RESUMO
INTRODUCTION: Intermuscular implantations of subcutaneous implantable cardioverter-defibrillators (S-ICD) have been recommended, but the position of the anterior border of the latissimus dorsi muscle (LDM) has not previously been evaluated in establishing an incision line to facilitate the intermuscular approach. The objective of this study is to evalua the position and trend of the anterior border of the LDM in patients who are candidates for implantable cardioverter-defibrillators. METHODS: The distance from the back to the anterior border of the LDM (A) and the anterior-posterior width of the chest wall (B) were measured on computed tomography retrospectively, and the ratio (=A/B) was used as the position of the anterior border of the LDM. In addition, the variability and factors affecting the values were evaluated. RESULTS: An analysis was performed on 78 patients, and the position of the anterior border of the LDM (=A/B) exhibited a normal distribution, with a mean value of 0.53 ± 0.062 (0.41-0.69). The position of the anterior border of the LDM tended to be more anterior in younger, taller, male, primary prevention, nonheart failure, low brain natriuretic peptide level, and nondiabetic patients. CONCLUSION: The position of the anterior border of the LDM varied from case to case with variable results. Conventional incisions on the midaxillary line may be inappropriate for intermuscular implantations, and the position of the anterior border of the LDM should be evaluated in each individual case to establish the incision line.
Assuntos
Desfibriladores Implantáveis , Músculos Superficiais do Dorso , Ferida Cirúrgica , Humanos , Masculino , Músculos Superficiais do Dorso/diagnóstico por imagem , Músculos Superficiais do Dorso/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Implantação de Prótese/efeitos adversos , Implantação de Prótese/métodosRESUMO
BACKGROUND: Lesion gaps assessed by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) are associated with the atrial fibrillation (AF) recurrence after pulmonary vein isolation. Animal studies have demonstrated that the catheter-contact force (CF), stability, and orientation are strongly associated with lesion formation. However, the impact of those procedural factors on the lesion characteristics associated with AF recurrence has not been well discussed. METHODS: A total of 30 patients with paroxysmal AF who underwent catheter ablation were retrospectively enrolled. Radiofrequency (RF) applications were performed with 35 W for 30 s in a point-by-point fashion under esophageal temperature monitoring. The inter-lesion distance was 4 mm. The lesions were visualized by LGE-MRI 3 months postprocedure and assessed by the LGE volume (ml), gap number (GN), and average gap length (AGL [mm]). The gaps were defined as nonenhancement sites of >4 mm. The procedural factors including the catheter-CF, stability, and orientation were calculated on the NavX system. RESULTS: Six (20%) of 30 patients had AF recurrences 12 months postablation. A univariate analysis demonstrated that the AGL was associated with AF recurrence (hazard ratio [HR]: 1.20, confidence interval [CI]: 1.03-1.42, p = .02). All AF recurrence were found in patients with an AGL of >7 mm. The catheter-CF and stability were associated with an AGL of >7 mm, but not the orientation (CF-HR: 0.62, CI: 0.39-0.97, p = .038; stability-HR: 0.8, CI: 0.66-0.98, p = .027). CONCLUSIONS: RF ablation with a low CF and poor catheter stability has a potential risk of creating large lesion gaps associated with AF recurrence.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Meios de Contraste , Gadolínio , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Ablação por Cateter/métodos , Recidiva , Veias Pulmonares/cirurgia , Átrios do Coração , Resultado do TratamentoRESUMO
BACKGROUND: Disseminated nontuberculous mycobacterial (NTM) infection usually occurs in immunodeficient patients, such as those with human immunodeficiency virus infection and idiopathic CD4 lymphopenia. However, disseminated NTM diseases have also been reported in immunocompetent patients. Autoantibodies to interferon-gamma (IFN-γ) are known to be involved in disseminated NTM disease, although anti-IFN-γ antibodies are mainly seen in immunocompetent patients rather than those with immunodeficiency. Here, we report a rare case of disseminated NTM patient with idiopathic CD4 lymphopenia and anti-IFN-γ antibodies. CASE PRESENTATION: A 64-year-old Asian male presented with fever, back pain, anorexia and weight loss. Physical examination revealed subcutaneous masses in the forehead, sternoclavicular joint, and right inguinal region. Computed tomography showed multiple osteosclerotic changes with soft structures and osteolytic changes. Both blood and sputum cultures were positive for Mycobacterium intracellulare, confirming the presence of disseminated NTM infection. Histopathological evaluation of the subcutaneous mass in the right inguinal region showed numerous granulomas consisting of epithelioid cells with Langhans-type giant cells. He was diagnosed with idiopathic CD4 lymphocytopenia. Interestingly, he also had anti-IFN-γ autoantibodies with suppression of IFN-γ-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation. Two-drug combination therapy with clarithromycin and ethambutol was started for the NTM infection, which resulted in a favorable disease course. CONCLUSIONS: In patients with disseminated NTM infection, idiopathic CD4 lymphocytopenia and anti-IFN-γ autoantibody-positive immunodeficiency can be coexisted. It is necessary to clarify the pathogenesis and clinical course of CD4 lymphocytopenic conditions and IFN-γ neutralizing antibody-positive in the disseminated NTM disease.
