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1.
J Affect Disord ; 298(Pt A): 644-655, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34800568

RESUMO

BACKGROUND: Despite the importance of Beck's theoretical cognitive model of psychopathology, the neural mechanisms underlying future thinking in cognitive behavioral therapy (CBT) remain elusive. Recent neuroimaging studies have shown that the function of the frontopolar cortex (Brodmann area 10 [BA10]) is associated with future thinking. We hypothesized that, compared with unstructured psychotherapy (talking control: TC), CBT may involve different neural responses in BA10 associated with future thinking. METHODS: This randomized clinical trial included 38 adult patients with moderate-to-severe major depressive disorder who underwent up to 16 weeks of CBT or TC with a 6-month follow-up period. We evaluated changes in BA10 activation during distant future thinking using functional magnetic resonance imaging with a future-thinking task. We assessed frontal neurocognitive function and clinical symptoms at baseline and post-treatment. Depression severity and automatic thoughts were assessed at the 6-month follow-up. RESULTS: We found decreased activation in the frontopolar cortex during distant future thinking after CBT (t = 3.00, df=15, p = 0.009) and no changes after TC. Further, the reduction in BA10 activity significantly correlated with changes in frontal cognitive function after the treatment (r = 0.48, p = 0.007), and in positive automatic thought after 6 months of treatments (r = 0.39; p = 0.03). LIMITATIONS: Relatively small sample size and homogenous clinical profile could limit the generalizability. Patients received pharmacotherapy including antidepressant. CONCLUSIONS: CBT appears to improve frontopolar cortex function during future thinking in a manner distinct from TC. Larger clinical trials are necessary to provide firm evidence whether BA10 activity may serve as a neuro-marker for monitoring successful depression treatment with CBT.

2.
Nat Commun ; 12(1): 7209, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893618

RESUMO

The rational design of high-temperature endurable Cu-based catalysts is a long-sought goal since they are suffering from significant sintering. Establishing a barrier on the metal surface by the classical strong metal-support interaction (SMSI) is supposed to be an efficient way for immobilizing nanoparticles. However, Cu particles were regarded as impossible to form classical SMSI before irreversible sintering. Herein, we fabricate the SMSI between sputtering reconstructed Cu and flame-made LaTiO2 support at a mild reduction temperature, exhibiting an ultra-stable performance for more than 500 h at 600 °C. The sintering of Cu nanoparticles is effectively suppressed even at as high as 800 °C. The critical factors to success are reconstructing the electronic structure of Cu atoms in parallel with enhancing the support reducibility, which makes them adjustable by sputtering power or decorated supports. This strategy will extremely broaden the applications of Cu-based catalysts at more severe conditions and shed light on establishing SMSI on other metals.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34906436

RESUMO

BACKGROUND: The development of ultra-high-resolution CT (U-HRCT) is expected to improve the accuracy of coronary stenosis evaluation. This study aimed to evaluate the accuracy of the stenosis severities of coronary artery phantoms estimated using U-HRCT by comparing them to those estimated with conventional CT. METHODS: Coronary artery phantoms with non-calcified and calcified lesions were scanned with conventional CT (64-row â€‹× â€‹0.625 â€‹mm) and U-HRCT (32-row â€‹× â€‹0.3125 â€‹mm). The coronary artery phantoms had lumen diameters of 2.0, 3.0, and 4.0 â€‹mm with non-calcified lesions representing 0%, 25%, 50%, and 75% stenosis and 3.0 and 4.0 â€‹mm with calcified lesions representing 0%, 25%, 50%, and 75% stenosis. The lumen diameters at the stenotic and non-stenotic regions were measured, and the stenosis severities were compared with the true values. RESULTS: For non-calcified lesions, conventional CT significantly underestimated the stenosis severity in the phantom showing 75% stenosis with lumen diameters of 2.0 and 3.0 â€‹mm (p â€‹< â€‹0.05), while the estimated stenosis severities were not significantly different from the true values at all settings with U-HRCT. For the calcified lesions, conventional CT overestimated the stenosis severities at all settings (p â€‹< â€‹0.05), while U-HRCT yielded estimations closer to the true values, although still with some overestimation (p â€‹< â€‹0.05). CONCLUSION: By using U-HRCT, the estimated stenosis severities of the coronary artery with non-calcified lesion become almost equal to the true value, while those with calcified lesion are still overestimated although they become closer to the true value.

