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OBJECTIVE: High plasma levels of mono-N-desethylamiodarone (MDEA), an active amiodarone metabolite, may be associated with tissue toxicity in heart failure (patients with heart rhythm disturbances); therefore, a tool that can identify patients for whom therapeutic drug monitoring (TDM) of MDEA is required. This multicenter study aimed to develop a decision tree (DT) model that can identify patients with heart rhythm disturbances at high MDEA concentrations. MATERIALS AND METHODS: A multicenter retrospective cohort study was conducted, including 157 adult patients with heart failure who received oral amiodarone treatment. A χ2 automatic interaction-detection algorithm was used to construct a DT model. In the DT analysis, the dependent variable was set as an MDEA trough plasma concentration of ≥ 0.6 µg/mL during the steady-state period. Explanatory variables were selected as factors with p < 0.05 in multivariate logistic regression analysis. RESULTS: The adjusted odds ratios for the daily dose of amiodarone and body mass index were 1.01 (95% coefficient interval: 1.008 - 1.021, p < 0.001) and 0.91 (95% confidence interval: 0.834 - 0.988, p = 0.025), respectively. For DT analysis, the risk of reaching plasma MDEA concentrations ≥ 0.6 µg/mL was relatively high, combined with a daily dose of amiodarone > 100 mg and body mass index ≤ 22.3 kg/m2 at 69.0% (20/29), and its trend was also detected in the sensitivity analysis. CONCLUSION: Patients taking a daily amiodarone dose > 100 mg and with a body mass index ≤ 22.3 kg/m2 warrant TDM implementation for MDEA to minimize the risk of MDEA-induced tissue toxicity.
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Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Cardíaca , Adulto , Humanos , Estudos Retrospectivos , Volume Sistólico , Creatinina , Função Ventricular Esquerda , Digoxina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Aprendizado de Máquina , Cardiotônicos/efeitos adversosRESUMO
[Purpose] Ankle foot orthosis (AFO) is widely used to regain gait function after injuries and/or stroke; however, limited information is currently available on their effects. We herein examined the effects of three-hour immobilization with AFO on corticospinal excitability and ankle joint movement during gait in healthy volunteers. [Participants and Methods] The participants comprised of seven healthy volunteers. Corticospinal excitability and ankle joint excursions were evaluated before and after three hours of immobilization with left limb AFO. We measured motor evoked potentials in the tibialis anterior (TA) and gastrocnemius (Ga) muscles induced by transcranial magnetic stimulation. In a kinematic analysis, we focused on transition points, such as the timing from dorsiflexion to plantarflexion of the ankle joint and/or vice versa, during gait. [Results] Corticospinal excitability in TA and Ga both significantly decreased. During the normalized gait cycle (GC), ankle angles showed less dorsiflexion at 0% GC and 100% GC, and during loading response and mid-swing and terminal swing phases. Furthermore, less plantarflexion was observed during the initial swing phase. [Conclusion] This study showed that short-term ankle joint immobilization with AFO induces a significant decrease in corticospinal excitability and has an effect on ankle joint excursion during gait. Further studies are needed on the effects of long-term immobilization by AFO.
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Objectives. Thoracic drainage is a common procedure to drain fluid, blood, or air from the pleural cavity. Some attempts to develop approaches to new thoracic drainage systems have been made; however, a simple tube is often currently used. The existing drain presupposes that it is placed correctly and that the tip does not require moving after insertion into the thoracic cavity. However, in some cases, the drain is not correctly placed and reinsertion of an additional drain is required, resulting in significant invasiveness to the patient. Therefore, a more effective drainage system is needed. This study aimed to develop and assess a new thoracic drain via a collaboration between medical and engineering personnel. Methods. We developed the concept of a controllable drain system using magnetic actuation. A dry laboratory trial and accompanying questionnaire assessment were performed by a group of thoracic and general surgeons. Objective mechanical measurements were obtained. Porcine experiments were also carried out. Results. In a dry laboratory trial, use of the controllable drain required significantly less time than that required by replacing the drain. The average satisfaction score of the new drainage system was 4.07 out of 5, indicating that most of the research participants were satisfied with the quality of the drain with a magnetic actuation. During the porcine experiment, the transfer of the tip of the drain was possible inside the thoracic cavity and abdominal cavity. Conclusion. This controllable thoracic drain could reduce the invasiveness for patients requiring thoracic or abdominal cavity drainage.
