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L-theanine, an amino acid component of the tea leaves of Camellia sinensis, is sold in Japan as a supplement for good sleep. Although several studies in humans and mice have reported the effects of L-theanine on brain function, only a few reports have comprehensively clarified the disposition of theanine administered to mice and its effects on concentrations of other blood amino acids. In this study, we aimed to determine the changes in the blood levels of L-theanine administered to mice and amino acid composition of the serum. L-theanine were administered to four-week-old Std-ddY male mice orally or via tail vein injection. L-theanine and other amino acids in serum prepared from blood collected at different time points post-dose were labeled with phenylisothiocyanate and quantified. The serum concentration of orally administered L-theanine peaked 15 min after administration. The area under the curve for tail vein injection revealed the bioavailability of L- theanine to be approximately 70%. L-theanine administration did not affect any amino acid levels in the serum, but a significant increase in the peak area overlapping the Glycine (Gly) peak was observed 30 min after administration. L-theanine administered to mice was rapidly absorbed and eliminated, suggesting that taking L-theanine as a supplement is safe without affecting its own levels or serum levels of other amino acids. However, considering that Gly, similar to L-theanine, is used as a dietary supplement for its anxiolytic effects and to improve sleep, determining the effects of L-theanine administration on Gly is important and needs further research.
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Aminoácidos , Fabaceae , Humanos , Camundongos , Masculino , Animais , Glicina , Glutamatos , Disponibilidade BiológicaRESUMO
BACKGROUND: For pharmacists expected to encounter the deaths of many of their patients in the near future, it is important to understand the perception of a "good death" for patients with cancer who are likely to be aware of the circumstances of their poor prognosis. In this study, we clarified pharmacists' perceptions of a "good death" and considered the differences in perception among patients with cancer, oncologists, and oncology nurses. METHODS: From April to June 2022, an anonymous questionnaire survey was conducted on pharmacists working in hospitals and pharmacies and on members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. The questionnaire consisted of 57 questions, called attributes, developed by Miyashita et al. to investigate the perception of "good death" in Japanese cancer medicine. The importance of those attributes was investigated using a 7-point Likert scale. RESULTS: Three thousand four hundred thirty-two pharmacists were made aware of this survey, and 207 participated in the survey. The responses of pharmacists to the 57 questions were very similar to those of the oncologists. Among them, "Fighting against disease until one's last moment" and "Not making trouble for others" had very low importance, which was the most significantly different from the responses of patients with cancer. "Fighting against disease until one's last moment" tended to be significantly underestimated by pharmacists engaged in patient guidance and interview compared to that by pharmacists not engaged in the duty (p = 0.02). Also, when we compared pharmacists with or without qualifications related to cancer and palliative care, there was no significant difference in the importance of "Fighting against disease until one's last moment." However, the importance of "Not making trouble for others" for qualified pharmacists was significantly underestimated (p = 0.04). CONCLUSION: Since pharmacists understand the limits of chemotherapy, they may want to be close to the patient but may not strongly agree with the "Fighting against cancer" component that patients with cancer prefer. It may be necessary to reconsider better ways of approaching the wishes and satisfaction of patients with cancer under the care of medical professionals in the field of oncology.
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OBJECTIVES: We aimed to investigate the protective effect of remote ischemic preconditioning against spinal cord ischemia and find a clue to its mechanism by measuring glutamate concentrations in the spinal ventral horn. METHODS: Male Sprague-Dawley rats were divided into 5 groups (n = 6 in each group) as follows: sham; SCI (only spinal cord ischemia); RIPC/SCI (perform remote ischemic preconditioning before spinal cord ischemia); MK-801/RIPC/SCI (administer MK-801, N-methyl-D-aspartate receptor antagonist, before remote ischemic preconditioning); and MK-801/SCI (administer MK-801 without remote ischemic preconditioning). Remote ischemic preconditioning was achieved by brief limb ischemia 80 minutes before spinal cord ischemia. MK-801 (1 mg/kg, intravenous) was administered 60 minutes before remote ischemic preconditioning. The glutamate concentration in the ventral horn was measured by microdialysis for 130 minutes after spinal cord ischemia. Immunofluorescence was also performed to evaluate the expression of N-methyl-D-aspartate receptor 2B subunit in the ventral horn 130 minutes after spinal cord ischemia. RESULTS: The glutamate concentrations in the spinal cord ischemia group were significantly higher than in the sham group at all time points (P < .01). Remote ischemic preconditioning attenuated the spinal cord ischemia-induced glutamate increase. When MK-801 was preadministered before remote ischemic preconditioning, glutamate concentration was increased after spinal cord ischemia (P < .01). Immunofluorescence showed that remote ischemic preconditioning prevented the increase in the expression of N-methyl-D-aspartate receptor 2B subunit on the surface of motor neurons (P = .047). CONCLUSIONS: Our results showed that remote ischemic preconditioning prevented spinal cord ischemia-induced extracellular glutamate increase in ventral horn and suppressed N-methyl-D-aspartate receptor 2B subunit expression.