4.
Front Cell Infect Microbiol ; 11: 796664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926330

RESUMO

Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.

5.
Ann Thorac Surg ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921813

RESUMO

A 52-year-old man underwent surgery due to shortness of breath caused by severe aortic regurgitation with right coronary cusp prolapse. Operative findings revealed three symmetrical cusps with small raphe between the right- and non-coronary cusps situated lower than the others, indicating a forme fruste bicuspid aortic valve (BAV). The BAV was successfully repaired by tricuspidization, including raphe suspension, right coronary cusp plication, and double annuloplasty. The postoperative course was uneventful, and echocardiography at 3 months showed mild aortic regurgitation with adequate left ventricular reverse remodeling. Here, we present the technical details of the raphe suspension procedure for forme fruste BAV.

6.
Kobe J Med Sci ; 67(2): E38-E47, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34795154

RESUMO

We previously reported that hepatitis C virus (HCV) NS5A (1b, Con1) protein accepts covalent ISG15 conjugation at specific lysine (Lys) residues (K44, K68, K166, K215 and K308), exhibiting proviral effects on HCV RNA replication. Here we investigated a role of NS5A-ISGylation via Lys residues in HCV propagation using HCV infectious clone. The alignment of amino acid sequences revealed that 5 Lys residues (K20, K26, K44, K139, and K166) of the 13 Lys residues within NS5A (genotype 2a, JFH1 strain) were conserved compared to those of HCV (genotype 1b, Con1 strain). The cell-based ISGylation assay revealed that the K26 residue in the amphipathic helix (AH) domain and the K139 residue in domain I of NS5A (2a, JFH1) had the potential to accept ISGylation. Use of the HCV replicon carrying luciferase gene revealed that the K26 residue but not K139 residue of NS5A (2a, JFH1) was important for HCV RNA replication. Furthermore, cell culture HCV revealed that the mutation with the K26 residue in combination with K139 or K166 on NS5A (2a, JFH1) resulted in complete abolishment of viral propagation, suggesting that the K26 residue collaborates with either the K139 residue or K166 residue for efficient HCV propagation. Taken together, these results suggest that HCV NS5A protein has the potential to accept ISGylation via specific Lys residues, involving efficient viral propagation in a genotype-specific manner.

