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1.
Ann Surg Oncol ; 29(5): 2773-2783, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35211857

RESUMO

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.


Assuntos
COVID-19 , Neoplasias , Cirurgiões , Oncologia Cirúrgica , COVID-19/epidemiologia , Humanos , Neoplasias/cirurgia , Pandemias
2.
Pharmazie ; 76(10): 515-518, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34620282

RESUMO

The incidence of hyperglycemia and diabetes induced by everolimus has been shown in previous studies. Our study analyzed diabetes time-to-onset profiles after everolimus use in patients who underwent transplantation and patients with cancer. Using data from April 2007 to December 2018 in the Japanese Adverse Drug Event Report database, the reports with everolimus were classified according to its use as an immunosuppressant or anticancer drug. The median (25%-75%) days of diabetes time-to-onset in patients who underwent transplantation and patients with cancer were 172 (56-315) and 32 (18.5-57), respectively. There were no significant variations among patients with breast cancer, neuroendocrine tumor, and renal cell carcinoma. By conducting a Weibull shape parameter test, the lower limits of the 95% confidence intervals of the shape parameter ß values for the indications of the cancer types were >1, indicating the wear out failure type profile, whereas those for transplantation data indicated a random failure type profile. The diabetes time-to-onset profiles after everolimus use differed between usage as an anticancer drug and immunosuppressant and there were no significant variations among the type of cancer. It was suggested that the incidence of diabetes should be monitored for 1-2 months in patients with cancer, whereas continuous monitoring is needed in patients who undergo transplantation.


Assuntos
Carcinoma de Células Renais , Diabetes Mellitus , Neoplasias Renais , Sistemas de Notificação de Reações Adversas a Medicamentos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Everolimo/efeitos adversos , Humanos
3.
Acta Neuropathol ; 139(3): 565-582, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31897643

RESUMO

Protein O-glucosyltransferase 1 (POGLUT1) activity is critical for the Notch signaling pathway, being one of the main enzymes responsible for the glycosylation of the extracellular domain of Notch receptors. A biallelic mutation in the POGLUT1 gene has been reported in one family as the cause of an adult-onset limb-girdle muscular dystrophy (LGMD R21; OMIM# 617232). As the result of a collaborative international effort, we have identified the first cohort of 15 patients with LGMD R21, from nine unrelated families coming from different countries, providing a reliable phenotype-genotype and mechanistic insight. Patients carrying novel mutations in POGLUT1 all displayed a clinical picture of limb-girdle muscle weakness. However, the age at onset was broadened from adult to congenital and infantile onset. Moreover, we now report that the unique muscle imaging pattern of "inside-to-outside" fatty degeneration observed in the original cases is indeed a defining feature of POGLUT1 muscular dystrophy. Experiments on muscle biopsies from patients revealed a remarkable and consistent decrease in the level of the NOTCH1 intracellular domain, reduction of the pool of satellite cells (SC), and evidence of α-dystroglycan hypoglycosylation. In vitro biochemical and cell-based assays suggested a pathogenic role of the novel POGLUT1 mutations, leading to reduced enzymatic activity and/or protein stability. The association between the POGLUT1 variants and the muscular phenotype was established by in vivo experiments analyzing the indirect flight muscle development in transgenic Drosophila, showing that the human POGLUT1 mutations reduced its myogenic activity. In line with the well-known role of the Notch pathway in the homeostasis of SC and muscle regeneration, SC-derived myoblasts from patients' muscle samples showed decreased proliferation and facilitated differentiation. Together, these observations suggest that alterations in SC biology caused by reduced Notch1 signaling result in muscular dystrophy in LGMD R21 patients, likely with additional contribution from α-dystroglycan hypoglycosylation. This study settles the muscular clinical phenotype linked to POGLUT1 mutations and establishes the pathogenic mechanism underlying this muscle disorder. The description of a specific imaging pattern of fatty degeneration and muscle pathology with a decrease of α-dystroglycan glycosylation provides excellent tools which will help diagnose and follow up LGMD R21 patients.