Assuntos
Maleato de Dizocilpina/farmacologia , Ácido Glutâmico/análise , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão , Isquemia do Cordão Espinal , Medula Espinal/irrigação sanguínea , Animais , Células do Corno Anterior/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Isquemia do Cordão Espinal/metabolismo , Isquemia do Cordão Espinal/prevenção & controle , Resultado do TratamentoRESUMO
OBJECTIVE: This experimental study aimed to assess the efficacy of hydrogen gas inhalation against spinal cord ischemia-reperfusion injury and reveal its mechanism by measuring glutamate concentration in the ventral horn using an in vivo microdialysis method. METHODS: Male Sprague-Dawley rats were divided into the following 6 groups: sham, only spinal ischemia, 3% hydrogen gas (spinal ischemia + 3% hydrogen gas), 2% hydrogen gas (spinal ischemia + 2% hydrogen gas), 1% hydrogen gas (spinal ischemia + 1% hydrogen gas), and hydrogen gas dihydrokainate (spinal ischemia + dihydrokainate [selective inhibitor of glutamate transporter-1] + 3% hydrogen gas). Hydrogen gas inhalation was initiated 10 minutes before the ischemia. For the hydrogen gas dihydrokainate group, glutamate transporter-1 inhibitor was administered 20 minutes before the ischemia. Immunofluorescence was performed to assess the expression of glutamate transporter-1 in the ventral horn. RESULTS: The increase in extracellular glutamate induced by spinal ischemia was significantly suppressed by 3% hydrogen gas inhalation (P < .05). This effect was produced in increasing order: 1%, 2%, and 3%. Conversely, the preadministration of glutamate transporter-1 inhibitor diminished the suppression of spinal ischemia-induced glutamate increase observed during the inhalation of 3% hydrogen gas. Immunofluorescence indicated the expression of glutamate transporter-1 in the spinal ischemia group was significantly decreased compared with the sham group, which was attenuated by 3% hydrogen gas inhalation (P < .05). CONCLUSIONS: Our study demonstrated hydrogen gas inhalation exhibits a protective and concentration-dependent effect against spinal ischemic injury, and glutamate transporter-1 has an important role in the protective effects against spinal cord injury.
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Traumatismo por Reperfusão , Isquemia do Cordão Espinal , Animais , Masculino , Ratos , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Modelos Animais de Doenças , Glutamatos/metabolismo , Hidrogênio/farmacologia , Isquemia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Isquemia do Cordão Espinal/prevenção & controle , Isquemia do Cordão Espinal/metabolismoRESUMO
BACKGROUND: The present study aimed to evaluate the reliability of hemodynamic changes induced by lung recruitment maneuver (LRM) in predicting stroke volume (SV) increase after fluid loading (FL) in prone position. METHODS: Thirty patients undergoing spine surgery in prone position were enrolled. Lung-protective ventilation (tidal volume, 6-7 mL/kg; positive end-expiratory pressure, 5 cmH2O) was provided to all patients. LRM (30 cmH2O for 30 s) was performed. Hemodynamic variables including mean arterial pressure (MAP), heart rate, SV, SV variation (SVV), and pulse pressure variation (PPV) were simultaneously recorded before, during, and at 5 min after LRM and after FL (250 mL in 10 min). Receiver operating characteristic curves were generated to evaluate the predictability of SVV, PPV, and SV decrease by LRM (ΔSVLRM) for SV responders (SV increase after FL > 10%). The gray zone approach was applied for ΔSVLRM. RESULTS: Areas under the curve (AUCs) for ΔSVLRM, SVV, and PPV to predict SV responders were 0.778 (95% confidence interval: 0.590-0.909), 0.563 (0.371-0.743), and 0.502 (0.315-0.689), respectively. The optimal threshold for ΔSVLRM was 30% (sensitivity, 92.3%; specificity, 70.6%). With the gray zone approach, the inconclusive values ranged 25 to 75% for ΔSVLRM (including 50% of enrolled patients). CONCLUSION: In prone position, LRM-induced SV decrease predicted SV increase after FL with higher reliability than traditional dynamic indices. On the other hand, considering the relatively large gray zone in this study, future research is needed to further improve the clinical significance. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000027966 . Registered 28th June 2017.