Assuntos
Linfopenia , Infecções por Mycobacterium não Tuberculosas , Infecções Oportunistas , Doenças da Imunodeficiência Primária , Humanos , Masculino , Pessoa de Meia-Idade , Interferon gama , Anticorpos Neutralizantes , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , AutoanticorposRESUMO
BACKGROUND: The novel coronavirus disease (COVID-19) pandemic emerged in Japan in February 2020, forcing the adoption of online education by university medical schools across Japan. The advantages and disadvantages of online education have been studied in Japan; however, the educational outcome of online classes conducted during the COVID-19 pandemic has not been completely evaluated. In this study, we examined the relationship between lecture format (e.g., face-to-face or online) and performance of third-year university students in their organ-specific cardiovascular course examination. METHODS: This retrospective, nonclinical, and noninterventional comparative educational study included 550 third-year medical students who took a cardiovascular course between April 2018 and May 2022. Cardiovascular coursework was conducted in-person in 2018 and 2019, online in 2020 and 2021, and again in-person in 2022. The course comprised 62 lecture and 2 problem-based learning (PBL) sessions. A quiz was set up in advance on Moodle based on all lectures conducted in 2021 and 2022. A written examination was administered at the end of the course to evaluate the knowledge of students. The student online course evaluation questionnaires were administered in 2020 and 2021. Examination scores and proportion of failures in each year were compared. RESULTS: The mean examination scores were significantly higher in 2021 and 2022 than in 2018, 2019, and 2020 (p < 0.05). Univariate and multivariate analyses adjusted for the class type, online quiz, and PBL revealed that only online quiz was significantly associated with better examination results (p < 0.05). A student course evaluation survey indicated that the online format did not interfere with the students' learning and was beneficial. CONCLUSIONS: The introduction of online classes into medical education due to the COVID-19 pandemic was as effective as face-to-face classes owing to learning management system and other innovations, such as online quizzes. Online education may confer more benefits when provided in a combination with face-to-face learning after COVID-19 pandemic.
Assuntos
COVID-19 , Estudantes de Medicina , Humanos , Pandemias , Japão/epidemiologia , Estudos Retrospectivos , COVID-19/epidemiologia , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The skin overlying cardiovascular implantable electronic devices (CIEDs) sometimes becomes very thin after implantations, which could cause a device erosion. The factors related to the skin thickness of device pockets have not been elucidated. This study aimed to evaluate the skin thickness of CIED pockets and search for the factors associated with the thickness. METHODS: Seventeen skin thickness points around the CIED pocket were measured through ultrasonography in each patient. RESULTS: A total of 101 patients (76 ± 11 years, 26 female) were enrolled. The median duration from the implantation to the examination was 95 months (quartile: 52.5-147.5). The median skin thickness overlying the device was 4.1 mm (3.3-5.9). Patients with heart failure and malignancy had thinner skin overlying the CIED than those without. A significant correlation existed between skin thickness and body mass index (BMI), hemoglobin, serum creatinine, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction. In contrast, age, gender, and device size did not exhibit a significant correlation with skin thickness. A multivariate logistic regression analysis revealed that chronic heart failure and a decrease in the eGFR and BMI were independent predictive factors of "very thin (â¦3.3 mm)" skin of the CIED pocket late after an implantation. CONCLUSION: Aside from a low BMI, the comorbidities (low hemoglobin, heart failure, and renal dysfunction) had a stronger impact on the skin thickness overlying the device than the device size. A careful observation of the device pocket should be performed in patients with those risk factors.
Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Desfibriladores Implantáveis/efeitos adversos , Eletrônica , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Humanos , Marca-Passo Artificial/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role.MethodsâandâResults: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). CONCLUSIONS: Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Caracteres Sexuais , Resultado do Tratamento , Recidiva , Átrios do Coração , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Ablação por Cateter/métodos , Tecido Adiposo/diagnóstico por imagemRESUMO
BACKGROUND: Several algorithms have been proposed for differentiating the right and left outflow tracts (RVOT/LVOT) arrhythmia origins from 12-lead electrocardiograms (ECGs); however, the procedure is complicated. A deep learning (DL) model, a form of artificial intelligence, can directly use ECGs and depict the importance of the leads and waveforms. This study aimed to create a visualized DL model that could classify arrhythmia origins more accurately.MethodsâandâResults: This study enrolled 80 patients who underwent catheter ablation. A convolutional neural network-based model that could classify arrhythmia origins with 12-lead ECGs and visualize the leads that contributed to the diagnosis using a gradient-weighted class activation mapping method was developed. The average prediction results of the origins by the DL model were 89.4% (88.2-90.6) for accuracy and 95.2% (94.3-96.2) for recall, which were significantly better than when a conventional algorithm is used. The ratio of the contribution to the prediction differed between RVOT and LVOT origins. Although leads V1 to V3 and the limb leads had a focused balance in the LVOT group, the contribution ratio of leads aVR, aVL, and aVF was higher in the RVOT group. CONCLUSIONS: This study diagnosed the arrhythmia origins more accurately than the conventional algorithm, and clarified which part of the 12-lead waveforms contributed to the diagnosis. The visualized DL model was convincing and may play a role in understanding the pathogenesis of arrhythmias.
Assuntos
Ablação por Cateter , Aprendizado Profundo , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Inteligência Artificial , Ablação por Cateter/efeitos adversos , Eletrocardiografia/métodos , Ventrículos do Coração , Humanos , Complexos Ventriculares Prematuros/diagnósticoRESUMO
BACKGROUND: A computer simulation model has demonstrated that atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome. METHODS: A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group. RESULTS: Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in seven, AT conversion in eight patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p = .023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients, but AF did not. CONCLUSIONS: FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Simulação por Computador , Meios de Contraste , Estudos de Viabilidade , Gadolínio , Humanos , Pessoa de Meia-Idade , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. OBJECTIVE: The purpose of this study was to evaluate the LGE properties of AF rotors in patients with persistent AF. METHODS: A total of 287 segments in 15 patients with persistent AF (long-standing persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity and the density which was evaluated by the entropy (LGE-entropy) and the volume ratio of the enhancement voxel (LGE-volume ratio), respectively. RESULTS: NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7% and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments; p = .001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of five patients with AF recurrence, NPAs outside the PV antrum were not ablated in three patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. CONCLUSION: AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Meios de Contraste , Gadolínio , Átrios do Coração/cirurgia , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. METHODS: Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. RESULTS: Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (ß = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. CONCLUSION: Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.