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Engenharia Biomédica/instrumentação , Tubos Torácicos , Drenagem , Imãs , Animais , Drenagem/instrumentação , Drenagem/métodos , Desenho de Equipamento , Humanos , Cirurgiões , Inquéritos e Questionários , SuínosRESUMO
OBJECTIVES: In recent years, video-assisted thoracoscopic surgery (VATS) has increasingly become the preferred technique for thoracic surgery. However, the inherent characteristics of the lungs as large, soft, slippery, and delicate creates difficulties for pulmonary surgery. In this article, we outline the development and assessment of a balloon-based organ retractor for VATS via collaboration between medical and engineering personnel. METHODS: A dry lab trial and accompanying questionnaire assessment were performed by a group of thoracic surgeons. Objective pressure measurements were obtained, and animal experiment on pigs was performed. RESULTS: In the dry lab trial, use of the developed organ retractor required significantly less time and resulted in fewer difficulties than using a Cherry Dissector. The measured pressure per mm2 of the developed retractor was clearly lower than that for the Cherry Dissector. The questionnaire completed by the surgeons following the dry lab and animal experiments showed that most of the surgeons (7 surgeons out of 9) were satisfied with the quality of the balloon-based retractor based on a score of 3.13 ± 0.28 (mean ± standard deviation) out of 4.0. During the animal experiment, the balloon-based retractor provided stable and clear viewing with minimal need for adjustment. CONCLUSION: This balloon-based retractor could contribute to increased safety and less-invasive VATS.
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Instrumentos Cirúrgicos , Cirurgia Torácica Vídeoassistida/instrumentação , Cirurgia Torácica Vídeoassistida/métodos , Animais , Engenharia Biomédica , Desenho de Equipamento , SuínosRESUMO
Aging often results in a decline in cognitive function, related to alterations in the prefrontal cortex (PFC) activation. Maintenance of this function in an aging society is an important issue. Some practices/drills, moderate exercise, mastication, and a cognitive task itself could enhance cognitive function. In this validation study, before evaluating the effects of some drills on the elderly, we examined the neural substrate of blood oxygenation changes by the use of four cognitive tasks and fNIRS. Seven healthy volunteers (mean age 25.3 years) participated in this study. Each task session was designed in a block manner; 4 periods of rests (30 s) and 3 blocks of four tasks (30 s). The tasks used were: a computerized Stroop test, a Wisconsin Card Sorting Test, a Sternberg working memory paradigm, and a semantic verbal fluency task. The findings of the study are that all four tasks activated PFC to some extent, without laterality except for the verbal fluency task. The results confirm that NIRS is suitable for measurement of blood oxygenation changes in frontal brain areas that are associated with all four cognitive tasks.
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Circulação Cerebrovascular/fisiologia , Cognição/fisiologia , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/metabolismo , Adulto , Mapeamento Encefálico/métodos , Lateralidade Funcional/fisiologia , Humanos , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Semântica , Espectroscopia de Luz Próxima ao Infravermelho , Fala/fisiologia , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. METHODS: We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. RESULTS: The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. CONCLUSION: On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.
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Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Exposição Ocupacional , Material Particulado/análise , Farmacêuticos , Cromatografia Líquida , Monitoramento Ambiental , Japão , Serviço de Farmácia Hospitalar , Espectrometria de Massas em TandemRESUMO
An 82-year-old woman presented with hematochezia and was diagnosed with resectable colon cancer. Laboratory analysis revealed prolonged activated partial thromboplastin time and false-positive reactions in serological tests for syphilis; results that were subsequently found to be caused by the presence of antiphospholipid antibody. Because she had no history of thrombotic events or pregnancy morbidity, she was considered to be an asymptomatic antiphospholipid antibody carrier (aaPL carrier). Throughout the perioperative period, anticoagulation was performed without complications, including thrombosis. aaPL carriers are not uncommon in clinical practice, and the attending gastroenterologist should assess the risk of future thrombotic events and the most effective means of preventing thrombosis. However, there are few evidence-based recommendations for primary thrombosis prevention in aaPL carriers over the long-term and in high-risk periods, such as the perioperative period. Here, we discuss aaPL carrier management with a focus on the perioperative period together with a review of the literature.