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Hidratação/métodos , Cuidados Intraoperatórios/métodos , Respiração com Pressão Positiva/métodos , Fenômenos Fisiológicos Respiratórios , Coluna Vertebral/cirurgia , Volume Sistólico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Decúbito Ventral , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND AIM: Prophylactic clipping (PC) after polypectomy has the potential to prevent post-polypectomy bleeding (PPB). We aimed to evaluate the effectiveness of PC in preventing PPB for < 20-mm polyps. METHODS: This multicenter, open-label, randomized controlled trial conducted from December 2013 to June 2017 at 10 institutions randomly assigned 1080 patients with < 20-mm colon polyps to the non-PC and PC groups. Allocation factors were institution, antiplatelet drug use, and polyp number. The primary endpoint was differences in PPB rates between the groups. The severity of PPB and post-procedural abdominal symptoms were also investigated. These endpoints in intention-to-treat and per-protocol (PP) analyses were evaluated. RESULTS: We investigated 1039 patients with 2960 lesions. There was no significant difference between the groups in characteristics including age, sex, hypertension, diabetes, hyperlipidemia, antiplatelet drug use, and lesion characteristics such as type and size. Excluding the clip used in the non-PC group, intraoperative bleeding, and deviation of protocol, 903 patients were investigated in PP analysis. There was no significant difference in the PPB rate between the non-PC and PC groups (2.7% vs 2.3%, P = 0.6973 [intention-to-treat analysis]; 3.0 vs 2.4%, P = 0.7353 [PP analysis]). Severe PPB (≥ grade 3) was similar between the groups. Total procedure time was significantly shorter in the non-PC group than in the PC group (31 vs 36 min, P = 0.0002). Post-procedural abdominal fullness was less common in the non-PC group than in the PC group (20.8% vs 25.6%, P = 0.0833). CONCLUSION: Prophylactic clipping is not effective in preventing PBB for < 20-mm colon polyps (UMIN000012163).
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Pólipos do Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Instrumentos Cirúrgicos , Idoso , Pólipos do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the effect of systemic vascular resistance (SVR) on the reliability of the ClearSight system (Edwards Lifesciences, Irvine, CA) for measuring blood pressure (BP) and cardiac output (CO). DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BP, measured using ClearSight and an arterial line, and CO, measured using ClearSight and a pulmonary artery catheter, were recorded before (T1) and two minutes after phenylephrine or ephedrine administration. Bland-Altman analysis was used to compare BP and CO measurements at T1. A polar plot was used to assess trending abilities. Patients were divided into the following three groups according to the SVR index (SVRI) at T1: low (<1,200 dyne s/cm5/m2), normal (1,200-25,00 dyne s/cm5/m2), and high (>2,500 dyne s/cm5/m2). The bias in BP and CO was -4.8 ± 8.9 mmHg and 0.10 ± 0.81 L/min, respectively, which was correlated significantly with SVRI (p < 0.05). The percentage error in CO was 40.6%, which was lower in the normal SVRI group (33.3%) than the low and high groups (46.3% and 47.7%, respectively). The angular concordance rate was 96.3% and 95.4% for BP and 87.0% and 92.5% for CO after phenylephrine and ephedrine administration, respectively. There was a low tracking ability for CO changes after phenylephrine administration in the low-SVRI group (angular concordance rate 33.3%). CONCLUSION: The ClearSight system showed an acceptable accuracy in measuring BP and tracking BP changes in various SVR states; however, the accuracy of CO measurement and its trending ability in various SVR states was poor.