Assuntos
Fibrilação Atrial , Remodelamento Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Meios de Contraste , Gadolínio , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Imageamento por Ressonância Magnética , Monócitos , RecidivaRESUMO
BACKGROUND: The left ventricular apex commonly has a paper-thin structure. However, available data about its structure are limited to variable samples, methodologies, and results. OBJECTIVE: To investigate the structural anatomy of the left ventricular apex using living heart datasets with the latest computed tomography scanner. METHODS: One hundred thirty-one consecutive patients (median age, 73 years; 58% men) who underwent cardiac computed tomography were retrospectively analyzed. Patients with severe aortic stenosis were analyzed separately. Thickness and diameters of the thinnest part of the left ventricular apex during mid-diastole were measured using orthogonal multiplanar reconstruction images. The area of thinning was estimated using the formula for the ellipse. RESULTS: In 88 patients without severe aortic stenosis, the median thickness of the thinnest area of the left ventricular apex was only 0.9 mm. Among them, 74%, 99%, and 100% of cases displayed a left ventricular apex thinner than 1.0, 3.0, and 5.0 mm, respectively. The median area of the thinnest region was 5.6 mm2 . In 43 patients with severe aortic stenosis, the median thickness of the thinnest area of the left ventricular apex was 1.2 mm. Among them, 51%, 93%, and 100% of cases displayed a left ventricular apex thinner than 1.0, 3.0, and 5.0 mm, respectively. The median area of the thinnest region was 3.9 mm2 . CONCLUSIONS: Localized thinning of the left ventricular apex is unexceptional, regardless of aortic stenosis with concentric left ventricular hypertrophy, thus highlighting the need for a reappreciation of this feature to avoid inadvertent catastrophic complications.
Assuntos
Cardiopatias/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Feminino , Cardiopatias/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Índice de Gravidade de Doença , Função Ventricular Esquerda , Remodelação Ventricular , Adulto JovemRESUMO
Inflammation has been suggested to play a key role in the pathogenesis of atrial fibrillation (AF). Our hypothesis was that this inflammation, mediated by intermediate monocytes and toll-like receptor 4 (TLR4), causes the formation and expansion of low-voltage zones (LVZs). Prior to ablation, the monocyte subsets of 78 AF patients and TLR4 expression of 66 AF patients were analyzed via a flow cytometric analysis. Based on the CD14/CD16 expression, the monocytes were divided into three subsets: classical, intermediate, and non-classical. At the beginning of the ablation session, voltage mapping was performed. LVZs were defined as all bipolar electrogram amplitudes of < 0.5 mV. Correlations between the flow cytometric analysis results and presence of LVZs, as well as the total area of the LVZ, were examined. Patients with LVZs clearly had a higher proportion of intermediate monocytes (10.0 ± 3.6% vs. 7.2 ± 2.7%, p < 0.001) than those without LVZs. TLR4 was much more frequently expressed in the intermediate monocytes than other two monocyte subsets (p < 0.001). Moreover, the TLR4 expression level in intermediate monocytes correlated positively with the total area of the LVZs (r = 0.267, p = 0.030), especially in patients with paroxysmal AF (r = 0.365, p = 0.015). The intermediate monocytes and TLR4 expression positively correlated with LVZs in AF patients.
Assuntos
Potenciais de Ação , Fibrilação Atrial/sangue , Frequência Cardíaca , Mediadores da Inflamação/sangue , Inflamação/sangue , Monócitos/metabolismo , Receptor 4 Toll-Like/sangue , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Inflamação/diagnóstico , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de IgG/sangueRESUMO
The high rates of mortality and hospitalization among elderly asthmatics, as well as their increasing healthcare costs have become an important public health issue. It would be worthwhile to assess whether inhaled corticosteroid (ICS) can resolve these problems. To explore ICS prescription rates for elderly asthmatics and the factors influencing them and to investigate their association with hospitalization and healthcare costs, we analyzed data from the National Health Insurance Claims Database for the same time frame (December 1 to February 28) across three different periods (2011-2012; 2014-2015; and 2017-2018), from which we identified 6,619, 5,619, and 6,880 elderly individuals, respectively. The prescription rates of ICS increased (52.8%, 65.5% and 68.8%, in the first, second and third survey period, respectively) and inversely the hospital admission rates declined (3.7%, 3.2% and 2.5%, in the first, second and third survey period, respectively). The total healthcare costs per month were significantly lower for patients who received ICS-containing regimens than for those who did not. A multivariate analysis revealed that increasing age, rural residence, receiving a prescription from a clinic, hospital admission, and prescription of asthma medications other than ICS were associated with non-prescription of ICS, whereas cross-boundary treatment increased the ICS-prescription rate. Our study suggests that increases in the prescription rate of ICS are associated with reduced hospital admission rates and lower medical costs in the real-world. ICS prescription rates in rural areas and at clinics, which remain low, need to be increased.