Assuntos
Distroglicanas/metabolismo , Glucosiltransferases/genética , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Animais , Animais Geneticamente Modificados , Drosophila melanogaster , Feminino , Estudos de Associação Genética , Glicosilação , Humanos , Masculino , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Mutação , Linhagem , Células Satélites de Músculo Esquelético/patologia
4.
Br J Surg ; 107(6): 705-711, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32077101

RESUMO

BACKGROUND: Oesophageal squamous cell carcinoma is an aggressive disease owing to early and widespread lymph node metastases. Multimodal therapy and radical surgery may improve prognosis. Few studies have investigated the efficacy of radical lymph node and thoracic duct resection. METHODS: Patients with oesophageal squamous cell carcinoma who underwent transthoracic minimally invasive oesophagectomy (TMIE) for cancer at Keio University Hospital between January 2004 and December 2016 were selected. Between 2004 and 2008, TMIE was performed in the lateral decubitus position without thoracic duct resection (standard TMIE). From 2009 onwards, TMIE with extended lymph node and thoracic duct resection was introduced (extended TMIE). Demographics, co-morbidity, number of retrieved lymph nodes, pathology, postoperative complications and recurrence-free survival (RFS) were compared between groups. RESULTS: Forty-four patients underwent standard TMIE and 191 extended TMIE. There were no significant differences in clinical and pathological tumour stage or postoperative complications. The extended-TMIE group had more lymph nodes removed at nodal stations 106recL and 112. Among patients with cT1 N0 disease, RFS was better in the extended-TMIE group (P < 0·001), whereas there was no difference in RFS between groups in patients with advanced disease. CONCLUSION: Extended TMIE including thoracic duct resection increased the number of lymph nodes retrieved and was associated with improved survival in patients with cT1 N0 oesophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ducto Torácico/cirurgia , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Ducto Torácico/patologia , Resultado do Tratamento
5.
Acta Psychiatr Scand ; 142(2): 87-95, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32627168

RESUMO

BACKGROUND: To date, there have been no studies evaluating adherence to clozapine with electronic adherence monitoring (EAM) such as the Medication Event Monitoring System (MEMS® ). METHODS: In outpatients with schizophrenia, we conducted a 3-month prospective study investigating antipsychotic adherence with EAM (eCAP® ). Participants were treated with different oral antipsychotics, including clozapine, and blind to EAM monitoring; all were on antipsychotic monotherapy administered once daily. Outcome measures included adherence rate, missed dose, and medication gap. Adherence trajectory patterns were also analyzed for clozapine vs. other antipsychotics collectively. RESULTS: A total of 111 patients were included in the study; 33 and 78 patients received clozapine or other antipsychotics, respectively. Adherence rates, defined as proportion of days that the subject took the medication at the prescribed time ± 3 h and proportion of subjects with ≥80% adherence, were numerically higher in patients receiving clozapine vs. other antipsychotics (72.0% vs. 65.1%, P = 0.10; 49.5% vs. 35.7%, P = 0.11, respectively). Along similar lines, some of the missed dose and medication gap outcomes were significantly better in patients receiving clozapine vs. other antipsychotics. Three adherence trajectory patterns were identified for both clozapine and other antipsychotics, with two shared by both groups (i.e., low adherence with a slight decrease over time; high and stable adherence). CONCLUSION: Findings suggest that in patients with schizophrenia clozapine adherence is at least comparable, if not slightly better, compared with other antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Estudos Prospectivos
6.
Acta Psychiatr Scand ; 142(3): 242-248, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32677065

RESUMO

OBJECTIVE: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. METHODS: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. RESULTS: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10-7 ); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10-30 ); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10-75 ); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10-10 ) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. CONCLUSION: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.


Assuntos
Glucocorticoides , Psicotrópicos , Estudos Transversais , Prescrições de Medicamentos , Glucocorticoides/efeitos adversos , Humanos , Prescrições , Psicotrópicos/efeitos adversos , Estudos Retrospectivos
7.
Clin Genet ; 94(2): 232-238, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29700822

RESUMO

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.