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Procedimentos Cirúrgicos Cardíacos , Monitorização Hemodinâmica , Débito Cardíaco , Humanos , Monitorização Intraoperatória , Reprodutibilidade dos Testes , Termodiluição , Resistência VascularRESUMO
BACKGROUND: Transthoracic oesophagectomy is associated with major morbidity and mortality, which may be reduced by goal-directed therapy (GDT). The aim of this multicentre, RCT was to evaluate the impact of intraoperative GDT on major morbidity and mortality in patients undergoing transthoracic oesophagectomy. METHODS: Adult patients undergoing transthoracic oesophagectomy were randomised to receive either minimally invasive intraoperative GDT (stroke volume variation <8%, plus systolic BP maintained >90 mm Hg by pressors as necessary) or haemodynamic management left to the discretion of attending senior anaesthetists (control group; systolic BP >90 mm Hg alone). The primary outcome was the incidence of death or major complications (reoperation for bleeding, anastomotic leakage, pneumonia, reintubation, >48 h ventilation). A Cox proportional hazard model was used to examine whether the effects of GDT on morbidity and mortality were independent of other potential confounders. RESULTS: A total of 232 patients (80.6% male; age range: 36-83 yr) were randomised to either GDT (n=115) or to the control group (n=117). After surgery, major morbidity and mortality were less frequent in 22/115 (19.1%) subjects randomised to GDT, compared with 41/117 (35.0%) subjects assigned to the control group {absolute risk reduction: 15.9% (95% confidence interval [CI]: 4.7-27.2%); P=0.006}. GDT was also associated with fewer episodes of atrial fibrillation (odds ratio [OR]: 0.18 [95% CI: 0.05-0.65]), respiratory failure (OR: 0.27 [95% CI: 0.09-0.83]), use of mini-tracheotomy (OR: 0.29 [95% CI: 0.10-0.81]), and readmission to ICU (OR: 0.09 [95% CI: 0.01-0.67]). GDT was independently associated with morbidity and mortality (hazard ratio: 0.51 [95% CI: 0.30-0.87]; P=0.013). CONCLUSIONS: Intraoperative GDT may reduce major morbidity and mortality, and shorten hospital stay, after transthoracic oesophagectomy. CLINICAL TRIAL REGISTRATION: UMIN000018705.
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Esofagectomia/mortalidade , Hidratação/mortalidade , Hidratação/métodos , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagectomia/métodos , Feminino , Humanos , Cuidados Intraoperatórios/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. METHODS: This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. RESULTS: A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. CONCLUSIONS: A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.
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Doenças Inflamatórias Intestinais/psicologia , Transtornos do Sono-Vigília/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores Sexuais , Transtornos do Sono-Vigília/etiologia , Estresse Psicológico/etiologiaRESUMO
BACKGROUND: This study investigated the ability of stroke volume variation (SVV) during deep breathing to discriminate fluid responders among spontaneously breathing patients. METHODS: Thirty patients undergoing general anaesthesia were enrolled and assessed before anaesthetic induction. Haemodynamic variables, including stroke volume (SV) and SVV, were measured using the ClearSight system during normal breathing. After these measurements, each patient was required to maintain deep breathing (6 breaths min-1 ) and haemodynamic variables were recorded. Then, the table was adjusted to the Trendelenburg position (15°) for 2 minutes, and haemodynamic variables were measured. Receiver operating characteristic curves were created for SVV during normal and deep breathing, and the difference in SVV between normal and deep breathing (ΔSVV) to discriminate fluid responders (SV increase >10% after changing position). The correlation between SV increase and ΔSVV was examined using Pearson's correlation coefficient. The grey zone approach was used to assess the inconclusive range of the haemodynamic variables. RESULTS: Receiver operating characteristic curve analysis indicated that ΔSVV showed good reliability in predicting fluid responsiveness (AUC: 0.850; 95% CI: 0.672-0.953; threshold: 4%, sensitivity: 75.0%, specificity: 88.9%], while SVV during normal breathing did not (AUC: 0.579; 95% CI: 0.386-0.756)]. Although SVV during deep breathing exhibited acceptable predictability (AUC: 0.778; 95% CI: 0.589-0.908), the sensitivity was not good (58.3%). With the grey zone approach, the inconclusive range of ΔSVV was small with the range of 1.4%-4.2% (23% of patients). CONCLUSION: Deep breathing could improve the reliability of dynamic indices in spontaneously breathing patients. TRIAL REGISTRATION: UMIN-CTR, identifer: UMIN000027970. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000032040.