Assuntos
Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Asma/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Administração por Inalação , Corticosteroides/economia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Asma/economia , Análise Custo-Benefício , Bases de Dados Factuais , Quimioterapia Combinada/economia , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Hospitalização/economia , Humanos , Revisão da Utilização de Seguros , Japão/epidemiologia , Masculino , Estudos de Validação como AssuntoRESUMO
Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.
Assuntos
Antígenos de Superfície/metabolismo , Fluorescência , Corantes Fluorescentes/química , Glutamato Carboxipeptidase II/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Antígenos de Superfície/análise , Linhagem Celular Tumoral , Glutamato Carboxipeptidase II/análise , Humanos , Masculino , Estrutura Molecular , Imagem Óptica , Células PC-3 , Neoplasias da Próstata/metabolismo , Proteínas Recombinantes/análise , Proteínas Recombinantes/metabolismo , Espectrometria de Fluorescência , Especificidade por SubstratoRESUMO
Poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood compatibility because of the existence of intermediate water. Various modifications of PMEA by changing its main or side chain's chemical structure allowed tuning of the water content and the blood compatibility of numerous novel polymers. Here, we exploit a possibility of manipulating the surface hydration structure of PMEA by incorporation of small amounts of hydrophobic fluorine groups in MEA polymers using atom-transfer radical polymerization and the (macro) initiator concept. Two kinds of fluorinated MEA polymers with similar molecular weights and the same 5.5 mol % of fluorine content were synthesized using the bromoester of 2,2,3,3,4,4,5,5,6,6,7,7,8,8-pentadecafluoro-1-octanol (F15) and poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) as (macro) initiators, appearing liquid and solid at room temperature, respectively. The fibrinogen adsorption of the two varieties of fluorinated MEA polymers was different, which could not be explained only by the bulk hydration structure. Both polymers show a nanostructured morphology in the hydrated state with different sizes of the features. The measured elastic modulus of the domains appearing in atomic force microscopy and the intermediate water content shed light on the distinct mechanism of blood compatibility. Contact angle measurements reveal the surface hydration dynamics-while in the hydrated state, F15- b-PMEA reorients easily to the surface exposing its PMEA part to the water, the small solid PTFEMA block with high glass-transition temperature suppresses the movement of PTFEMA- b-PMEA and its reconstruction on the surface. These findings illustrate that in order to make a better blood compatible polymer, the chains containing sufficient intermediate water need to be mobile and efficiently oriented to the water surface.
Assuntos
Materiais Biocompatíveis/síntese química , Plaquetas , Fibrinogênio/química , Ácidos Polimetacrílicos/síntese química , Adsorção , Materiais Biocompatíveis/química , Halogenação , Humanos , Nanoestruturas/química , Ácidos Polimetacrílicos/química , Água/químicaRESUMO
It is a long-term goal of cancer diagnosis to develop tumor-imaging techniques that have sufficient specificity and sensitivity to detect small tumor nodules during surgery or endoscopic surgery. Here, we introduce an avidin-conjugated fluorescence probe, Avidin-Leu-HMRG, which consists of a cancer-targeting macromolecule (avidin) and a protease-activatable probe. The conjugate has a high affinity for lectin on cancer cells and undergoes endocytosis, followed by irreversible fluorescence activation due to cleavage by lysosomal leucine aminopeptidase. In a mouse model of peritoneal ovarian metastases, the probe could detect submillimeter-sized tumor nodules with a high S/N ratio at 1â¯h after intraperitoneal injection.