7.
Cochrane Database Syst Rev ; 9: CD013335, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34596901

RESUMO

BACKGROUND: The main goal of enteral nutrition (EN) is to manage malnutrition in order to improve clinical outcomes. However, EN may increase the risks of vomiting or aspiration pneumonia during gastrointestinal dysfunction. Consequently, monitoring of gastric residual volume (GRV), that is, to measure GRV periodically and modulate the speed of enteral feeding according to GRV, has been recommended as a management goal in many intensive care units. Yet, there is a lack of robust evidence that GRV monitoring reduces the level of complications during EN. The best protocol of GRV monitoring is currently unknown, and thus the precise efficacy and safety profiles of GRV monitoring remain to be ascertained. OBJECTIVES: To investigate the efficacy and safety of GRV monitoring during EN. SEARCH METHODS: We searched electronic databases including CENTRAL, MEDLINE, Embase, and CINAHL for relevant studies on 3 May 2021. We also checked reference lists of included studies for additional information and contacted experts in the field. SELECTION CRITERIA: We included randomized controlled trials (RCTs), randomized cross-over trials, and cluster-RCTs investigating the effects of GRV monitoring during EN. We imposed no restrictions on the language of publication. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for eligible studies and extracted trial-level information from each included study, including methodology and design, characteristics of study participants, interventions, and outcome measures. We assessed risk of bias for each study using Cochrane's risk of bias tool. We followed guidance from the GRADE framework to assess the overall certainty of evidence across outcomes. We used a random-effects analytical model to perform quantitative synthesis of the evidence. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous and mean difference (MD) with 95% CIs for continuous outcomes. MAIN RESULTS: We included eight studies involving 1585 participants. All studies were RCTs conducted in ICU settings. Two studies (417 participants) compared less-frequent (less than eight hours) monitoring of GRV against a regimen of more-frequent (eight hours or greater) monitoring. The evidence is very uncertain about the effect of frequent monitoring of GRV on mortality rate (RR 0.91, 95% CI 0.60 to 1.37; I² = 8%; very low-certainty evidence), incidence of pneumonia (RR 1.08, 95% CI 0.64 to 1.83; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD 2.00 days, 95% CI -2.15 to 6.15; heterogeneity not applicable; very low-certainty evidence), and incidence of vomiting (RR 0.14, 95% CI 0.02 to 1.09; heterogeneity not applicable; very low-certainty evidence). Two studies (500 participants) compared no GRV monitoring with frequent (12 hours or less) monitoring. Similarly, the evidence is very uncertain about the effect of no monitoring of GRV on mortality rate (RR 0.87, 95% CI 0.62 to 1.23; I² = 51%; very low-certainty evidence), incidence of pneumonia (RR 0.70, 95% CI 0.43 to 1.13; heterogeneity not applicable; very low-certainty evidence), length of hospital stay (MD -1.53 days, 95% CI -4.47 to 1.40; I² = 0%; very low-certainty evidence), and incidence of vomiting (RR 1.47, 95% CI 1.13 to 1.93; I² = 0%; very low-certainty evidence). One study (322 participants) assessed the impact of GRV threshold (500 mL per six hours) on clinical outcomes. The evidence is very uncertain about the effect of the threshold for GRV at time of aspiration on mortality rate (RR 1.01, 95% CI 0.74 to 1.38; heterogeneity not applicable; very low-certainty evidence), incidence of pneumonia (RR 1.03, 95% CI 0.72 to 1.46; heterogeneity not applicable; very low-certainty evidence), and length of hospital stay (MD -0.90 days, 95% CI -2.60 to 4.40; heterogeneity not applicable; very low-certainty evidence). Two studies (140 participants) explored the effects of returning or discarding the aspirated/drained GRV. The evidence is uncertain about the effect of discarding or returning the aspirated/drained GRV on the incidence of vomiting (RR 1.00, 95% CI 0.06 to 15.63; heterogeneity not applicable; very low-certainty evidence) and volume aspirated from the stomach (MD -7.30 mL, 95% CI -26.67 to 12.06, I² = 0%; very low-certainty evidence) We found no studies comparing the effects of protocol-based EN strategies that included GRV-related criteria against strategies that did not include such criteria. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of GRV on clinical outcomes including mortality, pneumonia, vomiting, and length of hospital stay.


Assuntos
Nutrição Enteral , Unidades de Terapia Intensiva , Nutrição Enteral/efeitos adversos , Humanos , Tempo de Internação , Volume Residual , Estômago
8.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661519

RESUMO

Ubiquitin and ubiquitin-like protein modification play important roles in modulating the functions of viral proteins in many viruses. Here we demonstrate that hepatitis B virus (HBV) X protein (HBx) is modified by ISG15, which is a type I IFN-inducible, ubiquitin-like protein; this modification is called ISGylation. Immunoblot analyses revealed that HBx proteins derived from four different HBV genotypes accepted ISGylation in cultured cells. Site-directed mutagenesis revealed that three lysine residues (K91, K95 and K140) on the HBx protein, which are well conserved among all the HBV genotypes, are involved in acceptance of ISGylation. Using expression plasmids encoding three known E3 ligases involved in the ISGylation to different substrates, we found that HERC5 functions as an E3 ligase for HBx-ISGylation. Treatment with type I and type III IFNs resulted in the limited suppression of HBV replication in Hep38.7-Tet cells. When cells were treated with IFN-α, silencing of ISG15 resulted in a marked reduction of HBV replication in Hep38.7-Tet cells, suggesting a role of ISG15 in the resistance to IFN-α. In contrast, the silencing of USP18 (an ISG15 de-conjugating enzyme) increased the HBV replication in Hep38.7-Tet cells. Taken together, these results suggest that the HERC5-mediated ISGylation of HBx protein confers pro-viral functions on HBV replication and participates in the resistance to IFN-α-mediated antiviral activity.