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Hidratação , Respiração , Volume Sistólico/fisiologia , Anestesia Geral , Feminino , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
This study aimed to compare the prognostic performance of the ratio of mixed and central venous-arterial CO2 tension difference to arterial-venous O2 content difference (Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2, respectively) with that of the mixed and central venous-to-arterial carbon dioxide gradient (Pv-aCO2 and Pcv-aCO2, respectively) for adverse events after cardiac surgery. One hundred and ten patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled. After catheter insertion, three blood samples were withdrawn simultaneously through arterial pressure, central venous, and pulmonary artery catheters, before and at the end of the operation, and preoperative and postoperative values were determined. The primary end-point was set as the incidence of postoperative major organ morbidity and mortality (MOMM). Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed to evaluate the prognostic reliability of Pv-aCO2, Pcv-aCO2, Pv-aCO2/Ca-vO2, and Pcv-aCO2/Ca-cvO2 for MOMM. MOMM events occurred in 25 patients (22.7%). ROC curve analysis revealed that both postoperative Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2 were significant predictors of MOMM. However, postoperative Pv-aCO2 was the best predictor of MOMM (area under the curve [AUC]: 0.804; 95% confidence interval [CI] 0.688-0.921), at a 5.1-mmHg cut-off, sensitivity was 76.0%, and specificity was 74.1%. Multivariate analysis revealed that postoperative Pv-aCO2 was an independent predictor of MOMM (odds ratio [OR]: 1.42, 95% CI 1.01-2.00, p = 0.046) and prolonged ICU stay (OR: 1.45, 95% CI 1.05-2.01, p = 0.024). Pv-aCO2 at the end of cardiac surgery was a better predictor of postoperative complications than Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2.
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Artérias/metabolismo , Gasometria , Dióxido de Carbono/sangue , Cardiopatias/cirurgia , Veias/metabolismo , Idoso , Área Sob a Curva , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar , Feminino , Ventrículos do Coração , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oxigênio/sangue , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Choque Séptico/sangue , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Peyer's patches (PPs) play a major role in intestinal mucosal immunity; however, their role in ulcerative colitis (UC) is not well investigated. We evaluated endoscopic features of PPs on narrow-band imaging with magnifying endoscopy (NBI-ME) and investigated their association with clinical factors. METHODS: We prospectively recruited 105 patients with UC, 18 with Crohn's disease, 16 with disease control, and 33 healthy control subjects at three institutions from 2014 to 2017. NBI-ME images of the villi of PPs were evaluated according to the Villi Index, and patients were divided into the Villi Index low (L) and high (H) types. The 1-year sustained clinical remission rate was evaluated between L-type and H-type PPs in patients with UC. RESULTS: The proportions of patients with H-type PPs were significantly higher among UC, Crohn's disease, and disease control patients than among healthy control patients (P = 0.0125, 0.018, 0.0007). In UC, age, gender, endoscopic score, and extent of disease involvement were not significantly different between L-type and H-type PPs, whereas the sustained clinical remission rate was significantly higher in L-type PPs than in H-type PPs (88% [57/65] vs 65% [17/26], P = 0.019). Multivariate analysis revealed that the L type of PPs was a significant factor for sustained clinical remission (odds ratio 3.8, 95% confidence interval 1.1-12.9, P = 0.033). CONCLUSIONS: Patients with UC showed endoscopic alterations in PPs on NBI-ME, and highly altered appearance of PPs can be associated with a high risk of clinical relapse in patients with UC.
