skin graft loss, tendon exposure, and other complications. NPWT improved hand functionality earlier; nonetheless, the cost of the device and dressings was a disadvantage. The use of NPWT for skin graft fixation in the RFFF donor site is not generally recommended.
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Retalhos de Tecido Biológico , Tratamento de Ferimentos com Pressão Negativa , Procedimentos de Cirurgia Plástica , Antebraço/cirurgia , Humanos , Estudos Retrospectivos , Transplante de PeleRESUMO
Studies demonstrating the effectiveness of hydrosurgery for chronic wounds are extremely limited. This systematic review aimed to evaluate the efficacy of hydrosurgery compared with conventional debridement in chronic wounds, skin ulcers, and non-acute wounds. This PROSPERO-registered review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A systematic search was performed in PubMed, Scopus, and Cochrane Library databases. Abstracts of all studies were screened independently by two reviewers. The bias of prospective randomised controlled studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias and RevMan 5.4 software, whereas the bias of retrospective comparative studies was evaluated using the Risk of Bias Assessment Tool for Non-randomised Studies. Two prospective randomised controlled trials, two retrospective comparative studies, and three prospective non-comparative studies were included. Hydrosurgery enabled rapid debridement. The Versajet Hydrosurgery System saved 8.87 minutes compared with the conventional methods. Similarly, the debridement quality was high with this system. The debridement number needed to achieve adequate wound beds was fewer in the hydrosurgery group than in the conventional group. These superiorities lead to subsequent success and cost-effectiveness. As there were only two prospective randomised controlled studies, and much information was missing, the risk of bias was unclear. This review confirmed that hydrosurgery is useful for the debridement of chronic wounds, considering the procedural speed and quality.
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Desbridamento , Análise Custo-Benefício , Desbridamento/métodos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , ÁguaRESUMO
Various suture materials have been used for tendon repair. Barbed suture in particular has been demonstrated to be effective for both wound closure and tendon repair. Ten fresh-frozen flexor digitorum profundus tendons of pig were transected and repaired using the two-strand modified Kirchmayr-Kessler technique. The samples were divided into two groups: 4-0 barbed absorbable polyglyconate sutures and 4-0 monofilament absorbable polyglyconate sutures. We measured tensile strength and distance that the testing system pulled the tendon using a universal testing machine. Tensile strength at which 1 and 2 mm of gapping occurred was measured visually at the repair site. Tendons repaired by barbed sutures showed greater tensile strength than monofilament sutures forming still 2-mm gap. However, statistical significance was obtained only at 1-mm gap formation. We concluded that for tendon repair, barbed sutures were superior material to monofilament sutures because of their greater tensile strength, reducing both the initial tendon load and the risk of dehiscence.
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Suturas , Traumatismos dos Tendões/cirurgia , Animais , Polímeros , Técnicas de Sutura/instrumentação , Suturas/normas , Suínos , Tendões/cirurgia , Resistência à TraçãoRESUMO
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis for which an effective therapy remains to be established. This study investigated the therapeutic potential of gene delivery using suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of intracellular signaling pathways, for the treatment of MPM. We infected MPM cells (MESO-4, H28 and H226) with adenovirus-expressing SOCS-1 vector to examine the effect of SOCS-1 overexpression on MPM cells. We evaluated the antitumor effect of SOCS-1 gene delivery combined with cisplatin plus pemetrexed by cell proliferation, apoptosis and invasion assay. We also investigated the regulation of NF-κB and STAT3 signaling related to apoptotic pathways. Furthermore, we evaluated the inhibition of tumor growth by SOCS-1 gene delivery combined with cisplatin plus pemetrexed in vivo. SOCS-1 gene delivery cooperated with cisplatin plus pemetrexed to inhibit cell proliferation, invasiveness and induction of apoptosis in MPM cells. SOCS-1 regulated NF-κB and STAT3 signaling to induce apoptosis in MESO-4 and H226 cells. Furthermore, SOCS-1 gene delivery cooperated with cisplatin plus pemetrexed to regulate NF-κB signaling and significantly inhibit tumor growth of MPM in vivo. These results suggest that SOCS-1 gene delivery has a potent antitumor effect against MPM and a potential for clinical use in combination with cisplatin plus pemetrexed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Proteínas Supressoras da Sinalização de Citocina/genética , Adenoviridae/genética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Terapia Combinada , Ativação Enzimática , Feminino , Expressão Gênica , Terapia Genética , Vetores Genéticos , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Interferon gama/farmacologia , Interferon gama/fisiologia , Mesotelioma/patologia , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , NF-kappa B/metabolismo , Invasividade