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Adenocarcinoma/cirurgia , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Neoplasias do Colo Sigmoide/cirurgia , Trombose/prevenção & controle , Idoso , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Período Perioperatório , Prevenção Primária , Neoplasias do Colo Sigmoide/patologiaRESUMO
We present a rare case of colorectal carcinoma in which hemiparesis was the initial symptom. A 75-year-old woman presented with incomplete left-sided hemiparesis. Brain magnetic resonance imaging(MRI)revealed a 13-mm mass in the right frontal lobe; the mass was resected via craniotomy. Pathological findings, which included the results of immunohistochemical analysis, indicated brain metastasis from colorectal cancer. Colonoscopy revealed advanced colon cancer in the ascending colon, and computed tomography(CT)did not reveal any extracranial metastases. Left-sided hemicolectomy was performed. Whole-brain radiotherapy was scheduled, but before initiation of the therapy, metastases were detected in the neck lymph node and right arm skin, and the brain metastases relapsed. The relapsed brain metastatic lesions were resected, and radiotherapy was administered to the whole brain and the severely painful site of skin metastasis. However, the patient died 201 days after presentation. Historically, systemic chemotherapy was considered ineffective for metastatic brain tumor, and the standard treatments for brain metastasis were surgery and radiotherapy. Although recent advances in systemic chemotherapy for colorectal cancer have resulted in improved patient survival, patients with brain metastases from colorectal cancer still have a poor prognosis. Modern chemotherapeutic agents, including molecularly targeted agents such as bevacizumab, should be validated for the management of brain metastases.
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Neoplasias Encefálicas/secundário , Neoplasias do Colo/patologia , Paresia/etiologia , Idoso , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Colonoscopia , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
A 61-year-old woman presented with fever and was diagnosed with choledocholithiasis, which was removed endoscopically. Incidentally, a markedly elevated serum α-fetoprotein(AFP)level was detected(1,951 ng/mL), but computed tomography( CT)showed only diffuse gallbladder wall thickening. Subsequently, markedly elevated serum AFP-L3 and human chorionic gonadotropin(HCG)levels were detected(99.6%and 2,867mIU/mL, respectively). Fluorodeoxyglucose(FDG)- positron emission tomography/CT demonstrated high FDG uptake only in the gallbladder. Gallbladder cancer was suspected and the patient was scheduled for a cholecystectomy. However, CT just prior to surgery revealed multiple liver metastases. Percutaneous gallbladder biopsy revealed a moderately differentiated adenocarcinoma positive for AFP but not HCG. The patient underwent chemotherapy consisting of gemcitabine and cisplatin. A CT scan obtained 12 weeks later showed disease progression and AFP and HCG levels were found to have increased to 4,021 ng/mL and 66,000mIU/mL, respectively. Although immunohistochemistry of biopsy specimen did not demonstrate HCG production, increased serum HCG level on disease progression definitely suggested HCG production of gallbladder cancer. We believe the biopsy specimen was very small and therefore did not prove HCG production. Gallbladder cancer with simultaneous production of AFP and HCG is rare, and we therefore report this case together with a review of the literature.