Assuntos
CADASIL/genética , Predisposição Genética para Doença , Leucoencefalopatias/genética , Receptor Notch3/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , CADASIL/diagnóstico por imagem , CADASIL/fisiopatologia , Estudos de Coortes , Fator de Iniciação 2B em Eucariotos/genética , Testes Genéticos , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/fisiopatologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação , Fenótipo , RNA Polimerase III/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Sequenciamento do Exoma
8.
Dis Esophagus ; 31(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29701761

RESUMO

Recurrent laryngeal nerve paralysis (RLNP) is a frequent and serious complication following esophageal cancer surgery. Therefore, this study aims to evaluate the correlation between recurrent laryngeal nerve (RLN) size and RLNP. This was a retrospective study of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2012 to December 2014. Eighty-four patients were included in the primary analysis. Diameter of the RLN was measured using the digital video recording of surgical procedures by the ratio between scissor and RLN. For evaluation of vocal cord paralysis or paresis, indirect laryngoscopy was performed. Because RLNP more frequently occurs on the left side than the right, we evaluated the correlation between size of the left RLN and left RLNP. The median size of the left RLN was 1.51 mm. We found that the incidence of postoperative left RLNP (Clavien-Dindo classification ≥1) was significantly higher (71% vs. 24%; P < 0.001) in thin RLNs (≤1.5 mm) than in thick RLNs (>1.5 mm). Thin RLN (P < 0.001), female sex (P = 0.025), and being overweight (P = 0.034) were identified as significant independent risk factors for postoperative RLNP. RLNP more easily occurred when the RLN was thin. It is difficult to confirm occurrence of postoperative RLNP before and at extubation. Therefore, it is helpful to know its risk factors including size of RLN.


Assuntos
Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Nervo Laríngeo Recorrente/patologia , Paralisia das Pregas Vocais/etiologia , Idoso , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
Mol Psychiatry ; 21(12): 1781-1789, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26728566

RESUMO

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.


Assuntos
Encéfalo/crescimento & desenvolvimento , Jogos de Vídeo/efeitos adversos , Adolescente , Encéfalo/ultraestrutura , Criança , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Feminino , Lobo Frontal/fisiologia , Globo Pálido , Hipocampo , Humanos , Inteligência , Estudos Longitudinais , Masculino , Estudos Prospectivos , Putamen , Tálamo , Comportamento Verbal , Adulto Jovem
10.
Dis Esophagus ; 30(2): 1-8, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-26919154

RESUMO

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Esofagectomia/métodos , Terapia Neoadjuvante/métodos , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Esquema de Medicação , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Fluoruracila/administração & dosagem , Humanos , Japão , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
11.
Acta Psychiatr Scand ; 134(3): 234-40, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27182769

RESUMO

OBJECTIVE: While it is recommended that clozapine be administered in a divided dosing regimen, it is unclear whether this recommendation is followed in real-world clinical practice. In two large datasets, we examined clozapine dosing frequency and patient characteristics across different dosing regimens. METHOD: We conducted a cross-sectional survey, collecting data on patients receiving clozapine in August/September 2015 from the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, and The Zucker Hillside Hospital (ZHH) in New York, United States. RESULTS: Of 676 and 308 patients included in CAMH and ZHH datasets, clozapine was prescribed once daily in 75.1% and 74.4%, even though doses exceeding 200 mg/day were administered in 88.6% and 84.4% of the respective samples. No significant difference was found in the rates of positive symptom remission between once-daily vs. divided dosing (79.7% vs. 80.5%, P = 1.00). Higher clozapine dose and use of anticholinergic medications were significantly associated with divided dosing in both datasets. Older age or male gender was related to divided dosing in CAMH or ZHH dataset respectively. CONCLUSION: Despite the product monograph recommendation, clozapine is frequently prescribed once daily in North America. Further studies are needed to compare clinical outcomes between once-daily vs. divided clozapine dosing.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Prescrições de Medicamentos/estatística & dados numéricos , Transtornos Mentais/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Canadá , Clozapina/efeitos adversos , Estudos Transversais , Esquema de Medicação , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , New York , Resultado do Tratamento
12.
Pharmacopsychiatry ; 48(7): 286-91, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26506574