Neoplásica , Pemetrexede , Neoplasias Pleurais/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Despite the revolutionary effects of imatinib on advanced gastrointestinal stromal tumors (GISTs), most patients eventually develop disease progression following primary resistance or acquired resistance driven by secondary-resistant mutations. Even in radiographically vanishing lesions, pathology has revealed persistent viable cells during imatinib therapy, which could lead to the emergence of drug-resistant clones. To uncover the mechanisms underlying these clinical issues, here we examined imatinib-induced phosphoproteomic alterations in GIST-T1 cells, using our quantitative tyrosine phosphoproteomic analysis method, which combined immunoaffinity enrichment of phosphotyrosine-containing peptides with isobaric tags for relative and absolute quantitation (iTRAQ) technology. Using this approach, we identified 171 tyrosine phosphorylation sites spanning 134 proteins, with 11 proteins exhibiting greater than 1.5-fold increases in tyrosine phosphorylation. Among them, we evaluated FYN and focal adhesion kinase (FAK), both of which are reportedly involved in proliferation and malignant alteration of tumors. We confirmed increased tyrosine phosphorylation of both kinases by western blotting. Inhibition of FYN and FAK phosphorylation each increased tumor cell sensitivity to imatinib. Furthermore, a FAK-selective inhibitor (TAG372) induced apoptosis of imatinib-resistant GIST-T1 cells and decreased the imatinib IC50 . These results indicate that FYN or FAK might be potential therapeutic targets to overcome resistance to imatinib in GISTs. Additionally, we showed that the iTRAQ-based quantitative phosphotyrosine-focused phosphoproteomic approach is a powerful method for screening phosphoproteins associated with drug resistance.
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Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/metabolismo , Fosfoproteínas/análise , Apoptose/efeitos dos fármacos , Benzamidas/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Fosforilação , Fosfotransferases , Piperazinas/administração & dosagem , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/administração & dosagem , Tirosina/metabolismoRESUMO
Lung cancer (LC) is the major cause of death by cancer and the number of LC patients is increasing worldwide. This study investigated the therapeutic potential of gene delivery using suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of intracellular signaling pathways, for the treatment of LC. To examine the antitumor effect of SOCS-1 overexpression on non-small-cell lung cancer (NSCLC) cells, NSCLC cells (A549, LU65, and PC9) were infected with adenovirus-expressing SOCS-1 vector. The cell proliferation assay showed that A549 and LU65, but not PC9, were sensitive to SOCS-1 gene-mediated suppression of cell growth. Although JAK inhibitor I could also inhibit proliferation of A549 and LU65 cells, SOCS-1 gene delivery appeared to be more potent as SOCS-1 could suppress focal adhesion kinase and epidermal growth factor receptor, as well as the JAK/STAT3 signaling pathway. Enhanced phosphorylation of the p53 protein was detected by means of phospho-kinase array in SOCS-1 overexpressed A549 cells compared with control cells, whereas no phosphorylation of p53 was observed when JAK inhibitor I was used. Furthermore, treatment with adenoviral vector AdSOCS-1 in vivo significantly suppressed NSCLC proliferation in a xenograft model. These results suggest that the overexpression of SOCS-1 gene is effective for antitumor therapy by suppressing the JAK/STAT, focal adhesion kinase, and epidermal growth factor receptor signaling pathways and enhancing p53-mediated antitumor activity in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Proteínas Supressoras da Sinalização de Citocina/genética , Adenoviridae/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Transplante de Neoplasias , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Transdução Genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
End-of-life patients with cancer may find expressing their symptoms difficult if they can no longer communicate verbally because of deteriorating health. In this study, we assessed these symptoms using machine learning, which has excellent predictive capabilities and has recently been applied in healthcare. We performed a retrospective clinical survey involving 213 patients with cancer from August 2015 to August 2016. We divided the reported symptoms into two groups-visible and nonvisible symptoms. We used decision tree analysis, an analytical machine learning method that organizes and analyzes information in the form of a tree diagram to visually represent the information structure. Our machine learning model used patient background data and visible symptoms to predict nonvisible symptoms: pain, dyspnea, fatigue, drowsiness, anxiety, delirium, inadequate informed consent, and spiritual issues. The highest and/or lowest values for prediction accuracy, sensitivity, and specificity were 88.0%/55.5%, 84.9%/3.3%, and 96.7%/24.1%, respectively. This work will facilitate better assessment and management of symptoms in patients with cancer. This study was the first to predict nonvisible symptoms using decision tree analyses for patients with cancer receiving palliative care. Notably, applications based on our results may assess symptoms to the same extent as healthcare professionals.