Assuntos
Citocinas/metabolismo , Vírus da Hepatite B/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transativadores/metabolismo , Ubiquitinas/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Replicação Viral , Linhagem Celular , Farmacorresistência Viral , Vírus da Hepatite B/genética , Humanos , Interferon-alfa/farmacologia , Interferon beta/farmacologia , Interferons/farmacologia , Transativadores/química , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais Reguladoras e Acessórias/química
9.
Medicine (Baltimore) ; 100(37): e27233, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664865

RESUMO

ABSTRACT: To investigate fatigue, health-related quality of life (HR-QOL), and sleep quality in women with primary Sjogren syndrome (pSS) or rheumatoid arthritis (RA) as compared with healthy controls using self-reports and wrist actigraphy.In this cross-sectional observational study, we evaluated a total of 25 patients (aged 40-75 years) with pSS, 10 with RA, and 17 healthy control subjects living in Japan. The HR-QOL was assessed using the Short Form-36. Fatigue was evaluated using the Short Form-36 vitality score, visual analog scale (VAS) for fatigue, and 2 questionnaire items using scores based on a 4-point Likert scale. Sleep quality was measured using the Japanese version of the Pittsburgh Sleep Quality Index, VAS for sleep quality, and wrist actigraphy for 14 days.Patients with pSS reported severer fatigue and lower HR-QOL than healthy controls, especially in mental health. Based on the Pittsburgh Sleep Quality Index score, 56% of the patients with pSS were poor sleepers, which was higher than healthy controls (29.4%). Furthermore, the patients with pSS scored significantly lower on the VAS for sleep quality than healthy controls (40.5 vs 63.7, P = .001). Although subjective assessments revealed slight sleep disturbances in patients with pSS, wrist actigraphy revealed no differences when compared with healthy controls for total sleep time (421.8 minutes vs 426.5 minutes), sleep efficiency (95.2% vs 96.4%), number of awakenings (1.4 vs 0.9), and wake after sleep onset (22.4 minutes vs 16.1 minutes). Poor subjective sleep quality was associated with enhanced fatigue. However, sleep efficiency, as determined by actigraphy, was not associated with fatigue. Notably, the patients with RA and healthy controls did not differ significantly in terms of fatigue or sleep quality, although patients with RA experienced more nocturnal awakenings than healthy controls (1.7 vs 0.9, P = .04).Patients with pSS experience severe fatigue, poor HR-QOL, and sleep disturbances, which are associated with fatigue. However, wrist actigraphy did not reveal differences in sleep quality, suggesting that it may not be an appropriate measure of sleep in patients with pSS.


Assuntos
Artrite Reumatoide/complicações , Fadiga/classificação , Síndrome de Sjogren/complicações , Sono/fisiologia , Actigrafia/instrumentação , Actigrafia/métodos , Actigrafia/estatística & dados numéricos , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Estudos Transversais , Fadiga/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Qualidade de Vida , Autorrelato/estatística & dados numéricos , Síndrome de Sjogren/epidemiologia , Inquéritos e Questionários , Punho/fisiologia , Punho/fisiopatologia
10.
Regen Ther ; 18: 321-333, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34522725