RESUMO

INTRODUCTION: Due to high inter-individual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics currently relies on clinical trial-and-error, and predicting antipsychotic plasma concentrations before changing a dose has been a challenge. METHODS: Patients with schizophrenia receiving a stable dose of olanzapine were included. 2 plasma samples were collected at 2 given time points for the measurement of plasma olanzapine concentrations. At least 7 days after a dosage change of olanzapine, a third sample was collected. The plasma concentration of the third sample was predicted in a blinded fashion using a mixed-effects model with NONMEM(®), using the following information: the 2 baseline plasma concentrations, the interval between the last dose and blood draw, and clinical and demographic information. RESULTS: 31 subjects (mean±SD age=56.0±11.6; 19 men) were enrolled. The mean prediction (95% confidence interval) errors were 1.6 (-2.8 to 6.0) ng/mL. A highly significant correlation was observed between the observed and predicted concentrations of the third sample (r=0.91, p<0.001). DISCUSSION: Plasma olanzapine concentrations following an actual dosage change can be predicted in advance with a high degree of certainty.


Assuntos
Antipsicóticos/farmacocinética , Benzodiazepinas/farmacocinética , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Benzodiazepinas/administração & dosagem , Benzodiazepinas/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Esquizofrenia/sangue
13.
Mol Psychiatry ; 18(5): 618-23, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22614289

RESUMO

Many survivors of severe disasters, even those without posttraumatic stress disorder (PTSD), need psychological support. To understand the pathogenesis of PTSD symptoms and prevent the development of PTSD, the critical issue is to distinguish neurological abnormalities as vulnerability factors from acquired signs of PTSD symptoms in the early stage of adaptation to the trauma in the normal population. The neurological underpinnings of PTSD have been well characterized, but the causal relationships with the traumatic event are still unclear. We examined 42 non-PTSD subjects to find brain morphometric changes related to the severity of PTSD symptoms in a longitudinal magnetic resonance imaging study extending through the Great East Japan Earthquake. We found that regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex (OFC) through the earthquake were negatively associated with PTSD symptoms. Our results indicate that subjects with smaller GMV in the ACC before the earthquake, and subjects with decreased GMV in the OFC through the earthquake were likely to have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our results indicate that these processing are related to vulnerability for PTSD symptoms. In addition, decreased OFC volume was induced by failing to extinct conditioned fear soon after the traumatic event. These findings provide a better understanding of posttraumatic responses in early stage of adaptation to the trauma and may contribute to the development of effective methods to prevent PTSD.


Assuntos
Encéfalo/patologia , Terremotos , Transtornos de Estresse Pós-Traumáticos/patologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Psicológicos , Adulto Jovem
14.
Br J Anaesth ; 113(3): 491-500, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24838806

RESUMO

BACKGROUND: We wanted to demonstrate the feasibility of a novel computer-assisted ventilator alarm system, the support system for care of mechanically ventilated patients (SCMVP), to detect gas leaks and provide graphical information on the site of the leak in a manikin model. METHODS: We tested six leakage scenarios. Four scenarios were applied to both the respiratory circuits with the SCMVP and without the SCMVP (conventional system), and two scenarios were each specific to one of the systems. Fifteen registered nurses were asked to manage three scenarios each (two mutual and one system-specific scenario). Time to identify the site of the leak was measured and compared between the two systems. RESULTS: The SCMVP showed significantly shorter time for troubleshooting in one of the four mutual scenarios and shorter accumulated time for troubleshooting in the four mutual scenarios [18.0 (range, 14.5-19.5) and 48.5 (9.0-180.0) s, respectively] compared with the conventional system [76.0 (47.0-133.8) and 82.5 (16.0-180.0) s, respectively]. In the mutual scenarios, SCMVP resulted in significantly more frequent incidences of successful troubleshooting within 30 s and less frequent incidences of troubleshooting requiring >180 s [43.3% (13/30) and 6.7% (2/30), respectively] compared with the conventional system [13.3% (4/30) and 30% (9/30), respectively]. CONCLUSIONS: The SCMVP can facilitate rapid and successful recognition of the site of leak in a respiratory circuit in a simulation environment.