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Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Estudos Retrospectivos , Dor/diagnóstico , Neoplasias/diagnóstico , Neoplasias/terapia , Aprendizado de MáquinaRESUMO
Understanding the formation process of organic-inorganic halide perovskite (OIHP) thin films is important for the fabrication of high-quality thin films, which, in turn, are crucial for achieving high-performance devices. To address this challenge, we developed an in situ system of infrared multiple-angle incidence-resolved spectroscopy (IR-MAIRS) combined with a vacuum deposition system. "Orientation-free" isotropic spectra constructed from IR-MAIRS spectra enable us to perform quantitative analysis of the formation process of C(NH2)3SnI3 (GASnI3) thin films from unreacted C(NH2)3I (guanidine hydroiodide (GAI))/SnI2 bilayer structures predeposited in a vacuum. The analysis of the dependence of the GASnI3 formation rate on the reaction temperature using the Avrami model has revealed that a diffusion-controlled reaction process of GAI and SnI2 governs the formation kinetics. The present study points to the usefulness of in situ IR-MAIRS analysis in understanding the growth mechanisms of vacuum-deposited OIHP thin films and hence the potential to accelerate the development of vacuum processes for the fabrication of high-quality OIHP thin films.
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Tumor-treating fields have potential as minimally invasive cancer treatment. This study aimed to explore the optimum tumor-treating field conditions that minimize unpredicted variations in therapeutic outcomes resulting from differences in cell size and electrical properties. The electric field concentration that induces a dielectrophoretic force near the division plane of a mitotic cell was calculated by finite element analysis for 144 cases, based on different combinations of six noise factors associated with cells and four controllable factors including frequency, as determined by the Taguchi method. Changing the frequency from 200 to 400 kHz strongly increased robustness in producing a dielectrophoretic force, irrespective of noise factors. However, this frequency change reduced the force magnitude, which can be increased by simply applying a higher voltage. Based on additional simulations that considered this trade-off effect, a frequency of 300 kHz is recommended for a robust TTF treatment with allowable variations. The dielectrophoretic force was almost independent of the angle of applied electric field deviated from the most effective direction by ±20 degrees. Furthermore, increased robustness was observed for extracellular fluid with higher conductivity and permittivity. The Taguchi method was useful for identifying robust tumor-treating field therapy conditions from a considerably small number of replicated simulations.
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Terapia por Estimulação Elétrica , Neoplasias/terapia , Terapia por Estimulação Elétrica/métodos , Eletricidade , Humanos , Modelos Biológicos , Razão Sinal-RuídoRESUMO
Background: Following clipping surgery for intracranial aneurysm, computed tomography angiography (CTA) is often used to confirm complete aneurysm obliteration. However, artifacts from the titanium clips usually degrade the images around them. The ultra-high-resolution computed tomography (UHR-CT) system recently became available in clinical practice. Here, we report a case in which CTA using the UHR-CT system successfully pointed out a small aneurysmal remnant after the clipping surgery, which was validated by digital subtraction angiography. Case Description: A patient underwent clipping surgery for an unruptured aneurysm using two titanium alloy clips. CTA using the UHR-CT system demonstrated a small remnant aneurysm. Digital subtraction angiography confirmed the minor remnant. The UHR-CTA images were comparable to three-dimensional reconstructed images from the rotational angiography. Conclusion: We propose that UHR-CTA is a reliable postoperative assessment method for intracranial clipping surgeries.