RESUMO

Introduction: Our group has conducted extensive basic and preclinical studies of the use of human induced pluripotent cell (iPSC)-derived neural stem/progenitor cell (hiPSC-NS/PC) grafts in models of spinal cord injury (SCI). Evidence from animal experiments suggests this approach is safe and effective. We are preparing to initiate a first-in-human clinical study of hiPSC-NS/PC transplantation in subacute SCI. Setting: NS/PCs were prepared at a Good Manufacturing Practice-grade cell processing facility at Osaka National Hospital using a clinical-grade integration-free hiPSC line established by the iPSC Stock Project organized by the Kyoto University Center for iPS Cell Research and Application. After performing all quality checks, the long-term safety and efficacy of cells were confirmed using immunodeficient mouse models. Methods: The forthcoming clinical study uses an open-label, single-arm design. The initial follow-up period is 1 year. The primary objective is to assess the safety of hiPSC-NS/PC transplantation in patients with subacute SCI. The secondary objective is to obtain preliminary evidence of its impact on neurological function and quality-of-life outcomes. Four patients with C3/4-Th10 level, complete subacute (within 24 days post-injury) SCI will be recruited. After obtaining consent, cryopreserved cells will be thawed and prepared following a multi-step process including treatment with a γ-secretase inhibitor to promote cell differentiation. A total of 2 × 106 cells will be transplanted into the injured spinal cord parenchyma 14-28 days post-injury. Patients will also receive transient immunosuppression. This study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000035074; Japan Registry of Clinical Trials [jRCT] number, jRCTa031190228). Discussion/conclusion: We plan to start recruiting a patient as soon as the COVID-19 epidemic subsides. The primary focus of this clinical study is safety, and the number of transplanted cells may be too low to confirm efficacy. After confirming safety, a dose-escalation study is planned.

11.
Urol Oncol ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34332846

RESUMO

PURPOSE: We herein compared the diagnostic performance of Vesical Imaging-Reporting and Data System (VI-RADS) scoring with diagnostic cystoscopy and evaluated diagnostic accuracies based on tumor locations. MATERIALS AND METHODS: Among 112 bladder cancer patients who underwent multiparametric magnetic resonance imaging and diagnostic cystoscopy preoperatively to detect bladder cancer, 61 were analyzed. VI-RADS was categorized into 5 stages by 2 radiologists (R1 and R2). Cut-off values ≥3 indicated muscle-invasive bladder cancer (MIBC). Muscle invasion (MI) was visually evaluated using diagnostic cystoscopy by 2 urologists (U1 and U2). The sensitivity and specificity of VI-RADS scores and diagnostic cystoscopy for diagnosing MI were compared. RESULTS: 16 patients (26.2%) were pathologically diagnosed with MIBC. Regarding MI diagnostic accuracy, the sensitivity/specificity of VI-RADS scores were 93.8/88.9% by R1 and 87.5/86.7% by R2, while those of diagnostic cystoscopy were 56.3/68.9% by U1 and 68.8/84.4% by U2. Therefore, the diagnostic accuracy of VI-RADS was significantly higher than that of cystoscopy, particularly for tumors located on the bladder neck, trigone, dome, and posterior and anterior walls. Over- and under-diagnosis rates were higher with VI-RADS than with diagnostic cystoscopy (25.9% vs. 14.8%) for tumors located on the lateral wall or ureteral orifice. CONCLUSION: VI-RADS had superior diagnostic performance for detecting MI, especially in tumors located at the bladder neck/trigone/dome/posterior and anterior wall. However, VI-RADS was inferior to cystoscopy in terms of MI detection for tumors located on the lateral wall or ureteral orifice. Therefore, a combination of diagnostic tools is recommended for the accurate staging of these tumors.