Assuntos
Avidina/química , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Peptídeo Hidrolases/química , Rodaminas/química , Animais , Linhagem Celular Tumoral , Humanos , Lectinas/química , Lectinas/metabolismo , Leucil Aminopeptidase/metabolismo , Camundongos , Microscopia de Fluorescência , Neoplasias Experimentais , Imagem ÓpticaRESUMO
Recently, we and other group have reported that furosemide administration along with hypertonic saline solution enhanced diuretic efficiency of furosemide. However, little is known about factors which associated with high diuretic efficiency by hypertonic saline solution with furosemide therapy. To identify predictors of diuretic efficiency in the hypertonic saline solution with furosemide therapy, we recruited 30 consecutive hospitalized heart failure (HF) patients with volume overload (77 ± 10 years, systolic blood pressure > 90 mmHg, and estimated glomerular filtration rate > 15 ml/min/1.73 m2). Hypertonic saline with furosemide solution, consisting of 500 ml of 1.7% hypertonic saline solution with 40 mg of furosemide, was administered continuously over 24 h. The patients were divided into two groups on the basis of 24-h urine volume (UV) after initiation of diuretic treatment ≥ 2000 ml (high urine volume: HUV) and < 2000 ml (low urine volume: LUV). The basal clinical characteristics of both groups were analyzed and the predictors of HUV after receiving the treatment were identified. There were not significant differences between two groups in baseline clinical characteristics and medication. Univariate logistic analysis revealed that blood urea nitrogen/creatinine ratio, urine urea nitrogen/creatinine ratio (UUN/UCre), fractional excretion of sodium, and tricuspid annular plane systolic excursion positively associated with HUV. Multivariate logistic regression analysis revealed that UUN/UCre at baseline was independently associated with HUV, and UUN/UCre best predicts HUV by the therapy with a cut-off value of 6.16 g/dl/g Cre (AUC 0.910, 95% CI 0.696-0.999, sensitivity 80%, specificity 87%). The Kaplan-Meier curves revealed significant difference for HF rehospitalization and death rate at 180 days between patients with UUN/UCre ≥ 6.16 g/dl/g Cre and those with UUN/UCre < 6.16 g/dl/g Cre (log-rank P = 0.0489). UUN/UCre at baseline strongly predicted of diuretic efficiency in the hypertonic saline solution with furosemide therapy, and was associated with HF prognosis.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Furosemida/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Solução Salina Hipertônica/administração & dosagem , Sódio/urina , Urodinâmica/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Diuréticos/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/urina , Humanos , Infusões Intravenosas , Masculino , Prognóstico , Estudos Retrospectivos , Sístole , UrináliseRESUMO
Symmetrical and unsymmetrical pentacenes carrying two perfluoroalkyl (Rf) chains, at the 6 and 13 positions, were synthesized from easily available pentacene-6,13-quinone via facile three or four step reactions. After extensive evaluation, it was clearly found that the control of both the electron density of the aromatic rings on the pentacene core and molecular alignment in the crystalline state nicely affected their physical properties. Thus, we successfully prove in this article that (1) their anti-oxidation ability was significantly enhanced due to a decrease in the HOMO and LUMO energy and (2) a distinct difference in charge-transporting properties was observed between the symmetrical and unsymmetrical pentacenes.
RESUMO
Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen's kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.
Assuntos
Creatinina/urina , Guias de Prática Clínica como Assunto , Proteinúria/complicações , Proteinúria/urina , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Albuminúria/urina , Diabetes Mellitus/urina , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
A 70-year-old man had developed a high fever and arthralgia in his right elbow 6 months prior. Loxoprofen improved the symptoms temporarily, but arthropathy developed in other joints. Long-term recurrent arthropathy and the fever caused activity reduction and progressive debilitation. We performed fluorine-18 fluorodeoxyglucose-positron emission tomography and detected a positive accumulation in multiple joints and lymph nodes. A lymph node biopsy revealed epithelioid cell granulomas, which, along with elevated angiotensin-converting enzyme levels, led to the diagnosis of sarcoid arthropathy. After prednisolone administration, the fever and arthralgia resolved, and his activities of daily living improved. Clinicians should be aware of this type of sarcoid arthropathy.