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Adenocarcinoma/sangue , Gonadotropina Coriônica/sangue , Neoplasias da Vesícula Biliar/sangue , alfa-Fetoproteínas/análise , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Evolução Fatal , Feminino , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , GencitabinaRESUMO
BACKGROUND: Laryngopharyngeal reflux (LPR) is defined as the retrograde flow of gastric contents up through the esophagus to the larynx and hypopharynx; this is an extra-esophageal manifestation of gastroesophageal reflux disease (GERD). Although both LPR and GERD are caused by reflux of stomach contents, their clinical presentations and treatments differ. PATIENTS AND METHODS: In the present study, we assessed esophago-gastroendoscopic findings related to GERD, specifically endoscopic-positive esophagitis (EE), laryngopharyngeal findings, and GERD symptoms on the 12-question frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Then, independent predictors of EE were analyzed, and relationships among EE, laryngopharyngeal findings, and patients' symptoms and characteristics were investigated. RESULTS: Hiatal hernia (odds ratio [OR]: 2.70; 95% confidence interval [CI]: 1.17-6.23, P-value 0.019) and edema of theinterarytenoid mucosa (OR, 3.77; 95% CI, 1.26-16.3; P-value 0.035) were significantly related with EE and independent predictors of EE. However, patients' characteristics and the FSSG score had no significant relationship with EE; there was no relationship between patients' characteristics and EE, regardless of its severity. CONCLUSIONS: Although LPR symptoms had no significant relationship with the findings of EE, hiatal hernia and edema of the interarytenoid mucosa were significantly related with EE and were considered to be independent predictors of EE.
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Edema/epidemiologia , Edema/patologia , Esofagite/diagnóstico , Esofagite/epidemiologia , Mucosa Laríngea/patologia , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Causalidade , Comorbidade , Diagnóstico Diferencial , Endoscopia , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Hérnia Hiatal/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.
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Malignant lymphoma sometimes originates from extranodal sites; however, the uterus has rarely been reported as the site of the primary lesion. We present a patient with malignant lymphoma of the uterus complicating bilateral hydronephrosis. A 67-year-old previously healthy woman was seen at a clinic because of massive genital bleeding. She was referred to our hospital for further examination of a uterine tumor. Computed tomography scans revealed a pelvic tumor invading to the retroperitoneal region, which caused bilateral obstruction of the ureters and hydronephrosis. No lymph node swelling was detected. Magnetic resonance imaging showed a bulky uterine tumor that was homogenously low on T1-weighted imaging and isointense on T2-weighted imaging, while the endometrium was intact. A pathological examination of the biopsy specimen from the uterine cervix revealed diffuse infiltration of CD20-positive atypical large lymphoid cells, which was compatible with diffuse large B-cell lymphoma (DLBCL). Since the tumor expanded from the uterus and no other abnormal lesion was observed in imaging studies including gallium scintigraphy, a diagnosis of DLBCL of the uterus, clinical stage IE was made. The patient received six cycles of rituximab plus CHOP chemotherapy followed by involved field irradiation. She achieved complete remission and has been alive for more than two years without relapse.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidronefrose/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Uterinas/etiologia , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Feminino , Humanos , Hidronefrose/complicações , Hidronefrose/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Rituximab , Neoplasias Uterinas/patologiaRESUMO
Six years have passed since the introduction of legislation mandating at least 1 year of clinical training for those who have passed the national dentist examination. To determine whether clinical training has been appropriately implemented at the General Dentistry Department of Tokyo Dental College Chiba Hospital, a managed-type clinical training facility, the number of patients treated and types of dental and dental technical work performed by dental residents trained by the department were summarized and analyzed. The number of patients treated per dental resident increased from 11 in 2006 to 15 in 2011. By treatment type, periodontic treatment was the most frequently performed throughout the study period, followed by endodontic treatment. Conservation treatment, prosthodontic treatment with crowns/bridges, and prosthodontic treatment with dentures were performed at a similar moderate frequency, while oral surgical treatment was performed least frequently throughout the study period. The frequency of periodontic treatment increased slightly, whereas that of endodontic treatment decreased slightly or remained almost unchanged after introduction of the mandatory clinical training system. When the distribution of dental treatment performed at our department was compared with that of dental treatment performed by general dentists across Japan in 2011, our department showed a slightly lower frequency of periodontic treatment and higher frequency of endodontic treatment than the national total, whereas the frequency of other types of treatment was similar between the two populations. These results demonstrated that appropriate clinical training has been provided by our department to meet the purpose of offering dentists the opportunity to acquire the basic diagnostic and treatment abilities that would enable them to provide appropriate treatment for injuries and diseases frequently encountered in daily practice. The study also revealed some problems, such as a decreasing number of residents engaging in dental technical work each year. For additional improvement in the quality of dental clinical training, more analyses are needed to further identify and address potential problems in the system.