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The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) is a recently identified fusion-type oncoprotein that exists in approximately 5% of non-small cell lung cancer (NSCLC). It has been demonstrated that NSCLC driven by EML4-ALK is strongly addicted to this fusion-type oncokinase. A clinical trial of crizotinib (PF-02341066) sponsored by Pfizer has proven this oncogene addiction in humans by demonstrating a high response rate to inhibition of ALK kinase activity. In the present study, we report on three cases harboring EML4-ALK rearrangement who were enrolled in the trial (A8081001, NCT00585195). All three patients showed favorable responses to the ALK-specific tyrosine kinase inhibitor.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Adulto , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe , Humanos , Neoplasias Pulmonares/genética , MasculinoRESUMO
Background: The more the cancer treatments progress, the more the needs increase to taper and discontinue opioids in cancer patients. Furthermore, opioid dependence of cancer survivors has become a bigger problem. However, a safe opioid tapering and discontinuation method has not yet been established in cancer patients. Objective: To suggest a safe opioid tapering and discontinuation method in cancer patients. Design: We reviewed opioid type, dose, administration route, administration duration, reason for tapering and discontinuation, and presence/absence of opioid withdrawal symptoms in cancer patients whose opioids needed to be tapered and discontinued. Setting/Subjects: We recruited cancer patients referred to the palliative care team of Kyoto University Hospital-Japan whose opioids were tapered and discontinued. Measurements: Opioid withdrawal symptoms were assessed by two physicians, one nurse, and one pharmacist of palliative care team. Results: Opioids were tapered and discontinued in 25 out of 145 cancer patients (17%). Opioid withdrawal symptoms were observed in 3 of the 25 cases (12%). In withdrawal symptom cases and nonwithdrawal symptom cases, the mean maximum oral morphine-equivalent doses of opioids were 352.0 and 55.7 mg/day, and the mean administration duration of opioid were 82.3 and 28.7 days, respectively. Withdrawal symptoms occurred in patients receiving higher-dose opioids with longer administration duration and their symptoms tended to appear at approximately 10% of the maximum dose. Conclusions: We suggest that withdrawal symptoms may be prevented by using a two-stage method rather than a monotonous tapering method in cancer patients whose higher-dose opioid with longer administration duration needed to be tapered and discontinued.
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BACKGROUND: The subcallosal artery (ScA) is a single dominant artery arising from the anterior communicating artery. Its injury causes amnesia and cognitive disturbance. The conventional computed tomographic angiography (C-CTA) is a common evaluation method of the intracranial artery. However, to image tinny perforating arteries such as the ScA is technically demanding for C-CTA. The purpose of this study is to investigate whether the ultra-high-resolution CTA (UHR-CTA) could image the ScA better than C-CTA. UHR-CTA became available in clinical practice in 2017. Its novel features are the improvement of the detector system and a small X-ray focus. METHODS: Between April 2019 and May 2020, 77 and 49 patients who underwent intracranial UHR-CTA and C-CTA, respectively, were enrolled in this study. Two board-certified neurosurgeons participated as observers to identify the ScA based on UHR-CTA and C-CTA images. RESULTS: UHR-CTA and C-CTA detected the ScA in 56-58% and 30-40% of the patients, respectively. In visualization of the ScA, UHR-CTA was better than C-CTA (P < 0.05, Fisher's exact test). Between the two observers, the Cohen's kappa coefficient was 0.77 for UHR-CTA and 0.78 for C-CTA. CONCLUSIONS: UHR-CTA is a simple and accessible method to evaluate intracranial vasculature. Visualization of the ScA with UHR-CTA was better than that with C-CTA. The high quality of UHR-CTA could provide useful information in the neurosurgery field.