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Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Endoscopia Gastrointestinal/métodos , Nódulos Linfáticos Agregados/diagnóstico por imagem , Nódulos Linfáticos Agregados/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Imagem de Banda Estreita/métodos , Estudos Prospectivos , Recidiva , Indução de Remissão , Risco , Adulto JovemRESUMO
BACKGROUND AND AIM: Transabdominal ultrasonography (US) examination for the intestine is often difficult, and its precedence for intestinal examination depends on accessibility to experienced ultrasonographers. Real-time virtual sonography (RVS) assists examination of US as a fusion method by synchronizing US images with pre-captured computed tomography or magnetic resonance images. We aimed to evaluate the feasibility to use RVS for the examination of the intestine. METHODS: The time to scan three parts of the intestine was compared between conventional US and RVS in seven participants without intestinal diseases. Whether RVS accurately synchronized US images with reference images of intestinal target lesions was judged in 20 patients with inflammatory bowel disease. RESULTS: Examination time to scan the ascending colon and the ileocecum using intestinal RVS was significantly shorter than that using conventional US alone (36.7 vs 50.0 s [P = 0.0313] and 35.4 vs 66.4 s [P = 0.0156], respectively) in participants without intestinal diseases. Well-synchronized US images of the intestinal lesions, such as stenosis, with reference computed tomography/magnetic resonance images were obtained by RVS in all the lesions in the fixed parts of the colon (ascending and descending colon), and images of nine lesions in 12 lesions (75%) were well synchronized in the unfixed part of the intestine in Crohn's disease patients. CONCLUSION: Real-time virtual sonography significantly reduced the examination time of intestinal US. Intestinal RVS can help the ultrasonographer to guide the US probe to detect and monitor intestinal lesions by synchronizing reference images, especially in inflammatory bowel disease patients (UMIN Clinical Trials Registry number: UMIN000011571).
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Doenças Inflamatórias Intestinais/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Ultrassonografia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Valor Preditivo dos Testes , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Fatores de Tempo , Tomografia Computadorizada por Raios X , Fluxo de Trabalho , Adulto JovemRESUMO
KIF1Bß, a member of the kinesin superfamily of motor proteins, is a haploinsufficient tumor suppressor mapped to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors, including neuroblastoma and pheochromocytoma. While KIF1Bß acts downstream of the nerve growth factor (NGF) pathway to induce apoptosis, further molecular functions of this gene product have largely been unexplored. In this study, we report that KIF1Bß destabilizes the morphological structure of mitochondria, which is critical for cell survival and apoptosis. We identified YME1L1, a mitochondrial metalloprotease responsible for the cleavage of the mitochondrial GTPase OPA1, as a physical interacting partner of KIF1Bß. KIF1Bß interacted with YME1L1 through its death-inducing region, as initiated the protease activity of YME1L1 to cleave the long forms of OPA1, resulting in mitochondrial fragmentation. Overexpression of YME1L1 promoted apoptosis, while knockdown of YME1L1 promoted cell growth. High YME1L1 expression was significantly associated with a better prognosis in neuroblastoma. Furthermore, in NGF-deprived PC12 cells, KIF1Bß and YME1L1 were upregulated, accompanied by mitochondrial fragmentation and apoptotic cell death. Small interfering RNA-mediated knockdown of either protein alone, however, remarkably inhibited the NGF depletion-induced apoptosis. Our findings indicate that tumor suppressor KIF1Bß plays an important role in intrinsic mitochondria-mediated apoptosis through the regulation of structural and functional dynamics of mitochondria in collaboration with YME1L1. Dysfunction of the KIF1Bß/YME1L1/OPA1 mechanism may be involved in malignant biological features of neural crest-derived tumors as well as the initiation and progression of neurodegenerative diseases.