12.
ESC Heart Fail ; 8(5): 3917-3928, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34323007

RESUMO

AIMS: Heart failure (HF) patients have a high risk of mortality due to sudden cardiac death (SCD) and non-SCD, including pump failure death (PFD). Anaemia predicts more severe symptomatic burden and higher morbidity, as noted by markedly increased hospitalizations and readmission rates, and mortality, underscoring its importance in HF management. Herein, we aimed to determine whether haemoglobin (Hb) level at discharge affects the mode of death and influences SCD risk prediction. METHODS: We evaluated the data of 3020 consecutive acute HF patients from a Japanese prospective multicentre registry. Patients were divided into four groups based on discharge Hb levels. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The mode of death (SCD, PFD or other cause) was adjudicated by a central committee. Finally, we investigated whether adding Hb level to the Seattle Proportional Risk Model (SPRM; established risk score utilized to estimate 'proportion' of SCD among death events) would affect its performance. RESULTS: The mean age of studied patients was 74.3 ± 12.9 years, and 59.8% were male. The mean Hb level was 12.0 ± 2.1 g/dL (61.3% of patients had anaemia defined by World Health Organization criteria). During the 2-year follow-up, 474 deaths (15.7%) occurred, including 93 SCDs (3.1%), 171 PFDs (5.7%) and 210 other deaths (7.0%; predominantly non-cardiac death). Absolute risk of PFD (P < 0.001) or other death (P < 0.001) increased along with the severity of anaemia, whereas the incidence of SCD was low but remained consistent across all four groups (P = 0.440). As a proportion of total deaths in each Hb level group, the contributions from non-SCD increased and from SCD decreased along with anaemia severity (P = 0.007). Adding Hb level to the SPRM improved the overall discrimination (c-index: 0.62 [95% confidence interval (CI) 0.56-0.69] to 0.65 [95% CI 0.59-0.71]), regardless of the baseline ejection fraction (EF) (c-index: 0.64 [95% CI 0.55-0.73] to 0.67 [95% CI 0.58-0.75] for reduced EF and 0.55 [95% CI 0.45-0.66] to 0.61 [95% CI 0.52-0.70] for preserved EF). CONCLUSIONS: The discharge Hb level provides information about both absolute and proportional risks for each mode of death in acute HF patients, and the addition of Hb level improves the performance of SPRM by identifying more non-SCD cases. Future 'proportional' SCD risk models should incorporate Hb level as a covariate to meet this high performance.


Assuntos
Insuficiência Cardíaca , Alta do Paciente , Idoso , Idoso de 80 Anos ou mais , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
BMJ Open Sport Exerc Med ; 7(2): e001014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249373

RESUMO

Objectives: This study aimed to compare the estimation error of physical activity level (PAL) estimated using a tri-axial accelerometer between an independent walking group and an assisted walking group with walking aids. Methods: Subjects were 6 older adults who could walk independently and 10 older adults requiring walking assistance during gait. Total energy expenditure (TEE) was measured using the doubly labelled water (DLW) method over 2 weeks and PAL was calculated as the measured TEE divided by the basal metabolic rate measured using indirect calorimetry (PALDLW). The participants wore a tri-axial accelerometer (Active style Pro HJA-750C) on the waist simultaneously as the DLW period, and the estimated PAL was derived from it (PALACC). Results: The median PAL estimation error in the assisted walking group was -0.30 kcal/day (range: -0.77 to -0.01 kcal/day) and more underestimated than that in the independent walking group (p=0.02). The estimation error of PALACC was significantly correlated with PALDLW (r=-0.80, p<0.01). Conclusions: Using the accelerometer, PAL was underestimated for older adults who used walking aids but not for those who walked independently under free-living conditions.

14.
Lancet Gastroenterol Hepatol ; 6(6): 429-437, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887262

RESUMO

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab. METHODS: We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092. FINDINGS: Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80·4% [95% CI 66·1-90·6]) of 46 patients in the infliximab-continued group and 25 (54·3% [39·0-69·1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26·1% (95% CI 7·7-44·5; p=0·0076) before adjustment and 27·3% (95% CI 8·0-44·1; p=0·0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3·9% [95% CI -10·3 to 18·1]; p=0·59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66·7%, 95% CI 34·9-90·1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions. INTERPRETATION: Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account. FUNDING: Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Infliximab/efeitos adversos , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Suspensão de Tratamento/estatística & dados numéricos , Administração Intravenosa , Adulto , Estudos de Casos e Controles , Colite Ulcerativa/patologia , Colite Ulcerativa/prevenção & controle , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/uso terapêutico
15.
J Clin Med Res ; 13(1): 48-63, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33613800