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Assistência Odontológica/estatística & dados numéricos , Educação em Odontologia/estatística & dados numéricos , Hospitais de Ensino , Internato e Residência/estatística & dados numéricos , Programas Obrigatórios , Faculdades de Odontologia , Estudantes de Odontologia/estatística & dados numéricos , Coroas/estatística & dados numéricos , Profilaxia Dentária/estatística & dados numéricos , Restauração Dentária Permanente/estatística & dados numéricos , Prótese Total/estatística & dados numéricos , Prótese Parcial/estatística & dados numéricos , Educação em Odontologia/legislação & jurisprudência , Odontologia Geral/estatística & dados numéricos , Humanos , Internato e Residência/legislação & jurisprudência , Programas Obrigatórios/legislação & jurisprudência , Procedimentos Cirúrgicos Bucais/estatística & dados numéricos , Pacientes/estatística & dados numéricos , Doenças Periodontais/terapia , Tratamento do Canal Radicular/estatística & dados numéricos , Tecnologia Odontológica/estatística & dados numéricos , TóquioRESUMO
Gadolinium ethoxybenzyl diethylenetriamine pantaacetic acid (Gd-EOB-DTPA) is incorporated into liver cells, and liver parenchyma show hyperintensity due to the T1 shortening effect. The T1 value of liver parenchyma in the hepatocyte phase changes from the pre-contrast phase. However, in patients with liver dysfunction, the difference of T1 value is generally small. In examination of hepatic disease, the optimal flip angle should be selected according to the patient's state. The definition of hepatic dysfunction based on biochemical data is diverse. Therefore, if the image findings can estimate liver dysfunction, the operator will select the optimal flip angle. Hence, we defined the criteria of liver dysfunction based on the image data; one or more of the following abnormalities-irregular liver surface, splenomegaly, and expansion of portal trunk. In classification by imaging data, we compared the T1 value of liver parenchyma in the hepatocyte phase, and found that the T1 value was significantly different between normal and cirrhotic liver. Then, in a phantom study simulating normal and cirrhotic liver, we set the optimal flip angle (FA)-21 degrees for the normal liver state, and 18 degrees for the LC state. In Gd-EOB-DTPA-enhanced study, the operator can select the optimal FA for each patient according to the image findings.
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Gadolínio DTPA , Hepatócitos/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cirrose Hepática/diagnóstico , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Imagens de FantasmasRESUMO
BACKGROUND: Polypharmacy, defined as the concurrent use of over six drugs, is common in the treatment of heart failure (HF); however, unpredictable drug interactions with bepridil may occur. In this study, we have elucidated the influence of polypharmacy on plasma bepridil concentrations in patients with HF. METHODS: We conducted a multicenter retrospective study involving 359 adult patients with HF who received oral bepridil. Because QT prolongation is an adverse effect following plasma bepridil concentrations ≥800 ng/mL, the risk factors for patients achieving these concentrations at steady state were elucidated via multivariate logistic regression. The correlation between bepridil dose and plasma concentration was examined. The effect of polypharmacy on the value of the concentration-to-dose (C/D) ratio was investigated. RESULTS: A significant relationship was observed between bepridil dose and plasma concentration (p < 0.001), and the intensity of the correlation was moderate (r = 0.503). Based on multivariate logistic regression, the adjusted odds ratios for a daily dose of bepridil ≥1.6 mg/kg, polypharmacy, and concomitant of aprindine, a cytochrome P450 2D6 inhibitor, were 6.82 (95% coefficient interval: 2.104-22.132, p = 0.001), 2.96 (95% coefficient interval: 1.014-8.643, p = 0.047), and 8.63 (95% coefficient interval: 1.684-44.215, p = 0.010), respectively. Despite the moderate correlation in non-polypharmacy, the correlation was not observed in polypharmacy. Therefore, inhibiting metabolism, along with other mechanisms, may contribute to the polypharmacy-induced increase in plasma bepridil concentrations. Moreover, the C/D ratios in the groups receiving 6-9 and 10≤ concomitant drugs were 1.28- and 1.70-fold higher than in those receiving <6 drugs, respectively. CONCLUSIONS: Plasma bepridil concentrations may be influenced by polypharmacy. Moreover, the plasma bepridil concentration increased in correlation with the number of concomitant drugs used. Although the mechanism of this increase could not be determined, plasma bepridil concentrations should be periodically monitored for safe use in patients with HF. TRIAL REGISTRATION: Retrospectively registered.