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ATPases Associadas a Diversas Atividades Celulares/metabolismo , Apoptose/fisiologia , Cinesinas/metabolismo , Metaloendopeptidases/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Neuroblastoma/patologia , ATPases Associadas a Diversas Atividades Celulares/genética , Neoplasias das Glândulas Suprarrenais/patologia , Linhagem Celular Tumoral , GTP Fosfo-Hidrolases/metabolismo , Genes Supressores de Tumor , Células HeLa , Humanos , Cinesinas/genética , Metaloendopeptidases/genética , Proteínas Mitocondriais/genética , Neuroblastoma/mortalidade , Feocromocitoma/patologia , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81â%) patients using VKAs and 17 (46â%) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2â% vs. 16.4â%, P â=â1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P â<â0.0001). Myocardial infarction occurred during pre-endoscopic HB in one patient using VKAs. Conclusion DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.
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OBJECTIVES: To assess whether a tissue Doppler imaging (TDI)-based parameter consisting of the sum of early diastolic velocities of the mitral annulus (Me') and tricuspid annulus (Te') can serve as a predictor of adverse outcomes after cardiac surgery. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 100 patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After anesthetic induction, transesophageal echocardiography was performed to obtain the values of the early transmitral flow velocity (E), Me', and Te'. The primary endpoint was the incidence of postoperative major organ morbidity and mortality (MOMM) events, including death, redo surgery, prolonged ventilation, stroke, sternal infection, and dialysis. Receiver operating characteristic and multivariate logistic analyses were used to examine the prognostic performance of TDI-based parameters for predicting MOMM incidence. The secondary endpoint was the incidence of death or rehospitalization for cardiovascular disease within 1 year post-discharge. TDI-based parameters were measured in 87 of the 100 patients enrolled. Me' plus Te' had better prognostic ability (area under the curve 0.771; threshold 13 cm/s; sensitivity 86.7%; specificity 64.9%) than that of Me' or E to Me' (E/Me')% and was an independent predictor of MOMM (odds ratio 0.45; 95% confidence interval 0.28-0.74, pâ¯=â¯0.001), whereas Me' was not. Lower Me' plus Te' (≤13 cm/s) was associated with a significantly higher incidence and earlier onset of cardiovascular events within 1 year post-discharge (pâ¯=â¯0.012). CONCLUSIONS: Compared with Me' and E/Me', which traditionally are used for assessing diastolic function, Me' plus Te' showed better prognostic ability for both short- and long-term outcomes of cardiac surgery.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Doenças das Valvas Cardíacas/cirurgia , Valva Mitral/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico , Valva Tricúspide/diagnóstico por imagem , Idoso , Diástole , Ecocardiografia Doppler/métodos , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Valva Mitral/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Estudos Prospectivos , Valva Tricúspide/cirurgiaRESUMO
PURPOSE: This study aimed to investigate the efficacy of the ClearSight™ system (Edwards Lifesciences, Irvine, CA) for reducing the incidence of hypotension compared with the traditional oscillometric blood pressure monitoring in cesarean delivery under spinal anesthesia. METHODS: Forty patients undergoing cesarean delivery under spinal anesthesia were enrolled. The patients were randomly divided into two groups (Control and ClearSight groups). All patients received spinal anesthesia using 0.5% hyperbaric bupivacaine (11.5 mg) and fentanyl (10 µg). Blood pressure was managed with the same protocol using the ClearSight™ system (ClearSight group) and oscillometric blood pressure monitoring (Control group). Furthermore, we compared the accuracy of the ClearSight™ system with the traditional oscillometric monitoring for blood pressure measurement using Bland-Altman, four-quadrant plot, and polar plot analyses. RESULTS: The incidence of hypotension was significantly lower in the ClearSight group from induction to delivery (45% vs. 0%, p < 0.001) and to the end of surgery (50% vs. 20%, p = 0.049). Intraoperative nausea occurred more frequently in the Control group (45% vs. 10%, p = 0.012). The ClearSight™ system demonstrated acceptable accuracy with a bias of - 4.3 ± 11.7 mmHg throughout the procedure. Four-quadrant analysis revealed an excellent trending ability of the ClearSight™ system with a concordance rate of approximately 95%. In the polar plot analysis, the angular bias and concordance rate were - 13.5° ± 19.0° and 76.9%, respectively. CONCLUSIONS: The accuracy and trending ability of the ClearSight™ system for blood pressure measurement was clinically acceptable in cesarean delivery under spinal anesthesia, leading to reductions in maternal hypotension and nausea.