RESUMO

Background: The effects of plateau pressure during the initial days of mechanical ventilation on outcomes for patients with acute respiratory distress syndrome have not been fully examined. We conducted meta-regression analysis of plateau pressure during the first 7 days using randomized control trials to investigate the optimal upper limits of plateau pressure on different days of mechanical ventilation. Methods: Randomized controlled trials comparing two mechanical ventilation strategies with lower and higher plateau pressures in patients with acute respiratory distress syndrome were included. Meta-regression analysis was performed to determine the association of plateau pressure with mortality on days 1, 3, and 7 of mechanical ventilation. Results: After evaluation of 2,975 citations from a comprehensive search across electronic databases, 14 studies were included in the final qualitative analysis. A total of 4,984 patients were included in the quantitative analysis. As a result of the pairwise comparison, overall short-term mortality was significantly higher for patients with plateau pressures over 32 cm H2O during the first 3 days after intensive care unit (ICU) admission (day 1: relative risk (RR), 0.77; 95% confidence interval (CI), 0.66 - 0.89; I2 = 0%; day 3: RR, 0.76; 95% CI, 0.64 - 0.90; I2 = 0%), but not on day 7 (RR, 0.82; 95% CI, 0.65 - 1.04; I2 = 16%). Plateau pressures below 27 cm H2O and 30 cm H2O were not associated with an absolute risk reduction of short-term mortality. According to univariable meta-regression analysis, mortality was significantly associated with plateau pressure on day 1 (ß = 0.01 (95% CI, 0.002 - 0.024), P = 0.02). On days 3 and 7, however, no significant difference was detected. When the cutoffs were set at 27, 30 and 32 cm H2O on day 1, which showed a significant difference, plateau pressure tended to be associated with increased mortality at pressures above the cut-off values, and there were no significant differences at pressures below the cut-off values, regardless of the cutoff used. Conclusions: This study suggests that the optimal cut-off value for plateau pressure may be 27 cm H2O especially during the initial period of mechanical ventilation, although this association may not continue during the latter period of mechanical ventilation.

16.
J Affect Disord ; 282: 1011-1020, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601673

RESUMO

BACKGROUNDS: Antidepressants are widely used to treat major depressive disorder. First-line treatments with antidepressants are only successful in one-third of patients; however, evidence from randomized controlled trials on second-line treatments is limited. Moreover, recently acceptability is suggested to be a good indicator of overall treatment success. METHODS: This is a multi-center two-arm, three-phased randomized controlled trial performed in Japan from December 2013 to March 2017 comparing the acceptability of escitalopram and duloxetine as a second-line drug. Patients, who failed to respond to antidepressants such as sertraline, paroxetine, fluvoxamine, milnacipran or mirtazapine for at least 3 weeks, were randomized to either escitalopram (Group A) or duloxetine (Group B) in Step 1 (8 weeks). In Step 2 (8 weeks), the drug was switched to the other if the first drug failed. The discontinuation rate at the end of Step 1 was the primary endpoint and non-inferiority of escitalopram vs duloxetine was tested. In addition, change in clinical measures from baseline were also assessed at the end of Step 1, 2 and up to 52 weeks. RESULTS: At the end of Step 1, Group A (n = 82) was significantly superior to Group B (n = 78) in discontinuation rate (4.9% to 19.2%, P = 0.007). The change in clinical indices from baseline were not different between the groups at either timepoint. LIMITATIONS: As the major reason for discontinuation in Group B was the "withdrawal of consent" the concrete reason could not be verified. CONCLUSIONS: As a second-line treatment drug, escitalopram was suggested to be non-inferior to duloxetine in acceptability. TRIAL REGISTRATION: UMINCTR(UMIN000012367), registered on December 1st, 2013 and last updated on April 4th, 2017.


Assuntos
Citalopram , Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Humanos , Japão , Pacientes Ambulatoriais , Resultado do Tratamento
17.
J Intensive Care ; 9(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407891

RESUMO

BACKGROUND: The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). METHODS: This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. RESULTS: We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9-8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7-14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4-1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7-10.0), respectively. CONCLUSION: PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. TRIAL REGISTRATION: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).