Assuntos
Alarmes Clínicos , Tomada de Decisões Assistida por Computador , Segurança do Paciente , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Simulação por Computador , Computadores , Apresentação de Dados , Desenho de Equipamento , Falha de Equipamento , Estudos de Viabilidade , Humanos , Manequins , Modelos Organizacionais , Enfermeiras e Enfermeiros , Projetos Piloto , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo
15.
Dis Esophagus ; 27(7): 654-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23980622

RESUMO

Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high-risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease-free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Esofagectomia , Fibrinogênio/metabolismo , Recidiva Local de Neoplasia/sangue , Idoso , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos
17.
Phys Rev Lett ; 110(17): 175301, 2013 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-23679740

RESUMO

We investigate the magnetic response of a dirty-normal-Fermi-liquid-spin-triplet-superfluid proximity system consisting of liquid 3He and aerogel. In contrast to bulk superfluids, Pauli spin susceptibility in the proximity system exceeds its normal-state value locally around the interface. This enhanced Pauli paramagnetism originates from odd-frequency s-wave pairing arising due to spatial inhomogeneity. A characteristic observable signature of the paramagnetic effect can be found in the spin susceptibility temperature dependence.

18.
Dis Esophagus ; 26(6): 616-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23237474

RESUMO

An identification of bronchial arteries (BAs) is critical in esophageal cancer surgery to avoid tracheobronchial ischemia and unexpected massive bleeding during surgical procedure particularly in thoracoscopic video-assisted esophagectomy. We describe the efficacy of three-dimensional computed tomographic angiography (3D-CTA) of BAs for preoperative evaluation in esophageal cancer surgery. Sixty-four patients with esophageal cancer who preoperatively underwent multidetector computed tomography examination were included in this study. We evaluated the number, origin, and intraoperative preservation rate of BAs, and we compared the number of thoracic paratracheal lymph nodes harvested between two groups comprising patients who either underwent preoperative 3D-CTA of BAs (3D-CTA group) or did not (non-3D-CTA group). The right and left BAs were preoperatively identified in 62 patients (97%) and 55 patients (86%), respectively, using 3D-CTA. In 34 patients (53%), the right BA originated as a common trunk with the right intercostal artery. In 48 patients (75%), the left BA originated from the descending aorta as a single or double branch. Some anomalies such as the right BA originated from the left subclavian artery were observed. In all patients, either the right or the left BA was preserved. The number of harvested lymph nodes in left side of paratrachea was significantly increased in 3D-CTA group, than those in non-3D-CTA group. 3D-CTA clearly revealed BA anatomy, contributing to BA preservation and safe and precise lymphadenectomy in esophageal cancer surgery. 3D-CTA of BAs is useful for preoperative evaluation in esophageal cancer surgery.


Assuntos
Angiografia/métodos , Artérias Brônquicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Perda Sanguínea Cirúrgica/prevenção & controle , Brônquios/irrigação sanguínea , Artérias Brônquicas/lesões , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Esofagectomia/métodos , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Isquemia/prevenção & controle , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Respiração Artificial , Costelas/irrigação sanguínea , Artéria Subclávia/diagnóstico por imagem , Traqueia/irrigação sanguínea , Cirurgia Vídeoassistida/métodos
19.
Eur Surg Res ; 51(3-4): 181-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24434684

RESUMO

BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. MATERIALS AND METHODS: In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. RESULTS: The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). CONCLUSION: These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.


Assuntos
Proteína HMGB1/sangue , Hemoperfusão/métodos , Adsorção , Animais , Proteína HMGB1/isolamento & purificação , Falência Hepática Aguda/sangue , Falência Hepática Aguda/terapia , Masculino , Suínos
20.
Phys Rev Lett ; 108(22): 225307, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23003616

RESUMO

We present a combined experimental and theoretical study of the drag force acting on a high porosity aerogel immersed in liquid (3)He and its effect on sound propagation. The drag force is characterized by the Knudsen number, which is defined as the ratio of the quasiparticle mean free path to the radius of an aerogel strand. Evidence of the Knudsen-hydrodynamic crossover is clearly demonstrated by a drastic change in the temperature dependence of ultrasound attenuation in 98% porosity aerogel. Our theoretical analysis shows that the frictional sound damping caused by the drag force is governed by distinct laws in the two regimes, providing excellent agreement with the experimental observation.

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