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PURPOSE: Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer. PATIENTS AND METHODS: We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment. RESULTS: A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p = 0.007), and a smoking history (OR, 0.1; p = 0.03) were significant risk factors for early death. CONCLUSION: Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Proteína C-Reativa , Neoplasias Hepáticas/secundárioRESUMO
BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. METHODOLOGY: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. RESULTS: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. CONCLUSIONS: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.
Assuntos
Adenocarcinoma/cirurgia , Dissecação/métodos , Mucosa Gástrica/cirurgia , Gastroscopia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecação/efeitos adversos , Dissecação/instrumentação , Desenho de Equipamento , Feminino , Mucosa Gástrica/patologia , Gastroscopia/efeitos adversos , Gastroscopia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/patologia , Equipamentos Cirúrgicos , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
S-1 and capecitabine are orally administered fluoropyridines reported to be effective in the treatment of advanced gastric cancer(AGC). In fact, both S-1/CDDP and capecitabine/CDDP are considered to be the standard first-line treatments for AGC.However, no information concerning on the activity of capecitabine in S-1-pretreated patients with AGC has been reported. Here, we present a case of recurrent gastric cancer that showed a partial response resulting in 6 months of progres-sion-free survival, thanks to capecitabine/CDDP after the failure of multiple anticancer drugs such as S-1/CDDP. S -1 and capecitabine may exhibit cross-resistance because they both have the same final active metabolite: 5-fluorouracil(5-FU). Dihydropyrimidine dehydrogenase(DPD)is the rate-limiting enzyme in the degradation of 5-FU, and S-1 contains the inhibitor of DPD. Thus, S-1, but not capecitabine, is active against tumors with high DPD expression. On the other hand, capecitabine is activated to 5-FU by thymidine phosphorylase(TP)within the tumor tissue and is more effective against tumors with high TP expression. The present case suggests that S-1 and capecitabine do not always exhibit cross-resistance, and that capecitabine may be effective in S-1-pretreated patients with AGC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Combinação de Medicamentos , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Ácido Oxônico/administração & dosagem , Recidiva , Terapia de Salvação , Tegafur/administração & dosagemRESUMO
RATIONALE: Mycobacterium peregrinum is a member of the group of rapidly growing nontuberculous mycobacteria. It mainly causes surgical site and catheter-related infections, while pulmonary infection is rare. We herein present a case of pulmonary infection caused by M peregrinum. PATIENT CONCERNS: A 62-year-old woman visited our hospital with dyspnea and was admitted for the treatment of pneumonia in July 2018. DIAGNOSIS: Chest computed tomography showed patchy opacities and consolidation in the bilateral lungs and a cavity in the right upper lobe, which persisted after the treatment of bacterial pneumonia 5 years ago. She was administered ceftriaxone and azithromycin. Consolidation in the bilateral lungs improved, whereas the cavity in the right upper lobe remained and the consolidation surrounding it gradually spread. On admission, the sputum acid-fast bacillus culture was positive, and M peregrinum was identified twice by mass spectrometry. The cavity and consolidation surrounding it were diagnosed as pulmonary mycobacteriosis caused by M peregrinum. INTERVENTIONS: Although we recommended treatment for mycobacteriosis, the patient refused it. OUTCOMES: The patient is regularly followed up; however, the cavity wall is thickening and shadows have become mildly enhanced over the course of 3 years. LESSONS: We herein present a rare case of pulmonary mycobacteriosis caused by M peregrinum and discuss the literature. Since limited information is currently available on pulmonary mycobacteriosis caused by M peregrinum, the accumulation of further case reports and the clarification of its clinical features are needed.