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Raquianestesia/métodos , Determinação da Pressão Arterial/métodos , Cesárea/métodos , Hipotensão/epidemiologia , Adulto , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/métodos , Pressão Sanguínea , Bupivacaína/administração & dosagem , Feminino , Fentanila/administração & dosagem , Humanos , GravidezRESUMO
This study assessed the ability of a continuous non-invasive blood pressure (BP) monitoring system to reduce intra-anesthetic hemodynamic fluctuation compared with intermittent BP cuff measurement. Forty patients undergoing total knee arthroplasty under general anesthesia were enrolled and randomly divided into two groups (Control and CS group). BP management was performed using the same protocol with BP measured by intermittent BP cuff in the Control and that by continuous non-invasive BP monitoring in the CS group. We assessed the accuracy and precision of the continuous non-invasive BP monitoring compared with BP cuff measurement using Bland-Altman, four-quadrant plot, and polar-plot analyses. Additionally, the occurrence of hypotension and hypertention during general anesthesia was compared between the two groups. The continuous non-invasive BP monitoring showed excellent accuracy of - 1.1 ± 8.1 mmHg during surgery and an acceptable trending ability with a concordance rate of 95.1% according to the four-quadrant plot analysis and an angular concordance rate of 86.7% by polar-plot analysis. Hypotension was less common in the CS group during induction of anesthesia (p = 0.002) and surgery (p = 0.008). Hypertension occurred more frequently in the Control group during emergence from anesthesia (p = 0.037). The duration of hemodynamic stability (systolic BP 80-110% of baseline) intraoperatively was longer in the CS group than in the Control group (87.7 vs. 61.9%; p < 0.001). Accuracy and trending ability of the continuous non-invasive BP monitoring was clinically acceptable, and lead to hemodynamic stability and reduction of intra-anesthetic hypotension and hypertension intraoperatively.
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Anestesia Geral/efeitos adversos , Determinação da Pressão Arterial/métodos , Monitorização Hemodinâmica/métodos , Monitorização Intraoperatória/métodos , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Determinação da Pressão Arterial/estatística & dados numéricos , Feminino , Monitorização Hemodinâmica/estatística & dados numéricos , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Hipotensão/etiologia , Hipotensão/fisiopatologia , Hipotensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/estatística & dados numéricosRESUMO
BACKGROUND AND AIM: Differentiation between gastric adenocarcinoma and low-grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aim to clarify the incidence of carcinoma in specimens, obtained by endoscopic resection (ER), from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy. METHODS: In this multicenter, prospective, observational study, patients with gastric adenoma (Vienna category 3 or 4.1) diagnosed on endoscopic forceps biopsy were enrolled. All the specimens were subjected to histopathological central review. Primary endpoint was the incidence of carcinoma (Vienna category 4.2 or over) among the biopsy-proven gastric LGA. Secondary endpoints were the histological findings of resected specimens, clinicopathological features of carcinoma, and short-term outcomes of all ER cases. RESULTS: Ninety-five patients with 104 lesions diagnosed as gastric adenoma were enrolled. After central review of the biopsy specimens, 47 lesions were diagnosed as LGA and seven lesions (15%) as adenocarcinoma (95% confidence interval, 7.6-28%). Carcinoma was detected in lesions that had a minimum size of 6 mm; the incidence of carcinoma was higher in the larger lesions. There was a histological discrepancy between biopsy and ER material in more than 60% of the cases. CONCLUSIONS: A substantial proportion of biopsy-proven gastric LGA specimens were diagnosed as adenocarcinoma after ER. This indicated histological discrepancy between biopsy-proven gastric LGA and histology of the resected material.
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Adenocarcinoma/patologia , Adenoma/patologia , Gastroscopia/métodos , Neoplasias Gástricas/patologia , Adenocarcinoma/epidemiologia , Adenoma/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diagnóstico Diferencial , Ressecção Endoscópica de Mucosa/métodos , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Distribuição por Sexo , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.