18.
Infect Genet Evol ; 88: 104703, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401005

RESUMO

Noroviruses are recognized as a leading cause of outbreaks and sporadic cases of acute gastroenteritis (AGE) among individuals of all ages worldwide, especially in children <5 years old. We investigated the epidemiology of noroviruses among hospitalized children at two hospitals in East Java, Indonesia. Stool samples were collected from 966 children with AGE during September 2015-July 2019. All samples were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for the amplification of both the RNA-dependent RNA polymerase (RdRp) and the capsid genes of noroviruses. The genotypes were determined by phylogenetic analyses. In 2015-2019, noroviruses were detected in 12.3% (119/966) of the samples. Children <2 years old showed a significantly higher prevalence than those ≥2 years old (P = 0.01). NoV infections were observed throughout the year, with the highest prevalence in December. Based on our genetic analyses of RdRp, GII.[P31] (43.7%, 31/71) was the most prevalent RdRp genotype, followed by GII.[P16] (36.6%, 26/71). GII.[P31] was a dominant genotype in 2016 and 2018, whereas GII.[P16] was a dominant genotype in 2015 and 2017. Among the capsid genotypes, the most predominant norovirus genotype from 2015 to 2018 was GII.4 Sydney_2012 (33.6%, 40/119). The most prevalent genotype in each year was GII.13 in 2015, GII.4 Sydney_2012 in 2016 and 2018, and GII.3 in 2017. Based on the genetic analyses of RdRp and capsid sequences, the strains were clustered into 13 RdRp/capsid genotypes; 12 of them were discordant, e.g., GII.4 Sydney[P31], GII.3[P16], and GII.13[P16]. The predominant genotype in each year was GII.13[P16] in 2015, GII.4 Sydney[P31] in 2016, GII.3[P16] in 2017, and GII.4 Sydney[P31] in 2018. Our results demonstrate high detection rates and genetic diversity of norovirus GII genotypes in pediatric AGE samples from Indonesia. These findings strengthen the importance of the continuous molecular surveillance of emerging norovirus strains.

19.
Ann Surg Oncol ; 28(1): 465-473, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32840743

RESUMO

PURPOSE: To evaluate the oncological feasibility of pure laparoscopic radical nephroureterectomy (p-LRNU) for upper tract urothelial carcinoma (UTUC) compared with conventional LRNU (c-LRNU) using a propensity-adjusted multi-institutional collaboration dataset. METHODS: Among the 503 UTUC patients who underwent RNU, we identified 219 who underwent c-LRNU (laparoscopic nephrectomy with open bladder cuff resection) and 72 who underwent p-LRNU (dissecting the kidney, ureter, and bladder cuff under complete laparoscopy). We adopted a propensity score (PS) matching method to achieve homogeneity with respect to patient backgrounds. PS matching-adjusted Cox-regression analysis was performed to evaluate the risk factors that influenced oncological outcomes. RESULTS: Sixty-eight p-LRNU and 68 c-LRNU patients were matched. Overall, 51 (37.0%) developed intravesical recurrence (IVR), 21 (15.4%) had disease recurrence, and 20 (14.7%) died. Patients who underwent p-LRNU had a significantly shorter operation time and less blood loss than those who underwent c-LRNU. Although no significant differences in 3-year recurrence-free survival were found between the two methods, atypical recurrence sites were observed in the p-LRNU group, including the brain, sigmoid colon, vagina, and peritoneum. Regarding IVR, the 3-year IVR-free survival rate was 41.8% in the p-LRNU group, which was significantly lower than that in the c-LRNU group (66.6%, p = 0.004). Multivariate analysis demonstrated that a history of bladder cancer, ureteral cancer, and p-LRNU were independent risk factors for subsequent IVR. CONCLUSION: Although p-LRNU is less invasive, the current technique may increase the incidence of atypical disease recurrence and subsequent IVR due to extravesical and intravesical tumor dissemination.


Assuntos
Nefroureterectomia , Neoplasias Ureterais , Neoplasias Urológicas , Estudos de Coortes , Feminino , Humanos , Laparoscopia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Ureterais/cirurgia , Neoplasias Urológicas/cirurgia
20.
Jpn J Clin Oncol ; 51(2): 287-295, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32893303

RESUMO

BACKGROUND: Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy. METHODS: We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group). RESULTS: No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007). CONCLUSIONS: Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.


Assuntos
Cistectomia , Uretra/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos , Idoso , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Uretra/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos/efeitos adversos
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